Archive for April, 2018

Phenergan : Drug class, uses, dosage, side effects and contraindications

Apr 27 2018 Published by under Medicines

What is Phenergan?

Phenergan is the brand name of the drug promethazine which is used as an antihistamine, sedative, and anti-nausea medication.

In order to relieve allergy symptoms such as a runny nose, watery eyes, red eyes, or to prevent motion sickness, your doctor may prescribe you this medication.

Moreover, it can also help with allergic skin conditions or reactions to blood or plasma products.

It may be used to treat some common problems such as common cold, sneezing, cough, and runny nose.

Doctors often combine promethazine with other medications in order to relieve a sudden allergic reaction known as anaphylaxis. Phenergan is also given before or after surgery, during labor for causing the sedation in the patient.

Phenergan is sometimes also used to treat post-surgery nausea and vomiting. It can improve the effectiveness of pain medication when combined with narcotic pain medication after surgery.

Phenergan is marketed by Morton Grove Pharmaceuticals, Inc., and is available as a tablet, syrup, or a suppository to use rectally.

Phenergan : Drug class, uses, dosage, side effects and contraindications

Phenergan’s active ingredient molecular structure, weight, formula, IUPAC name and drug class

The molecular structure of promethazine:

What is Phenergan 25 mg used for?

Molecular formula: C17H21ClN2S

Molecular weight: 320.879 g/mol

IUPAC name: N,N-dimethyl-1-phenothiazine-10-ylpropan-2-amine;hydrochloride

Phenergan drug class: This compound belongs to the class of organic compounds known as phenothiazines. These are polycyclic aromatic compounds containing a phenothiazine moiety, which is a linear tricyclic system that consists of two benzene rings joined by a para-thiazine ring.

Phenergan (promethazine) mechanism of action

Like other H1-antagonists, promethazine competes with free histamine for binding at H1-receptor sites in the GI tract, uterus, large blood vessels, and bronchial muscle.

The relief of nausea appears to be related to central anticholinergic actions and may implicate activity on the medullary chemoreceptor trigger zone.

Phenergan pharmacokinetics

Phenergan which contains promethazine is well absorbed from the gastrointestinal tract. After 20 minutes of oral administration, the clinical effect of the drug starts which lasts for 4 to 6 hours, and may persist as long as 12 hours.

The metabolism of promethazine is done by the liver, and after metabolism, it turns into a variety of compounds which are the sulfoxides of promethazine and N-demethylpromethazine. These are predominant metabolites that appear in the urine.

How long Phenergan stays in your system?

The elimination half-life of Phenergan is 16 to 19 hours and the elimination time of a drug is five times than that of its half-life, therefore it will be eliminated in 2 to 3 days completely.

What are the indications and usage of Phenergan?

Phenergan, either orally or by suppository, is useful for:

  • Perennial and seasonal allergic rhinitis
  • Vasomotor rhinitis
  • Allergic conjunctivitis due to inhalant allergens and foods
  • Mild and uncomplicated allergic skin manifestations including urticaria and angioedema
  • Amelioration of allergic reactions to blood or plasma
  • Dermographism
  • Anaphylactic reactions, as adjunctive therapy to epinephrine and other standard measures, after the acute manifestations have been controlled
  • Preoperative, postoperative, or obstetric sedation
  • Prevention and management of nausea and vomiting after anesthesia and surgery
  • Therapy adjunctive to meperidine or other analgesics for control of post-operative pain
  • Sedation in both children and adults, as well as relief of apprehension and production of light sleep from which the patient can be easily aroused
  • Active and prophylactic treatment of motion sickness
  • Antiemetic therapy in postoperative patients

Phenergan (Promethazine): Side Effects, Interactions, Warning

What are the contraindications of Phenergan?

Phenergan is contraindicated for use in pediatric patients who are less than two years old. Additionally, it is contraindicated in comatose states, in patients who are hypersensitive to promethazine or even in those who have an idiosyncratic reaction to promethazine or to other phenothiazines.

Phenergan tablets and suppositories are contraindicated in comatose states, and in individuals known to be hypersensitive or to have had antihistamines are contraindicated for use in the treatment of lower respiratory tract symptoms including asthma.

What are the precautions that one should take while using Phenergan?

Phenergan needs to be used with caution because it can cause marked drowsiness or impair the mental and/or physical abilities required for the performance of potentially hazardous tasks, such as driving a vehicle or operating machinery.

The impairment can be enhanced by the use of alcohol or other central-nervous-system depressants such as sedatives/hypnotics (including barbiturates), narcotics, narcotic analgesics, general anesthetics, tricyclic antidepressants, and tranquilizers. Pediatric patients should be counseled to avoid potential harm in bike riding or in other hazardous activities.

One should also avoid the exposure to the sun. In patients with cardiovascular disease or with impairment of liver function, Phenergan Tablets and Suppositories should be used cautiously.

Drugs having anticholinergic properties should be used with caution in patients with narrow-angle glaucoma, prostatic hypertrophy, stenosing peptic ulcer, pyloroduodenal obstruction, and bladder-neck obstruction.

Can Phenergan be taken in pregnancy?

Phenergan comes under pregnancy category C, which means its risk, cannot be ruled out. There are no sufficient and adequate, well-controlled human studies and animal studies have shown the risk to the fetus or the lacking as well.

If the drug given during pregnancy, there is a chance of fetal harm, however, the potential benefits may outweigh the potential risk.

Can Phenergan be taken by nursing mothers?

The excretion of Phenergan in human milk is not known. However, Phenergan tablets and suppositories have the potential for serious adverse reactions in nursing infants, one should make a decision that whether to discontinue, breastfeeding or discontinue Phenergan administration because many drugs can excrete in human milk.

Can Phenergan be given to pediatric patients?

Phenergan tablets and suppositories are contraindicated in pediatric patients especially in patients who are less than 2 years of age. Precaution is also necessary in case of administration of Phenergan syrup in such patients.

What happens if I overdose Phenergan?

The overdose of promethazine can cause serious side effects and symptoms such as mild depression of the central nervous system and cardiovascular system to profound hypotension, respiratory depressions, unconsciousness, and sudden death. Therefore one should completely avoid overdosing on promethazine which is present in Phenergan.

The patient can also suffer from other symptoms such as hyperreflexia, hypertonia, ataxia, athetosis, and extensor-plantar reflexes.

Atropine-like signs and symptoms–dry mouth, fixed, dilated pupils, flushing, as well as gastrointestinal symptoms–may occur.

In children, receiving a single dose of 75 mg to 125 mg orally can suffer from the paradoxical-type reaction, mainly characterized by hyperexcitability and nightmares.

What are the side effects of Phenergan?

Common side effects of promethazine include:

  • Dizziness
  • Drowsiness
  • Dry mouth
  • Blurred vision
  • Stuffy nose
  • Ringing in the ears
  • Constipation
  • Weight gain
  • Impotence or trouble having an orgasm

Serious side effects of promethazine

If you notice any of the following, quit taking your medicine and call your doctor right away:

  • Restlessness or feeling jittery or agitated
  • Twitching or uncontrolled movements of your eyes, lips, tongue, face, legs, or arms
  • Uncontrolled shaking
  • Problems swallowing or drooling
  • Trouble with balance or walking
  • Feeling like you might pass out
  • Seizure
  • Vision problems or increased sensitivity to light
  • Pale skin
  • Bruising or bleeding easily
  • Fever
  • Flu symptoms
  • A sore throat
  • Hallucinations
  • Nausea/stomach pain
  • Skin rash
  • Yellowing of the skin or eyes (Jaundice)
  • Problems with urination
  • Joint pain and swelling
  • Swollen glands

Other symptoms that necessitate a call to your doctor include:

  • Slow heart rate
  • Muscle aches and stiffness
  • Chest pain
  • Vomiting
  • Unusual thoughts or behavior
  • Pale skin color
  • Weak pulse
  • Fainting
  • Slow breathing

Get emergency help if you notice any signs of an allergic reaction such as hives, itching, trouble breathing or swelling of the mouth, face, lips, or tongue.

Can Phenergan be abused?

For achieving the sedative effects and to achieve a state of delirium, the promethazine containing substances are abused widely.

Promethazine/codeine when used with flavored soda or jolly rancher candy produces a new mood-boosting drink which is usually designed to help you unwind after a stressful day.

When using with opioids, promethazine augments opioid-induced euphoria and allows for a lower dose of opioid.

Promethazine alone can cause drowsiness, tachycardia, agitation, confusion, slurred speech, hallucinations, dizziness, and hypertension.

The combination formulation of promethazine can cause frequent drowsiness and tachycardia when used in higher doses.

Can Phenergan be taken for sleep?

Phenergan is used for many conditions such as allergies, motion sickness, nausea, vomiting, and anxiety before sleep and pain after sleep. It is used as a sleep aid before and after surgery.

There are many medications that you can take to sleep along with promethazine, however, you may suffer from a drowsiness which is extreme and may last longer.

Such drugs include chloral hydrate, estazolam, eszopiclone, flurazepam, temazepam, triazolam, zaleplon, and zolpidem.

Can Phenergan be taken for motion sickness?

Phenergan is also prescribed for the treatment of nausea and motion sickness, however, it causes more drowsiness and sedation as compared to other antihistamines.

Other medications that can be used are sympathomimetics which proved helpful in preventing as well treating the motion sickness.

However, they are not shown to be more superior than other medications along with addictive potential; therefore they are not as often prescribed.

Phenergan for preventing and treating the motion sickness should be used with extreme caution as it is a controlled substance and can be abused.

One can use caffeine for getting relief from motion sickness but should be used along with promethazine as it shows some other pharmacological benefits when used concurrently.

Can Phenergan be given to the patients with cardiovascular disease?

Phenergan which is a phenothiazine, after parental dose can cause hypotension including orthostatic hypotension, reflex tachycardia, increased pulse rate, syncope, and dizziness, however, these effects are rare with an oral dose.

These effects mainly occurred by low-potency agents, for example, chlorpromazine and thioridazine which subsides after few hours of administration. After severe hypotension, a fatal cardiac arrest can occur but rarely.

Other reported adverse cardiovascular effects include edema, thrombosis, and ECG abnormalities such as PR and QT interval prolongation, diffuse T-wave flattening, and ST-segment depression.

Therefore in patients with cardiovascular diseases, phenothiazines should be avoided or used with extreme caution.

One should monitor the patient closely for cardiovascular status, including ECG changes, is recommended at all dosages.

If parenteral therapy is given, patients should be in a supine position during administration and for at least 30 to 60 minutes afterward.

Patients who experience orthostatic hypotension should be cautioned not to rise too abruptly. Occasionally, when severe, hypotension may require treatment with vasoconstrictive agents such as norepinephrine or phenylephrine.

Epinephrine should not be used, however, since phenothiazines can reverse its vasopressor effects and cause a further lowering of blood pressure.

Can Phenergan be used with amitriptyline?

If you are already using promethazine (Phenergan) and your doctor is going to prescribe you amitriptyline, tell your doctor about the administration of this medication.

In order to take these medications safely, you may need a dose adjustment or even some special tests because co-administration of a phenothiazine with a tricyclic antidepressant (amitriptyline) may result in elevated plasma concentrations of one or both drugs as well as additive adverse effects.

In elderly patients, this combination should be used with precautions. If you have signs of bladder problems, dry mouth, stomach pain, fever, blurred vision, confusion, dizziness, or reduced heart rate, tell your doctor immediately.

Until you know how these medicines work to you, you should also avoid driving. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using your medications without first talking to your doctor first.

Can Phenergan be taken with moxifloxacin?

When administered concurrently promethazine and moxifloxacin can cause major interactions.

Moxifloxacin can increase the risk of an irregular heart rhythm that may be serious and potentially life-threatening when used with promethazine, although it is a relatively rare side effect.

In case, you are having a heart condition called congenital long QT syndrome, other cardiac diseases, conduction abnormalities, or electrolyte disturbances (for example, magnesium or potassium loss due to severe or prolonged diarrhea or vomiting)., you may be more susceptible.

You should talk to your doctor if you have any questions or concerns. Your doctor may already be aware of the risks but has determined that this is the best course of treatment for you and has taken appropriate precautions and is monitoring you closely for any potential complications.

If you develop sudden dizziness, lightheadedness, fainting, shortness of breath, or heart palpitations during treatment with these medications, whether together or alone, seek medical attention immediately.

Let your doctor know if you are taking any other medications, herbs, vitamins, prescribed or non-prescribed medications. Before stopping this medication, let your doctor know about this too.

Can Phenergan be taken with tramadol?

If medications such as tramadol administered with other medications that can cause seizures such as promethazine, it can cause increased seizures and also can increase the risk, however, such effects occur rarely.

The elderly patients are more susceptible, if they are undergoing alcohol or drug withdrawal, have a history of seizures, or have a condition affecting the central nervous system such as a brain tumor or head trauma.

In case of concerns and doubts, you should always check with your doctor.

Your doctor may be able to prescribe alternatives that do not interact, or you may need a dose adjustment or more frequent monitoring by your doctor to safely use both medications.

While being treated with these medications, you should avoid or limit the use of alcohol.

The activities which require mental alertness such as driving, or operating hazardous machinery, should also be avoided until you know how these medications affect you.

Let your doctor know if you are taking any other medications, herbs, vitamins, prescribed or non-prescribed medications. Before stopping this medication, let your doctor know about this too.

Can Phenergan be taken with clomipramine?

If you are already taking clomipramine, talk to your doctor if he is going to prescribe you Phenergan.

You should notify your doctor promptly if you have signs of bladder problems, dry mouth, stomach pain, fever, blurred vision, confusion, or reduced heart rate.

You should avoid driving until you know how these medications will affect you.

It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using your medications without first talking to your doctor first.

Can Phenergan be taken with doxepin?

Let your doctor know that you are taking Phenergan before taking doxepin because when taken together, they can cause an interaction.

Your doctor may need to make dose adjustment or special tests in order to prescribe you both medications together. Especially in the elderly patient, the combination should be used cautiously.

If you see any symptoms of bladder problems, dry mouth, stomach pain, fever, blurred vision, confusion, dizziness, or reduced heart rate, notify your doctor promptly.

You should tell your doctor about the other medications that you are taking and you should also avoid driving until and unless you are aware of the effects of these medications. Before ceasing on these medications, let your doctor about it too.

What is the use of Raloxifene?

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Raloxifene : Drug class, mechanism of action, uses dosage and side effects

Apr 26 2018 Published by under Medicines

What is raloxifene?

Raloxifene belongs to drug class of second-generation selective estrogen receptor modulator (SERM). It is used as a prophylactic treatment to prevent osteoporosis (thinning of bones) in women after menopause.

It acts like estrogen and has estrogen agonistic effect on the metabolism of bone and cholesterol and at the same time it act on mammary gland and uterine tissue as an estrogen antagonist.

Raloxifene does not use for the treatment hot flashes cause due to menopause but may cause hot flashes. It is most commonly known under the brand name Evista.

Raloxifene IUPAC name, molecular formula, weight, structure

IUPAC name:  (2-(4-Hydroxyphenyl)-6-hydroxybenzo(b)thien-3-yl)(4-(2-(1 piperidinyl) ethoxy) phenyl) methanone

Molecular formula: C28H27NO4S

Molecular weight: 473.584 g/mol

Molecular formula:

What is the use of raloxifene?

Drug class: Raloxifene belongs to the class of organic compounds known as aryl-phenylketones, which are aromatic compounds containing a ketone substituted by one aryl group, and a phenyl group.

What are the indications of raloxifene

Raloxifene is indicated in following conditions:

For treatment and prevention of osteoporosis
Raloxifene is recommended for the treatment and prevention of osteoporosis in women after menopause.

For breast cancer
Raloxifene is indicated for reducing the risk of persistent breast cancer in postmenopausal women associated with osteoporosis.

The risk of breast cancer was not completely eliminated by raloxifene. Before starting raloxifene treatment, patients should have breast examination and mammograms.

Then start medication and should have regular breast exams and mammograms in keeping with good medical follow-up with continue treatment with raloxifene.

After an assessment of the risk that breast cancer may develop, the decision regarding the initiation of raloxifene therapy should be based upon an individual evaluation of the benefits and risks.

The reduction of breast cancer was shown in women of menopause. 27% of the participants received the drug for 5 years. The long-term effects and the recommended length of treatment are not known.

Important limitations of use for breast cancer risk reduction

There is no adequate data is available regarding the effect of raloxifene therapy in invasive breast cancer incidence in women with inherited mutations traits (BRCA1, BRCA2) to be able to make specific recommendations on the effectiveness of raloxifene.

• Raloxifene is not indicated for the treatment of risk of recurrence of invasive breast cancer.
• Raloxifene is not indicated for the reduction in the risk of noninvasive breast cancer.

How raloxifene sjould be administered?

Recommended Dosing
Raloxifene is available in tablet dosage form in the strengths of 60mg per tablet. The recommended dose may differ for different patients.

The mentioned dosage schedule is on average basis. Raloxifene is for oral use only (tablets) which can take with or without food.

  • For preventing bone loss:
    • Adults—60 mg once a day, with or without meals.
  • For treating bone loss:
    • Adults—60 mg once a day, with or without meals.
  • For preventing invasive breast cancer:
    • Adults—60 mg once a day, with or without meals

Recommendations for calcium and vitamin D supplementation

For the treatment and prevention of osteoporosis, because osteoporosis calcium and vitamin D is inadequate in daily diet so it is recommended to add calcium supplement with or without vitamin D supplement in a daily diet.

In postmenopausal women average requirement of elemental calcium is 1500mg/day. High intake of calcium has not shown additional benefits for bones while very high intake of calcium of about 2000mg/day may cause associated adverse events, which includes hypercalcemia and kidney stones.

The daily suggested intake of vitamin D is 400-800 IU. Patients who have vitamin D insufficiency need additional vitamin D supplements.

Patients with gastrointestinal malabsorption syndromes higher doses of vitamin D supplementation and measurement of 25-hydroxyvitamin D should be considered.

Raloxifene use and venous thromboembolism

Raloxifene is contraindicated in women with an active or past history of venous thromboembolism (VTE), such as deep vein thrombosis, pulmonary embolism, and retinal vein thrombosis.

In clinical trials, increase risk of venous thromboembolism (deep vein thrombosis and pulmonary embolism) was observed due the treatment of raloxifene in postmenopausal women.

A less serious outcome, superficial thrombophlebitis, also has been reported more frequently with raloxifene than with placebo.

There was greatest risk of deep vein thrombosis and during the first 4 months of treatment pulmonary embolism occurs, and the magnitude of risk appears to be similar to the reported risk associated with use of hormone therapy.

Because immobilization increases the risk for venous thromboembolic events independent of therapy, raloxifene should be discontinued at least 72 hours prior to and during prolonged immobilization (e.g., post-surgical recovery, prolonged bed rest), and raloxifene therapy should be continued only after the patient is fully ambulatory.

In addition, women taking raloxifene should be advised to move about periodically during prolonged travel.

The risk-benefit balance should be considered in women at risk of thromboembolic disease for other reasons, such as congestive heart failure, superficial thrombophlebitis, and active malignancy.

How does Raloxifene work in the body?

Raloxifene use during pregnancy and breastfeeding

Raloxifene is contraindicated during pregnancy, in women who may become pregnant, and in nursing mothers. Raloxifene can cause serious side effects when it is given to a pregnant woman.

In pregnancy or in mother who can become pregnant, this drug should only be prescribed by keeping in mind the risk-benefit ratio to the patient and should inform patient the harm that may cause to a fetus by this drug. In animal studies, multiple dose-dependent serious problems occurred.

Raloxifene storage

  • Store the medicine in a closed container at room temperature and away from heat. Store in air resistant container to avoid moisture. Use amber color container to protect from direct light. Keep from freezing.
  • Keep out of the reach of children.
  • Do not keep outdated medicine or medicine no longer needed.

Raloxifene and death due to stroke

Clinical trial shows that there is risk of coronary heart disease in postmenopausal women. There is also increased risk of death due to stroke was observed after treatment with raloxifene.

Raloxifene and cardiovascular disease

Raloxifene should not be used in the patients with primary or secondary cardiovascular disease.

Raloxifene and premenopausal use

There is no indication for premenopausal use of raloxifene. Safety of raloxifene in premenopausal women has not been established and its use is not recommended.

Raloxifene and hepatic impairment

Raloxifene should be administered with caution in patients with hepatic impairment. Safety and efficacy have not been established in patients with hepatic impairment.

Limited clinical data suggest that some women with a history of marked hypertriglyceridemia (>5.6 mmol/L or >500 mg/dL) in response to treatment with oral estrogen or estrogen plus progestin may develop increased levels of triglycerides when treated with raloxifene. Serum triglycerides should be monitored in patient with this medical history.

Raloxifene and renal impairment

In renal impaired patient raloxifene should be used with caution. In moderate to severe renal impaired patients safety and efficacy have not been confirmed.

Raloxifene and unexplained uterine bleeding

Any unexplained uterine bleeding was observed as clinically indicated. Raloxifene-treated and placebo-treated groups had similar incidences of endometrial proliferation.

Raloxifene and breast abnormalities

Any unexplained breast abnormality occurring during raloxifene therapy should be investigated. Raloxifene does not eliminate the risk of breast cancer.

Raloxifene mechanism of action

Raloxifene has dual property. It acts as estrogen agonist as well as it also acts as an estrogen antagonist, while raloxifene is commonly referred as selective estrogen receptor modulator (SERM).

Biologically, raloxifene shows its action by mediating through binding with estrogen receptors. In the result of this binding, in some tissues activation of estrogenic pathways (agonism) and in some tissues blockade of estrogenic pathways (antagonism) occurs.

The agonistic or antagonistic effect of raloxifene depends upon the degree of employment of co-activators and co-repressors to estrogen receptor (ER) target gene promoters.

In bones, raloxifene appears to act as an estrogen agonist. It decreases bone resorption and bone turnover, improves bone mineral density (BMD) and decreases the incidence of fracture.

Preclinical data shows that raloxifene acts as an estrogen antagonist in uterine and breast tissues. These results are consistent with findings in clinical trials which suggest that raloxifene lacks estrogen-like effects on the uterus and breast tissue.

