Archive for June, 2015

Clopidogrel

Jun 27 2015 Published by under Medicines

What is Clopidogrel (Plavix)?

  • Clopidogrel is an oral, thienopyridine-class drug that is used to inhibit blood clots formation.

What is the generic and brand name of the drug?

  • The drug is available under generic name Clopidogrel and marketed by Bristol-Myers Squibb and Sanofi under brand names Plavix

What is the source of the drug (natural or synthetic)?

  • Clopidogrel is a synthetic (man-made) pharmaceutical anti platelet agent or platelet aggregation inhibitor. 

Why is this medication prescribed?

  • Clopidogrel is an antiplatelet agent (pharmaceuticals agent that decreases platelet aggregation) that is chemically and pharmacologically similar to ticlopidine (Ticlid).
  • The drug is used to prevent or inhibit the formation of blood clots in a variety of medical conditions i.e. coronary artery disease, peripheral vascular disease, and cerebrovascular disease.
  • The drug is used to reduce the risk of stroke and myocardial infarction (heart attack) in people who have already had a history of myocardial infarction, other forms of acute coronary syndrome, unstable angina, stroke, and peripheral artery disease.
  • Clopidogrel is also used in combination with acetylsalicylic acid (ASA, aspirin), to prevent thrombosis (blood clotting) following placement of a coronary stent (a tube shaped appliance that is used to keep the arteries open in the treatment of coronary heart disease).
  • Clopidogrel is also used in combination with acetylsalicylic acid as an alternative antiplatelet drug in people with a history of gastric ulceration or when aspirin cannot be used (Aspirin intolerant).
  • As per the norms of American Heart Association and the American College of Cardiology, Clopidogrel or a related drug is recommended for patients with myocardial infarction with ST-elevation, percutaneous coronary intervention (PCI, fibrinolytic therapy, non-ST elevation myocardial infarction or unstable angina and stable ischemic heart disease.

Pharmacophore structure: Information about the chemical structure of the drug.

Clopidogrel chemically belongs to the class of organic compounds which are known as alpha amino acid esters. The alpha amino acid esters are chemically characterized as ester derivatives of alpha amino acids .The detailed chemical classification of Clopidogrel  is described below:

Kingdom Organic compounds 
Super Class Organic acids and derivatives
Class Carboxylic acids and derivatives
Sub Class Amino acids, peptides, and analogues
Direct Parent Alpha amino acid esters

Chemical information of the drug.

  • Clopidogrel is a synthetic pharmaceutical organic compound named as methyl (2S)-2-(2-chlorophenyl)-2-{4H,5H,6H,7H-thieno[3,2-c]pyridin-5-yl}acetate.
  • The compound has molecular formula C16H16ClNO2S and the molecular weight of 822 Da.
  • The melting point of Clopidogrel is 158 °C.
  • Clopidogrel is available as bisulfate salt and is white to off-white in color.
  • Clopidogrel is almost insoluble in water at neutral pH (pH-7.0), however solubility is increased dramatically at pH 1.

 What is the available strength of the drug?

  • The medication is supplied as either pink, round, biconvex, or pink, oblong film-coated tablets for oral administration by mouth.
  • Clopidogrel tablet is usually recommended to be taken once a day and with or without food.
  • Clopidogrel tablet is available in two strengths-(75 mg and 300 mg).
  • Each 75 mg Clopidogrel tablet is embossed with “75” on one side and “1171” on the other and contains 97.875 mg of Clopidogrel bisulfate molar equivalent of 75 mg of Clopidogrel.
  • Each 300 mg Clopidogrel tablet is embossed with “300” on one side and “1332” on the other side and contains 391.5 mg of Clopidogrel bisulfate molar equivalent of 300 mg of Clopidogrel.
  • Besides Clopidogrel, each tablet contain other inactive ingredients such as mannitol, hydrogenated castor oil, microcrystalline cellulose, hydroxypropylcellulose, and polyethylene glycol 6000 as inactive ingredients.
  • The film coating of tablet contains hypromellose 2910, ferric oxide, titanium dioxide, lactose monohydrate, and triacetin. The tablets are polished with carnauba wax.

How the medicine works (mode of action)?

  • Clopidogrel is an antiplatelet agent that prevents the formation of blood clots.
  • When metabolized by the body, the active metabolite of the drug binds irreversibly to the P2Y12 subtype of adenosine diphosphate (ADP) receptor on the platelets.
  • The occupancy of the platelet receptor (involved in the aggregation of platelets and cross-linking by fibrin protein) by the drug impairs the binding of ADP to the receptor and thus, the activation of the glycoprotein GPIIb/IIIa complex.
  • GPIIb/IIIa complex is the major receptor for fibrinogen whose impaired activation prevents binding of fibrinogen to platelets and inhibits platelets from sticking to each other.
  • Clopidogrel interference with the platelet function prevents blot clots formation inside of the blood vessels.
Clopidogrel : Mode of action.

Clopidogrel : Mode of action.

What are the recommended doses of Clopidogrel?

The Clopidogrel is available in tablet form to be administered by mouth once a day. It can be taken with or without food. The dosage depends upon the diseased state of the patient and medical history.

  • Acute Coronary Syndrome: For patients with non-ST-elevation (NSTEMI):
    • The initial dose is a single 300 mg oral loading dose followed by 75 mg dose once daily.
    • Aspirin (75–325 mg once daily) is also recommended in combination with Clopidogrel.
  • Acute Coronary Syndrome: For patients with STEMI:
    • Clopidogrel may be initiated with or without a loading dose.
    • The recommended dose of Clopidogrel is 75 mg once a day to be administered orally, in combination with aspirin (75–325 mg once daily), in presence or absence of thrombolytics (medicines that dissolve blood clots).
  • Peripheral arterial disease, or  recent MI (myocardial infarction) or  stroke:
    • The recommended dose of Clopidogrel is 75 mg once a day orally, with or without food.

This medicine should not be stopped abruptly. If there is an urgency to stop it, it should be done under the supervision of the doctor.

When should I discontinue, withhold or modify the dose of Clopidogrel?

  • The dose of Clopidogrel should be adjusted based on the patient’s clinical status, and medical history.
  • The drug is contraindicated in case of pregnancy or breastfeeding.
  • The use of the drug is restricted in patients who are hypersensitive to any component of the drug.
  • Clopidogrel is contraindicated in case of peptic ulcer or intracranial hemorrhage.
  • The use of Clopidogrel has not been evaluated in case of severe or moderate renal impairment.
  • Safety and effectiveness of the drug has not been evaluated in case of pediatric populations.
  • No dosage adjustment is necessary in elderly people and hepatic impairment patients.

What are the pharmacokinetic properties of the drug?                                          

  • Following administration (single or repeated multiple doses of 75 mg per day), Clopidogrel is rapidly absorbed (approximately 50 %) by the body.
  • Bioavailability of Clopidogrel is not affected by the food.
  • The peak plasma concentration of unchanged Clopidogrel is achieved approximately 45 minutes after dosing (single 75 mg oral dose).
  • Following absorption, the majority of the drug (98 %) is bound to human plasma proteins.
  • The drug is mainly metabolized by the hepatic system.
  • Pharmacokinetic studies with Clopidogrel have shown that the excretion of the drug is 50 % renal (urine) and 46 % biliary (feces).
  • The details regarding average steady state volume of distribution of the drug is not available.
  • The biological half-life of Clopidogrel is 7-8 hours (inactive metabolite).

Which pregnancy category (A; B; C; D; X) has been assigned to Clopidogrel?

  • The Clopidogrel is classified by US FDA pregnancy category: B.
  • Due to lack of adequate and well-controlled studies, the use and safety of Clopidogrel in pregnant women is contraindicated and recommended only if clearly needed.
  • No adequate data is available on excretion of Clopidogrel into human breast milk. However, the use of drug is not recommended in nursing mothers.
  • Due to these facts caution should be exercised when taking Clopidogrel during pregnancy.

How to use the drug?

  • Follow the instructions carefully as directed on prescription leaflet and take Clopidogrel exactly as directed by your health care professional.
  • Clopidogrel is available in tablet form for oral administration.
  • Clopidogrel can be taken with or without food once a day.
  • The drug should be taken with a full glass of water.
  • It is also recommended to take drug at almost the same time every day.
  • Take the medication regularly, even if you feel well.
  • Try to take the medicine at the same time every day.
  • Do not stop taking the medication abruptly without consulting your doctor.
  • Do not change the dose of the drug as prescribed by your doctor. Since, dosage and duration of treatment are based on your medical condition and response to treatment.
  • In case of surgery, tell your doctor beforehand that you are taking Clopidogrel.
  • If you have any queries about the drug immediately consult your doctor.