Raloxifene pharmacodynamics

Oophorectomy or menopause leads to the decreases in estrogen levels which lead to increases in bone resorption, decrease in Bone mineral density and accelerated bone loss.

Lost in bones becomes rapid because the compensatory increase in bone formation is not sufficient to overcome the resorption effect or loss.

Due to the low levels of estrogen, the balance between formations and desorption of bones become imbalance and this imbalance is age-related.

Eventually, in many women, this leads to the decrease in bone mass, osteoporosis, and increase risk for fracture for fracture especially in spine, hips and wrist.

The most common type of osteoporotic fracture is vertebral fractures in postmenopausal women.

In both the osteoporosis treatment and prevention trials, raloxifene treatment showed consistent, statistically significant suppression of bone resorption and bone formation, and reflects by the change in serum and urine markers of bone turnover like bone-specific alkaline phosphatase, osteocalcin, and collagen breakdown products.

The suppression of bone turnover markers was apparent by 3 months and persisted throughout the 36-month and 24-month observation periods.

Treatment with either raloxifene or hormone therapy was associated with a reduction in bone resorption and a positive response in calcium balance.

However, there was a small decrease in serum total calcium, inorganic phosphate, total protein, and albumin, which was less decrease as compared to hormone therapy. Platelet count was also decreased slightly and was not different from estrogen therapy.

Raloxifene pharmacokinetics

Effect of raloxifene for the treatment and prevention of osteoporosis was evaluated in 3000 postmenopausal women. Pharmacokinetic data also were obtained in conventional pharmacology studies in 292 postmenopausal women.

Absorption: Raloxifene has a fast absorption after oral administration. About 60% of an oral dose is absorbed in the conjugate and can for presystemic glucuronide conjugation.

The absolute bioavailability of raloxifene is about 2%. The time needed to achieve maximum plasma concentration and bioavailability depend on systemic interconversion and enterohepatic cycling of raloxifene and its glucuronide metabolites.

Administration of raloxifene is increased with a standardized, high-fat meal, but does not lead to clinically meaningful changes in systemic exposure. Raloxifene can be taken with or without meals.

Distribution: After oral administration of a single dose of raloxifene ranging from 30 to 150 mg o, the apparent volume of distribution is 2348 L/kg and is not dose dependent. Raloxifene and the monoglucuronide conjugates have a high (95%) plasma proteins binding. Raloxifene binds to both albumin and α1-acid glycoprotein.

Metabolism: with the help of oral administration of 14C-labeled raloxifene, biotransformation and disposition of raloxifene in humans have been evaluated. Raloxifene face wide range first-pass effect or metabolism to form three main glucuronide conjugates: raloxifene-4′-glucuronide, raloxifene-6-glucuronide, and raloxifene-6, 4′-diglucuronide.

No other metabolites have been detected, this gives the proof that raloxifene is metabolized by cytochrome P450 enzyme pathways. Non-conjugated raloxifene comprises less than 1% of the total radiolabeled material in plasma.

This is consistent with interconversion of raloxifene and the glucuronide metabolites.

Following intravenous administration, raloxifene is cleared at a rate approximating hepatic blood flow. Apparent oral clearance is 44.1 L/kg/hr.

Raloxifene and its glucuronide conjugates are interconverted by reversible systemic metabolism and enterohepatic pathway, thereby prolonging its plasma elimination half-life to 27.7 hours after oral dosing.

Excretion: Raloxifene is primarily excreted in feces and less than 0.2% is excreted unchanged in urine. Less than 6% of the raloxifene dose is eliminated in urine as glucuronide conjugates.

What are adverse reactions of raloxifene use

During the clinical study trials and post-market surveillance some adverse effects were reported. Some are serious, some are moderate and some are rare.

  • Body as a Whole
    • Infection
    • Flu Syndrome
    • Headache
    • Leg Cramps
    • Chest Pain
    • Fever
  • Cardiovascular System
    • Hot Flashes
    • Migraine
    • Syncope
    • Varicose Vein
  • Digestive System
    • Nausea
    • Diarrhea
    • Dyspepsia
    • Vomiting
    • Flatulence
    • Gastrointestinal Disorder
    • Gastroenteritis
  • Metabolic and Nutritional
    • Weight Gain
    • Peripheral Edema
  • Musculoskeletal System
    • Arthralgia
    • Myalgia
    • Arthritis
    • Tendon Disorder
  • Nervous System
    • Depression
    • Insomnia
    • Vertigo
    • Neuralgia
    • Hypesthesia
  • Respiratory System
    • Sinusitis
    • Rhinitis
    • Bronchitis
    • Pharyngitis
    • Cough Increased
    • Pneumonia
    • Laryngitis
  • Skin and Appendages
    • Rash
    • Sweating
  • Special Senses
    • Conjunctivitis
  • Urogenital System
    • Vaginitis
    • Urinary Tract Infection
    • Cystitis
    • Leukorrhea
    • Uterine Disorderb
    • Endometrial Disorderb
    • Vaginal Hemorrhage
    • Urinary Tract Disorder
    • Breast pain
    • Vaginal bleeding

Raloxifene use in geriatric population

Of the total number of patients in placebo-controlled clinical studies of raloxifene, 61% were 65 and over, while 15.5% were 75 and over.

No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Based on clinical trials, there is no need for dose adjustment for geriatric patients.

Raloxifene overdose and its management?

In an 8-week study in which 63 postmenopausal women were evaluated, and a dose of raloxifene used was 600mg/day and it was observed that 600mg/day dose was safely tolerated. In clinical trials, no raloxifene overdose has been reported.

In post-market surveillance, raloxifene overdose has been reported very rarely (less than 1 out of 10,000 [<0.01%] patients treated).

Even at a very high dose of 1.5gram/ day raloxifene was well tolerated and no fatalities was associated with raloxifene.

While adverse reactions were reported in approximately half of the adults who took ≥180 mg raloxifene and included leg cramps and dizziness.

Two 18-month-old children each ingested raloxifene 180 mg. In these two children, symptoms reported included ataxia, dizziness, vomiting, rash, diarrhea, tremor, and flushing, as well as elevation in alkaline phosphatase.

There is no specific antidote for raloxifene. No mortality was seen after a single oral dose in rats or mice at 5000 mg/kg (810 times the human dose for rats and 405 times the human dose for mice based on surface area, mg/m2) or in monkeys at 1000 mg/kg (80 times the AUC in humans).

Raloxifene and hypertriglyceridemia

Studies on women with a history of marked hypertriglyceridemia (>5.6 mmol/L or >500 mg/dL) in response to therapy with oral estrogen or a combination therapy with estrogen and progestin showed that they may develop increased levels of triglycerides when treated with raloxifene.

Women with this medical history should have serum triglycerides monitored when taking raloxifene.

Raloxifene and levothyroxine interaction

Some reports showed that concurrent use of raloxifene and levothyroxine may interfere with the gastrointestinal absorption of levothyroxine. The mechanism of interaction is although unknown.

Raloxifene and cholestyramine interaction

Concomitant use of cholestyramine with raloxifene is not recommended. Because it is predictable that other anion exchange resins would have a similar effect.

Raloxifene should not be co-administered with other anion exchange resins.

Raloxifene and warfarin interaction

If Raloxifene is given concomitantly with warfarin or other warfarin derivatives, prothrombin formation time should be monitored more closely during the raloxifene treatment.

Raloxifene interaction with highly protein-bound drugs

Raloxifene with other highly protein binding drugs like diazepam, diazoxide, and lidocain should be prescribed with very caution.

Although potential of raloxifene to affect the protein binding of other drugs was not seen. Plasma protein binding of raloxifene is more than 95%.

Is Risedronate the most effective medication for osteoporosis?
What is quetiapine and what is it used for?

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Quetiapine : Mechanism of action, uses, dosage, side effects and overdose

Apr 25 2018 Published by under Medicines

What is quetiapine?

Quetiapine is a potent antipsychotic agent that belongs to dibenzothiazepine derivatives. Quetiapine shows its antipsychotic properties by antagonizing serotonin activity mediated by two serotonin receptors i.e. 5-HT1A and 5-HT2 receptors.

In the mesolimbic and mesocortical areas of the brain quetiapine reversibly bind with dopamine D1 and D2 receptors with low affinity leading to decreased psychotic symptoms, such as hallucinations and delusions.

In addition, quetiapine also has an affinity for adrenergic and histamine receptors and binds to alpha-1, alpha-2 adrenergic and histamine H1 receptors.

Quetiapine IUPAC name, molecular formula, weight and structure

IUPAC name of quetiapine:

2-(2-(4-Dibenzo[b,f][1,4]thiazepine-11-yl-1-piperazinyl)ethoxy)ethanol

Molecular formula: C21H25N3O2S

Molecular weight: 383.5099 g/mol

Chemical structure:

Quetiapine IUPAC name, molecular formula, weight and structure

Quetiapine description and synthesis

Quetiapine was developed in 1985 and approved for medical uses in United State in 1997. Patent rights for the product ended in 2012; however, in many regions the long acting version remains under patent until 2017.

Quetiapine is tetracyclic compound and its structure is closely related to clozapine, olanzapine, loxapine, and other tetracyclic antipsychotics.

The synthesis of quetiapine begins with a dibenzothiazepinone. First of all, dibenzothiazepine is formed when lactam ring is treated with phosphoryl chloride.

Side chain on the lactam ring is introduced with the reaction  of nucleophilic substitution

Quetiapine uses and administration

Quetiapine is used for the treatment of schizophrenia, bipolar disorder, and major depressive disorder. Quetiapine may be sometimes prescribed for some other indications as well, like sleep aid due to its sedative effect but this is not as recommended. Seroquel is the best-known brand name for Seroquel.

Quetiapine is available in tablets form as the fumarate salt. Quetiapine fumarate is a white to off-white in colored crystalline powder which is moderately soluble in water.

It is available in oral dosage form in strengths of  25 mg, 50 mg, 100 mg, 200 mg, 300 mg, and 400 mg tablets.

Excipients which are used to form quetiapine tablet are povidone, dibasic dicalcium phosphate dihydrate, microcrystalline cellulose, sodium starch glycolate, lactose monohydrate, magnesium stearate, hypromellose, polyethylene glycol and titanium dioxide.

What is the mechanism of action of quetiapine?

Quetiapine works as an antagonist of various neurotransmitter receptors in the brain such as serotonin 5HT1A and 5HT2, dopamine D1 and D2, histamine H1, and adrenergic α1 and α2 receptors. Quetiapine has no significant affinity at cholinergic muscarinic and benzodiazepine receptors.

However, the antagonistic effect of quetiapine on dopamine type 2 (D2) and serotonin type 2 (5HT2) causes the drug’s efficacy for schizophrenia. Treatment for somnolence is explained by quetiapine antagonism effect on histamine H1 receptors.

Quetiapine dose-related effects

Quetiapine, at very low doses, this drug acts mainly as a histaminergic receptor blocker (antihistamine) and α1-adrenergic blocker.

As the dose is increased, quetiapine may activate the adrenergic system and has a potent binding capacity to serotonin receptors and autoreceptors.

At high doses, quetiapine starts acting as a strong dopamine receptor blocker. In off-label prescriptions, quetiapine is use for chronic insomnia, low-dose of quetiapine is not recommended due to the harmful side-effects.

What are the indications of quetiapine?

Qutiapine is approved for following indications:

  • Schizophrenia:

Schizophrenia is one of the most important and primary indications of quetiapine. It efficacy was established in adolescents of 13-17 years of age.

  • Bipolar disorder:

Quetiapine is directed for the acute treatment of manic episodes associated with bipolar I disorder, both as monotherapy and add-on therapy with lithium or divalproic sodium.

Its efficacy was proven in two monotherapy trials in adults, in one 3-week adjunctive trial in adults, and in one 3-week monotherapy trial in pediatric patients (10-17 years)

  • Depressive disorder

Quetiapine as monotherapy is indicated for the treatment of acute depressive episodes associated with bipolar disorder. Quetiapine efficacy was proved in studies on adult patients with bipolar I and bipolar II disorder.

Pharmacokinetics of quetiapine

The activity of quetiapine is primarily due to the parent drug. The multiple dose pharmacokinetics of quetiapine is proportional to dose within the proposed clinical dose range, and there is a chance of accumulation of quetiapine upon multiple dosing.

Quetiapine is most commonly eliminated via hepatic metabolism with an elimination half-life of about 6 hours. Steady-state concentration can be achieved within two days of dosing. Quetiapine do not interfere the metabolism of other drugs which are metabolized by cytochrome P450 enzymes.

  • Absorption:

Quetiapine is readily absorbed after oral administration, peak plasma concentrations reach within 1.5 hours. The bioavailability of tablet formulation is almost 100% relative to solution.

The bioavailability of quetiapine is affected if it is taken with food, with Cmax and AUC values increased by 25% and 15%, respectively.

  • Distribution:

Quetiapine is distributed widely throughout the body with an apparent volume of distribution of 10.4 L/kg. It has plasma protein binding of 83% at therapeutic concentrations.

In vitro studies showed that quetiapine did not affect the binding of narrow therapeutic index drugs like warfarin or diazepam to human serum albumin. Warfarin and diazepam also do not alter the binding of quetiapine with plasma protein.

  • Metabolism and elimination:

Out of the single oral dose, only less than 1% is excreted as unchanged drug, this means that quetiapine is highly metabolized. Approximately 73% and 20% of the drug is eliminated through urine and feces, respectively.

Metabolism and elimination for Quetiapine

How long quetiapine stays in your body?

The terminal half-life of quetiapine is about 6 hours.

What are the contraindications of quetiapine?

Quetiapine is contraindicated in patients with known hypersensitivity to quetiapine or of any other excipient of the product.

What are the warnings associated with the use of quetiapine?

  • If the patient is allergic to quetiapine then he/she should avoid quetiapine.
  • Quetiapine due to its anti-histamine properties causes sedation. Patient having a driving job or those who operate with heavy machinery should use quetiapine with caution.
  • Patient with heart problems, especially cardiac arrhythmia should use quetiapine with caution because it causes QT prolongation.

Use of quetiapine in pregnancy and lactation

Quetiapine is categorized as a pregnancy category C medicine. There is insufficient evidence to rule out any risk to the fetus but available data suggests it is unlikely to result in any major malformations in the fetus. Quetiapine is secreted in breast milk and hence quetiapine-treated mothers are advised not to breastfeed.

Can quetiapine cause orthostatic hypotension?

At the begining of therapy and dose titration with quetiapine, orthistatic hypotension may occur. Probably it is due to α1-adrenergic antagonist properties of the drug. Syncope was reported in only 1% of the patients treated with quetiapine.

Can quetiapine cause cardiovascular problems?

Many trails and studies showed that there is clear chance that during the treatment of quetiapine cardiac problem can become severe or cardiac problems which are under control can become uncontrolled.

So it is advised that quetiapine should be used with caution in patients with known cardiovascular disease specially with the history of myocardial infarction or ischemic heart disease, heart failure or conduction abnormalities, cerebrovascular disease or conditions which may predispose patients to hypotension (dehydration, hypervolemia and treatment with antihypertensive medications).

If hypotension appears during dose titration, return to the previous dose in the titration schedule is appropriate.

Can quetiapine cause cataract?

In animal experiment level, cataract development was observed during the treatment of quetiapine in dog studies.

Can quetiapine cause seizures?

Clinical trials showed that seizures occurred during quetiapine treatment in 0.6% of patients treated as compared to 0.2% on placebo and 0.7% on active control drugs.

Like any other antipsychotic drug, quetiapine should also be used cautiously in patients with a history of seizures or with conditions that may potentially lower the seizure threshold.

Can quetiapine cause cholesterol and triglyceride elevations?

In schizophrenia treatment trials, quetiapine treated patient shows a higher level of cholesterol and triglycerides of 11% and 17% as compared to the controlled group. These change are of transient phase occurs only for initial few weeks like weight increase.

Can quetiapine cause hyperprolactinemia?

During quetiapine experiments on lab rats, increase in prolactin was observed.

Does qutiapine has a potential for cognitive and motor impairment?

Somnolence is one of the most commonly reported side effects that can occur in patients who are on treatment with quetiapine especially during the 3-5 day period of initial dose titration.

In schizophrenia trials, 18% of patients on quetiapine reported somnolence adverse effect as compared to 11% patients on placebo reported somnolence.

During the trials for effect quetiapine in acute bipolar mania disorder, when quetiapine is taken as monotherapy it caused somnolence in 16% while in placebo group in 4% patient’s somnolence occurred.

In acute bipolar mania during quetiapine treatment, occurrence of somnolence was in 34% patients, as compared to placebo group this ratio is 9%.

Can quetiapine cause priapism?

Quetiapine has good affinity to alpha-adrenergic receptors and drug may block these receptors causing the adverse effect of priapism.

Can quetiapine cause dysphagia?

Another adverse effect of antipsychotics including quetiapine is esophageal dysmotility and aspiration.

Can quetiapine cause hypothyroidism?

Quetiapine have effect on thyroxin and thyroid stimulating hormone as clinical trials on quetiapine also determines a dose-related decrease in total and free thyroxin (T4) of approximately 20% at maximum therapeutic dose range of quetiapine and was maximal in the first two to four weeks of treatment and maintained without adaptation or progression during more chronic therapy.

Generally, this change in thyroxin and TSH is reversible may be reversed once the quetiapine treatment is stopped. This reversal process is irrespective of the duration of treatment.

In studies where quetiapine is used as monotherpay there is increase in TSH levels in about 0.4% of quetiapine patients. While few number of the patients with TSH increases needed replacement thyroid treatment.

In the treatment of  mania, where quetiapine was used as add on therapy with lihium or divalproate, 12% of quetiapine treated patients showed elevated levels of TSH as compared to 7% of placebo treated patients.

Of the quetiapine treated patients with elevated TSH levels, had simultaneous low free T4 levels.

Quetiapine and the risk of suicide

The chances of a suicide attempt and suicidal behavior are very common in bipolar disorder and schizophrenia, thus close supervision of high risk patients should accompany drug therapy.

In order to reduce the risk of overdose, quetiapine treatment should be started with the smallest quantity of tablets consistent further dose is titrated to the appropriate dosage along with good patient management.

What if I overdose quetiapine?

Maximum non-fatal dose of quetiapine in human is estimated with in the range of 1200 mg to 9600 mg. In general, reported signs and symptoms for overdosing  includes drowsiness and sedation, tachycardia, hypotension hypokalemia and first degree heart block.

In post-marketing experience, there have been very rare reports of overdose of quetiapine alone resulting in death, coma, or QTC prolongation.

Quetiapine overdosing management

There is no specific antidote for the over dose of quetiapine. So in case of acute over dosage following supportive measurements should be done to avoid sever side effect. First of all establish and maintain an airway and ensure adequate oxygenation and ventilation.

Gastric lavage (after intubation, if patient is unconscious) and administration of activated charcoal together with a laxative should be considered.

If the patient is suffering from hypotension and circulatory collapse then he should be treated with intravenous fluids and/or sympathomimetic agents.

Do not use epinephrine and dopamine, since beta stimulation may worsen hypotension in the setting of quetiapine-induced alpha blockade.

If severe extrapyramidal symptoms are occurring then anticholinergic should be administered. Close medical supervision and monitoring should continue until the patient recovers.

What are precautions needed with quetiapine?

Quetiapine is not recommended for the use in psychotic problem related to dementia. Quetiapine increases the risk of death old age patient associated with dementia related conditions.

To ensure the safety during use of quetiapine treatment, inform your doctor if you have any problem of following

  • Liver or kidney disease
  • Heart disease, particularly heart arrhythmia, history of heart attack or stroke
  • High or low blood pressure
  • History of low white blood cells
  • Seizure or epilepsy
  • A person with family history of diabetes

Taking antipsychotic in the last trimester of pregnancy may cause serious problem to new born. If you become pregnant while taking the quetiapine medication, do not stop taking medication without consulting from your doctor.

Do not give extended release quetiapine to children. It is only adult use.

Can I use quetiapine if it is expired?

Do not use quetiapine after the expiry date mentioned on the pack because it may have no further efficacy or an unexpected or undesired effect if you take expired quetiapine.

How to store the quetiapine?

Store at 25C (771F). Store in a cool and dry place and protect from sunlight.

Keep away from the reach of children.

Quetiapine dosage and administration

  • For Bipolar Mania

Starting Dose: For Bipolar Mania quetiapine is started as follows with bid dosing

Day 1: 100mg/day

Day 2: 200mg/day

Day 3: 300mg/day

Day 4: 400 mg/day

Maintenance dose: Quetiapine should maintained after titration to the maximum dose of 800mg/day in two divided doses

  • For Schizophrenia:

Starting dose: In schizophrenia quetiapine should be started s follows

Day 1: 25mg bid

Day 2 and Day 3: increase up to 25-50mg bid or tid

Day 4: 300-400mg in divided doses

Dose is further adjusted in old age debilitated patients. Dose titration should be done slow and maintained at low dose.

Elderly patients should be started on quetiapine 50 mg/day and the dose can be increased in increments of 50 mg/day depending on the clinical response and tolerability of the individual patient.

Dose modifications in hepatic impaired patients

  • Reinitiating of treatment in patients previously discontinued:

It is recommended to restart the therapy in the patients who have discontinued the quetiapine treatment for more than 1week. If dose discontinuation is less than one week then gradual increase in dose is not required and maintenance dose may be reinitiated.

Switching from antipsychotics drugs

No specific protocol or procedure has been defined for the switching of patient from any other antipsychotic to quetiapine or the use of quetiapine with other antipsychotic.

In case of Schizophrenia immediate discontinuation of previous antipsychotic is acceptable to replace medication with quetiapine. While in other indication gradual decrease in dose of previous antipsychotic is recommender.

While titrating out previous medication keep in mind that the period of overlapping antipsychotic should be minimized to avoid the side effects.

What are the side effects of quetiapine?