How to store the drug?

  • Clopidogrel is stored at room temperature 25°C (77°F).
  • Brief excursion period is permitted at temperature 15–30°C (59–86°F).
  • The drug should be kept away from excess heat, direct sun light, moisture and reach of children.
  • The drug should not be stored in bathroom.

How to dispose the medicine?

  • Throw away unused and opened, outdated or no longer used drug.
  • Also dispose the old medicine after the expiration date.
  • Talk to your pharmacist about the proper disposal of your medication.

Does Clopidogrel has approval from government / FDA /or any other related agencies?

  • Clopidogre has received its official approval from US Food and Drug Administration (FDA) in 1997 for the treatment of acute coronary syndrome (ACS), which is defined as unstable angina and myocardial infarction (mild heart attack).
  • The drug has also received official approval from FDA for its use in the prevention of blood clot formation in patients who recently have stroke, myocardial infarction, or peripheral arterial disease.

Other uses of the drug.

  • Clopidogrel also finds an implication in the prevention of blood clot formation in patients with atrial fibrillation (a condition in which the heart beats irregularly).
  • Clopidogrel may also be used for other uses not listed here. It is advisable to ask your doctor or pharmacist for more detailed information regarding its use.

What special dietary precautions should I follow?

  • A high fat and standard meal is usually not recommended as it reduces inhibition of platelet
  • Avoid grape juice and alcoholic beverages.
  • Drink plenty of water when you take the medicine.

What special precautions should I follow?/ What should I avoid while using Clopidogrel?

  • First of all inform your doctor if you are allergic to any Clopidogrel or any of the ingredients present in the Clopidogrel product. Ask your pharmacist or check the prescription leaflet carefully for a list of the ingredients.
  • It is advisable to discuss with your doctor and pharmacist about what prescription and nonprescription medications, vitamins, and nutritional supplements you are taking or plan to take specially aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs); anticoagulants; selective serotonin reuptake inhibitors (SSRIs); and selective serotonin/norepinephrine reuptake inhibitors (SNRIs); esomeprazole (Nexium) etc.
  • Inform your doctor if you are breastfeeding or pregnant or plan to become pregnant. Tell your doctor if you are breastfeeding.
  • Inform your doctor about the use of Clopidogrel if you are having surgery, including dental surgery.
  • Clopidogrel use should be stopped under the supervision of doctor if you have bleeding ulcers, bleeding in the brain or a condition causing excessive bleeding.
  • Inform your doctor about the recent injury and try to avoid cuts or hurting yourself as it may lead to severe bleeding while you are taking Clopidogrel.
  • Before taking Vardenafil, tell your doctor about your medical history preferentially if you have any kind of liver or kidney disease, certain eye disorders, bleeding disorders etc.
  • Consult your doctor in case of any query.
  • It is recommended to avoid consuming alcohol as it may increase the risk of bleeding in stomach or intestines.

What are the possible side effects of this drug?

  • The active ingredient in Clopidogrel may result in some side effects that require medical attention. Check with your doctor immediately if these side effects persist for a long time and become bothersome.
  • Some commonly occurring side effects include:
  • Purple or red spots on the skin
  • Pain in general
  • Chest pain
  • Collection of blood under the skin
  • Deep, dark purple bruise
  • Itching, swelling, pain, or redness
  • There are some side effects that are less common. These include:
  • Vomiting of blood
  • Nosebleed
  • Breath shortness Painful urination
  • Vomiting of material that looks like coffee grounds

Most of the people who take this drug do not develop serious side effects. The symptoms can develop any time after you start taking the medicine.

In rare instances, serious blood disorder (thrombotic thrombocytopenic purpura-TTP) can occur. If any of following symptoms appears get immediate medical help.

  • Extreme skin paleness
  • Bleeding in the eyes, brain, or, stomach, gut
  • Unusual heartbeat
  • Bloody/black stools
  • Severe stomach pain
  • Sudden severe headache
  • Purple skin patches
  • Fainting
  • Uncontrolled bleeding from gums or nose
  • Confusion
    • Yellowing eyes/skin
    • Seizures
    • Change in amount of urine
  • Fever
  • Bloody/red/pink/dark urine
  • Unusual weakness/tiredness
    • Vision changes
    • Slurred speech

Severe allergic reaction on taking this drug is very rare. However, sometimes you may get the symptoms of a very serious allergic reaction to this drug. Get immediate medical help if you notice any of the following symptoms:

  • Severe itching, rash, swelling (especially of the throat /face/tongue)
  • Severe dizziness
  • Trouble breathing

There can be more side effects of the drug not mentioned here. Contact your doctor pharmacist if you notice any other unusual effect after taking this medicine.

What should I do in case of overdose?

  • Overdose usually occurs when someone by mistake or deliberately takes more than the prescribed limit of this medication.
  • Symptoms of overdose include unusual bruising or bleeding.
  • In case of overdose, contact with your doctor or emergency room immediately if the victim is not breathing and has collapsed.
  • Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

What should I do in case of missed a dose?

  • In case of missed dosage, take it as soon as you remember and maintain a regular dosing schedule. Keep in mind that takes the missed dose only on an empty stomach.
  • Skip the missed dose if it is almost time for your next scheduled dose. Keep in mind to not use a double dose to make up a missed dose

Does Clopidogrel have any interaction with drugs?

It has been observed that Clopidogrel may interact with or increase or decrease the effect of following drugs. Caution should be taken when co administrating Clopidogrel with one of the following drugs.

  • CYP2C19 inhibitors:Clopidogrel get metabolized to its active metabolite partly by CYP2C19. Co-administration of Clopidogrel with specific drugs that bring about inhibition of the activity of this enzyme causes reduction in the plasma concentrations of the active metabolite of the drug and a reduction in platelet inhibition.
  • Proton pump inhibitors (PPI): Proton pump inhibitors such as omeprazole and esomeprazole reduce the antiplatelet activity of Clopidogrel when co-administered with it. A higher dose of Clopidogrel is required to increase the antiplatelet activity in presence of omeprazole. Pantoprazole, dexlansoprazole, and lansoprazole exhibit less effect on the antiplatelet activity of Clopidogrel as compared to omeprazole or esomeprazole.
  • Warfarin (CYP2C9 Substrates):There is an increase in the risk of bleeding due to independent effect on hemostasis when Clopidogrel is coadministrated with warfarin.
  • Selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs): SSRIs and SNRIs affect platelet activation and increase the risk of bleeding when concomitantly administered with Clopidogrel.
  • Aspirin: Aspirin coadministration with Clopidogrel neither inhibit ADP-induced platelet aggregation nor increases the prolongation of bleeding time induced by Clopidogrel. However, the use of Clopidogrel increases the physiological reaction of aspirin on collagen-induced platelet aggregation.
  • Heparin: Clopidogrel does not modify the effect of heparin on coagulation. Coadministration of heparin shows no effect on inhibition of platelet aggregation induced by Clopidogrel.
  • Other concomitant therapy:
  • No clinically significant adverse interactions are seen in concomitant use of Clopidogrel with nifedipine or/and atenolol.
  • The activity of Clopidogrel is not influenced in presence of phenobarbital or estrogen.
  • Clopidogrel has no effect on the pharmacokinetics of digoxin or theophylline.
  • Clopidogrel when coadministered with a variety of medications (including coronary vasodilators, angiotensin converting enzyme inhibitors, antiepileptic agents, diuretics, thrombolytics, GPIIb/IIIa antagonists, calcium antagonists, cholesterol lowering agents, antidiabetic agents (including insulin), heparins, beta-blocking agents, and hormone replacement therapy exhibits no significant clinical adverse reactions.
  • No data is available on the concomitant use of chronic NSAIDs, oral anticoagulants, and oral anti-platelet drugs with Clopidogrel.
Clopidogrel drug interaction.

Clopidogrel drug interaction.

Does Clopidogrel have any interaction with diseases?