Very common (>10% incidence) adverse effects

  • Dry mouth
  • Dizziness
  • Headache
  • Somnolence

Common (1–10% incidence) adverse effects

  • High blood pressure
  • Orthostatic hypotension
  • High pulse rate
  • High blood cholesterol
  • Elevated serum triglycerides
  • Abdominal pain
  • Constipation
  • Increased appetite
  • Vomiting
  • Increased liver enzymes
  • Backache
  • Asthenia
  • Insomnia
  • Lethargy
  • Tremor
  • Agitation
  • Nasal congestion
  • Pharyngitis
  • Fatigue
  • Pain
  • Dyspepsia (Indigestion)
  • Peripheral oedema
  • Dysphagia
  • Extrapyramidal symptoms: there is relative less risk of Extrapyramidal side effect from Quetiapine and clozapine.
  • Weight gain:

Rare (<1% incidence) adverse effects

  • Prolonged QT interval (had an odds ratio for prolonging the QT interval over placebo of 0.17)
  • Sudden cardiac death
  • Syncope
  • Diabetic ketoacidosis
  • Restless legs syndrome
  • Hyponatraemia, low blood sodium.
  • Jaundice, yellowing of the eyes, skin and mucous membranes due to an impaired ability of the body to clear bilirubin, a byproduct of haem breakdown.
  • Pancreatitis, pancreas swelling.
  • Agranulocytosis, drop in white blood cell count. It becomes fatal some time.
  • Leukopenia, a drop in white blood cell count, severity is less than Agranulocytosis.
  • Neutropenia, a drop in neutrophils, the cell that provide immunity to the body against bacterial infection.
  • Eosinophilia
  • Anaphylaxis, a potentially fatal allergic reaction.
  • Seizure
  • Hypothyroidism, underactive thyroid gland.
  • Myocarditis, swelling of the myocardium.
  • Cardiomyopathy
  • Hepatitis, swelling of the liver.
  • Suicidal ideation
  • A prolonged and painful erection.
  • Stevens-Johnson syndrome. A potentially fatal skin reaction.
  • Neuroleptic malignant syndrome a rare and potentially fatal complication of antipsychotic drug treatment. It is categorized by the following symptoms: tremor, rigidity, hyperthermia, tachycardia, mental status changes (e.g. confusion), etc.
  • Tardive Dyskinesia. A rare and often irreversible neurological condition causing involuntary movements of the face, tongue, lips and rest of the body. Most commonly it occurs due to prolonged treatment with antipsychotics. Particularly there is less chances of this side effect with atypical antipsychotics, especially quetiapine and clozapine.

Discontinuation and withdrawal during quetiapine use

Abrupt discontinuation of quetiapine may causes withdrawal symptoms so it should be discontinued or titrate out gradually, with careful consideration from the prescribing doctor, to avoid withdrawal symptoms or relapse.

According to the British National Formulary when discontinuation of anti-psychotic treatment is required, gradual decrease in dose is recommended to avoid acute withdrawal syndrome or rapid relapse.

In quetiapine treatment, gradual discontinuation is needed due to compensatory changes at dopamine, serotonin, adrenergic and histamine receptor sites in the central nervous system and withdrawal symptoms can occur during abrupt or over-rapid reduction in dosage.

However, although increasing demand for safe and effective antipsychotic withdrawal protocols or dose-reduction schedules there are no specific guidelines with proven safety and efficacy are currently available.

Withdrawal symptoms that are reported from abrupt discontinuation of antipsychotics include nausea, emesis, lightheadedness, diaphoresis, dyskinesia, orthostatic hypotension, tachycardia, insomnia, nervousness, dizziness, headache, excessive non-stop crying, and anxiety.

Can quetiapine be given to person with renal or liver impairment?

Renal and liver impairment is great concern for prescribing any drug because many drugs are metabolised and eliminated either renal route or liver route or in some cases through both routes.

So if the patient have renal or liver impairment then dose adjustment becomes necessary especially when concern drug is better than the alternate one.

What are some drugs that can interact with quetiapine?

Quetiapine do not effect on metabolism or absorption of many drugs because quetiapine has very low interference with cytochrome P450 enzyme activity.

This is the reason quetiapine have less drug to drug interaction specially with the narrow therapeutic index drugs like warfarin, phenytoin etc. but yet it have little effect of some drugs

  • Quetiapine should be cautiously co-prescribed with other centrally acting drugs.
  • Since quetiapine may cause hypotension, it may potentiate the effect of antihypertensive agents.
  • Quetiapine may antagonize the effect of levodopa and dopamine agonists.
  • Since co-administration of quetiapine and hepatic enzyme inducers e.g. phenytoin, carbamazepine, barbiturates, rifamine and glucocorticoids, increase the mean oral clearance of quetiapine, higher dose of quetiapine may be required to be given in such patients to ensure optimum efficacy in schizophrenia.
  • Thioridazine increases the oral clearance of quetiapine.
  • Though cimetidine causes about 20% decrease in the mean oral clearance of quetiapine, dosage adjustment for quetiapine is not required when it is given with simetidine.
  • Co-administration of ketoconazole, a potent inhibitor of cytochrome P450-3A, reduces oral clearance of quetiapine up to 84% causing an increase in maximum plasma concentration of quetiapine of about 335%. Hence quetiapine should be cautiously given with ketoconazole and 15 other inhibitors of cytochrome P450-3A e.g. itraconazole, fluconazole, and erythromycine.
  • Concomitant use of fluoxetine, imipramine, haloperidol, or risperidone with quetiapine did not alter the steady-state pharmacokinetics of quetiapine.

Effect of quetiapine on other drugs

Lorazepam: The administration quetiapine (dose of 250mg tid) with lorazepam (2mg, single dose) causes the reduction of mean learance of lorazepam by 20%.

Divalproic acid: When divalproic acid (500mg bid) is administered with quetiapine the mean maximum concentration and extent of absorption of total and free valproic acid at steady state were decreased by 10 to 12%.

The mean oral clearance of total valproic acid (administered as divalproic 500 mg bid) was increased by 11% when divalproic is administered with quetiapine (150 mg bid).

Lithium: Concomitant use of quetiapine (250 mg tid) with lithium had no effect on any of the steady-state pharmacokinetic parameters of lithium.

Antipyrine: Quetiapine had no clinically relevant effect on the clearance of antipyrine or urinary recovery of antipyrine metabolites even after the multiple doses of quetiapine. This is probably due to least interference of quetiapine with hepatic cytochrome p450 enzyme

What does Suboxone strips do to you?

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Suboxone strips : Ingredients, uses, side effects and drug test

Apr 24 2018 Published by under Medicines

What are Suboxone strips?

Dependence and addiction are essential components which are to be considered in substance use. A person can show either physical dependence or psychological dependence. Suboxone is a combination medication that is used to treat and maintain opioid dependence.

This formulation contains buprenorphine and naloxone. Buprenorphine is an opioid drug which is also classified as a narcotic. Naloxone is an opioid antagonist which inhibits the effects of the opioid drug.

One of the common routes for the administration of Suboxone is via strips. This is sometimes called as Suboxone film. This strip is administered to the patient sublingually in which it is positioned under the tongue and allow it to dissolve.

The time for dissolving of the drug is within 1 minute. Special care is needed while administrating the strip that it should not be cut, chewed or even swallowed.

At times, the Suboxone strip can be positioned on the inside of the left or right cheek. If placed in such a place, it will dissolve in the same manner as that when it is placed under the tongue.

What are the ingredients of Suboxone strips?

Active ingredients of suboxone strips include buprenorphine and naloxone.

Excipients used are polyethylene oxide, hydroxypropyl methylcellulose, maltitol, acesulfame potassium, lime flavor, citric acid, sodium citrate, FD&C yellow #6, and white ink.

Suboxone strips’ active ingredients molecular structure, weight, IUPAC name, and drug class

Buprenorphine:

Buprenorphine is a derivative of the opioid alkaloid thebaine that is a more potent (25 – 40 times) and longer lasting analgesic than morphine.

It works as a partial agonist at mu and kappa opioid receptors and as an antagonist at delta receptors. The lack of delta-agonist activity has been suggested to account for the observation that buprenorphine tolerance may not develop with chronic use.

IUPAC name: (1S,2R,6S,14R,15R,16R)-3-(cyclopropylmethyl)-16-[(2S)-2-hydroxy-3,3-dimethylbutan-2-yl]-15-methoxy-13-oxa-3-azahexacyclo[13.2.2.1²,⁸.0¹,⁶.0⁶,¹⁴.0⁷,¹²]icosa-7,9,11-trien-11-ol

Molecular formula: C29H41NO4

Molecular weight: 467.64 g/mol

Molecular structure:

Suboxone strips' active ingredients molecular structure, weight, IUPAC name, and drug class

Drug class: Buprenorphine belongs to the class of organic compounds called phenanthrenes and derivatives which are polycyclic compounds containing a phenanthrene moiety, that is a tricyclic aromatic compound with three non-linearly fused benzene.

Naloxone: Naloxone is an opioid antagonist medication used to block or reverse the effects of opioid drugs in the setting of drug overdoses which are rapidly becoming a leading cause of death worldwide.

More specifically, naloxone has a high affinity for μ-opioid receptors, where it acts as an inverse agonist, causing the rapid removal of any other drugs bound to these receptors.

When taken in large quantities, opioid medications such as morphine, hydromorphone, methadone, heroin, or fentanyl are capable of causing life-threatening symptoms such as respiratory depression, reduced heart rate, slurred speech, drowsiness, and constricted pupils.

If untreated, this can progress to vomiting, absent pulse and breathing, loss of consciousness, and even death.

Naloxone is indicated for the rapid reversal of these symptoms of central nervous system depression in opioid overdose. It’s important to note that naloxone only works on opioid receptors within the body, and is therefore not capable of reversing the effects of non-opioid medications such as stimulants like methamphetamine or cocaine, or benzodiazepines like lorazepam or diazepam.

IUPAC name: (1S,5R,13R,17S)-10,17-dihydroxy-4-(prop-2-en-1-yl)-12-oxa-4-azapentacyclo[9.6.1.0^{1,13}.0^{5,17}.0^{7,18}]octadeca-7(18),8,10-trien-14-one

Molecular formula: C19H21NO4

Molecular weight: 327.37 g/mol

Molecular structure:

How long does the blocker last in Suboxone?

Drug class: Naloxone belongs to the class of organic compounds named phenanthrenes and derivatives which are polycyclic compounds with a phenanthrene moiety, which is a tricyclic aromatic compound with three non-linearly fused benzene.

How do Suboxone strips work?

Recently, FDA has approved a new method of drug delivery system which is termed as “buccal delivery system”. This is a type of mucoadhesive system in which the drug is absorbed directly into the mucosa of the cheek.

The product is made by using an adhesive that shows rapid absorption through the cheek mucosa. This delivery system of drug has demonstrated twice the bioavailability of the suboxone film in comparison to the conventional dosage form.

How do you take a Suboxone strip?

How do you take a Suboxone strip?

How do Suboxone strips exert their actions?

Buprenorphine is a drug which is a partial agonist at the mu-opioid receptor and acts as an antagonist at the kappa opioid receptor at the same time.

Whereas, naloxone is a potent antagonist acting on the mu opioid receptors and generates opioid withdrawal signs and symptoms in patients who have developed physical dependence on opioids especially when they are administered parenterally. Here the primary rationale of combining naloxone with buprenorphine is to act as a deterrent to injection.

What does Suboxone strips do to you?

What is the need for Suboxone strips?

Buprenorphine has a poor absorption in the gastrointestinal region and ultimately a low bioavailability. When given in oral dosage form, less than 10% of the drug would be absorbed in the bloodstream.

When prepared in sublingual form, the percentage of drug availability increases from 10% to 30%. Sometimes this can increase up to 50%. In the gastric and intestinal environment, certain other factors including pH, motility and micro flora can also decrease the bioavailability of the drug.

One another reason to poorer bioavailability of drug is first pass effect. All these problems are resolved when preparing the buccal drug delivery system.

In such a formulation which has a higher bioavailability, only a small quantity of drug is used in manufacture. When small quantity of drug is needed the unit price will eventually be less.

Suboxone strips dosage

Suboxone film/ strip is administered to the patient either sublingually or buccally in a single daily dose.

However, while prescribing this product, number of revisits of patients should be kept in consideration as multiple refills are not recommended in the treatment especially during the early phase. If in a case, refills are advised, appropriate patient follow up shall be done.

For every individual, the dose of the medicine is different. Any change required in dosing should not be done without the consultation of the doctor.

The amount of the medicine a patient is prescribed is solely dependent on the strength of the drug.

Also, the number of doses given in a single day, the time in between two doses and the duration of the therapy recommended to the patient is dependent on the severity of the problem a patient is suffering.

The following dosage information comprises only the average doses of Suboxone.

FOR BUCCAL DOSAGE FORM (FILM)

  • For induction treatment of opioid treatment
  • Adults: For patients who are dependent on heroin or any other short acting opioid may be inducted either Suboxone sublingual film or even with sublingual buprenorphine monotherapy.
  • On the initiation of treatment, the first dose of Suboxone is administered when signs and symptoms of opioid withdrawal appears in a time period of not less than six hours after the patient last used opioid intake.

Day 1: an induction dosage of up to 8mg/2mg of Suboxone film is advised. Clinicians should start the therapy with a starting dose of 2mg/ 0.5mg or 4mg/ 1mg of buprenorphine/ naloxone.

This ratio can be titrated up to 2 or 4mg escalation of buprenorphine, at an approximate time interval of 2 hours. In special cases, this can raise upto 8mg/ 2mg of buprenorphine/naloxone depending on the control of acute withdrawal symptoms.

Day 2: a single dose containing 16mg/ 4mg of Suboxone is advised.

The patients who are dependent on long acting opioid such as methadone are at a higher risk of precipated and prolonged withdrawal symptoms. In such individuals, combination products such as Suboxone, have not yet established well controlled studies.

Naloxone in such a combination, even present in small quantity could further deteriorate the condition. For this rationale, buprenorphine alone is recommended.

  • Children: Use and dose must be directed by the doctor.
  • For maintaince treatment of opioid treatment
  • From Day 3, the dosage should be adjusted whether increasing or decreasing the quantities of buprenorphine/ naloxone to a level that stabilizes the patient condition and continue to lessen the withdrawal signs and symptoms.
  • One the patient is stabilized, the maintenance dose is given within a range of 4mg/ 1mg to 24mg/ 6mg of buprenorphine/ naloxone per day. No maximum duration of maintenance therapy is suggested till now.
  • Children: Use and dose must be directed by the doctor.

What if a dose of Suboxone strips is missed?

In case when a dose is missed, the patient is advised to take as soon as he remembers it. However, if it is time for next dose, the patent should skip the missed dose and continue with the regular prescribed dosing schedule. Doubling of the dose at a single time is not recommended.

Suboxone strips dosage form and available strengths

Suboxone strip is manufactured as an orange rectangular film engraved with a white printed logo. It is available is four different dosage strengths.

  • Buprenorphine 2 mg/naloxone 0.5 mg,
  • Buprenorphine 4 mg/naloxone 1 mg,
  • Buprenorphine 8 mg/naloxone 2 mg
  • Buprenorphine 12 mg/naloxone 3 mg

Proper use of Suboxone strips

For using the buccal film, the following steps should be followed.

  • Use your tongue to wet the sides of cheeks or rinse the mouth with water.
  • Do not cut or tear the film. By using a dry hand/ finger hold the film facing upwards.
  • Carefully place the film inside the mouth on the cheek.
  • Slightly press the film against the mucosa for 5 seconds.
  • Leave the film allowing the drug to dissolve.
  • Avoid touching or moving of the film by the action of the tongue. The film should not be chewed or swallowed by the patient.
  • In cases where more than one film is advised, place the second film on the other side of mouth.
  • Until the film is completely dissolved, the patient should avoid eating or drinking anything.

For using the sublingual film, the following steps should be followed.

  • Make sure the mouth is moist. For this purpose, intake of water in sufficient quantities is recommended.
  • By using clean dry finger, carefully place the strip under the tongue and allow it to dissolve completely.
  • When 2 strips are prescribed for a single time, place the second strip on the opposite side from the first strip.
  • Do not cut, chew, swallow or move the film.

Side effects of Suboxone strips

Suboxone, even though has the ability to undo the effects of narcotics but itself can cause addiction.  Following are some of the serious side effects that are observed on the use of Suboxone sublingual film.

  • Sleepiness, dizziness and other coordination problems
  • Dependency or abuse
  • Respiratory problems: trouble breathing
  • Low blood pressure
  • Allergic reaction: rash, hives, swelling of face and peripheries and wheezing.
  • Liver problems: jaundice, dark colored urine, pale stools, decreased appetite, abdominal pain & nausea.
  • Signs of opiod withdrawal: sweating, shaking, goose bumps, diarrhea, confusion, seizures, feeling hot and cold more than normal, muscle aches.
  • Raised cerebrospinal fluid pressure
  • Raised intracholedochal pressure
  • Adrenal insufficiency

Common side effects of Suboxone strip include:

  • Headache
  • Sweating
  • Numb mouth
  • Painful tongue
  • The inside of mouth is redder than normal
  • Intoxication (drunk)
  • Lack of attention
  • Insomnia
  • Irregular heartbeats (palpitations)
  • Blurred vision
  • Backpain
  • Fainting

Contraindications for using Suboxone strips

Suboxone strip is contraindicated in patients who have a history of hypersensitivity to any of the two ingredients. Before prescribing of Suboxone strip, the healthcare provider should check for

  • Liver and kidney problems
  • Breathing or any other lung problems
  • Having enlarged prostate gland (in men)
  • Head injury or any brain problem
  • Having difficulty in urinating
  • Having a curve in spine which affects breathing
  • Any gallbladder problems
  • Any adrenal gland problems
  • Addison’s disease
  • Hypothyroidism

Suboxone strips use during pregnancy and breastfeeding

Those women who are pregnant or planning to start a family soon should discuss it with their healthcare provider.

Studies haven’t yet established the effect of Suboxone on the unborn baby but chances are that the baby may develop symptoms of withdrawal at the time of birth as this drug belongs to Pregnancy Category C.

In case of breast feeding mothers who are using sSuboxone it should be bought in their knowledge that the drug can pass through mother’s milk to the baby and cause harm.

It is suggested to avoid breast feeding while Suboxone therapy is in process. In cases where this is not possible, it should be discussed with the doctor for finding out the best alternate way to breast feed the baby.

Suboxone strips use in geriatrics

Dose selection in geriatric patients should be done vigilantly. The treatment is usually started at the lowest effect dose of the medicine.

This imitates the greater frequency of diminished hepatic, renal or cardiac function and also of concomitant disease or other drug therapy.

Pharmacokinetics of Suboxone strips

  • Absorption: A combination of one 8mg/ 2mg and two 2mg/ 0.5mg Suboxone strips sublingually administered shows comparable relative bioavailability to the same total dose of Suboxone sublingual tablets while buccally administered strips have demonstrated higher relative bioavailability.
  • Distribution: Buprenorphine is 96% protein bound whereas Naloxone is more or less 45% protein bound.
  • Elimination: when the strip is given sublingually or buccally, elimination half life of buprenorphine ranges between 24 to 42 hours and naloxone’s half life is between 2 to 12 hours.
  • Metabolism: Buprenorphine undergoes N-dealkylation and glucuronidation. Norbuprenorphine is the major metabolite obtained in glucuronidation pathway. Naloxone undergoes glucuronidation to form naloxone-3-glucoronide.

What drugs can interact with Suboxone strips?

Although Suboxone have established safety and efficacy profiles over time but certain drugs when used together with Suboxone have caused clinically significant interactions.

Some of the most major drug interaction that have occurred with the concomitant use of Suboxone are as below.

Benzodiazepines and other CNS depressants

  • Clinical Effect: due to additive effect, the simultaneous use of BZD or other CNS depressants have lead to an increased risk of respiratory depression, sedation and in severe cases coma and eventually death.
  • Intervention: stopping of BZD or any other anti depressants. However, in some cases, observing in a higher level of care for taper may be correct.
  • While in other patients, gradually decreasing the dose of prescribed BZD or any other anti-depressant to the lowest effective dose may be appropriate.
  • Examples: Alcohol, barbiturates, anxiolytics, tranquilizers, general anesthestics and muscle relaxants.

Inhibitiors of CYP3A4

  • Clinical Effect: due to the concomitant use of suboxone and inhibitors of CY3A4, the plasma concentration of buprenorphine increases as a result of which drug stays in blood for longer time prolonging the effects of buprenorphine.
  • This happens particularly when an inhibitor is added to a dose on which the patient stabilized. However, when the administration of the inhibitor of CYP3A4 is ceased, the plasma concentration of of buprenorphine also decreases.
  • This results in decreased opioid efficacy or can even result in the development of withdrawal symptoms in patients who have become physically dependent on the drug.
  • Intervention: If both the drugs are important to use at the same time then consideration should be given to reducing the dose of Suboxone strip until stable drug effects are observed.
  • Constant monitoring of such patients should be done in order to check for respiratory depression and sedation at frequent intervals.
  • Examples: Macrolide Antibiotics, protease inhibitors, azole-antifungal agents.

Diuretics

  • Clinical Effect: The simultaneous use of these drugs can diminish the efficacy of diuretics by inducing the release of antidiuretic hormone.
  • Interventions: Regular monitoring of patients for signs of diminished diuresis and also changes occurring in blood pressure.

Serotogenic agents

  • Clinical Effect: The concomitant use of these drugs has resulted in serotonin syndrome.
  • Interventions: careful observation of the patient is required especially during the initiation phase of therapy. Impede Suboxone if serotonin syndrome is suspected.
  • Examples: SSRIs, SNRIs, TCAs

Suboxone strips overdosage

Clinical Presentation:

the patient is presented with pinpoint pupils, sedation, hypotension, respiratory depression and in most severe cases death occurs.

Treatment:

When overdosage occurs, respiratory and cardiac status of the patient should be examined cautiously. In such a condition, primary consideration shall be given to the re-establishment of adequate and sufficient respiratory exchange by providing a clear airway and introducing an assisted or controlled ventilation. Oxygen, IV fluids, vasopressors and other supportive actions shall be taken immediately.