Before you begin to take Clopidogrel, it is necessary to discuss any medical condition or allergies you have or any other significant fact. It has been observed that following medical conditions (disease) may interact with Clopidogrel:

  • Allergy: People who are allergic to other antiplatelet medications like ticlopidine or prasugrel also show allergic reactions to Clopidogrel. Before you start taking Clopidogrel, it is recommended to inform your doctor about any side effect you have experienced on taking medications, especially anti-platelet medications.
  • Bleeding problems:Risk of bleeding increases in presence of Concomitant use of Clopidogrel with other medications (e.g., warfarin, NSAIDs) may further enhance the risk of bleeding. History of bleeding disorders can affect the way the medicine works, the dose and effectiveness of the drug, and whether any special monitoring is required.
  • Kidney function:Impaired kidney function or kidney disease may affect the working of the drug, dosing, drug effectiveness and may require special monitoring.
  • Lactose intolerance: If you suffer from galactose intolerance (glucose-galactose malabsorption, galactosemia, or Lapp lactase deficiency) avoid taking this medicine as it also contain lactose as its ingredient.
  • Liver function:It is not recommended to take this medicine in case of impaired liver function or liver disease as it may affect the working, dosing, and effectiveness of the drug.
  • Stomach ulcers and severe heartburn:Proton pump inhibitors (PPIs) are used to treat the patients with stomach ulcers and severe heartburn. Coadministration of Clopidogrel with proton pump inhibitors in patients of stomach ulcers and severe heart burn make it less effective.
  • Surgery: Use of Clopidogrel need to be stopped a few days prior to any surgery to prevent any unnecessary bleeding.

Where can I get more information?

Your pharmacist can provide more information about Clopidogrel.

Clinical research and current scenario of the drug

  • Clinical studies indicate the effectiveness of Clopidogrel in reduction of the risk of cardiovascular or cerebrovascular events (new myocardial infarction (MI), new ischemic stroke, and vascular death) in patients with a history of recent MI, recent ischemic stroke, or established peripheral arterial disease for treatment of hypercholesterolemia, lipid abnormalities in patients with cardiovascular disease, including Type 2 diabetes and/or metabolic syndromes.
  • Studies with Clopidogrel revealed its use in the secondary prevention of cerebrovascular disease (vascular death, fatal or non-fatal stroke and myocardial infaraction).
  • The use of Clopidogrel / Aspirin combination therapy provides additional protection against cerebrovascular disease particularly in patients who do not respond to aspirin therapy.
  • The ongoing studies in patients with unstable angina and myocardial infarction aim to examine the combination effect of Clopidogrel and aspirin in prevention of coronary thrombosis.
  • Studies indicate the use of Clopidogrel in combination with aspirin for reduction of the rate of ischemic cardiovascular and cerebrovascular events in patients with STEMI (ST-Segment Elevation MI).
  • Clopidogrel/aspirin combination therapy has been recommended as an alternative to warfarin for prevention of stroke and systemic embolism in patients with atrial fibrillation

References from chemical, biological and toxicological databases.

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Moxifloxacin

Jun 27 2015 Published by under Medicines

What is Moxifloxacin (Avelox)?

Moxifloxacin is a broad spectrum antibacterial drug that is used for the treatment of bacterial infections.

What is the generic and brand name of the drug?

  • The drug is available under generic name Moxifloxacin and marketed worldwide (as the hydrochloride) under brand names Avelox,Avalox, and Avelon.
  • Moxifloxacin is also available as ophthalmic solution (eye drop) under Vigamox and Moxeza brand names.
  • The drug was developed by Bayer AG (initially calledBAY 12-8039).
  • Bayer HealthCare Pharmaceuticals is responsible for its manufacture and is marketed by Bayer’s partner Merck.

What is the source of the drug (natural or synthetic)?

  • Moxifloxacin is a fourth generation synthetic (man-made) pharmaceutical antibiotic class of drug.

Why is this medication prescribed?

  • Moxifloxacin is a bactericidal agent that acts by killing the bacteria that cause infections.
  • Moxifloxacin acts against a wide range of bacteria (Broad range antibacterial spectrum) such as Haemophilus influenzae, enteric gram negative rods (i.e. Proteus species, Escherichia coli, Klebsiella species), Streptococcus pneumoniae, atypical bacteria (i.e. Chlamydia, Mycoplasma, Legionella), and anaerobic bacteria.
  • The drug is used to treat bacterial infections in lungs, eye, brain, skin, nose (sinus) and abdomen (stomach area).
  • Moxifloxacin is used in the treatment of respiratory tract infections (such as pneumonia, bronchitis and secondary infections in chronic bronchitis), sinusitis, skin infections and intra-abdominal infections, cellulitis, conjunctivitis, meningitis and tuberculosis.
  • However, this drug does not provide any protection against flu, cold and other viral infections.
Broad range antibacterial spectrum of

Broad range antibacterial spectrum of Moxifloxacin.

Pharmacophore structure: Information about the chemical structure of the drug

Moxifloxacin chemically belongs to the class of organic compounds which are known as quinoline carboxylic acids, which are characterized by substituted carboxyl group at one or more positions in the quinoline ring system. The detailed chemical classification of Moxifloxacin is described below:

Kingdom Organic compounds
Super Class Organoheterocyclic compounds
Class Quinolines and derivatives
Sub Class Quinoline carboxylic acids
Direct Parent Quinoline carboxylic acids

Chemical information of the drug

  • The active moiety of Moxifloxacin is fluoroquinolone (characterized by fluoride as a central part of drug).
  • The drug is available as a monohydrochloride salt.
  • The drug is a synthetic aromatic quinoline carboxylic acids broad spectrum antimicrobial agent with a molecular formula C21H24FN3O4.
  • The molecular weight of the drug is 401.431g/mol.
  • Chemically, Moxifloxacin is known as 7-[(4aS,7aS)-octahydro-1H-pyrrolo[3,4-b]pyridin-6-yl]-1-cyclopropyl-6-fluoro-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid .
  • Moxifloxacin is slightly yellow to yellow crystalline and has a water solubility of 0.168 mg/mL.
  • The melting point of Moxifloxacin is 238°C-242 °C.

What is the available strength of the drug?

  • Moxifloxacin is available in tablet form for oral administration: regular tablets and orally disintegrating tablets.
  • It is available in parental form for intravenous infusion (I.V.) in most of the countries.
  • Moxifloxacin is also used in the form of ophthalmic solution (eye drop) for the treatment of conjunctivitis (pink eye).
  • The tablet is dull red in color, film-coated, oblong and coded with M400 on one side corresponding to the dose of the drug and “BAYER” on other side.
  • Each tablet contains active Moxifloxacin hydrochloride which is equivalent to the 400 mg of Moxifloxacin.
  • MoxifloxacinV. (intravenous infusion) contains 400 mg Moxifloxacin in 0.8% saline (aqueous solution of Moxifloxacin hydrochloride in sterile 0.8% sodium chloride).

How the medicine works (mode of action)?

  • Moxifloxacin binds with bacterial DNA gyrase (topoisomerase II) and topoisomerase IV and therefore inhibits the activity of these enzymes.
  • DNA gyrase and topoisomerase IV are involves in the bacterial DNA replication, transcription, DNA repair and partitioning of the chromosomal DNA during the division of the bacterial cell..
  • Moxifloxacin prevents the replication, repair and separation of bacterial DNA, therefore inhibits the replication and causes death of bacterial cell (antibiotic or bactericidal effect).
  • It is a broad spectrum antibiotic and effective against both gram negative and gram positive bacteria.
  • Moxifloxacin is quite different from previous fluoroquinolone antibiotics (such as levofloxacin and ciprofloxacin) in its potent activity against gram-(+) bacteria and anaerobes.
  • Due to higher activity against the common respiratory pathogen Streptococcus pneumoniae, the Moxiflaxacin is also known as “respiratory quinolone”.
Moxifloxacin : Mode of action.

Moxifloxacin : Mode of action.

What are the recommended doses of Moxifloxacin?

  • The recommended dose of the drug for adults is usually 400 mg once a day.
  • The drug can be taken orally with water either in presence or absence of food.
  • Duration of the doses depends upon the type of infection:
    • Acute bacterial sinusitis: dose of 400 mg every 24 hour orally or I.V. for 10 days.
    • Acute bacterial exacerbation of chronic bronchitis: dose of 400 mg every 24 hour orally or I.V. for 5 days.
    • Community acquired pneumonia: dose of 400 mg every 24 hour orally or I.V. for 7-14 days.
    • Uncomplicated skin and skin structure infections (SSSI): dose of 400 mg every 24 hour orally or I.V. for 7 days.
    • Complicated (SSSI): dose of 400 mg in every 24 hour orally or I.V. for 7-21 days.
    • Complicated intra-abdominal infections: dose of 400 mg every 24 hour orally or I.V. for 5-14 days.

When should I discontinue, withhold or modify the dose of Moxifloxacin?

  • The drug is not recommended in patients who are hypersensitive to the drug or any member of the quinoline class of antimicrobial agents, or any of the components of the formulation.
  • Moxifloxacin use should be withheld in case of nerve damage; pain and burning in arms and legs; change in ability to sense heat, cold and pain.
  • Moxifloxacin is generally not recommended for children younger than 18 years old.
  • It has been observed that prolonged use of Moxifloxacin may cause swelling or tearing of a tendon mostly in geriatric population.
  • The use of Moxifloxacin is contraindicated if you take steroid medication, or if you have had a heart, kidney, or lung transplant.
  • It is generally recommended to stop the medication if you feel sudden pain, tenderness, stiffness, or movement problems or swelling, in any of your joints.

What are the pharmacokinetic properties of the drug?

  • Pharmacokinetic studies suggested that after oral administration, Moxifloxacin is rapidly absorbed from the gastrointestinal tract and has a bio-availability of approximately 90%.
  • Following absorption, approximately 50% of the drug is bound to plasma proteins.
  • Approximately 52% of the drug is metabolized via glucuronide conjugates (accounts for 14%) and sulphate conjugation (accounts for 38%).
  • It has been observed that following a 400 mg dose of the drug maximum (or peak) plasma concentration (approximately 3.56 mg/L) is achieved in 2 hours.
  • The average median half-life of Moxifloxacin is 11.5-15.6 hours.
  • P450 system does not play any role in the metabolism of Moxifloxacin.
  • Approximately 45% of dose of Moxifloxacin is mainly excreted in the feces (~20%) and urine (~25%) in the form of uncharged drug.
  • The average steady state volume of distribution of the drug is 1.7-2.7 L/kg.

Which pregnancy category (A; B; C; D; X) has been assigned to Moxifloxacin?

  • The Moxifloxacin is classified by US FDA pregnancy category: C.
  • Due to lack of adequate and well-controlled studies, the use of Moxifloxacin in pregnant women is contraindicated and recommended only when benefit justifies the risk but studies in animals have shown adverse effect on fetus.
  • Studies support the excretion of the drug into animal milk. However, no adequate data is available on excretion of Moxifloxacin into human breast milk.

Despite these facts caution should be exercised when taking Moxifloxacin.

How to use the drug?

  • Moxifloxacin is available in tablet form for oral administration by mouth with or without food.
  • Moxifloxacin is also available in the parental form for intravenous infusion and in form of ophthalmic solution (eye drop).
  • The time duration between the drug use should be at least 24 hours.
  • Moxifloxacin is taken with water (one glass or more) at same time each day.
  • It is advisable not to take more than one tablet daily.
  • Follow the instructions carefully as directed on prescription leaflet and take Moxifloxacin exactly as directed.
  • Do not change the dose of the drug as prescribed by your doctor. Since, the dosage is based on patient medical condition, treatment responses and usage with other drugs.

How to store the drug?

  • Moxifloxacin is stored at 25°C (77°F) and excursion permitted to 15-30°C (59-86°F).
  • Moxifloxacin should not be refrigerated (precipitated on refrigeration).
  • Medicine should not be stored in the bathroom.
  • The drug should be kept away from excess heat, direct sun light and reach of children.
  • Do not freeze or store the medicine at extreme cold too.

How to dispose the medicine?

  • Throw away unused and opened, outdated or no longer used medication.
  • Also dispose the old medicine after the expiration date.
  • Parental drug products containing visible particulates should not be used and it is for single-use only, therefore, discard the unused portion.

Does Moxifloxacin has approval from government / FDA /or any other related agencies?

  • Moxifloxacin has received its initial official approval from US Food and Drug Administration (FDA) in December 1999 for the treatment of acute exacerbations of chronic bronchitis (AECB), community acquired pneumonia (CAP), and acute bacterial sinusitis (ABS).
  • In April 2001, Moxifloxacin was approved for treatment of uncomplicated skin and skin structure infections.
  • Later in year 2004-2005, the drug has also received approval for treatment of community acquired pneumonia caused by multi-drug resistant Streptococcus pneumonia, complicated skin and skin structure infections and complicated intra-abdominal Infections.

Other uses of the drug.

  • Moxifloxacin is sometimes used for the treatment of tuberculosis, and endocarditis (heart lining and valves infection), when other medication cannot be used.
  • In certain cases, Moxifloxacin can also be used to treat or prevent the anthrax (a lethal bacterial infection that is caused by the bacterium Bacillus anthracis) in people who have been exposed to bacterial germs causing anthrax, when other drugs are not available or cannot be used for this purpose.
  • Moxifloxacin may also be used for other uses not listed here. It is advisable to ask your doctor or pharmacist for more information.

What special dietary precautions should I follow?

  • Drink plenty of water during the course of medication (with and after oral dose of Moxifloxacin).
  • Also use other fluids like fruit juice during the course of treatment.

What special precautions should I follow/ What should I avoid while using Moxifloxacin?

  • Do not use the medicine if you are hypersensitive or allergic to Moxifloxacin or other fluoroquinolones such as ciprofloxacin, norfloxacin, lomefloxacin, nalidixic acid gatifloxacin, levofloxacin, gemifloxacin and others.
  • Before taking Moxifloxacin, tell your doctor about your medical history specially if you have myasthenia gravis (chronic autoimmune neuromuscular disease characterized by varying degrees of weakness of the skeletal muscles of the body).
  • Do not use Moxifloxacin if you have muscle disorder.
  • Keep in mind that Moxifloxacin should not be taken at least 4 hours before or at least 8 hours after the use of antacids containing magnesium or aluminium (Maalox, Mylanta, Tums, others), vitamin or mineral supplements containing iron or zinc, didanosine powder or chewable tablets (videx), and sucralfate (carafate).
  • Inform your health care provider, if you are pregnant or plan to become pregnant or if you are breast-feeding.
  • During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.
  • Do not share this medication with other persons having the similar kind of problems. Consult your doctor for more details.
  • Do not use tanning beds, sunlamps and keep away from unnecessary or prolonged exposure of sunlight.
  • Since use of Moxifloxacin sometime cause dizziness and light headedness, therefore it is usually recommended to avoid driving, use of machinery or any chore requiring alertness or clear vision while taking Moxifloxacin.
  • Consult with your doctor and pharmacist if you are taking any prescription and non-prescription medications or herbal products.
  • Consult your doctor in case of any query. Avoid use of other drugs used for the treatment of impotence.

What are the possible side effects of the drug?

In addition to the associated benefits, Moxifloxacin is also accompanied with the side effects. Some of the side effects are more common, others less common whereas some that fade away with time while you take the drug. It is always recommended to consult a doctor if you encounter any of the side effects.

Some of the less commonly occurring side effects but requiring medical attention is outlined as:

  • Change in ability to taste food
  • Constipation
  • Diarrhea
  • Dry mouth
  • Headache
  • Loss of appetite
  • Nausea
  • Sores on tongue or in the mouth
  • Stomach pain
  • Sweating
  • Vaginal itching
  • Vomiting
  • Weakness
  • White patches in the mouth

Moxifloxacin can cause some serious side effects. On appearance of these symptoms, do not stop taking the Moxifloxacin and immediately contact to your doctor. These include:

  • Agitation
  • Confusion
  • Depression
  • Difficulty falling asleep or staying asleep
  • Dizziness
  • Hallucinations (seeing things or hearing voices that do not exist)
  • Nervousness
  • Nightmares
  • Not trusting others or feeling that others want to hurt you
  • Restlessness
  • Severe diarrhea (watery or bloody stools) that may occur with or without fever and stomach cramps (may occur up to 2 months or more after your treatment)
  • Thinking about harming or killing yourself
  • Uncontrollable shaking of a part of the body

Sometime, it may cause severe side effects. On appearance of these symptoms or symptoms related to the rupture of tendons, stop taking the medicine and immediately talk to your doctor:

  • Dark urine
  • Decreased urination
  • Difficulty breathing or swallowing
  • Fainting
  • Fast heartbeat
  • Feeling or blistering of the skin
  • Fever
  • Hives
  • Hoarseness
  • Itching
  • Joint or muscle pain
  • Loss of consciousness
  • Rash
  • Seizures
  • Swelling of the eyes, face, mouth, lips, tongue, throat, hands, feet, ankles or lower legs.
  • Unusual bruising or bleeding
  • Yellowing of the skin or eyes.

Besides these, Moxifloxacin also associated with damaging of nerves. It also causes some other side effect like problems with joints, bones and tissue.Some other symptoms of side effect includes pain, burning, numbness in arms or legs, change in the capability to sense pain, cold, heat or light touch. On feeling these symptoms, do not take any more Moxifloxacin and immediately talk to your doctor.

What should I do in case of overdose?