Naloxone acts as an antagonist to buprenorphine. Higher than normal doses and repeated administration may be required to overcome the overdosage.

Suboxone strips abuse and dependence

  • Controlled Substance

Buprenorphine is a drug mentioned in Schedule III narcotic under the Controlled Substance Act. Under another Drug Addiction Treatment Act, the prescription use of this product is only limited to physicians and no other healthcare providers who meet certain qualifying requirements.

  • Abuse

Buprenorphine like other opioids have the potential for being abused and is subject to criminal pastime. Abuse of the product increases the risk of overdosage which will ultimately cause death of the user.

  • Dependence

Prolong use of Suboxone strip has produced physical dependence which is distinguished by moderate withdrawal symptoms occurring on sudden discontinuation or rapidly decreasing the dose of the drug from a high strength to a lower strength.

What precautionary measure should be taken during Suboxone strips use?

Before going under any kind of surgery (even dental surgery) or procedure required in emergency treatment, the patient should inform the doctor or any healthcare provider in charge that he is using Suboxone strips.

After the initiation of the therapy with Suboxone strips the patient might feel dizziness, lightheadedness, or even faint when he suddenly gets up from lying or sitting position. It is better to get up slowly and while standing up hold on to something as a support.

Excessive use of Suboxone strips has demonstrated infertility in both men and women. It is thus necessary to take the prescribed amount for prescribed duration of time. At the same time, sudden discontinuation of Suboxone will cause the patient to suffer from opioid withdrawal symptoms.

Suboxone strips storage conditions

Suboxone strip should be stored in a safe place, away from the reach of children.

It should be stored at a room temperature at 25°C.

Disposal of unused strips

When the Suboxone strips are no longer needed, disposal of all unopened film/ strips is necessary. This can be done by:

  • Remove the strip from its foil pouch.
  • Drop only the strip into the toilet.
  • Repeat these 2 steps for each strip.
  • Flush the toilet after all the strips have been put into the toilet.

It is to keep in mind, that only the strips are flushed and not the foil pouches or cartons.

How long do Suboxone strips stay in your system?

To find out how long the drug is likely to stay in the system after the last dose is taken, it is necessary to consider Suboxone’s elimination half-life, or more specifically, the half-lives of its active ingredients buprenorphine and naloxone.

The elimiantion half-life of buprenorphine is an calculate to be 37 hours, which is considered extremely long compared to naloxone which is eportedly between 30 minutes and 1 hour 21 minutes.

Thus it will take your body nearly 2 full days to excrete just half of the buprenorphine within a Suboxone dose.  Considering the 37 hour half-life of buprenorphine, it could be estimated to be fully cleared from your system in about 9 days.

This means that the naloxone component of Suboxone strips is cleared from the body well before buprenorphine.

Most people will excrete naloxone within 8 hours post-ingestion as a result of its extremely short elimination half-life.

It is important to note that although the elimination half-life of buprenorphine is around 37 hours, it is metabolized into “norbuprenorphine” which has a half-life that exceeds 37 hours.

Though the specific half-life of the metabolite “norbuprenorphine” hasn’t been scientifically elucidated, it is likely to remain in the body for longer than 9 days.

This means that Suboxone metabolites may remain in your system for potentially up to 2 weeks after your last dose.

Suboxone strips and patient counseling information

Following instructions shall be made available to every patient each time Suboxone strip is dispensed.

  • The strip must be administered as whole. It should not be cut, torn apart or even chewed or swallowed by the patient.
  • Advise patients that Suboxone contains opioid that can be a target for people who abuse prescription medication or street drugs. It is important to protect such drugs from theft.
  • It is important to keep Suboxone strips away from children as it may cause respiratory depression that can result in death.
  • Advise the patient to not to handover the Suboxone film to anyone even if that person is suffering same signs and symptoms. It may cause harm and death of that person.
  • Warn the patient that selling of the film is against the law.
  • Inform the patient to take the Suboxone strip once daily.
  • Advise the patient that the Suboxone strip may produce orthostatic hypotension in ambulatory patients.
  • Inform the patient that prolonged use of Suboxone had decreased fertility and it is still unknown whether the effects are reversible or not.
  • Suggest the patient to avoid taking any other drug whether its over the counter drug or prescription drug or even any herbal supplements.
  • Direct the patient to inform their closest family member or friend that in case of any emergency they should inform the healthcare provider that the patient is physically dependent on an opioid and is currently using Suboxone strip.

Is it safe to take Xanax and Suboxone together?
What is Nebivolol 5 mg used for?

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Nebivolol : Drug class, uses, contradictions and side effects

Apr 23 2018 Published by under Medicines

What is nebivolol?

Nebivolol belongs to the group of drugs called beta blockers. It acts only on the heart and vessels and hence is called cardiovascular specific. Nebivolol is used to treat hypertension and left heart failure.

Nebivolol is available in four different strengths: 2.5 mg, 5 mg, 10 mg and 30 mg. It is not available as generic nebivolol till now and will be available as generic medicine after the year 2021 after which its price is expected to fall. Currently it is marketed under different brand names such as Bystolic, Nodon, Nubeta etc. In most countries, it is available as prescription only drug.

Nebivolol is also available as a mixture product. The name of that drug is Byvalson and contains nebivolol 5 mg and valsartan 80 mg in each of its tablets.

Nebivolol molecular structure, weight, formula, IUPAC name, desription and drug class

Nebivolol is a highly cardioselective vasodilatory beta1 receptor blocker used in treatment of hypertension. In most countries, this medication is available only by prescription.

IUPAC name: 1-(6-fluoro-3,4-dihydro-2H-chromen-2-yl)-2-[[2-(6-fluoro-3,4-dihydro-2H-chromen-2-yl)-2-hydroxyethyl]amino]ethanol

Molecular formula: C22H25F2NO4

Molecular weight: 405.442 g/mol

Molecular structure:

What is Nebivolol 5 mg used for?

Drug Class: Nebivolol is an organic compound belonging to the class of 1-benzopyrans. These compounds contain a bicyclic compound made up of a benzene ring which is fused to a pyran, so that the oxygen atom is at the 1-position.

Nebivolol appearence and identification

Nebivolol Identification: Nebivolol is a white to off white powder that is soluble in dimethylsulfoxide, methanol and N,N-dimethylformamide. It is sparingly soluble in propylene glycol, polyethylene glycol and ethanol and only slightly soluble in methylbenzene, hexane and dichloromethane.

What is the mechanism of action of nebivolol?

The mechanism of action of nebivolol has not been clearly understood till now. However the following factors contribute towards the antihypertensive action of nebivolol

  • It is a selective β1-receptor antagonist. These receptors are present on the sinoatrial node as well as on the muscular wall of the heart. Normally epinephrine and norepinephrine bind with these receptors to increase the heart rate and contractility of myocardium which will pump more blood into the vessels and increase blood pressure.
  • Nebivolol being an antagonist will block these two action from taking place and contribute towards decreasing blood pressure.
  • Nebivolol is also found to suppress the release of renin, an enzyme which converts angiotensinogen to angiotensin I which is then converted to angiotensin II. Angiotensin II is a vasoconstrictor.
  • It also stimulates the release of aldosterone which is responsible for salt and water retention. Blocking renin will block this entire pathway and result in a decreased blood pressure.
  • Nebivolol is also responsible for vasodilation as it has a nitric oxide like action on the beta-3 receptors present directly on the wall of the vessels. This will reduce the total peripheral resistance and bring down the blood pressure.

What are the indications of nebivolol?

The only FDA approved indication of nebivolol is treatment of essential hypertension. However it can be given to other individuals suffering from diabetic nephropathy or left sided heart failure.

What are the contraindications of nebivolol?

Nebivolol is absolutely contraindicated in the following patients

  • Severe bradycardia
  • Heart block greater than 1st degree
  • Patients suffering from cardiogenic shock
  • Decompensated heart failure
  • Sick sinus syndrome (not a contraindication if a pacemaker is inserted)
  • Patients with moderate to severe hepatic disease
  • Patients with known hypersensitivity to nebivolol or any other component of the pill

Nebivolol and abrupt cessation of therapy

Abrupt cessation of nebivolol in patients with coronary artery disease will cause exacerbation of the condition any may present as angina, myocardial infarction or ventricular arrhythmias.

Patients should be informed about these side effects. If discontinuation is needed, it should be gradual and planned. Dose should be tapered over 1 to 2 weeks and patients should be advised to minimize physical activity. In case ischemic pain or arrhythmias develop, restart nebivolol immediately.

Nebivolol and bronchospastic diseases

Beta receptors present on the airways are responsible for bronchodilation. Giving a beta blocker will therefore cause bronchoconstriction. If an individual is suffering from a bronchospastic disorder e.g. asthma, his condition is likely to be worsened with the use of beta blockers.

Anesthesia and major surgery and nebivolol

There are certain anesthetics that depress myocardial function. Giving nebivolol (which also reduces contractility of the heart) raises the possibility of significant reduction in cardiac output. However, when beta blockers are given there is usually overexpression of the adrenergic receptors on the heart.

So when therapy is withdrawn and epinephrine released due to the stress of major surgery, the heart rate and contractility both will increase by many folds. This will increase myocardium oxygen demand and exacerbate underlying ischemia of the heart.

Evaluating both the pros and cons of stopping therapy, it has been advised to continue giving nebivolol during the perioperative period but such pateints should be monitored closely

Nebivolol and diabetes

One of the signs of hypoglycemia is shivering. This is because during hypoglycemia, skeletal muscle glycogen is broken down to glucose (this step is mediated by beta receptors).

The muscle uses this glucose and contracts and the patient appears to be shivering. So when a beta blocker is given, the conversion of glycogen to glucose is inhibited.

As a result, shivering due to hypoglycemia does not take place. Another sign of hypoglycemia is tachycardia. Since nebivolol is responsible for keeping a check on the heart rate, this sign too can be masked with the use of nebivolol. Beta blockers may also potentiate insulin-induced hypoglycemia.

All these things mean that mild hypoglycemia will go undiagnosed and will only be diagnosed when it is quite severe. Such severe hypoglycemia can cause brain damage.

Nebivolol and thyroid storm

Patients with thyrotoxicosis are usually prescribed beta blockers to treat tachycardia. They are also found to inhibit the peripheral conversion of T4 to T3.

Sudden withdrawal of beta blockers in such patients will expose the heart to unopposed action of thyroid hormones and can cause arrhythmias such as atrial fibrillation. Sudden withdrawal can also precipitate a thyroid storm.

Nebivolol and peripheral vascular disease

Generally beta blockers are known to worsen the condition of patients with peripheral vascular disease. Although nebivolol is one of the 4 beta blockers which can cause vasodilation and can be expected to improve the condition, however since no research has been done on it, the general rule for beta blockers should be applied to observe caution in patients with PVD.

Nebivolol and pheochromocytoma

Patients suspected of having pheochromocytoma should be given alpha blockers before prescribing beta blockers. Beta blockers alone will cause unopposed vasoconstriction of the vessels which will further increase blood pressure.

Pharmacokinetics of nebivolol

Absorption: Nebivolol is given through the oral route. Its bioavailability has not been studied. The absorption of nebivolol is not affected by food. Peak plasma concentration of nebivolol is reached between 1.5 to 4 hours and depends upon how quicly an individual can metabolize the drug.

Distribution: Nebivolol is highly bound to plasma proteins. At any given time, the amount of drug bound to these proteins is 98%.

Metabolism: Nebivolol undergoes a number of metabolic pathways. The most common pathway is glucoronidation. Other pathways the parent drug might undergo are hydroxylation, N-dealkylation and oxidation. All these reactions occur in the liver and are carried out by the P450 enzymes of the liver (enzyme subgroup involved is the CYP2D6 system).

The main metabolic pathway yields an active metabolite called d-nebivolol. The half-life of the drug varies from individual to individual as the ability to metabolize the drug varies from person to person.

Those who have a very active CYP2D6 system of enzymes are called extensive metabolizers (EMs) and those who a slow CYP2D6 system of enzymes are called poor metabolizers (PMs). The half-life in extensive metabolizers is 12 hours while the half-life in poor metabolizers is 19 hours.

Excretion: Urinary and fecal route are the two most common routes for the excretion of nebivolol. In extensive metabolizers 38% of the drug is excreted via the urinary route while 44% of the drug is excreted in the feces.

In poor metabolizers 67% of the drug is excreted via the urinary route while 13% of the drug is excreted in the feces. All of the drug is excreted as metabolic products and the amount of parent drug which is excreted is very little.

How is nebivolol stored and dispensed?

Nebivolol is stored at temperatures of 20 °C to 25 °C. The environment should be moisture free and it should be stored in an air tight container whose lid is child-proof.

The rules for dispensing the medicine vary for each country. In most countries it is a prescription only drug.

Side effects of nebivolol

The following side effects of nebivolol are considered to be mild in nature and usually, do not require any immediate medical attention:

  • Mild headache
  • Diarrhea
  • flatulence or bloating
  • rash
  • agitation
  • trouble sleeping
  • mild anxiety

The following side effects of nebivolol are considered to be severe and need immediate medical attention:

  • Fatigue
  • Swelling of the subcutaneous tissues of the face, arms, hands, lower legs, or feet (angioedema)
  • Pain in the chest or epigastrium
  • Feeling of squeezing the chest
  • Difficulty in breathing
  • Fast breathing
  • lightheadedness, dizziness, or fainting
  • weight gain in a short period of time
  • Unexplained weight loss
  • slow heartbeat
  • irregular heartbeat
  • tingling sensations in the hinds or feet
  • unusual tiredness or weakness
  • new onset wheezing

What should I do if I overdose on nebivolol?

The following are the signs and symptoms of an overdose on nebivolol:

  • Absent body movement
  • Decreased body movements
  • anxiety
  • blue lips, fingernails, or skin (signs of cyanosis)
  • change in visual acuity
  • chills
  • cold sweats
  • coma
  • confusion
  • cold and pale skin
  • continuous cough
  • decreased urine output
  • depression
  • dilated neck veins
  • signs of postural hypotension: dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
  • dry mouth
  • extreme fatigue
  • fast heartbeat
  • headache
  • increased hunger
  • increased sweating
  • increased thirst
  • irregular, fast or slow, or shallow breathing
  • loss of appetite (anorexia)
  • mood changes
  • muscle pain or cramps
  • nauseaor vomiting
  • nervousness
  • nightmares
  • noisy breathing: stridor or wheeze
  • numbnessin the hands, feet, or lips
  • seizures
  • shakiness
  • slurred speech
  • troubled breathing

If you have taken or suspect of taking more than the prescribed dose of nebivolol and are now experiencing any of the following signs and symptoms, go to your nearest ER immediately.

Management in the ER involves stomach wash as well as symptomatic treatment. The supportive measure should continue till the time the patient is clinically stable.

The half-life of normal doses of nebivolol is between 12 to 19 hours but in cases of overdose it is expected to be much higher. Therefore it might take 3 to 4 days for the patient to achieve clinical stability.

Common symptoms of overdose along with their specific treatment is given below:

  • Bradycardia: Give IV atropine immediately. If the clinical response is unsatisfactory, give isoproterenol or any other drug which has a positive chronotropic affect. Observe the patient while giving these drugs. In some cases, transvenous or transthoracic pacemaker installation maybe needed.
  • Hypotension: Immediately administer 500 to 1000 ml of fluids. If the response is insufficient add vasopressors. Intravenous glucagon may also be given.
  • Second or third degree heart block: Initiate isoproterenol infusion and monitor the patient. In some cases, transvenous or transthoracic pacemaker installation maybe needed.
  • Congestive cardiac failure: First line of therapy includes giving digoxin and diuretics. Other drugs which are shown to reduce mortality in congestive heart failure are beta blockers, hydralazine, spironolactone and installation of a pacemaker.
  • Bronchospasm: Short acting beta agonists such as albuterol are given as the first line of therapy. Other drugs used in case of no response are inhaled corticosteroids, anticholinergics (e.g. ipratropium), systemic steroids, magnesium, and finally epinephrine. If all fails endotracheal intubation is done. Aminophylline is no longer used in cases of acute bronchospasm.
  • Hypoglycemia: Initiate IV glucose or 5% dextrose. Monitor blood sugar level every 20-30 mins. Repeated doses of IV glucose or 5% dextrose or glucagon infusion maybe needed to treat hypoglycemia.

Nebivolol dosage

The initial recommended dose of nebivolol for the treatment of hypertension is 5 mg orally once a day. If needed, the dose can be increased to a maximum of 40 mg once a day. For increasing the dose, it is recommended to titrate the dose after every 2 weeks. Titrating dose earlier than 2 weeks is not considered to be beneficial.

The minimum dose needed for maximum response is called the optimum dose and is variable for every individual.

Bystolic (nebivolol) Drug Side Effects, Interactions

Nebivolol can be used alone, or in combination with other antihypertensive drugs.

Nebivolol should be taken once a day at the same time each day with or without food. If you have missed a dose, you can take it as soon as you remember, however, if the next dose is close, skip the missed dose. Never take double the dose.

General consideration

  • Transient worsening of bradycardia, heart failure or hypotension may take place during the titration period. If these are severe, therapy should be discontinued.
  • During the titration period, following monitoring is needed:
  • Monitoring of heart rate and blood pressure
  • Be on the lookout for signs and symptoms of heart failure (e.g., shortness of breath which worsens by lying down, edema, and weight gain), angina and myocardial infarction.

Price and prescription of Nebivolol

Nebivolol is used to treat hypertension and when it is compared with other antihypertensives, it is a relatively expensive drug. If you’re covered by the government funded medicare or have private insurance, nebivolol is most likely to be covered by it.

However if you don’t have any medical cover, you should look out for various coupons and discounts by pharmacies as it is an expensive drug.

An example of such a pharmacy is the online drug retailer GoodRx where the cheapest price a 30 tablet pack is $138.44. This price is 15% less than the average retail price of Bystolic which is $163.49.

Can I take nebivolol if I am pregnant?

There is no scientific research in humans to answer this question. However research was carried out on animals, the results of which are given below:

When very high dose nebivolol was administered to rats during organogenesis period, reduced fetal body weight was observed. Apart from this, there were small reversible delays in sternal and thoracic ossification.

When very high dose nebivolol was administered to pups during the perinatal period, prolonged gestation, dystocia, increases in late fetal deaths and stillbirths and decreased birth weight were observed.

Due to the above data collected in animals, nebivolol has been classified as a pregnancy category C drug i.e. not enough research has been done to determine if these drugs are safe during pregnancy hence should only be given when benefits far outweigh the risks.

Can I take nebivolol if I am breastfeeding?

There is no scientific research to assess the safety of breastfeeding while breastfeeding in humans. However it has been seen in rats that both nebivolol as well as its metabolic products cross the placental barrier and their presence is also found in the breast milk of rats.

Once that milk is ingested by the infant, he is now exposed to nebivolol himself which can cause bradycardia or heart block in the infant. It is due to this potential side effect that you should either breastfeed your child or take nebivolol, but don’t do both things at the same time.

Can I take nebivolol if I have liver impairment?

Almost all of the nebivolol that is absorbed undergoes metabolization in the liver. Therefore hepatic dysfunction is going to be associated with slow metabolization and increased half-life of the drug. The peak plasma concentration of nebivolol is also seen to be raised by 3 folds in such a population.

Patients having moderate hepatic impairment can initiate nebivolol at 2.5 mg once a day and titrated slowly if needed up to a level that is well tolerated. However there has been no study on the dosing and pharmacokinetics of nebivolol in patients with severe hepatic impairment and as a result this drug is contraindicated in this population.

Can I take nebivolol if I have kidney dysfunction?

Patients with mild renal dysfunction (ClCr 50 to 80 mL/min) showed no change in the clearance of nebivolol. Patients with moderate renal dysfunction (ClCr 30 to 50 mL/min) showed only minor reduction in clearance of nebivolol, however, patients with severe renal dysfunction (ClCr <30 mL/min) showed a 53% decrease in the clearance of nebivolol.

Another problem with nebivolol is that it shows 98% plasma protein binding. Therefore hemodialysis will not be useful.

From the above data the following recommendations have been drawn:

  • Patients with mild or moderate kidney dysfunction do not need any dose adjustments and should continue their normal dose. Those who are starting this medicine can start with the usual 5 mg dose once a day.
  • Patients with severe kidney dysfunction are recommended to start with an initial dose of 2.5 mg and if needed, it can be titrated up slowly.

Does nebivolol cause infertility?

When nebivolol was given to mice at a dose which were 0.3 to 5 times the maximum recommended human dose for 2 years, it was noticed that there was a significant increase in the incidence of testicular Leydig cell hyperplasia and adenomas.

Co-administration of dihydrotestosterone reduced blood LH levels and decreased the incidence of Leydig cell hyperplasia. Effect of nebivolol on sperms was noted to be reversible.

In humans, there has only been one research and that too for only 4 weeks to determine the effects of nebivolol on adrenal function, luteinizing hormone, and testosterone levels.

The study concluded that nebivolol had no effect on adrenal function or fertility of males. However since the study was short term, it cannot completely rule out the risk of Leydig cell hyperplasia and adenomas which were seen in mice. Therefore caution must be exercised when taking nebivolol for years.

Can nebivolol cause cancer?

Nebivolol was not found to be harmful to DNA in a number of assays. However it did cause testicular adenomas (benign tumors) in mice when administered for 2 years. Therefore more research needs to be done to ascertain the relationship between nebivolol and cancer.

Should I stop using nebivolol now that I have heart failure?

1067 patients suffering from congestive heart failure taking nebivolol were compared with 1061 patients suffering from congestive heart failure but on placebo.

There was no worsening of heart failure while taking nebivolol. From the conclusion of this study, the recommendation made was that you can continue to use nebivolol even if you suffer from heart failure, but if it starts to worse, then discontinue nebivolol.

How safe is nebivolol for people aged above 65 years of age?

The incidence of adverse effects and efficacy of nebivolol was studied on 478 patients above the age of 65and compared with 2322 patients below the age of 65. There was no overall difference in the safety or efficacy between older and younger patients.

What are some drugs that can interact with nebivolol?