  • Try to avoid taking the overdose of the drug. If you overdose the drug contact with your doctor or pharmacist for symptomatic and supportive measures.
  • In case you or some other person has taken overdose of this medication contact your local poison control centre at 1-800-222-1222 or emergency room immediately.
  • Call local emergency services at 911 in case a patient collapses or faces difficulty in breathing.

What should I do in case of missed a dose?

  • In case of missed dosage, take it as soon as you remember and maintain a regular dosing schedule.
  • Skip the missed dose if it is almost time for your next scheduled dose. Keep in mind not to use a double dose to make up the missed dose.

Does Moxifloxacin have any interaction with other drugs?

Moxifloxacin may interact with one of the following drugs. Care should be taken when you are taking these medications together.

  • Clinical studies have suggested that use of Moxifloxacin in combination with corticosteroids can increased the risk of tendonitis and disability.
  • Studies with Moxifloxacin have suggested that co-administration of a nonsteroidal anti-inflammatory drug (NSAIDs) with a fluoroquinolone may enhance the risks ofcentral nervous system stimulation and convulsions.
  • Absorption of Moxifloxacin was reduced when taken concomitantly with Antacids, minerals and vitamins containing multivalent cations (except calcium) form nonabsorbable complexes with Moxifloxacin. Formation of this complex results in inhibition or reduced absorption of Moxifloxacin.
  • Ulcer medicine such as sucralfate (carafate) and antiretroviral medication such as didanosine (videx) powder or chewable tablets interact with Moxifloxacin and therefore reduce its absorption.
  • Moxifloxacin has shown a strong potential for a serious drug interaction with NSAIDS.
  • No significant or clinically relevant interaction was observed between Moxifloxacin and digoxin, probenecid, warfarin, theophylline, glyburide, or any other oral contraceptives.

Does Moxifloxacin have any interaction with diseases?

  •  Muscular disorder: Clinical studies suggested that Moxifloxacin administration may be associated with muscular disorder and it is recommended not to take Moxifloxacin if you have myasthenia gravis (chronic autoimmune neuromuscular disease caused by varying degrees of weakness of the skeletal muscles of the body).
  • Tendinitis and tendon rupture: Fluoroquinolones, such as Moxifloxacin consumption is associated with an increased risk of tendinitis and tendon rupture in all ages. However, chance of incidence was higher in geriatric population (older patients usually over 60 years of age); in patients with kidney, heart or lung transplants and in patients taking corticosteroid drugs.
  • Neurological disorder: Moxifloxacin use is contraindicated in patients with epilepsy or other seizure disorders. Use of Moxifloxacin with other drugs that induce bradycardia (e.g., beta-blockers, amiodarone) should be avoided.
  • Use of Moxifloxacin is contraindicated in case of heart rhythm disorder , prolonged QT interval (a rare heart associated problem that characterized by irregular heartbeat, fainting, or sudden death), kidney or liver disease, joint problems, cerebral arteriosclerosis (narrowing of blood vessels in or near the brain that can lead to stroke or mini-stroke), low levels of potassium in your blood (hypokalemia), trouble in breathing, and chest pain.
  • Caution should be taken while administrating Moxifloxacin in patients suffering from diabetes, since Moxifloxacin may alter glucose regulation.

Where can I get more information?

Your pharmacist or health care provider can provide more information about Moxifloxacin.

Clinical research and current scenario of the drug.

  • Convenient once-daily administration schedule, good tissue penetration, availability in intravenous and oral formulations, good efficacy, well tolerability made Moxifloxacin as an important option in the treatment of bacterial infections.
  • At present, Moxifloxacin is widely used for treatment of community-acquired pneumonia (CAP), acute exacerbations of chronic bronchitis (AECB), acute bacterial sinusitis and uncomplicated skin and skin structure infections.
  • Clinical studies suggested that Moxifloxacin acts as a broad-spectrum fluoroquinolone and offers the benefits of excellent activity against penicillin-resistant Pneumococci, with a very low propensity for drug interactions.
  • The drug has improved coverage against gram-positive cocci and atypical pathogens compared with older fluoroquinolone agents, and retain good activity against gram-negative bacteria. Furthermore, in vitro laboratory studies have suggested that emergence of Moxifloxacin resistance was less common than with some other fluoroquinolone.
  • The propensity of Moxifloxacin was relatively low (relative to other fluoroquinolones) for causing phototoxic reactions and animal laboratory studies suggest that Moxifloxacine has a low potential for causing excitatory CNS and hepatotoxic effects.

References from chemical, biological and toxicological databases.

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Insulin Glargine, drug class, uses, strength, side effects, mechanism of action
Clopidogrel, drug class, uses, strength, side effects, mechanism of action

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Insulin Glargine

Jun 27 2015 Published by under Medicines

What is Insulin Glargine (Lantus)?

  • Insulin Glargine is recombinant human insulin analogue that act as blood-glucose-lowering agent.

What is the generic and brand name of the drug?

  • The drug is available under generic name Insulin Glargine and brand names Lantus , Toujeo,Abasaglar, and Basaglar

What is the source of the drug (natural or synthetic)?

  • Insulin Glargine is a synthetic bioengineered (man-made) injectable form of long-acting insulin.

Why is this medication prescribed?

  • Insulin Glargine acts as a long lasting (upto 24 hour duration) insulin, which reduces the amount of sugar in the blood and urine.
  • The drug is used to treat patients with type 1diabetes or diabetes mellitus type 1. In type 1diabetes the insulin-producing beta cells in the pancreas were non functional and unable to produce insulin.
  • The drug is also used to treat type 2 diabetes or noninsulin-dependent diabetes mellitus, (condition in which insulin is not produced in sufficient amount or not effective due to insulin resistance) to control the blood sugar level.
  • Insulin Glargine is recommended in combination with other short acting insulin in case of type 1 diabetes, while in case of type 2 diabetes, insulin Glargine may be used with short acting insulin or with oral drugs used to treat diabetes.
Difference between Insulin and Insulin Glargine

Difference between Insulin and Insulin Glargine

Pharmacophore structure: Information about the chemical structure of the drug

  • Insulin Glargine chemically belongs to the class of organic compounds which are known as s Amino Acids, Peptides, and Analogues. The drug is prepared by recombinant DNA technology in non pathogenic bacteria coli. The detailed chemical classification of Insulin Glargine  is described below:
Kingdom Organic compounds 
Super Class Organic Acids
Class Carboxylic Acids and Derivatives
Sub Class Amino Acids, Peptides, and Analogues
Direct Parent Peptides and proteins

Chemical information of the drug.

  • Insulin Glargine is a bioengineered synthetic pharmaceutical recombinant protein/peptide containing two chains (chain A and B) of 21 and 32 amino acids.
  • The drug (Insulin Glargine) is almost identical to that of natural insulin (protein regulates blood sugar level) and differs mainly in two aspects. First the amino acid Aspargine in chain A (A21) of insulin is replaced by Glycine amino acid and second, addition of two Arginines at C-terminus of the chain B.
  • The drug has molecular formula C17H19N3O3Sand the molecular weight of 6063 Da.
  • The melting point of Insulin Glargine is 81 °C.
  • The hydrophobicity and isoelectric point of Insulin Glargine is 098 and 6.88, respectively.

What is the available strength of the drug?

  • Insulin Glargine is supplied in the form of clear aqueous injectable solution to inject subcutaneously (under the skin).
  • Each millilter (ml) of Insulin Glargine solution contains 100 units of (3.6378 mg) insulin glargine.
  • It is available as 10 mL vial (1000 Units/10 mL), 3 mL Cartridge systems (300 Units/3 mL) and 3 mL disposable insulin device (300 Units/3 mL).
  • Besides Insulin Glargine, each ml of solution contains 30 mcgzinc, 20 mg glycerol 85%, 20 mcg polysorbate 20, 2.7 mg m-cresol, and water.

How the medicine works (mode of action)?