Nebivolol has a number of minor, moderate and major drug interactions. The major drug interactions are:

  • CYP2D6 Inhibitors: Nebivolol is metabolized by CYP2D6 enzyme system of liver. Any drug which inhibits these enzymes will cause the metabolism of nebivolol to be delayed and its half-life increased. Examples of CYP2D6 inhibitors include quinidine, propafenone, fluoxetine, paroxetine, etc.
  • Hypotensive Agents: Do not use nebivolol with other beta blockers.  Patients receiving catecholamine-depleting drugs, such as reserpine or guanethidine should be closely monitored because using nebivolol in combination with these drugs may produce excessive reduction in sympathetic activity.
  • Cardiac Glycosides: Cardiac glycosides such as digoxin slow atrioventricular conduction and decrease heart rate. This same effect is also brought on by beta blockers. Concomitant use of digoxin with beta blockers increases the risk of bradycardia and heart block.
  • Calcium Channel Blockers: Non-dihydropyridine Calcium Channel Blockers such as verapamil and diltiazem will slow atrioventricular conduction and decrease heart rate. Concomitant use of these calcium channel blockers with beta blockers increases the risk of bradycardia and heart block.
  • Aminophylline: Aminophylline and beta blockers work in opposition to each other. Combined use of these two drugs with produce only a partial response.
  • Alpha-2 adrenergic agonist: Alpha-2 adrenergic agonist such as clonidine decrease the activity of the autonomic nervous system. This has the potential to decrease blood pressure and heart rate. Combined use of Alpha-2 adrenergic agonist can cause hypotension, bradycardia or heart block.

How long does nebivolol stay in your system?

In a normal healthy individual, nebivolol has a half-life of 12 hours in early metabolizers and it may increase up to 19 hours in poor metabolizers. It takes 5.5 half-lives to completely remove any drug from our body.

Therefore the time needed to completely remove nebivolol from an individual’s system after complete cessation of the drug is variable and ranges from 66 hours to 105 hours.

The time for complete removal of the drug is also influenced by kidney function, liver function as well as age of the patient. Therefore it is advisable to adjust the dose of nebivolol if you are aged, or have suboptimum renal or liver function.

Can I take alcohol with nebivolol?

Coadministration of alcohol with antihypertensives and other hypotensive agents, in particular vasodilators and alpha-blockers such as nebivolol, may result in additive effects on blood pressure and orthostasis.

Nebivolol and ethanol may have additive effects in lowering your blood pressure. You may experience headache, dizziness, lightheadedness, fainting, and/or changes in pulse or heart rate.

These side effects are most likely to be seen at the beginning of treatment, following a dose increase, or when treatment is restarted after an interruption. Let your doctor know if you develop these symptoms and they do not go away after a few days or they become troublesome.

Avoid driving or operating hazardous machinery until you know how the medications affect you, and use caution when getting up from a sitting or lying position. It is important to tell your doctor about all other medications you use, including vitamins and herbs.

Do not stop using any medications without first talking to your doctor.

May nebivolol provoke high cholesterol levels

Beta-adrenergic receptor blocking agents including nebivolol may alter serum lipid profiles. Increases in serum VLDL and LDL cholesterol and triglycerides, as well as decreases in HDL cholesterol, have been reported with some beta-blockers.

Patients with preexisting hyperlipidemia may require closer monitoring during beta-blocker therapy, and adjustments made accordingly in their lipid-lowering regimen.

Can I take nebivolol and verapamil together?

dditive reductions in heart rate, cardiac conduction, and cardiac contractility may occur when calcium channel blockers, especially verapamil and diltiazem, are used concomitantly with beta-blockers.

While this combination may be useful and effective in some situations, potentially serious cardiovascular adverse effects such as congestive heart failure, severe hypotension, and/or exacerbation of angina may occur.

Ventricular asystole, sinus arrest, and heart block have also been reported. The risk is increased with high dosages, IV administration, left ventricular dysfunction, or AV conduction abnormalities. Beta-blocker ophthalmic solutions may also interact, as they are systemically absorbed and can produce clinically significant systemic effects even at low or undetectable plasma levels.

Bradycardia (36 bpm) with wandering atrial pacemaker occurred in a patient receiving oral verapamil and timolol ophthalmic drops.

The proposed mechanisms include additive slowing in AV conduction, reduced cardiac contractility secondary to beta-blockade, and decreased peripheral vascular resistance secondary to calcium channel blockade. Verapamil and diltiazem may also decrease the clearance of some beta-blockers.

Can I take nebivolol and aminophylline together?

The pharmacologic effects of theophyllines and beta-blockers are opposite. Nonselective and high doses of cardioselective beta-blockers may cause severe or fatal bronchospasm by opposing theophylline-induced bronchodilation.

Ophthalmic beta-blockers undergo significant systemic absorption and may also interact.

In addition, propranolol and other beta-blockers may reduce the CYP450 hepatic metabolism of theophylline, and serum theophylline levels may be increased.

Can I take nebivolol and digoxine together?

Concomitant use of digitalis glycosides and beta-blockers may increase the risk of bradycardia. These agents slow atrioventricular conduction and decrease heart rate, hence they may have additive cardiac effects during coadministration.

Some beta-blockers such as carvedilol, esmolol, and talinolol have also been reported to increase the systemic bioavailability of digoxin.

The mechanism may involve enhanced absorption as well as reduced renal excretion of digoxin due to inhibition of intestinal and renal P-glycoprotein efflux transporter.

Can Travoprost treat Glaucoma?

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Travoprost : Mechanism of action, dosage and side effects

Apr 20 2018 Published by under Medicines

What is travoprost?

Travoprost is an ophthalmic solution which is used for treating the conditions like increased intraocular pressure and is also used for controlling the progression of glaucoma or ocular hypertension. Travoprost is a synthetic analog of prostaglandin F2alpha.

Travoprost IUPAC name, molecular formula, weight, structure and drug class

Molecular formula: C26H35F3O6

Molecular weight of travopost: 500.555 g/mol

IUPAC Name:  propan-2-yl (Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(E,3R)-3-hydroxy-4-[3-(trifluoromethyl)phenoxy]but-1-enyl]cyclopentyl]hept-5-enoate

Molecular structure:

Travoprost IUPAC name, molecular formula, weight, structure and drug class

Drug class: This compound belongs to the class of organic compounds known as prostaglandins and related compounds. These are unsaturated carboxylic acids consisting of a 20 carbon skeleton that also contains a five member ring, and are based upon the fatty acid arachidonic acid.

What is the mechanism of action of travoprost?

Travoprost is known to reduce the intraocular pressure by enhancing the drainage of aqueous humor as it is a selective FP prostanoid receptor agonist. The drainage of the aqueous humor is done by increasing the uveoscleral outflow and to a lesser extent, trabecular outflow facility.

What is the pharmacokinetics of travoprost?

Travoprost is systemically absorbed when administered to the eye and is metabolized by esterases as it is an isopropyl ester prodrug.  It is hydrolyzed or metabolized in the cornea and transferred to its free acid which is biologically active.

The topical ocular dose of the travoprost (less than 2%) is known to get excreted via urine as travoprost free acid with 4 hours of the administration. The elimination half-life of the travoprost free acid is 45 minutes.

How long travoprost stays in your system?

The elimination half-life of travoprost is 45 minutes (after it gets converted into free acid) and the elimination of the drug is equals to five-time to that of the elimination half-life, therefore, it will be out of your system in 4 to 5 hours completely.  

Travoprost dosage

The recommended dosage is one drop in the affected eye(s) once daily in the evening. Travoprost ophthalmic solution should not be administered more than once daily since it has been shown that more frequent administration of prostaglandin analogs may decrease the intraocular pressure lowering effect.

Reduction of the intraocular pressure starts approximately 2 hours after the first administration with maximum effect reached after 12 hours.

Travoprost may be used concomitantly with other topical ophthalmic drug products to lower intraocular pressure (IOP). If more than one topical ophthalmic drug is being used, the drugs should be administered at least 5 minutes apart.

What are the side effects of the travoprost?

When travoprost administered by the ophthalmic route it may cause some side effects, you should call your doctor immediately if you see any symptoms of allergic reactions for example hives, swelling of the face, lips, tongue, or throat or even difficulty in breathing. You should stop the administration of this medication immediately in case you see these side effects:

  • Eye swelling, redness, severe discomfort, crusting or drainage (may be signs of infection)
  • Red, swollen, or itchy eyelids
  • Increased sensitivity to light
  • Vision changes
  • Severe burning, stinging, or irritation after using this medicine

Common side effects may include:

  • Pain, itching, or redness of the eyes
  • Puffy eyelids
  • Blurred vision

How to use travoprost ophthalmic?

Before using this medication read all the instructions that are given on the prescription label carefully and follow them. Always use this medication in recommended amounts, do not use it more or less than recommended.

  • Every evening, put one drop of this medication in your affected eye and the usual recommended dose is 1 drop in the affected eye. It is important to follow the doctor’s instructions carefully.
  • Remove the contact lenses (if you wear), before applying this medication because it can discolor the soft contact lenses due to the presence of a preservative in it. After putting this medication into your eye, wait for at least 15 minutes before wearing your contact lenses.
  • Maintain hygiene while using this medication and do not forget to wash your hands before applying this medication.

How to apply travoprost eye drops?

To apply travoprost eye drops:

  • Tilt your head backward, and create a little pocket in the eye by pulling the lower eyelid downwards. Hold the dropper right above the eye and squeeze out one drop.
  • Without blinking or squinting, close your eyes for 2 to 3 minutes. As the liquid can drain into your tear duct, you should gently press your finger for one minute, to the inside corner of the eye in order to prevent the drainage.
  • In case your doctor has prescribed you any other eye drops, wait for 5 minutes before using any other medication.
  • Maintain hygiene and prevent the contamination of the dropper by not touching the tip of the dropper of the medication container as it can lead to contamination of the medication also. The contamination of the medication can cause serious vision disturbances.
  • If the medication contains any kind of particles or impurities in it, or even if the medication seems discolored, avoid using such medicine and buy a new one.
  • If you have an eye injury or eye infection, tell your doctor right away.
  • If you are using travoprost ophthalmic and you need surgery (such as eye surgery), let your doctor know that you are already using travoprost. Your doctor can stop this medication for a short period of time.
  • You should store this medication away from moisture and heat and should be placed at a cool temperature. When the container is not in use, close the container tightly.

how to apply travoprost

Can travopost be used for eyelashes growth?

Travoprost is a new drug which is used to lower the intraocular pressure in patients with ocular hypertension and glaucoma. It is proved more effective than timolol and proved to have equal efficacy as latanoprost in terms of reducing intraocular pressure. However, they showed similar side effects. The eyelashes growth was observed higher in case of travoprost as compared to timolol.

Travoprost increases length and darkness of the eyelash which is known to be associated with eyelash changes that occur at the time of treating ocular hypertension.  However, this prostaglandin analogs are not FDA approved for influencing eyelashes growth, not even for the treatment of the hypotrichosis.

Moreover, the efficacy of this agent has also not been evaluated. Therefore you should always consult your doctor before using this medication for eyelashes growth and should not be applied in the infected eye without prior consultation with your doctor.

Can I use travoprost in pregnancy?

The use of travoprost in Australia, during pregnancy is contraindicated. In UK and US, this drug can be used but only when benefit outweighs the risk to the fetus.

It comes under USFDA pregnancy category C which means that there are no sufficient data are given regarding the safety and efficacy of this drug during pregnancy, however the potential benefits can warrant the use of this drug in women who are pregnant, despite the potential risks, it carries.

Therefore pregnant women or even in those women who are trying to get pregnant should practice adequate precautions in order to avoid direct exposure to this medication or even to the container.

Travoprost carcinogenesis, mutagenesis, impairment of fertility

Two-year carcinogenicity studies in mice and rats at subcutaneous doses of 10, 30, or 100 mcg/kg/day did not show any evidence of carcinogenic potential. However, at 100 mcg/kg/day, male rats were only treated for 82 weeks, and the maximum tolerated dose (MTD) was not reached in the mouse study.

The high dose (100 mcg/kg) corresponds to exposure levels over 400 times the human exposure at the maximum recommended human ocular dose (MRHOD) of 0.04 mcg/kg, based on plasma active drug levels.

Travoprost was not mutagenic in the Ames test, mouse micronucleus test or rat chromosome aberration assay. A slight increase in the mutant frequency was observed in one of two mouse lymphoma assays in the presence of rat S-9 activation enzymes.

Travoprost did not affect mating or fertility indices in male or female rats at subcutaneous doses up to 10 mcg/kg/day (250 times the MRHOD of 0.04 mcg/kg/day on a mcg/kg basis). At 10 mcg/kg/day, the mean number of corpora lutea was reduced, and the post-implantation losses were increased. These effects were not observed at 3 mcg/kg/day (75 times the MRHOD).

Can I use travoprost during breastfeeding?

Untill there are safer alternative are present, the use of this medication is not recommended. This drug can excreted into the human milk, therefore one should definitely avoid taking this medication while breastfeeding. The effects of this medication are unknown in the nursing infant, still this drug should be strictly avoided or should not be used without prior consulation to your doctor.

Can I use travopost for hair growth?

As per studies, it has been observed that travoprost when administered on the non daily basis, can induce hair shaft growth more when administered on daily basis. The growth of hair shaft is observed more significant and better when taken on a non-daily basis. It induces growth of hair follicles, and the fact observed was that it is more effective when administered as single treatment as compared to repeated treatment (as seen in 7 days treatment).

Travoprost is known to be useful in reducing the hair loss and heterogenicity in the diameter of the hair shafts as well as it stimulates the growth and density of the hairs. For administration of compositions such as travoprost, one should maintain a time interval in applications, for example, an interval of greater than 24 hours.

Application of the travoprost should be carried out on the non-daily basis, for example, it should be applied every two, three, four, five, six, or seven days.

However, in this study, there were no significant side effects of travoprost was shown, but you should always consult your doctor before using this medication for the purpose of hair growth. Moreover, the excess of this analogs can cause some serious adverse reactions, therefore, avoid using it before consultation with your doctor.

Can travoprost be used for management of open-angle glaucoma and ocular hypertension?

Travoprost is a intraocular pressure (IOP) reducing agent and is a prostaglandin analog, it is significantly used to treat ocular hypertension and glaucoma. It acts by increasing the drainage of aqueous humor via uveoscleral and trabecular outflow channels both.

Travoprost proved to reduce the intraocular pressure and cause a relevant reduction in the mean IOP (i.e. 6.5-9.0mmHg) significantly and safely. Along with the reduction in the IOP, it is known to provide consistent diurnal IOP control that persists up to 84 hours after the administration of the dose.

Travoprost is mainly given for reducing the IOP due to its highly favorable safety profile, and in case the adverse reaction occurs, they are mostly cosmetic in nature such as iris hyperpigmentation and eyelash growth. However, sometimes serious side effects such as iritis and macular edema with travoprost and another prostaglandin analogue.

Travoprost is also coming as a combination with timolol and sold frequently as the fixed combination which should be administered as once daily. The combination is known to reduce the IOP by 7-11.5 mmHg.

However, the monotherapy of travoprost is also considered safe and effective in lowering the IOP, along with the convenience of once-daily dosing. While using, one should always follow the recommendation of the doctor in terms of the doses of such medications.

Can travoprost be taken with tafluprost?

One should generally avoid the concurrent administration of both travoprost and tafluprost. Using multiple prostaglandin analogs and more frequent administration of the prostaglandin (more than recommended) can reduce the main effects of these agents which are lowering intraocular pressure.

When administered concurrently, the combination can exceed the dose-response curve which can also lead to severe effects of intraocular pressure. One can also suffer from other factors such as patient compliance (difficulty in taking multiple medications), disease state (which can flare up if both medications interact with each other).

However, in one study, when two such prostaglandin analogue (bimatoprost and latanoprost) are given to a patient for the treatment of primary open angle glaucoma (non advanced), it showed mean reduction in IOP by 1.8 mmHg in four weeks, which is subsided after discontinuation of the one of the additive prostaglandin analogue (bimatoprost). Therefore the concurrent and frequent administration of travoprost and tafluprost is not recommended by the manufacturers.

Travoprost effects on pigmentation

Travoprost ophthalmic solution has been reported to cause changes to pigmented tissues. The most frequently reported changes have been increased pigmentation of the iris, periorbital tissue (eyelid) and eyelashes.

Pigmentation is expected to increase as long as travoprost is administered. The pigmentation change is due to increased melanin content in the melanocytes rather than to an increase in the number of melanocytes.

After discontinuation of travoprost, pigmentation of the iris is likely to be permanent, while pigmentation of the periorbital tissue and eyelash changes have been reported to be reversible in some patients. Patients who receive treatment should be informed of the possibility of increased pigmentation.

The long-term effects of increased pigmentation are not known.Iris color change may not be noticeable for several months to years. Typically, the brown pigmentation around the pupil spreads concentrically towards the periphery of the iris and the entire iris or parts of the iris become more brownish. Neither nevi nor freckles of the iris appear to be affected by treatment.

While treatment with travoprost ophthalmic solution 0.004% can be continued in patients who develop noticeably increased iris pigmentation, these patients should be examined regularly

Can travoprost be given in patient with macular edema?

Travopost, when given in patient with macular edema, can cause a moderate potential hazard. While treating with an ophthalmic prostaglandin analog (such as travopost), a patient can suffer from macular edema which may include cystoid macular edema also. In patients with aphakia, pseudophakia with a torn posterior lens capsule, the cases of macular edema more frequently reported.

In patients with risk factors for macular edema, for example, posterior uveitis, certain retinal disorders, they are more prone to macular edema. In such patients, the therapy with travopost should be generally avoided or if necessary, it should be used with extreme caution.

Can travoprost provoke bacterial keratitis?

There have been reports of bacterial keratitis associated with the use of multiple-dose containers of topical ophthalmic products. These containers had been inadvertently contaminated by patients who, in most cases, had a concurrent corneal disease or a disruption of the ocular epithelial surface.

Travoprost use with contact lenses

Contact lenses should be removed prior to instillation of travoprost and may be reinserted 15 minutes following its administration.

Can travoprost be given in patients with uveitis?

Some synthetic prostaglandin analogs are bimatoprost, latanoprost, and travoprost. These agents can interfere with the ocular inflammatory responses and also these agents can copy the endogenous prostaglandins.

However, the cases such as uveitis and iritis have been reported rarely. In a patient with active ocular inflammation, the therapy with travopost (and another ophthalmic prostaglandin analogue) should be used with extreme caution.

Can travoprost be given to a patient with liver or renal disease?

In the cornea, the prostaglandin analogs are hydrolyzed by the enzyme esterases and get converted to their active free acid form which is absorbed systemically. It is also get metabolized via fatty acid beta-oxidation by the liver and it is excreted by the kidney.

In patients with impaired renal and hepatic function, these agents have not been studied. Therefore in such patients, the travoprost or other prostaglandin analog therapy should be administered with caution.

Is it safe to use eye drops after expiration date?
What does focalin do? Is focalin considered a narcotic?

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Focalin : Mechanism of action, uses, dosage and side effects

Apr 19 2018 Published by under Medicines

What is Focalin?

Focalin is the name of a drug product which contains dexmethylphenidate hydrochloride as an active ingredient. Focalin is the brand name of the drug while the pharmacologically active ingredient which is present in the formulation is dexmethyphenidate hydrochloride. It acts on the central nervous system and stimulates it. The drug is used primarily for the treatment of attention deficit hyperactive disorder (ADHD).

Focalin is a drug which is available on the prescription of a registered medical practitioner. It stimulates the central nervous system therefore it belongs to the class of central nervous system stimulants.

It normally works by altering the levels of neurotransmitters in the brain which primarily includes norepinephrine and dopamine and the drug usually acts by increasing the levels of these chemicals. The drug may also be used by patients of narcolepsy for alleviating the symptoms.

Chemistry ad identification of Focalin

Focalin is a drug which consists of dexmethylphenidate hydrochloride as an active ingredient. This pharmacologically active ingredient is responsible for the beneficial effects of the drug. Each tablet consists of dexmethylphenidate hydrochloride which is taken orally.

Focalin’s active ingredient dexmethylphenidate hydrochloride IUPAC name, molecular structure, weight, formula and drug class

 IUPAC name: methyl (2R)-2-phenyl-2-[(2R)-piperidin-2-yl]acetate;hydrochloride

Molecular formula: C14H20ClNO2

Molecular weight: 269.769 g/mol

Molecular structure:

Focalin's active ingredient dexmethylphenidate hydrochloride IUPAC name, molecular structure, weight, formula and drug class

Drug class: This compound belongs to the class of organic compounds known as aralkylamines. These are alkylamines in which the alkyl group is substituted at one carbon atom by an aromatic hydrocarbyl group.

Focalin description:

Focalin which consists of dexmethylphenidate hydrochloride is an enantiomer of the racemic mixture of methylphenidate hydrochloride. This racemic mixture is a 50/50 mixture of two enantiomers namely d-threo and l-threo enantiomerof which Focalin is a d-threoenantiomer.

The drug acts as a stimulant of the central nervous system and is available as tablet dosage form in 3 strengths. Each tablet consists of dexmethylphenidate hydrochloride 2.5, 5 or 10 mg which is taken orally. This CNS stimulant is chemically described asmethyl α- phenyl-2-piperidineacetate hydrochloride, (R,R’)-(+)- having a molecular weight of 269.77 g/mol.

The colour of dexmethylphenidate hydrochloride is white to off-white and is in powder form. It forms acidic solutions. It is only slightly soluble in organic solvents like chloroform and acetone while it is freely soluble in water and alcohols like methanol. Focalin is a combination of pharmacologically active ingredients as well as pharmaceutical excipients. These excipients are inert and pharmacologically inactive in nature.

What are the active and inactive ingredients of Focalin?

Focalin is a mixture of pharmacologically active and inactive ingredients. The active ingredient is dexmethylphenidate hydrochloride which possesses the pharmacological activity while the inactive ingredients include pregelatinized starch, lactose monohydrate, sodium starch glycolate, microcrystalline cellulose, magnesium stearate, and dyes including FD&C Blue No.1 #5516 aluminium lake (present in 2.5 mg tablets), D&C Yellow lake #10 (present in 5 mg tablets) while the 10 mg tablets do not contain any dye.

What is the mechanism of action of Focalin?

The active ingredient in the drug is dexmethylphenidate hydrochloride which is a synthetic amine having sympathomimetic properties and also stimulates the central nervous system. It increases the release of neurotransmitters particularly norepinephrine and dopamine in the brain and also prevents their uptake.

This leads to an increase in the motor activity resulting in excitement, euphoria, mental alertness and suppression of appetite. Therefore, the drug is primarily used in attention deficit hyperactive disorder while it may also be used for the treatment of fatigue and other nervous system effects resulting from chemotherapy.

Focalin XR for ADHD: Uses, Side Effects, Dosage

How should Focalin be taken?

  • Focalin is a prescription drug and should be taken as prescribed by the doctor. The doctor may need to adjust the dose according to the condition of the patient.
  • The tablets are usually taken 2 times a day such that the total daily dose should not exceed 20 mg for immediate release tablets and should not exceed 40 mg for extended release dosage form.
  • The doses should be taken with an interval of at least 4 hours.
  • The patients who are new to the drug or those receiving other CNS stimulants should be given 5 mg per day. Dose may be adjusted on weekly basis and can be increased to a maximum of 20 mg per day.
  • The drug can be taken with or without food.
  • It is not recommended to take a dose at night as the drug causes insomnia.
  • The medication may result in blurred vision and may also alter the thinking process so caution must be taken if the patient needs to drive or do some work requiring alertness.
  • The doctor may stop the drug for short intervals to check the progress of the condition of the patient suffering from ADHD.
  • If the drug causes adverse events in patients or if the symptoms are aggravated then dose should be adjusted but if this adjustment does not prove to be beneficial then the use of the drug should be discontinued.

What if a dose of Focalin is missed?

In case a person forgets to take the drug and a dose is missed, the patient is advised to take the dose as soon as he remembers it. It is not advisable to take the dose late in the day as the drug may cause insomnia so it might be difficult to sleep.

In such cases, it is advisable to skip the dose and patient should continue with the prescribed dosing schedule. Moreover, doubling of the dose at a single time to make up for the missed dose is not recommended.

Description of dosage form and available strengths

Focalin is supplied as D shaped tablets. The tablets are 18 mm in size. The tablets have a “D” impression on the upper surface while the strength of the tablet is on the lower surface. The tablets are taken orally and are supplied in bottles of 100 tablets. Focalin is available on 3 different dosage strengths.

  • 5 mg tablets – blue
  • 5 mg tablets – yellow
  • 10 mg tablets – white

What are the indications of Focalin?

The primary indication in which Focalin is prescribed is attention deficit hyperactive disorder. It is also included in the total treatment programme for patients with ADHD along with other physiological, educational and social measures which are taken for the treatment of patients with this disorder.

Pharmacokinetics of Focalin

Absorption and distribution:

Upon oral administration of Focalin, dexmethylphenidate hydrochloride is readily absorbed from the gastrointestinal tract. The drug undergoes extensive first pass metabolism due to which the mean absolute bioavailability is 22 to 25%. When the drug is administered orally to patients with ADHD, plasma concentrations of dexmethylphenidate increase rapidly and reach to a maximum concentration within 60 to 90 minutes.

Since the pharmacokinetics of the drug are not altered followed by single or twice daily dosing, this indicates that the drug does not accumulate significantly in children with ADHD.When the drug is administered to children in single doses of 2.5 mg, 5 mg or 10 mg in the form of capsules, Cmaxand AUC0-inf of the drug were proportional to the dose.

Although the drug can be taken with or without food, a meal which is rich in fat might slow the absorption of the drug but does not affect the extent of absorption and even the peak concentration of the drug. There are also variations in the absorption patterns between men and women as AUC is higher in women as compared to men. When compared with children, AUC is lower as compared to adults.

It is not exactly known whether the drug enters breast milk or crosses placenta but upon oral administration the plasma concentrations show an exponential decline in children.

Metabolism and excretion:

The drug is metabolized in the liver by a process called de-esterification. This process metabolizes dexmethylphenidate to d-α-phenyl-piperidine acetic acid which is also known as d-ritalinic acid. This metabolite does not possess any pharmacological activity. Upon the oral administration of the radiolabelled methylphenidate, 90% of the radioactivity was recovered in urine.

Therefore, the drug is eliminated primarily in urine in the form of ritalinic acid. This metabolite of the drug is responsible for 80% of the dose as the drug is not excreted unchanged in urine but in the form of the metabolite. The drug neither induces nor inhibits the cytochrome P450 isozymes in the liver. The mean plasma elimination half-life of the drug is 2 to 3 hours in children while 2 to 4.5 hours in adults.

Side effects of Focalin

The drug may cause common to serious side effects. Many of these effects may be eliminated by the discontinuation of the drug. Following are some of the serious side effects which might need immediate medical attention, caused by Focalin:

  • chest pain
  • shortness of breath
  • extreme fatigue
  • fast, pounding or irregular heartbeat
  • changes in vision
  • slow or difficult speech
  • dizziness or fainting
  • seizures
  • aggressive behaviours
  • weakness or numbness in the arm or leg
  • having suspicion for others
  • hallucinations or believing false things
  • mood changes
  • depression
  • swelling of the face, tongue, lips, throat, or eyes
  • rash, hives, or itching
  • purples blotches under the skin
  • fever
  • joint pain
  • blistering or peeling skin
  • painful and frequent erections
  • having erections for more than 4 hours
  • numbness, pain, or sensitivity of temperature in the fingers and toes
  • changes in skin colour in the fingers and the toes

Common side effects caused by Focalin include:

  • weight loss and loss of appetite
  • pain in the stomach, nausea, and heartburn
  • dry mouth
  • difficulty to fall asleep and even difficulty in staying asleep
  • drowsiness
  • dizziness
  • insomnia
  • nervousness or jitteriness
  • headache

It is advisable to tell the doctor if any of the side effects persist for longer periods or even aggravate during the treatment.

What are certain conditions in which Focalin is contraindicated?

The use of Focalin is contraindicated in the following conditions:

  • Agitation: the drug is contraindicated in patients who have anxiety, tension and agitation as it may worsen the symptoms.
  • Hypersensitivity to methyphenidate: those individuals who are allergic to methyphenidate or any of the components of the drug including the inactive ingredients must not be given the drug. It is the duty of the doctor to ask the patients for their allergies to prevent any serious hypersensitivity reactions which include angioedema or anaphylactic reactions.
  • Glaucoma: the drug is contraindicated in this case.
  • Tics: those patients who are diagnosed with Tourette’s syndrome or have a family history of the syndrome or even those patients having motor tics are contraindicated to use the drug.

What are the drugs which are contraindicated with Focalin?

The use of Focalin is contraindicated with the following drugs:

  • Monoamine oxidase inhibitors: patients who are currently using monoamine oxidase inhibitors or those who had used them in the preceding 14 days are contraindicated to use the drug since this may lead to hypertensive crisis.

Focalin during pregnancy and breast-feeding

Those women who are planning to start a family soon or those who are pregnant should consult their doctor before starting the drug. The drug is included in the US FDA pregnancy category C and should only be recommended if the benefits of the drug outweigh the potential risks associated with the use of the drug.

Animal studies have shown that the drug affects the developing fetus while the studies on humans are not adequate therefore the drug should be used with caution.

Those women who are breastfeeding their young ones must use the drug with caution. Although, there is not enough evidence to support that the drug is excreted into breast milk in humans but animal data suggests that it is excreted in breast milk. If given in large doses, the drug might interfere with milk production therefore the drug should be used with caution and after consultation with the health care provider by nursing mothers.

Focalin in geriatrics and pediatrics

The use of the drug in children less than 6 years of age has not been well established in term of the safety and efficacy of the drug. However, those children who have with cardiac abnormalities or heart problems should not be given the drug as deaths have been reported in case of using the drug in normal doses by those patients.

In case of older patients, the drug should be used with caution and at such doses that the condition of the patient does not get worse. Since geriatric patients are already suffering from heart problems or are more susceptible to cardiac abnormalities therefore the patient must consult with the health care provider before using the drug.

What drugs can interact with Focalin?

Focalin is CNS stimulant, therefore, a number of drugs can interact with it. You should always consult with your doctor if you are using Focalin with other drugs because a number of drugs can have life threatening interactions when used concomitantly with Focalin. Some of the major interactions that have occurred with Focalin are mentioned below.

  • bupropion: bupropion has a tendency to cause seizures and when used concomitantly with medications such as dexmethylphenidate, it increases the risk. Elderly patients are at an increased risk as well as those having a history of seizures, undergoing drug or alcohol withdrawal, or those having a condition that affects the central nervous system such as brain tumor or head trauma.

Examples of drugs containing bupropion: Budeprion, Contrave, Forvivo XL, etc.

  • selegiline: the concomitant use of selegiline and dexmethyphenidate is not recommended. Using the two drugs are used together can increase the blood pressure to a dangerously high level and even death can occur.The patient may experience symptoms of excessively high blood pressure when treated with selegiline which includes severe headache, blurred vision, confusion, seizures, chest pain, nausea, numbness, speech difficulties, fever, sweating, lightheadedness, and even fainting. Before prescribing Focalin, the doctor should check if the patient has been using selegiline and should prescribe the drug only if selegiline has not been used by the patient for atleast 2 weeks otherwise these life-threatening events can occur.

Examples of drugs containing selegiline: Atapryl, Selgene, Zelapar, etc.

  • safinamide: if safinamide and dexmethylphenidate are used concomitantly then this may lead to increased cardiovascular events such as high blood pressure and increased heart rate. The blood pressure might increase to such a level which may require medical attention. Those patients who have a history of high blood pressure, irregular heart rhythm, or any other heart diseases should always consult the doctor before using these medications.

Examples of drugs containing safinamide: Xadago, etc.

  • tramadol:one of the most unwanted effects of tramadol is its tendency to cause seizures and if it is used in combination with drugs that cause seizures so it may aggravate the symptoms. Since dexmethylphenidate also has the tendency to cause seizures therefore both the drugs should not be used concomitantly as it may increase the risk of having seizures. The elderly patients or those who have a history of seizures or a condition like brain tumor or head trauma affecting the central nervous system are at an increased risk of having seizures.

Examples of drugs containing tramadol: Tramahexal, Tramedo, Zydol, etc.

  • citalopram: when dexmethylphenidate and citalopram are used concomitantly, this leads to increased blood levels and subsequently the effects of citalopram.The increased level of citalopram in blood can lead to confusion, hallucination, seizure, increased heart rate, fever, sweating, shivering, blurred vision, muscle cramps, tremors, muscle spasm or stiffness along with a serious condition called serotonin syndrome. The patient should seek immediate medical attention if he eperiences any of these symptoms when using the drugs.
  • guanfacine: if the patient has to use this drug, he should tell the doctor if he is currently using dexmethyphenidate since both of the drugs can interact with each other. If both the drugs are used concomitantly then this can affect the rhythm of the heart. If the patient experiences symptoms such as irregular heartbeat, chest tightness, blurred vision or nausea then he should contact the doctor and seek medical help.

Examples of drugs containing guanfacine: Intuniv etc.

What happens if I overdose Focalin?

If the drug is overdosed, this may lead to symptoms which include restlessness, tremor, muscle twitches, confusion, hallucinations, depression, tiredness, nausea, vomiting, diarrhea, stomach pain, uneven heartbeats, panic, muscle pain or weakness, urine becomes dark coloured, euphoria, flushing, sweating, palpitations, tachycardia, cardiac arrhythmias, mydriasis, feeling light-headed, fainting, seizures (convulsions), or coma. Rhabdomyolysis may also occur.

These symptoms require prompt and immediate treatment. This can be treated by using appropriate supportive measures along with gastric lavage of the stomach contents so that the drug which is not absorbed can be removed. The airways should be protected and the seizures should be controlled while doing gastric lavage. Activated charcoal can also be used along with other necessary measures as may be required for the detoxification of the gut.

Focalin abuse and dependence

Focalin is a drug which is included in the Schedule II under the Controlled Substances Act. This states that the drug has a high potential for abuse and can cause severe physical or physiological dependence. Focalin has potential for abuse and is used largely by abused by drug addicts. Abuse of the drug can cause over dosage and leads to life threatening symptoms which can eventually cause death if not given prompt treatment.

Many addicts become dependent on the drug since it has the potential to cause physical and physiological dependence. This dependence can be distinguished as the person experiences withdrawal symptoms upon sudden discontinuation of the drug or if the dose of the drug is decreased from a higher strength to a lower strength.

What precautions are needed with Focalin?

You should always talk to your doctor or pharmacist if you have any allergies and particularly if you are allergic to this drug or methylphenidate. This will also help him to identify if you are allergic to any excipient which is present in the preparation.

You should also discuss your medical history with your doctor or pharmacist especially history of having high blood pressure, blood circulation problems, glaucoma, heart problems including heart failure, previous heart attack, problems with heart structure, having any family history of heart problems like cardiac death or irregular heartbeat, mental or mood conditions such as anxiety, tension, agitation, if u have any personal or family history of any mental or mood disorder such as bipolar disorder, depression. psychosis, if u have any personal or family history of uncontrolled muscle movements like motor tics or Tourette’s syndrome, hyperthyroidism or seizure disorder.

If you use alcohol or marijuana along with this drug so this can make you dizzy. In such cases, driving, using heavy machinery or doing activities requiring mental alertness should be avoided. If such work needs to be done then alcoholic beverages and marijuana should be avoided.

This drug can affect a child’s growth rate, weight and final adult height if it is used for a long time. In order to reduce this risk, the doctor may advise the patient to stop using the rug from time to time and you should regularly check your child’s weight and height and inform you doctor or pharmacist accordingly.

The side effects associated with the drug occur more frequently in older adults including trouble sleeping, weight loss or chest pain. This drug should only be used in pregnancy if the benefits outweigh the risks and if the doctor or the pharmacist so recommends.

What are warnings associated with the use of Focalin?

Cardiovascular problems:

This drug can cause serious and life threatening cardiovascular events. Those children and adolescents who are suffering from serious heart problems or having structural cardiac abnormalities, when treated with the drug have had sudden deaths. Therefore, the drug should not be used in children or adolescents having serious structural cardiac abnormalities, cardiomyopathy, or serious heart rhythm problems.

In adults, the incidence of sudden deaths, stroke and myocardial infarction has also been reported when using Focalin for the treatment of ADHD. Therefore, Focalin should be used in adults suffering from coronary artery disease, heart rhythm abnormalities or other heart problems.

Focalin also causes an increase in the blood pressure and heart rate hence it should be used with caution in patients whose medical condition might get worse due to increase in the blood pressure or heart rate.

Psychiatric events:

Those patients who are suffering from psychotic disorder should not use the drug as it may exacerbate the symptoms of behaviour disturbance. Also, those patients who are suffering from bipolar disorder can experience a mixed/manic episode if treated with Focalin for ADHD. In such instances care must be taken. Focalin can induce aggressive behaviour or hostility in children when treated with the drug for ADHD.

The drug should not be given to patients suffering from seizures as it may exacerbate the condition. This drug also has the tendency to cause painful and prolonged erections in both paediatric and adult patients. Therefore, it should be used with caution and if such event occurs then the patient should seek immediate medical attention. Patients using the drug also experience blurring of vision and difficulties with accommodation.

How to store Focalin?

Focalin should be stored in a safe place at a temperature of 59°F to 86°F (15°C to 30°C). such temperature is necessary otherwise it may lose its effectiveness and lead to deterioration of the drug. Since it is a controlled drug hence it should be kept at a place where it is inaccessible for the children.

“Is Adderall and Focalin the same?”
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L-Lysine supplement – Benefits, dosage and side effects

Apr 18 2018 Published by under Vitamins

What is L-Lysine?

L-Lysine or just Lysine, is one of the most important and essential amino acid that is required in the body. Essential amino acids occur mostly in form of stereoisomers. Stereoisomers exist in two forms which are identical to one another as mirror images. These forms are D-form and L-form. Lysine is present is L-form.

Even though it is a basic amino acid yet it is not produced by the body itself. It has to be obtained from external sources which include food and supplements. Lysine and other various amino acids are the basic building blocks of proteins.  These proteins, in turn, are used in various processes.

Some of these processes which require lysine are in the development of immunity in the body against a number of diseases, helps in improving appetite and digestion. Lysine also boosts calcium absorption, increases the protein content in muscles and generates the production of hormones, antibodies, and various enzymes.

L-lysine molecular structure, weight, formula, class, chemical and other names for Lysine

Chemical name: L-2,6-diaminohexanoic acid

Other names: L-Lysine, L-Lysine Hydrochloride, Lisina

Chemical structure:

 What is L Lysine good for?

Drug class: This compound belongs to the class of organic compounds known as l-alpha-amino acids. These are alpha amino acids which have the L-configuration of the alpha-carbon atom.

Common ingredients of Lysine supplements

Active ingredient: L-Lysine Monohydrochloride

Inactive ingredients: gelatin(capsule), stearic acid, cellulose, rice flour, and Mg stearate  

How does Lysine work?

Lysine is transformed into acetyl CoA, which is an essential component in the carbohydrate metabolism and in generation of energy. Lysine is the originator of the amino acid carnitine, which helps in the transportation of long chain fatty acids into the mitochondria for energy production and other various metabolic pathways.

As soon as Lysine is bound to a polypeptide structure, the initiation of biosynthesis of carnitine occurs. This is done by methylating one if the amino group’s present in lysine compound.

Furthermore, Lysine have an antagonist association with the amino acid arginine. Lysine competes with this amino acid for the purpose of absorption in the intestinal region, reabsorption in tubules of kidney, and movement across the plasma membrane.

Pharmacokinetics and biochemistry of Lysine

Lysine, an amino acid which has a basic character, positively charged at physiological pH and is extremely soluble in water. It has a molecular weight of 146.19 Daltons.

Lysine supplementations are available in oral dosage forms such as soft gelatin capsules. Once ingested, it is absorbed from the intestinal region into the enterocytes through the processes of active transport and transport from gut to the liver by means of portal circulation. As soon as lysine reaches liver, it links with other amino acids to assist in protein synthesis.

Catabolism also takes place in liver, where it undergoes condensation with ketoglutarate to form saccharopine. Sacchropine is transformed to L-alpha-aminoadipic acid semialdehyde, which is then ultimately is converted acetoaceyl-CoA. Lysine does not go through transamination. However, it is ketogenic and glycogenic and can assist in the formation of D-glucose, glycogen, lipids and as a result in the generation of energy.

Pharmacokinetic studies have demonstrated that lysine supplements have the absorption rate in a same way to that after digestion of proteins, suggesting supplementation is an effective and efficient means of correcting a dietary lysine deficiency.

Lysine is quickly transferred into muscle tissue within a time period of 5-7 hours after it is administered. This is more concentrated in the intracellular space of muscle tissue in comparison to the concentration of other amino acids. From this observation, we can assume that the muscle tissues may act as a reservoir for un-conjugated lysine in the body.

Research studies are still being conducted to collect data on other pharmacokinetic parameters including route of elimination, half-life, clearance, protein binding, and volume of distribution.

What are the benefits of Lysine supplements

Lysine has been used over years for many purposes. It has proven to be useful as a herbal product and is often put up for sale as an herbal supplement.  Along with this, lysine is marketed as an alternative medicine product too.

Medicinal use of lysine hasn’t yet been approved by FDA and should not be substituted for a medical drug which has been prescribed by the doctor. But over time, a number of manufactures have formulated lysine in dosage forms which have enabled its use in more conveniently and removed the risk of contamination that was a major drawback in herbal formulations. Some of the benefits that are obtained by using L-Lysine are mentioned below:

L-Lysine in the treatment of herpes virus

Herpes simplex virus-1 causes the formation of cold sores (herpes). These are actually fluid-filled blisters which are visibly seen either on the lips or around the lips.  The major route of transmission is through the infected saliva. When saliva comes in contact the virus accumulates on the skin and causes these blisters to develop.

A number of studies have verified that taking lysine on regular basis or more preferably on daily basis has decreased the occurrence of genital herpes and cold sores. This is mainly due to the anti-viral action of Lysine which blocks the activity or arginine. Arginine is also an amino acid which upholds the replication of herpes simplex virus.

Actually, even though arginine and lysine are both amino acids but they are antagonist to each other. This means, when the levels of arginine in body are high, lysine levels are less. Lysine acts on the HSV virus and halts the replication. In one of research study that had been conducted, the individuals who used L-lysine for treating the cold sores had found it to be very effective.

Other studies have shown that L-lysine have not only been useful in reducing the rate of outbreaks but also have drastically decreased the duration of time for which the blisters had appeared on the skin.

However, L-lysine has yet not been efficient in completely stopping the eruption of such cold sores. Alongside the treatment of cold sores which are caused by herpes simplex virus-1 (HSV-1), L-lysine have also been valuable in helping to alleviate the genital herpes which occur due to herpes simplex virus-2 (HSV-2) possibly due to the same mechanism.

Does lysine prevent cold sores?

Can lysine help with cold sores?

L-lysine in the treatment of cancer

Scientists have been looking for natural cancer treatments which have the same effect as that of the conventional therapies including chemotherapy and other radiation. This is majorly due to negative effect these procedures have on healthy cells in addition to the diseased ones.

With time, new technologies and new products are being tested in order to discover more and more ways which can potentially target cancerous particularly malignant cells without killing the good ones. A study conducted at the Florida State University had observed the consequences of lysine conjugates on spoiled strands of DNA similar to those which were found in cancer.

Lysine works by locating a spoiled strand by identifying ‘cleavage’ and in turn allows the rest of the strand to tear apart. This cell is usually not repairable and hence progresses towards apoptosis i.e. suicidal death of cells. The cancer killing capability that lies in lysine conjugates is only triggered when exposed to specific type of light.

This allows the researchers, scientists or any doctors involved to inject or place the treatment in a region where the cancer cells are most concentrated and active. This method has increased the rate of destroying cells from 25% to 90%.