  • The mode of action of Insulin Glargine is similar to that of naturally occurring human insulin produced by the pancreatic beta cells but its action lasts for a longer duration of time.
  • Insulin Glargine works by replacing the insulin produced by the body, stops sugar production in liver and helps movement of sugar from the blood into other body tissues where it is used for energy.
  • The long lasting action of Insulin Glargine is due to the modification in its amino acid composition which increases its solubility at pH 4 and results in formation of microprecipitates at physiological pH 7.4.
  • The drug is released slowly from these microprecipitates and hence its action lasts for a longer time
  • The Insulin Glargine is human insulin analogue that acts on the insulin receptors present on the cell surface. Insulin receptors are present on the surface of every cell but the density of these receptors varies according to the cell type.
  • The insulin receptor is a receptor tyrosine kinase, a heterotetrameric glycoprotein that consists of two extracellular alpha and two transmembrane beta sub-units. The alpha subunits have insulin binding sites whereas beta subunits are associated with tyrosine kinase activity.
  • Insulin binding to the alpha subunits causes the beta subunits to phosphorylate themselves (due to activation of the tyrosine kinase activity) and hence, activation of the receptors occurs.
  • The activated receptor then phosphorylates a number of intracellular proteins known as insulin receptor substrates (IRS), proteins Cbl (E3 ubiquitin-protein ligase involved in cell signalling and protein ubiquitination), APS(an adapter protein that binds cbl), Shc(an adapter protein) and Gab 1(Adapterprotein that plays a role in intracellular signalling cascades triggered by activated receptor-type kinases).
  • The activity of the phosphorylated intracellular proteins get altered thereby bringing about signalling cascade and the biological response.
Insulin Glargine : Mode of action

Insulin Glargine : Mode of action

What are the recommended doses of Insulin Glargine?

The dose of Insulin Glargine varies from person to person and should be individualized only under the supervision of the doctor depending upon the needs of the patients. The dose is adjusted in accordance with the blood glucose measurements of the patients.

Type 1 diabetes:

  • The patients’ (6 years or older) total daily insulin requirement should be calculated individually.
  • The recommended initial dose of Insulin Glargine should be approximately one-third of the total daily insulin requirements to be administered subcutaneously once a day.
  • The maintenance dose is adjusted according to the patient’s need and should be given once per day.
  • Insulin Glargine must be co-administered with rapid or short acting insulin in order to satisfy the remainder of the daily insulin requirements.
  • The use of Insulin Glargine has not been established for paediatric patients younger than 6 years of age.

Type 2 diabetes:

  • The initial starting dose in patients who are presently not treated with insulin is 10 units (or 0.2 Units/kg).
  • The dose should be given subcutaneously once a day and almost at the same time.
  • The maintenance dose is determined based on the individual response to the drug.
  • The use of Insulin Glargine is not recommended in children.

When should I discontinue, withhold or modify the dose of Insulin Glargine?

  • The usual dosing of the drug may vary depending upon the age and glucose levels of the patient
  • The drug is contraindicated in case of pregnancy and breastfeeding.
  • Insulin Glargine can be given in case of breastfeeding women with diabetes Dosage adjustments are required in case of.
  • Insulin Glargine is not prescribed in children less than 6 years of age with type 1 diabetes and also in paediatric patients with type 2 diabetes.
  • In diabetic patients of older age, the drug should be used with caution to avoid hypoglycemic.  
  • Dose adjustment and increased frequency of glucose monitoring is required in case of co-administration of Insulin Glargine with drugs like clonidine, beta-blockers, alcohol, and lithium salts.
  • Insulin Glargine dose needs to be adjusted during renal impairment because of the increased risk of hypoglycemia.
  • The drug is not recommended during hepatic impairment due to increased risk of prolonged hypoglycemia (low blood sugar or glucose).
  • The use of the drug is contraindicated in patients in case of hypersensitivity to Insulin Glargine or its constituents.
  • The dosage needs to be adjusted during certain conditions such as:
  • Obese patients, concurrent use with medications having hyperglycemic effects, pregnancy, stress, illness, trauma, or after surgery : needs higher dose
  • Concurrent use of medications having hypoglycemic effects, weight loss, exercise, or low calorie diets: needs lower dose

What are the pharmacokinetic properties of the drug?

  • Pharmacokinetic studies suggest that after subcutaneous injection, insulin serum concentrations indicated a slower, more prolonged absorption and a relatively constant concentration over time (24 hours).
  • No peak serum concentration is achieved for the administered Insulin Glargine.
  • No data is available for the protein binding of Insulin Glargine following absorption.
  • The average median half-life of Insulin Glargine is not reported in humans; however, in vitro studies in mammalian reticulocytes indicate a half life of 30 hours.
  • The drug is partly metabolize in the subcutaneous depot at the carboxyl terminus of the B chain to form two active metabolites, namely, A21-Gly-insulin and A21-Gly-des-B30-Thr-insulin.
  • Unchanged drug and the degradation products have been found in the blood circulation.
  • The route of elimination of the drug is not known.
  • The average steady state volume of distribution of Insulin Glargine is not available.

Which pregnancy category (A; B; C; D; X) has been assigned to Insulin Glargine?

  • The Insulin Glargine is classified by US FDA pregnancy category: C
  • Due to lack of adequate and well-controlled studies the use of Insulin Glargine in pregnant women is contraindicated and recommended only when benefit justifies the risk.
  • No adequate data is available on excretion of Insulin Glargine into human breast milk.
  • Despite these facts caution should be exercised when taking Insulin Glargine.

How to use the drug?

  • Insulin Glargine is available as solution to be injected subcutaneously.
  • Try to take the medicine at the same time every day.
  • The drug is taken only once per day.
  • Follow the instructions carefully as directed on prescription leaflet and take Insulin Glargine exactly as directed.
  • Take the medication regularly, even if you feel well.
  • Do not change the dose of the drug as prescribed by your doctor. Since, the dosage is based on patient medical condition, glucose levels, age, and treatment responses.
  • Do not change the brand, strength or type of insulin without consulting your doctor as it may result in change of dosage.
  • Never share needles, syringes, or pens with others and avoid reuse of needles or syringes.
  • Never dilute the drug or mix it with any other type of insulin.
  • The drug should never be injected into a vein or muscle.
  • Always try to rotate the injection site to avoid the accumulation of fat at the site of injection.
  • Discard Insulin Glargine if it is coloured, cloudy, or consists of solid particles.

How to store the drug?

  • Unopened vials, pens, and cartridge systems should be kept refrigerated between 2° and 8 °C (36 °F and 46 °F).
  • Unopened vials, pens, and cartridge systems can be stored at room temperature for 28 days.
  • Opened vials and cartridge systems can be refrigerated or stored at room temperature below 30°C (86°F)
  • Cartridge systems inserted into the insulin delivery device and pens should be stored only at room temperature below 30°C (86°F).
  • Opened vials, pens, and cartridge systems are stable for 28 days after the first use.
  • Throw away any insulin that has been exposed to extreme heat or cold.

 How to dispose the medicine?

  • Throw away unused and opened, outdated or no longer used medication.
  • Also dispose the old medicine after the expiration date.
  • Consult your pharmacist for the proper disposal of the drug.

Does Insulin Glargine has approval from government / FDA /or any other related agencies?

  • Insulin Glargine has received its official approval from US Food and Drug Administration (FDA) in April 2000 to control blood sugar in diabetes
    (type I and type II) .

Other uses of the drug

  • Insulin Glargine may also be used for other uses not listed here. It is advisable to ask your doctor or pharmacist for more information.

What special dietary precautions should I follow?

  • It is recommended to follow the diet plan as directed by your doctor or dietician.
  • Try to eat a healthy diet with the same amounts of the same kinds of food at about the same times every day.
  • Skipping or delaying and changing the quantity or quality of food can cause changes in the amount of blood sugar.

What special precautions should I follow/ What should I avoid while using Insulin Glargine?

  • Do not use the medicine if you are hypersensitive or allergic to any of the ingredients.
  • Before taking Insulin Glargine, tell your doctor about your medical history preferentially if you have or ever had nerve damage caused by your diabetes or any other medical problem, including liver or kidney disease.
  • During pregnancy this medication is recommended only when it is essential and under doctor or pharmacist supervision.
  • Since the information about excretion of drug in milk is not explored consult your doctor before breast feeding to your child.
  • Consult with your doctor and pharmacist if you are taking any prescription and nonprescription medications, nutritional supplements, vitamins and herbal products such as certain cholesterol-lowering medications; angiotensin-converting enzyme inhibitors (ACE inhibitors); medications for asthma and colds, mental illness and nausea; salicylate pain relievers; AIDS antiviral medications; diuretics; oral contraceptives; beta-blockers; sulfa antibiotics; oral medications for diabetes; diuretics; and thyroid medications etc.
  • Do not share this medication with other persons having the similar kind of problems. Consult your doctor for more details.
  • Do not change the brand of Insulin Glargine or syringe you are using without consulting your doctor or pharmacist as it may change blood glucose levels.
  • Do not share this medication with other persons having the similar kind of problems. Consult your doctor for more details.
  • Avoid drinking alcohol. It lowers blood sugar and may interfere with your diabetes treatment.