L-lysine in the treatment of anxiety and other psychological problems

L-Lysine has been useful in reducing depression and other anxiety problems to a great extent. Intake of Lysine improves the absorption of calcium in body in turn it has proved to be beneficial in patients suffering from anxiety. Moreover, L-Lysine acts as an antagonist to the serotonin receptor. It binds to the serotonin receptors and put a stop to anxiety responses. There are a number of responses which occur due to stress including diarrhea.

Besides anxiety, L-Lysine also has demonstrated being useful in the people who are suffering from Schizophrenia. Here in such cases, it is necessary to continue the conventional therapy along with the intake of L-lysine. This combination helps to decrease the negative impact and general symptoms of Schizophrenia. Studies are still being conducted to determine the dosing and long term effects.

L-Lysine for diabetes-related problems

Over years, scientists have worked on diabetes and in its context to the presence of advanced glycation end metabolites which are termed as AGEs These advance glycation end metabolites are responsible for aging process in human beings and are present in a large quantity in diabetic patients.

These products are occupied in many diabetes associated problems thus provoking scientists to search and study over therapies that involve halting the AGEs from accumulating in large numbers. L-lysine have shown its effect towards the prevention of formation of advanced glycation end metabolites by avoiding the specific paths of glycation through which these products are generated and in turn helping to hold back infection.

L-Lysine as aids in calcium absorption

As mentioned above, L-lysine aids in Ca absorption in gut. The more the calcium absorbed the less the people will be at risk for developing osteoporosis and other joint disorders. It has been recommended to people who are having brittle bones. According to a study conducted, a total of 30 subjects were selected. 15 out of which were osteoporetic and 15 normal healthy women.

They were then given acute calcium loading dose. Half of these were given l-Lysine supplements. In the results obtained, the control group to which no lysine supplements were given had shown a diminished absorption of calcium. This was  analysed through urine sampling.

Besides treating bone problems, calcium consumption in suitable amounts is concerned with lowering the risk of cancer, healthy weight,  PMS symptom reduction, better dental health, improved nerve transmission and decreasing the chances of diabetes.

Moreover, it has been observed that those athletes who take L-Lysine on regular basis have shown better performance. This is due to the fact that there will be more Ca absorption hence better muscle movement.

L-Lysine for improvement of the functions of the heart

Low-density cholesterol (LDL) accumulates in the walls of arteries resulting in the hardening and narrowing of the lumen. This is known as atherosclerosis. When the arteries are hardened or the lumen decreases, the blood flow either is slowed down or is completely blocked. This increases the chances for the patient to suffer from heart attack.

Lysine generates carnitine in the body, which has a major function in using up the the fatty acids and LDL cholesterol. another benefit that is obtained by using L-lysine in combination with calcium, there is a reduction in the levels of lipoprotein-A (LPA).

LPA acts as a carrier to LDL in the blood. This means that the levels of LPA in blood are directly related to the risk of developing of plaque formation or clogging up of arteries. This, in turn, leads to a greater risk of developing diseases, stroke and even erectile dysfunction.

What are the side effects of taking lysine supplements

Even though lysine have got the approval by Food Drug Administration (FDA) for being used in any disease or condition but still it has not been completely assessed for its complete profile of safety, effectiveness and purity levels. Besides a few, all possible side effects or advantages are still to be studied. Moreover, yet no regulated marketing standards have been set up for such compound. Some of the side effects are:

  • stomach pain
  • diarrhea
  • hives
  • difficulty breathing
  • swelling of your face
  • lips
  • tongue
  • throat

Overdosage and toxicity of L-lysine

L-lysine supplementation, when taken in high doses greater than 10-15 g daily, have caused gastrointestinal upset, including nausea, abdominal cramps and diarrhea.

L-Lysine and allergic reactions

Patients can develop hypersentivity against medications. In the same manner individuals might become allergic to lysine supplement. Features of an allergic reaction can be as small as skin rashes, redness, hives to as large as anaphylaxis, shock.

L-lysine and formation of gallstones

Gallstones are solid substances which are hard in nature and are formed in the gallbladder. The formation of these stones has been painful for the patient. One of the major causes of formation of gallstones is due to cholesterol.

Using cholesterol lowering drugs for a prolonged time period leads to the accumulation of cholesterol in the bile in an attempt to remove the cholesterol. n a similar way, L-Lysine possesses cholesterol lowering property. Taking Lysine in high doses can cause the formation of gallstones.

L-lysine and abdominal cramps and diarrhea

No mechanism has yet been found but consumption of lysine in high doses has caused the patient to suffer from abdominal cramps and diarrhea.

L-Lysine interaction with arginine

Arginine is another amino acid that is present in the body in variable amounts. Presence of lysine in large amounts in the body has decreased the levels of arginine. Besides the role of arginine in the progression and spread of herpes virus, it has a vital function in maintaining a healthy normal system of body.

Arginine is converted into nitric oxide which is important to keep the blood vessels dilated to ensure a normal blood flow. Along with this arginine acts as a stimulator for growth hormones, insulin and various other substances in body.

L-Lysine requirements

The Food and Nutrition Board (FNB) of the U.S. Institute of Medicine set Recommended Dietary Allowances (RDAs) for essential amino acids in 2002. For lysine, for adults 19 years and older, 38 mg/kg body weight/day.

L-Lysine dietary sources

The nutritional requirement per day, in milligrams of lysine per kilogram of body weight, is: infants (3–4 months) 103 mg/kg, children (2 years) 64 mg/kg, older children (10–12 years) 44 to 60 mg/kg, adults 12 mg/kg. For a 70 kg adult, 12 milligrams of lysine per kilogram of body weight is 0.84 grams of lysine. Recommendations for adults have been revised upwards to 30 mg/kg.

Good sources of lysine are high-protein foods such as eggs, meat (specifically red meat, lamb, pork, and poultry), soy, beans and peas, cheese (particularly Parmesan), and certain fish (such as cod and sardines).

Lysine is the limiting amino acid (the essential amino acid found in the smallest quantity in the particular foodstuff) in most cereal grains, but is plentiful in most pulses(legumes). A vegetarian or low animal protein diet can be adequate for protein, including lysine, if it includes both cereal grains and legumes, but there is no need for the two food groups to be consumed in the same meals.

A food is considered to have sufficient lysine if it has at least 51 mg of lysine per gram of protein (so that the protein is 5.1% lysine). Foods containing significant proportions of lysine include:Infants (3-4 months old): 103mg/kg per a day:

  • Fish: 9.19%
  • Beef, ground, 90% lean/10% fat, cooked: 8.31%
  • Chicken, roasting, meat and skin, cooked, roasted: 8.11%
  • Azuki bean (adzuki beans), mature seeds, raw: 7.53%
  • Milk, non-fat: 7.48%
  • Soybean, mature seeds, raw: 7.42%
  • Egg, whole, raw: 7.27%
  • Pea, split, mature seeds, raw: 7.22%
  • Lentil, pink, raw: 6.97%
  • Kidney bean, mature seeds, raw: 6.87%
  • Chickpea, (garbanzo beans, Bengal gram), mature seeds, raw: 6.69%
  • Navy bean, mature seeds, raw: 5.73%

Requirements and dosage of L-Lysine

  • Toddlers (2 years old): 64mg/kg per a day
  • School-going children: 58mg/kg per a day
  • Adults (30+ years old): 30-35 mg/kg per a day

Intake of Lysine in a characteristic Western diet is 40-180mg/kg per a day with the upper range till 300-400 mg/kg per a day.

According to FDA, the suggested intake of Lysine is 1000 mg per a day.

It is advised to have a daily dose of up to 3 grams is harmless for therapeutic purposes when administered in separate in three different doses.

In certain conditions, the patients may require Lysine intake for a chronic period at a higher dose.

Such as in herpes patients, patients can advised to take Lysine up to 9 grams per day during an eruption phase.

What if I don’t take enough Lysine?

Taking Lysine either via food sources or through taking supplements is necessary. Vegans who entirely consume vegetables as their food are more prone of developing lysine deficiency. These typical symptoms of this lysine deficiency are as below:

  • decreased appetite
  • unnecessary loss of hair
  • fatigue
  • agitation, mood swings
  • bloodshot eyes
  • kidney stones
  • stunted growth
  • reproductive disorders
  • nausea, dizziness
  • lack of focus.

What drugs can interact with Lysine supplements

Supplements are formulated to provide a larger population with greater benefit. However, each individual is influenced by the medication in a different way from another. Each patient has its own body needs and may be already using some other drugs or substances n order to attain a specific therapeutic outcome. When Lysine is administered it shows interaction in the following situations:

  • Calcium:

If the patient is already taking calcium by means external sources including supplements, Lysine ingestion will accumulate and increase the plasma levels of calcium in the body. Excessive accumulation of calcium in blood is termed as hypercalemia. Excessive thirst, urination, lowered pain threshold, nausea and gastrointestinal upset majorly constipation.

Besides these, hypercalcemia can more seriously cause increased chances of heart diseases including hypertension or atherosclerosis.

  • Aminoglycoside antibiotics:

According to the studies conducted on animals, it has been seen that lysine and aminoglycoside antibiotics both bind to the same membrane vesicles present on the brush border lining of the small intestine.

When only a limited number of drug molecules bind to such membrane vesicles, it is not possible for them to move from side to side in intestine for the purpose of absorption or digestion. This mechanism has decreased the effectiveness of the drugs and may cause toxicity.

Aminoglyoside Antiobiotics include kanamycin, amikacin, tobramycin, gentamycin and neomycin.

  • Gastrointestinal agents (5-HT4 agonist):

This interaction is characterized as a minor interaction still studies are being conducted on human and animals both. It has been suggested that Lysine supplements inhibit the effects of these agents.

These drugs have their effect by acting on the serotonin receptor and decreasing the intestinal peristalsis, prevent gastric emptying but simultaneously increase the chances of esophageal reflux.  This interaction has been more prominent with prucalopride and tegaserod.

In which conditions Lysine supplements are contraindicated

Using lysine in certain conditions may bring about unwarranted effects. Some of these conditions are:

  • Hyperlysinemia or lyperlysinuria

Some people are genetically abnormal and may have uncontrolled production of lysine in the body. This leads to a condition known as hyperlysinemia, which are increased levels of lysine in blood.

Another possible condition due to certain factors including genetic or any underlying disease is the excessive loss of lysine in urine. This is termed as hyperlysinuria. In both conditions, intake of lysine from external sources such as supplements is contraindicated.

  • Liver and Kidney Problems

Lysine is not normally produced in the body. It has to be consumed via some external sources. It has been observed that it is metabolized by liver enterocytes and possible excreted through kidney. In recent studies, it has been seen that due to presence of kidney problems the lysine starts to build up in tubular nephrons. In a severe case as reported the patient had developed Fanconi syndrome along with tubulointerstitial nephritis.

  • Breastfeeding and Pregnancy:

Based on the results obtained from some studies, when lysine is given to pregnant patients who are already using other vitamin or mineral supplements such as iron, it has been observed that the levels of hemoglobin increases rapidly as compared to those who are kept on control and not given any other supplement.

Increased hemoglobin eventually means more number of red blood cells. This in turn increases the viscosity of blood, thickening its consistency. When the blood becomes thick, possibility of formation of clot occurs. Therefore those women who are either pregnant or breast-feeding their babies, they should consult their healthcare provider before taking these lysine supplements.

Use of L-Lysine in animal feed

Lysine production for animal feed is a major global industry, reaching in 2009 almost 700,000 tonnes for a market value of over €1.22 billion. Lysine is an important additive to animal feed because it is a limiting amino acid when optimizing the growth of certain animals such as pigs and chickens for the production of meat.

Lysine supplementation allows for the use of lower-cost plant protein (maize, for instance, rather than soy) while maintaining high growth rates, and limiting the pollution from nitrogen excretion. In turn, however, phosphate pollution is a major environmental cost when corn is used as feed for poultry and swine.

Lysine is industrially produced by microbial fermentation, from a base mainly of sugar. Genetic engineering research is actively pursuing bacterial strains to improve the efficiency of production and allow lysine to be made from other substrates.

L-Lysine storage requirements

Unlike the other amino acids, lysine is not stable in powder form and is hygroscopic in nature. It is thus required to keep the raw material of lysine at a temperature below 0°C.

Once formulated, the tablets must not be exposed of to a higher temperature and direct contact with sunlight should be avoided. Humidity content should not be very high.

Can psyllium husk be taken with food or on an empty stomach?

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Nabumetone : Drug class, uses, dosage, side effects and interactions

Apr 17 2018 Published by under Medicines

What is nabumetone?

Nabumetone is a nonsteroidal anti-inflammatory agent from the diclofenac family which is named as aryl alkanoic acid family. It is marketed under the brand name Relafen. Unlike other NSAIDs, nabumetone seems to have a lower risk of gastrointestinal side effects.

Nabumetone molecular structure, formula, weight, IUPAC name and srug class

IUPAC name: 4-(6-methoxynaphthalen-2-yl)butan-2-one

Molecular formula: C15H16O2

Molecular weight: 228.3 g/mol

Drug class: Nabumetone belongs to the class of organic compounds known as naphthalenes which are compounds containing a naphthalene moiety, that consists of two fused benzene rings.
Molecular structure:

nabumetone molecular structure

The mechanism of action of nabumetone

Nabumetone is a nonsteroid anti-inflammatory agent and its active component is a potent inhibitor of prostaglandin synthesis. It acts by binding the receptors named COX-1 and COX-2 thereby inhibiting the prostaglandin synthesis.

The parent compound of this drug is a prodrug which biotransformed into active component after undergoing hepatic metabolism. The active component of nabumetone is 6MNA (6-methoxy-2-naphthyl acetic acid).

Pharmacokinetics of nabumetone

Nabumetone is rapidly and well absorbed from gastrointestinal tract. The rate of absorption is increased when co-administration with food and also the appearance of its active metabolite (6MNA) in plasma is increased with concurrent administration of food. The active metabolite of nabumetone (6MNA) effectively bound to plasma protein (more than 99%).

It is metabolized into its principal active metabolite (6-methoxy-2-naphthyl acetic acid) followed by rapid biotransformation.  Half of the administered dose of nabumetone gets converted into unidentified metabolites which excreted in the urine. The elimination half-life of nabumetone is 23 hours, which is estimated for its active metabolite, 6-MNA. In patients with impaired renal function, the half-life is increased.

How long nabumetone stays in your system?

The elimination half-life of nabumetone is 23 hours and the elimination of the drug takes place is equal to 5 times to that of elimination half-life. Therefore nabumetone will be out of your system in 5 to 6 days completely.

What are the indications of nabumetone?

Nabumetone is mainly indicated for the treatment of signs and symptoms of osteoarthritis and rheumatoid arthritis. One should use the minimum effective dose and should also be used for the shortest duration which should remain consistent with treatment goals in a patient.

Nabumetone dosage for rheumatoid arthritis and osteoarthritis

The recommended starting dose of nabumetone is 1,000 mg taken as a single dose with or without food. Some patients may obtain more symptomatic relief from 1,500 mg to 2,000 mg per day. Nabumetone can be given in either a single or twice-daily dose. Dosages greater than 2,000 mg per day have not been studied.

The lowest effective dose should be used for chronic treatment. Patients weighing under 50 kg may be less likely to require dosages beyond 1,000 mg; therefore, after observing the response to initial therapy, the dose should be adjusted to meet individual patients’ requirements.

What are the side effects of the nabumetone?

Nabumetone can cause serious side effects, you should seek emergency medical help in case you have signs such as hives, swelling of the face, lips, tongue, or throat or difficulty in breathing. Stop immediately taking nabumetone if you see any of following side effects:

  • Chest pain, weakness, shortness of breath, slurred speech, problems with vision or balance
  • Black, bloody, or tarry stools
  • A cough associated with blood
  • Vomit like coffee grounds
  • Weight gain or swelling of the body
  • Urinating less than usual
  • No urination at all
  • Nausea, stomach pain, fever, loss of appetite, dark urine
  • Clay-colored stools
  • Yellowing of skin and eyes (Jaundice)
  • A sore throat, headache with skin rashes or bruising, severe tingling, numbness, pain, muscle weakness
  • Severe peeling or blistering of the skin often accompanied by a headache
  • Severe peeling or blistering of skin, often accompanied with headache

Less serious side effects of the nabumetone include:

  • Upset stomach, mild heartburn, stomach pain, diarrhoea, and constipation
  • Bloating and gas
  • A headache, nervousness, and dizziness
  • Skin rashes and itching of the skin
  • Vision disturbances
  • Ringing in ears
  • Blurred vision

Here the list of side effects given is not complete, you may suffer from other complicated or uncomplicated side effects, in such case, contact your doctor immediately.

Can nabumetone be taken with alcohol?

Nabumetone should never be administered with alcohol as their concurrent administration may cause severe gastrointestinal blood loss. It can also cause the reduced integrity of gastrointestinal lining because of combined local effects as well as combined inhibition of prostaglandins. You should refrain yourself from consuming alcohol while taking nabumetone or other potential NSAIDs.

Can nabumetone be taken with Aspirin?

The potential for serious gastrointestinal toxicity such as inflammation, bleeding, ulceration, and perforation is seen when low or high dose aspirin is taken along with nabumetone or other nonsteroidal anti-inflammatory drugs (NSAIDs).

The plasma concentration of many NSAIDs may be reduced by concurrent administration of NSAIDs which range from small (in case of drugs like piroxicam, meloxicam, naproxen, tolmetin etc.) to the substantial (in case of drugs like flurbiprofen, ibuprofen etc.). However the factor that does not appear to be effective is therapeutic effect.

The mechanism behind the reduced efficacy of NSAID is that aspirin may replace the NSAIDs from the actual plasma protein binding sites which may result in an enhanced concentration of free or unbound drug, or the drug available for clearance. This may also be responsible for some contributory anti-inflammatory effects from the aspirin and may result in an overall reduced therapeutic response.

One should practice the caution, when aspirin is co-administered with other NSAIDs such as nabumetone, especially at anti-inflammatory dosages. Due to the risk of adverse effects, the concurrent therapy is not advised.

In case the administration is necessary the patient should be advised to take the medication along with food and he should also consult for reporting to the doctor in case of severe signs and symptoms of gastric ulceration. (like abdominal pain, bleeding, bloating, sudden dizziness, or lightheadedness, nausea, vomiting, and anorexia.

What should be done in case of nabumetone overdose?

An overdose of NSAIDs such as nabumetone can cause lethargy, drowsiness, nausea, vomiting, and epigastric pain which can be treated with supportive care. One can also suffer from gastrointestinal bleeding. Some rare symptoms such as hypertension, acute renal failure, and respiratory depression can also occur.

After NSAIDs overdose, the patient should be managed by symptomatic and supportive care. There are no specific antidotes. In patients with the symptoms of NSAIDs overdose, emesis, activated charcoal or osmotic cathartic can be used. As nabumetone is highly protein bound, the methods such as forced diuresis, alkalinization of urine, hemodialysis, or hemoperfusion may not prove of much use.

Is nabumetone an opiate?

Nabumetone belongs to the non-steroidal anti-inflammatory drugs class and is used for joint pain and arthritis. It works by reducing hormones which are responsible for inflammation and pain in the body. Therefore it is not an opiate and also it cannot get you high.

Can nabumetone be taken during pregnancy?

Nabumetone comes under the pregnancy category C, which means there are no sufficient and well-controlled studies are given in humans, and animal reproduction studies showed the adverse effects on the fetus. It can be used for human only when benefit outweighs the potential risks.

This medication is not recommended in the last trimester of pregnancy as it can cause premature closure of ductus arterious. This medication is also not recommended in the women who are planning to get pregnant because it can impair the fertility of such women.

Can nabumetone be taken while breastfeeding?

Administration of other agents in case of joint pain or arthritis while breastfeeding is recommended due to lack of published clinical data. One should make a decision for either to stop the breastfeeding or to stop the medication, followed by the consideration of which one is important. This drug is not to get excreted into the human milk, however, the effect of this drug on the nursing infant is unknown.

Can nabumetone be taken during pregnancy?

Nabumetone comes under the pregnancy category C, which means there are no sufficient and well-controlled studies are given in humans, and animal reproduction studies showed the adverse effects on the fetus.

It can be used for human only when benefit outweighs the potential risks. This medication is not recommended in the last trimester of pregnancy as it can cause premature closure of ductus arterious. This medication is also not recommended in the women who are planning to get pregnant because it can impair the fertility of such women.

What are the contraindications of nabumetone?

Nabumetone is contraindicated in patients who have known hypersensitivity to nabumetone or to any ingredient present in the nabumetone formulation. Or in the patients, who have a history of the conditions like asthma, urticaria, or other sensitivity reaction precipitated by aspirin, or in patients who have undergone cardiac artery bypass grafting (CABG) surgery.

Can nabumetone increase the cardiovascular risk?

In patients with or without cardiovascular diseases or who have risk factors of cardiovascular disease, drugs like NSAIDs mainly COX2 inhibitor can increase the risk of serious adverse cardiovascular thrombotic events such as myocardial infarction (MI), stroke etc. As per recent FDA reports, these medications (NSAIAs) can increase the risk of such events by 10-50% or more (depend upon the dosage of drugs).

There is an increase in the risk of cardiovascular events in patient with or without cardiovascular diseases, however, the incidence of serious NSAIA-associated cardiovascular thrombotic events is higher in patients who are suffering from cardiovascular diseases as they already have elevated baseline risk.

After initiation of the therapy, the risk can be increased and also risk can appear early (most likely in few first weeks). Also, the risk can be increased with duration and high doses.

Can nabumetone cause constipation?

Yes, nabumetone can cause constipation as a common gastrointestinal side effect. The most common gastrointestinal side effects of nabumetone are diarrhea, dyspepsia, and abdominal pain.

The common side effects of (in 1% to 10%) nabumetone are constipation, flatulence, nausea, positive stool guaiac, gastritis, dry mouth, stomatitis, and vomiting. Some other gastrointestinal side effects are a duodenal ulcer, gastrointestinal bleeding, gastric ulcers, or stomatitis but they are uncommon or rare.

Can nabumetone be used for a migraine?