What are the possible side effects of this drug?

The use of Insulin Glargine may result in changes in the levels of blood sugar. However, sometimes, these changes may be associated with side effects. It is usually recommended to consult your doctor in case the symptoms are severe or persists for a long time. Some of the common side effects include:

  • Fat accumulation
  • Weight gain
  • Swelling of the hands or feet
  • Constipation
  • Swelling, redness, pain, or itching at the site of injection
  • Changes in skin texture
  • Little depression in the skin (fat breakdown)

Some side effects can be serious. If case you experience these symptoms, call your doctor immediately or get emergency treatment:

  • Muscle cramps
  • Hives
  • Weakness
  • Fast pulse
  • Whole body itching
  • Breath shortness
  • Difficulty swallowing
  • Abnormal heartbeat
  • Skin rashes
  • Sweating
  • Low blood pressure
  • Swelling of the lips, eyes, tongue, face, or throat
  • Trouble breathing
  • Hoarseness

Severe allergic reactions are also sometimes associated with the use of Insulin Glargine. These comprise:

  • Very low blood pressure
  • Chest tightening or bronchospasm
  • Swelling under the skin

Prolonged use of Insulin Glargine can lead to thickening of fat tissues at the site of injection.

Insulin Glargine may cause other side effects not included in the list. Consult your doctor if you have any unusual symptom while taking this medication.

What should I do in case of overdose?

Try to avoid taking the overdose of the drug.

  • In case you or some other person has taken overdose of this medication contact your local poison control center at 1-800-222-1222 or emergency room immediately.
  • Consult your doctor or pharmacist for symptomatic and supportive measures in any case of overdose.

 What should I do in case of missed a dose?

  • In case of missed dosage, take it as soon as you remember and maintain a regular dosing schedule.
  • Skip the missed dose if it is almost time for your next scheduled dose. Keep in mind to not use a double dose to make up a missed dose.
  • Avoid taking more than one dose in a 24-hour period unless directed by your doctor.

Does Insulin Glargine have any interaction with other drugs?

There are a number of drugs that brings about a change in the glucose metabolism and requires insulin dosage to be adjusted and close monitoring of glucose levels. These include:

  • Drugs that increase the risk of Hypoglycemia (low blood sugar or glucose): The blood glucose lowering effect of Insulin Glargine may be enhanced in presence of certain drugs that increases the chances of hypoglycemia. These include:
    • Fluoxetine
    • Salicylates
    • Anti-diabetic products
    • Pramlintide
    • Monoamine oxidase inhibitors
    • Pentoxifylline
    • Angiotensin converting enzyme (ace) inhibitors
    • Fibrates
    • Disopyramide
    • Propoxyphene
    • Somatostatin analogs
    • Sulfonamide antibiotics
    • Angiotensin II receptor blocking agents

Dose adjustment and increased glucose monitoring is required in case of co-administration of Insulin Glargine with these drugs.

  • Drugs that reduce the blood glucose lowering effect of Insulin Glargine : The blood glucose lowering effect of Insulin Glargine may get decreased in case of its co-administration with following drugs:
    • Danazol
    • Somatropin Protease inhibitors
    • Oral contraceptives (estrogens, progestogens)
    • Antipsychotics (e.g., clozapine and olanzapine)
    • Corticosteroids
    • Thyroid hormones
    • Sympathomimetic agents (e.g., terbutaline, albuterol, epinephrine)
    • Protease inhibitors
    • Glucagon
    • Isonazid
    • Diuretics
    • Niacin
    • Phenothiazines

The administration of these drugs with Insulin Glargine requires dose adjustment and enhanced glucose monitoring.

  • Drugs that may increase or decrease the blood glucose lowering effect of Insulin Glargine: When Insulin Glargine is co-administered with the following drugs, the glucose lowering effect of the drug may get increased or decreased.
    • Lithium salts
    • Alcohol
    • Beta-blockers
    • Clonidine
    • Pentamidine may cause hypoglycemia, which may sometimes be followed by hyperglycemia.

Dose adjustment and increased glucose monitoring is required when Insulin Glargine is co-administered with these drugs.

  • Drugs that may affect signs and symptoms of hypoglycemia: The signs and symptoms of hypoglycemia may get reduced or absent when Insulin Glargine is co-administered with
    • Guanethidine
    • Beta-blockers
    • Reserpine
    • Clonidine

Does Insulin Glargine have any interaction with Diseases?

There are some diseases that are known to interact with Insulin Glargine. These are renal dysfunction, liver disease and cancer. In first two cases lower initial dosages, careful monitoring of plasma glucose levels and dosing adjustments may be needed.

  • Renal impairment: Patients with renal impairment have reduced insulin metabolism and therefore, a reduction in the Insulin Glargine dose may be required in such cases.
  • Liver impairment: Patients suffering with hepatic impairment are characterized by reduced capacity for gluconeogenesis and reduced insulin metabolism. Hence, a reduction in the Insulin Glargine dose may be required in these patients.
  • Cancer: there are increased risk of cancer in patients who take Insulin Glargine.

Where can I get more information?

Your pharmacist or health care provider can provide more information about Insulin Glargine.

Clinical research and current scenario of the drug

Insulin Glargine is represented as an insulin analogue for controlling blood glucose levels in diabetic patients.

  • Studies indicate the effectiveness and safety of Insulin Glargine in treatment of type I and type II diabetes.
  • No clinical data is available to establish the cardiovascular safety of Insulin Glargine.
  • Clinical studies indicate the potential of Insulin Glargine for the development of antibodies in diabetic patients. In type 1 diabetes patients, 79% of patients and in type 2 diabetes patients, 25% of patients receiving drug once a day were positive for anti-insulin antibodies (AIA).
  • Current studies also provide the possibility of the development of cancer in patients who take Insulin Glargine.

References from chemical, biological and toxicological databases.

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Fondaparilux, uses, strength, side effects, mechanism of action
Moxifloxacin, uses, strength, side effects, mechanism of action

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Fondaparinux

Jun 27 2015 Published by under Medicines

What is Fondaparinux

  • Fondaparinux is a drug that prevents blood clots and used as an anticoagulant medication.

What is the generic and brand name of the drug?

  • The drug is available under generic name Fondaparinux and brand name Arixtra.
  • The drug is marketed primarily by GlaxoSmithKline, although a generic version of Fondaparinux developed by Alchemia is marketed (within the US) by Reddy’s Laboratories.

What is the source of the drug (natural or synthetic)?

  • Fondaparinux is a synthetic (man-made) pharmaceutical pentasaccharide Factor Xa inhibitor.

Why is this medication prescribed?

  • Fondaparinux is an anticoagulant (drugs that prevent the blood clotting), which is chemically similar to that of low molecular weight heparine. Enoxaparin.
  • Fondaparinux is used to reduce the risk of ischemic events (decrease in the blood supply to different body organs) in patients undergoing surgery.
  • Fondaparinux substantially prevent Deep Vein Thrombosis in patients undergoing hip surgery, abdominal surgery or hip or knee replacement.
  • DVT or Deep Vein Thrombosis is usually referred to formation of blood clot within the deep vein (usually in leg). It can form the blood clot in lungs and cause Pulmonary Embolism.
  • Fondaparinux is also used in combination with warfarin (Coumadin) to treat Deep Vein Thrombosis and Pulmonary Embolism.
  • Fondaparinux use in conjunction with streptokinase has been investigated to treat thrombolytic therapy in acute myocardial infarction.
  • Post surgery use of Fondaparinux decreases the risk of blood clot formation and maintains the blood flow to the heart in patients suffering from angina or heart attack. In this manner, Fondaparinux significantly improves the long-term mortality and morbidity.

Pharmacophore structure: Information about the chemical structure of the drug.

Fondaparinux chemically belongs to the class of organic compounds known as oligosaccharide/polysaccharide sulfates. Chemically these are carbohydrate molecules, which contain multiple sugar moiety (3-9) and one of them put up with one or more sulfate groups. The detailed chemical classification of Fondaparinux is described below:

Kingdom Organic compounds 
Super Class Organooxygen compounds
Class Carbohydrates and carbohydrate conjugates
Sub Class Oligosaccharides
Direct Parent Oligosaccharides sulfates

Chemical information of the drug.