Yes, nabumetone can also use for the prevention of tension headaches, and migraine. Just like other painkillers or NSAIDs, if taken before the main headache stage, nabumetone and other painkillers can prevent the condition from getting worse.

As per the study, it is proved safe and effective for a migraine, however, the number of studies has been a few. Moreover, no new studies have been published on the same, therefore one must talk to your doctor before switching to nabumetone for a migraine.

Can nabumetone be used in patients with high blood pressure?

Use of nonsteroidal anti-inflammatory drugs is reported to be associated with fluid retention and edema. In patients with preexisting fluid retention, hypertension, or even a history of heart attack, the NSAIDs therapy should be used with extreme caution.

During the initiation and throughout the course of the NSAIDs treatment, the close monitoring of blood pressure and cardiovascular status should be done.

Can nabumetone cause high blood pressure?

The onset of new hypertension or worsening of pre-existing hypertension can occur due to nabumetone or other NSAIDs. Such incidents can even enhance the risk of cardiovascular events. Therefore in patients with existing hypertension, the NSAIDs therapy should be used with extreme caution. Close monitoring of the patient for blood pressure and cardiovascular status should be done.

Can nabumetone be taken in patients with asthma

Approximately 10% of patients with asthma may have aspirin-sensitive asthma, characterized by nasal polyposis, pansinusitis, eosinophilia, and precipitation of asthma and rhinitis attacks after ingestion of aspirin. The use of aspirin in these patients has been associated with severe bronchospasm and fatal anaphylactoid reactions.

Since cross-sensitivity has been noted between aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) including nabumetone, therapy with any NSAID should be avoided in asthmatic patients with a history of aspirin or other NSAID sensitivity, and administered cautiously in all patients with preexisting asthma.

Prior to initiating therapy with NSAIDs, patients should be questioned about previous allergic-type reactions to these agents. Salicylate salts, salsalate, salicylamide, and acetaminophen may be appropriate alternatives in patients with a history of NSAID-induced bronchospasm, since cross-sensitivity to these agents appears to be low.

However, cross-sensitivity has been demonstrated occasionally with high dosages of these agents (e.g., acetaminophen >= 1000 mg), thus it may be appropriate to initiate therapy with low dosages and increase gradually.

There is some evidence suggesting that COX-2 inhibitors may be safely used in patients with aspirin-sensitive asthma, although the labeling for these products contraindicate such use. If necessary, aspirin desensitization may also be attempted in some patients under medical surveillance.

Can nabumetone be taken with diuretics?

Nabumetone can decrease the natriuretic effect of furosemide and thiazides such as chlorothiazide in some patients as per post marketing observations. This response has been attributed to inhibition of the renal prostaglandin synthesis. Renal failure can occur in such patients, therefore, they should be monitored closely during concomitant therapy. The diuretic efficacy should also be monitored.

Can nabumetone be taken with lithium?

An elevation in plasma lithium levels and reduction in renal lithium clearance have been reported in patients receiving NSAIDs therapy. Approximately 15% increased lithium concentration and 20% reduction in renal lithium renal concentration was noted.

NSAIDs can attribute to the inhibition of the prostaglandin synthesis. The patients should be monitored carefully for the signs of the lithium toxicity, during concurrent administration of the lithium and NSAIDs.

Can nabumetone be taken with methotrexate?

As per a study done on the rabbits, the NSAIDs have been reported to inhibit the methotrexate accumulation competitively in rabbits kidney. It means that they can enhance the toxicity of the methotrexate. When NSAIDs are administered with methotrexate, the caution is needed.

Can nabumetone be taken with warfarin?

Gastrointestinal bleeding can be increased when NSAIDs and warfarin are administered together because they show synergistic effects on gastrointestinal bleeding. The risk is higher in patients who take both drugs together as compared to either drug alone.

Can nabumetone be taken with naproxen?

No, nabumetone should not be administered with naproxen because naproxen is also a nonsteroidal anti-inflammatory drug and the recommended maximum number of medicine in this category (NSAIDs) to be taken is ONE. This combination can outweigh any risks associated with therapeutic duplication. However, you should always check with your doctor, before reaching any conclusion. You can even ask for any dose adjustment needed in this regard.

What if I miss nabumetone dose?

If you miss a dose of nabumetone, take it as soon as you remember, unless it’s almost time for your next dose. In that case, skip the missed dose and continue on your regular medication schedule. Do not double up on doses to make up for a missed one.

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Psyllium Husk – benefits, uses and side effects

Apr 16 2018 Published by under Medicinal Herb,Vitamins

What is Psyllium Husk?

Botanical Name: Plantago psyllium, Plantago ovate

Common Name: Ispaghula

Family: Plantaginaceae

Psyllium belongs to a family of plant species Plantaginaceae  cultivated in many parts of the world but largest cultivation is done in regions of India. Seeds of Psyllium plant obtained from the common fleawort are used for medicinal purposes. The stalks of the plant carry little seeds which are usually covered by husks.

These seeds are used for various purposes in foods. Although there are several species of psyllium present, but Plantago ovato consists of the maximum fiber content and is of best grade. Psyllium is soluble fiber which behaves like a sponge cleaning up the intestines.

In view of the fact that psyllium naturally consists of dietary fiber, it is used in various fiber and laxative supplements to treat constipation and prop up bowel movement regularity. It is also used to treat diarrhea and have been useful in lowering cholesterol levels in the body.

Although psyllium is used in several forms but the most important and chief product is the psyllium husk. The effectiveness of psyllium is due to the formation of thick mucilage, the action of which is entirely mechanical that is the husk swells into a jelly like substance on emulsifying it with liquids.

This is a white fibrous material obtained from the outer coating of psyllium seed. The husk consists of epidermis and crumpled adjacent layers. It is the only part which is used in the manufacturing of psyllium products.

Husk is the only part which is used in the manufacturing of psyllium products.  As it does not compose of any gluten, it can be easily used in people who are allergic to gluten. The nutrients which are present in it include glycosides, proteins, polysaccharides, vitamin B1 and choline.

What is psyllium husk powder for?

How psyllium husk is made?

Chemical composition of Psyllium Husk

Psyllium husk has the properties similar that of mucilage which chemically consists of the following compounds:

High proportion of hemicellulose, arabinose, xylose, glacturonic acid, partially dried fatty oil and minute quantities of aubicin.

How is Psyllium Husk obtained?

A country’s heavy investment is done on the cultivation and processing of psyllium. The plant is a shrubby perennial plant which has spikes of small flowers that ultimately mature into seedpops. The crop is then harvested in the morning, once the dew is evaporated.

This is done to minimize the shattering and field losses. In some areas, the mature plant is cut and bound and left for a few days to dry up. It is then thrashed and winnowed. Before the seeds are sent for further manufacturing procedures, it should be dried to below 12% moisture.

As soon as the raw material is received at the processing unit, the seeds are fumigated. This helps to get rid of any contaminated material with the help of certain fumes, gases or vapors. Mostly, this is done to remove pests, bacteria or any other disease causing agents. Ethylene Oxide and gamma radiation are mostly used.

Next, to this, the workers are employed for mechanical cleaning. This is done to remove any stones or mud particles. After cleaning of the seeds, the process of de-husking begins. It involves the crushing of the seeds with the help of certain kind of mills and the separation of husk in a closed circuit of pneumatic aspiration system.

Psyllium husk is then cleaned by sieving the blend of husk and ground remains of seeds and blowing away the impurities. For obtaining a high grade yield of psyllium husk, the processes used are aimed at minimizing breakage and size reduction of non husk core.

The husk is then allowed to pass through gravity separators for additional purification. Moreover, automatic sievers with a number of different mesh size screens and magnets can be used in the purity separation process. This separation of psyllium husk with other non husk parts of the plant are done on the basis of their density, particle size, and shape.

Psyllium Husk is categorized in a number of grades. This grading is done on the basis of the purity level or the mesh size used in purifying process. These grades are 99% pure, 98% pure, 95% pure and 85% pure.

Once obtained in the desired form, the husk is then packaged under extremely hygienic conditions for safe and secure transit of the product until it has been used by the consumer. Some of the most common packaging material used for psyllium husk includes coated and uncoated UV stabilized polypropylene woven bags, HDME laminated paper bags, plastic container, fiber paper drum and sliver plated ring.

How much psyllium husks should I take in a day?

How does Psyllium Husk exert its action?

A large proportion of the psyllium husk reaches caecum, the starting region of the large intestine. Almost it takes 4 hours for the psyllium to reach the cecum in an intact and very high polymerized form. Psyllium husk drastically raises the moisture level of the stool, in addition to wet and dry stool weight and reduces the gastrointestinal transit time.

Anaerobic fermentation of non starch polysaccharides solubilized from the psyllium results in the generation of short chain fatty-acids, acetate, butyrate and propionate in the intestine. Butyric acid is the favored oxidative substrate for colonocytes. This may be helpful in the treatment of ulcerative colitis. Along with this, psyllium husk also has cholesterol lowering property.

It is implicated that psyllium augments the action of cholesterol alpha-hydroxylase, HMG-CoA reductase and a proportional yield of chenodeoxycholic and cholic acids. This results in diminished cholesterol absorption and lessens the LDL levels in the blood.

What are the uses of Psyllium Husk?

Even though psyllium is a natural substance but over recent years studies have been conducted to find its use in different conditions. Following are some of the most prominent effects of psyllium husk for which healthcare provider recommends its use to the patients:

Psyllium husk chemoprotective effects

Colorectal cancer arises the abnormal cells of colon and rectum region join together to form polyps, which is eventually transformed into a cancerous mass/ lumps. One of the key element to the contribution of the formation of these cancerous mass/ lumps is the individual’s diet.

Those patients who are at a high risk of developing this cancer either due to some genetic factors or any underlying disease should be more caring towards their meal selection. It is suggested to have a maximum intake of dietary fiber. This not only reduces the chances of colorectal cancer but also lowers the chances of developing esophageal cancer.

The exact mechanism is still unknown but it is assumed that the insoluble fiber part lowers the concentration of cancer-causing bile acids and at the same time moves the faeces out from the colon at a faster rate. The more quickly faeces is propelled out of the intestines, the less time it will have to contact and the less quantity of carcinogens will be produced.

 Psyllium husk gastrointestinal effects

Constipation and diarrhea are two of the most occurring medical conditions. According to a survey, chronic constipation is more widespread in adults who are older than 50 years but symptoms appear in only about half of the affected population.

Supplementary intake of dietary fiber preferably in form of psyllium is suggested by research studies to improve the signs and symptoms by bringing about the regularity of the bowel movements and providing natural relief from constipation. Psyllium husk is preferred over magnesium containing laxatives as it may decrease the bowel movements and leads to toxicity.

When psyllium is taken in combination with water or any other fluid, the husk bloats and produces more bulk. This stimulates the intestines to contract helps to eliminate the stool through the digestive tract.

It has been studied that psyllium has better activity then docusate sodium for softening of the stool by increasing the water content. Psyllium has been also used in the treatment of hemorrhoids which occur frequently due to constipation.

In diarrhea, psyllium husk has been proven useful by soaking up the major amount of water in the digestive tract. This makes the stool harder and slows down the expulsion of contents. Psyllium husk is used in the treatment of mild to moderate degree diarrhea.

Psyllium Husk prebiotic effects

Psyllium husk has been known to contain such non-digestible compounds which provide nourishment to the intestinal bacteria and help in their growth. Therefore, psyllium husk is considered to have prebiotic effects. Psyllium is generally resistant to fermentation but some of its fibers can undergo fermentation which is carried out by the intestinal bacteria.

As a result of this fermentation, short chain fatty acids are produced which are known to have health benefits. Although fermentation results in the production of gas which can cause digestive discomfort but psyllium fibers undergo fermentation at a very slow rate which eliminated the chances of gas production and subsequent digestive discomfort.

These effects have shown to reduce the digestive symptoms in patients with ulcerative colitis. Hence, psyllium being rich in prebiotic fibers promotes the production of short chain fatty acids and also helps to reduce the gastric discomfort in patients suffering from ulcerative colitis and Crohn’s disease.

Psyllium: Benefits, safety, and dosage

Psyllium Husk cholesterol-lowering effect

One of the additional therapeutic effects that psyllium offer is its capability to lower the blood cholesterol levels. Even though the studies conducted give contradictory results, it has been suggested that cholesterol levels are reduced due to dislodgment of dietary fiber by soluble fiber. When psyllium husk is ingested it displaces the fats and cholesterol which is given in diet.

This reduces the amount which is available for absorption. It has been observed that psyllium has increased the excretion of bile acids and cholesterol in faeces, binds these in the intestines, permit decreased circulation for reabsorption and make available more of cholesterol to be converted into bile acids by the liver.

One more study had demonstrated that psyllium lowers LDL levels by increasing the production of chenodeoxycholic acids and cholic acids. Hence the cholesterol lowering effect is due to combined action imparted by the increased fecal elimination of bile acids with a compensatory rise in bile acid synthesis.

Psyllium Husk cardiovascular effects

Nowadays, people are suffering a lot from heart problems. The primary cause of these problems is increased levels of cholesterol and fats particularly triglycerides in the blood and eventually in the body. Psyllium husk, being rich in water soluble fibers help to reduce the levels of triglycerides in the blood and this, in turn, leads to reduced blood pressure and the risk of heart problems reduces.

Studies have confirmed that if psyllium is added to the diet it reduces the triglycerides levels to an appreciable extent. Increasing the levels of psyllium in the diet has additional beneficial effects as it helps to reduce the systolic blood pressure and subsequently the blood pressure of patients is reduced.

Obese persons who are already suffering from blood pressure can be given dietary modifications by adding psyllium husk to their diet. Studies have shown that this change can lead to substantial decrease in blood pressure. Hence the regular use of psyllium provides such fibers which help to reduce blood pressure and the triglycerides level of the blood which reduces the risk of heart diseases and helps maintain a healthy heart.

Psyllium Husk for weight loss

Psyllium husk contains a variety of fibers which help in controlling appetite and also aid in weight loss because of the ability of these fibers to form viscous compounds. Studies have revealed that if psyllium is given just before a meal, it affects the emptying of the stomach and slows it. This delay in the stomach emptying gives a feeling of fullness and results in reduced total fat intake throughout the rest of the day.

This effect plays a vital role in the reduction of weight loss as it reduces the total fat intake by the individual throughout the day. Other studies have revealed that if psyllium husk is taken along with a diet having reduced fat content, this has proven to be more beneficial for weight loss while receiving psyllium supplements along with a diet rich in fiber which can further cause a reduction in the body mass index and the percentage of total fat in the body.

Hence it can be concluded that psyllium husk helps people in controlling their appetite by reducing it and also slowing down the rate of stomach emptying. These effects further lead to a decreased calorie intake which in turn causes weight loss.

Psyllium Husk in lowering blood sugar levels

The fibers present in psyllium husk particularly the water-soluble fibers helps to control the glycemic response to a meal by reducing the blood sugar levels. In this regard, psyllium works particularly better than other fibers, because its fibers can slow the digestion of food which helps to regulate the blood sugar levels.

These effects can be applied to the treatment of diabetic patients. Studies have shown that including psyllium in the diet of diabetic patients has shown to reduce the blood sugar levels of such patients to an appreciable extent. These effects can be achieved if psyllium is given along with food and in this way, it helps to reduce the blood sugar levels more efficiently.

Psyllium can be used to reduce the effects of hyperglycemia which may occur after having a meal high in dextrose. In such cases, psyllium interferes with the intestinal absorption of glucose and hence decreases the hyperglycemic effect.

Pharmacokinetics of Psyllium Husk

Psyllium is a bulking agent which remains primarily in the gut. It is absorbed unchanged through the Gastrointestinal tract and is resistant to fermentation. The hemicellulose content of psyllium is high due to which its capacity to hold water is high.

Once administered, it takes 12 to 24 hours for the onset of its action. However, it may take 2 to 3 days to show its complete effect. When given along with breakfast, it significantly lowers the AUC value of plasma glucose.

Psyllium Husk dosage and requirement

Generally, the dosage suggested of psyllium husk depends on the condition for which it is prescribed. It has been observed that a general dose of 3g – 6g b.i.d or t.i.d. has shown desired effects. However, it can be increased to a slightly higher dose in certain conditions. In children, it is advised to half the adult dose and the maximum intake given in a single day should not be greater than 9grams.

Following are the adjustments made in general recommended guidelines depending on the medical condition.

  • Constipation (Adults)

Daily Fiber Requirement

Adults from 19 years old – 50 years old: For males 38g/day, for females 25g/day

During pregnancy: 28g/day

For breastfeeding women: 29g/day

Dose

1-2 teaspoonfuls dissolved in fluid or 5-6 capsules orally taken with 8 oz. of fluid (preferably water) 1 to 3 times per day.

  • Constipation (Pediatric):

Daily Fiber Requirement

From 1-3 years old: 19g/ day

From 4-8 years old: 25g/day

From 9-18 years old: In males 31g/day, in females 26 g/day

Dose

Children below 11 years can be given 1.25g to max 15g orally in a day in divided doses.

Children above 11 years can be given 2.5g to max 30g orally in a day in divided doses.

  • In hypercholesterolemia:

In the treatment of hypercholesterolemia, there had been suggestion given in conclusion to the studies conducted. In one study conducted it was suggested that a single dose of 10.2g was effective in lowering the LDL levels while in another study a dose range of 3g to 20.4g was advised.

  • Other medical conditions:

In diverticular disease, it is advised to take 7g/ day

In irritable bowel syndrome, it is advised to take 3.25g three times per day

In diabetes, it is advised to take 5.1g three times a day with the meal

For treating Hemorrhoids it is advised to take 7g three times per

Psyllium Husk consideration for use

Psyllium husk contains a high fiber content because of which it is recommended to drink a minimum of 8 ounces (oz.) of water (preferably) or any other liquid throughout the day to avoid constipation. If the patient’s diet up till now has been low in fiber content it is better to start off with a low dose of permitting the patient’s body to adjust to the change and reduces the chances of side effects including gas and bloating.

It is better to take the psyllium husk supplements, at least one hour before other medicines or supplements are ingested. In case of forgetfulness, take psyllium with a gap time of 2 – 4 hours after the medicines. It should be strictly followed to never take psyllium at the same time as it would decrease the bioavailability of other drugs to a great extent.

Depending upon the directions given by the doctor or the instruction available on the package, it can be taken on an empty stomach in the morning or just before bedtime if a single dose is to be taken. For the purpose of weight management, the required dose should be administered at least 30 minutes before having the meal.

Side effects of Psyllium Husk

Psyllium husk is a natural herb that is used medicinally for obtaining therapeutic outcomes. Although it is listed among safe herbal products, excessive dosage or chronic use have contributed drastically towards the developments of certain side effects. Among these side effects, the prominent ones are:

  • Hypersensitivity:

Even though the occurrence rate of hypersensitivity to psyllium husk is quite low but in some people once developed may lead to severe symptoms. They might be exposed to the psyllium from the inhalation of fine particles as the product is poured or dispersed. However, orally administered psyllium has fewer chances of provoking an allergic reaction.

Typical features of an allergic reaction can be as small as redness on the skin; skin hives to as severe as anaphylaxis, vomiting, chest tightness and breathing difficulties.

  • Intestinal obstruction:

This is the major side effect that is faced with taking laxatives. Psyllium husk has been responsible for causing partial obstruction or even complete blockage of the gastrointestinal tract particularly colon. This obstruction has more chances to occur when inadequate mixing of psyllium with the liquid portion is done.

This is also seen in patients who have recently undergone bowel surgery. Patients suffering from throat problems or having swallowing difficulty, the accumulation of improperly digested occurs in the digestive tract.

  • Gas and bloating:

Bloating is the swelling of the stomach due to the presence of some air or fluid. Using psyllium husk for prolonged period give the patient a feeling of fullness in the abdominal region or bloating.

This is usually due to the formation of gas within the gastrointestinal tract. The more the generation of gas occurs, the more will be flatulence. When the bloating becomes unbearable, the patient should be immediately taken to the emergency department.

  • Hematologic:

In rare cases, it has been observed that psyllium has adversely affected the blood components. Eosinophilia was reported in few cases. This can be a sole demonstration of a hypersensitivity reaction.

Psyllium Husk drug interactions

It has been noted that psyllium may bring delay or decrease the absorption of certain drugs. Certain drug interactions occur when used concomitantly with psyllium husk. In few cases, these interactions have been used but in most cases, it brings undesirable effects.  Some of the clinically significant interactions are listed below:

Tricyclic Antidepressant Agents (TCAs)

Dietary fiber has been responsible to decrease the blood levels of tricyclic antidepressant agents and in turn, the effectiveness of these drugs is reduced. If the patient has to take these medications for a certain medical condition it is essential to discuss it with the doctor as there might be a need to raise the dose or frequency of TCAs.

Some of the drugs under the class of TCAs which have most frequently shown these interactions are amitriptyline, doxepin, and imipramine.

Lithium

Lithium is used as an anti-epileptic drug. However, when it is used in combination with psyllium husk, it has been observed that psyllium has lowered the plasma levels of lithium thus reducing the action. When both are to be used by the patient, psyllium should be administered at least 2-3 hours before or after the administration of lithium. It is advised to constantly monitor the levels of lithium present in the body.

Anti-diabetic agents

Patients who rely on diabetic medications for keeping their blood sugars levels at normal should not use psyllium for any of their medical conditions. Fiber present in psyllium husk joins up with the drug molecules in the blood. As a consequence, it is expected that the patient becomes hypoglycemic and may faint.

Cholesterol-lowering drugs

A class of drugs, bile acid sequestrants which are used for their cholesterol-lowering property have also interacted negatively with psyllium husk. The serum levels of these drugs are reduced, so does its effectiveness. As a result, the quantity of LDL molecules and triglycerides increases. On the other hand, the chances for side effects to occur also reduce. This class includes cholestyramine and colestipol.

Psyllium Husk storage conditions

Psyllium husk is a natural organic herb that can keep its effectiveness for a period of 2 years it is stored in an airtight container.

Direct exposure to sunlight and humidity should be avoided as it may affect the moisture and ash content present in psyllium husk.

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