  • Fondaparinux is a synthetic pharmaceutical organic compound available as sodium salt and named as methyl O-2-deoxy-6-O-sulfo-2-(sulfoamino)-α-D-glucopyranosyl-(1→4)-O-β-D-glucopyranuronosyl-(1→4)-O-2-deoxy-3,6-di-O-sulfo-2-(sulfoamino)- α -D-glucopyranosyl-(1→4)-O-2-Osulfo- α -L-idopyranuronosyl-(1→4)-2-deoxy-6-O-sulfo-2-(sulfoamino)- α -D-glucopyranoside, decasodium salt.
  • The compound has molecular formula C31H45N3Na10O49S8 and the molecular weight of 1728.082 Da.

What is the available strength of the drug?

  • The medication is supplied in form of injectable sterile preservatives free solution for subcutaneous use.
  • Fondaparinux is usually supplied as single dose in prefilled syringe attached with an automatic needle protection system.
  • Each prefilled syringe contains 5 ml sodium chloride and water solution which contains Fondaparinux sodium at a concentration of 2.5 mg/0.2 ml.
  • The pH of solution ranges between 5.0-8.0.
  • The solution is optically clear and colorless or slightly yellow in color.
  • No antidote is available for Fondaparinux.

Warning*

Clinical studies suggested that use of low molecular weight heparins (LMWH), heparinoids, or Fondaparinux sodium as anticoagulants or in patients undergoing neuraxial anesthesia or spinal puncture can cause epidural or spinal hematomas. Epidural or spinal hematomas may result in serious long-term or permanent paralysis. Therefore, benefits and risk factors should be considered while prescribing these drugs for neuraxial intervention in patient’s anticoagulated or to be anticoagulated for thromboprophylaxis.

How the medicine works (mode of action)?

  • Fondaparinux is a class of medications known as Factor Xa inhibitors (Factor Xa is a natural human blood anticoagulant that is involved in blood clotting).
  • The active ingredient of the drug is Fondaparinux sodium that binds specifically to antithrombin III (ATIII).
  • Binding of Fondaparinux sodium to antithrombin III results in an increased activity (neutralization of Factor Xa)  of antithrombin III.
  • On selective binding to ATIII, Fondaparinux enhances neutralization of Factor Xa approximately 300 times.
  • Neutralization of Factor Xa results in reduced conversion of prothrombin to thrombin, and fibrinogen to fibrin in a cascade manner, which ultimately inhibits the blood clot formation.
  • Fondaparinux has no direct inhibitory effect on thrombin (activated Factor II) and platelets.
  • Clinical studies have suggested that recommended doses of Fondaparinux do not affect fibrinolytic activity or bleeding time.
Fondaparinux : Mode of action.

Fondaparinux : Mode of action.

What are the recommended doses of Fondaparinux?

The prescribed dose of Fondaparinux varies depending upon the age and diseased state of the patient.

  • In case of patients undergoing orthopaedic or abdominal surgery.
    • The prescribed dose of Fondaparinux is 2.5 mg per day to be injected subcutaneously.
    • The initial dose should be administered only 6-8 hours hours following surgery.
    • The drug should be administered for a period of 5-9 days.
  • Treatment of ST segment elevation myocardial infarction (STEMI).
    • The prescribed Fondaparinux dose of is 2.5 mg per day.
    • The initial dose of drug should be administered intravenously and subsequent doses by subcutaneous injection.
    • Treatment should be start at the earliest following diagnosis.
    • The drug treatment should continue for a period of 8 days or until hospital discharge.
  • Treatment of superficial-vein thrombosis.
    • The prescribed dose of Fondaparinux is 2.5 mg per day to be administered by subcutaneous injection.
    • Treatment should continue for a period ranging from 30 days to .45 days in patients who are more prone to thromboembolic complications.
  • Treatment of Deep Vein Thrombosis (DVT) and Pulmonary Embolism(PE).
    • The recommended dose of Fondaparinux to be administered subcutaneously per day depending upon the body weight are as follows:
    • 5 mg for body weight < 50 kg,
    • 5 mg (body weight 50-100 kg) or
    • 10 mg (body weight > 100 kg)
    • The drug treatment should be continued for at least a period of 5 days.
  • Treatment of unstable angina/non- ST segment elevation myocardial infarction (UA/NSTEMI).
    • The prescribed Fondaparinux dose of is 2.5 mg per day to be administered by subcutaneous injection.
    • Treatment should be started as early as possible following the disease diagnosis.
    • The drug treatment should continue for a period of 8 days or until hospital discharge.

When should I discontinue, withhold or modify the dose of Fondaparinux?

  • The dosing of the drug may vary depending upon the diseased state and the body weight of the patient.
  • No dosage adjustment is necessary in mild to moderate hepatic impairment patients.
  • The drug is contraindicated in case of pregnancy, breastfeeding or hypersensitive response to any component of the drug.
  • Fondaparinux is not prescribed in children less than 17 years of age.
  • The drug should be discontinued in patients who develop severe renal insufficiency after orthopaedic surgery.
  • The drug should be used with high caution in case of elderly people and people with weight < 50 kg.
  • Fondaparinux use is contraindicated in patients with
  • Known hypersensitivity to sodium or any of the other ingredients of the drug
  • Clinically significant bleeding
  • Acute bacterial endocarditis (an infection of the heart) or
  • Severe kidney problems

What are the pharmacokinetic properties of the drug?

  • Pharmacokinetic studies suggest that after subcutaneous injection, Fondaparinux is rapidly and completely absorbed with a bioavailability of 100%.
  • The peak plasma levels are obtained after Fondaparinux administration in 3-4 hours. and plasma concentrations range from 0.1 – 0.5 mg/L for adult patients on thromboprophylaxis and from 0.6 to 1.5 mg/L for adults on therapeutic doses.
  • Following absorption the majority (94%) of the drug is bound to proteins.
  • The drug is mainly metabolized by the renal system.
  • The drug is eliminated mainly in urine mainly (64 – 77 % ) as unchanged drug.
  • The average median half-life of Fondaparinux 17 to 21 hours.
  • The average steady state volume of distribution of Fondaparinux is approximately 7-11 liters.

Which pregnancy category (A; B; C; D; X) has been assigned to Fondaparinux?

  • The Fondaparinux is classified by US FDA pregnancy category: B.
  • Due to lack of adequate and well-controlled studies the use of Fondaparinux in pregnant women is contraindicated.
  • Laboratory animal studies have shown no adverse effects on the fetus.
  • No adequate data is available on excretion of Fondaparinux into human breast milk.
  • Despite these facts caution should be exercised when taking Fondaparinux.

How to use the drug?

  • Follow the instructions carefully as directed on prescription leaflet and take Fondaparinux exactly as directed.
  • Fondaparinux is available as injectable solution. Learn proper technique from the doctor how to use it in case you use it at home.
  • The drug should not be used if it turns cloudy, discolored or contains particle and syringe gets cracked or damaged.
  • The drug is taken only once per day and should be injected under the skin of the stomach and not into muscle.
  • The injection should be given at different sites every time to decrease the injury.
  • Try to take the medicine at the same time every day.
  • No other medication should be co-administered with the drug in the same injection.
  • Take the medication regularly, even if you feel well.
  • Do not change the dose of the drug as prescribed by your doctor. Since, the dosage is based on patient medical condition treatment responses and weight.

How to store the drug?

  • Fondaparinux is stored at at room temperature 77°F (25°C).
  • Brief excursion period is permitted at temperature 15–30°C (59–86°F).
  • The drug should be stored away from excess heat, direct sun light, moisture and reach of children.
  • Do not freeze or store the medicine at extreme cold too.

How to dispose the medicine?

  • Discard any unused portion of the drug in the syringe as it is used only once.
  • Dispose the old medicine after the expiration date.
  • The drug should neither be flushed down in the toilet nor poured in the drain
  • Consult your pharmacist or local waste disposal company for proper disposal.

Does Fondaparinux has approval from government / FDA /or any other related agencies?

  • Fondaparinux had received the marketing authorisation (authorisation holder: Glaxo Group Ltd.) from the European Commission which is valid for an indefinite period throughout the European Union on 21 March 2002.
  • Fondaparinux has received its official approval from US Food and Drug Administration (FDA) in July 2011.
  • The drug has received official approval from FDA to prevent Venous Thromboembolic Events (VTE) in adults undergoing major orthopaedic or abdominal surgery.
  • The FDA has also approved Fondaparinux for treatment in adults for
  • Unstable angina or non-ST segment elevation myocardial infarction (UA/NSTEMI)
  • ST segment elevation myocardial infarction (STEMI)
  • Acute symptomatic spontaneous superficial-vein thrombosis of the lower limbs

Other uses of the drug

  • Fondaparinux can also be used to prevent blood clots in heart attack patients. Although, it should be used under proper medical guidance.
  • Fondaparinux may also be used for other uses not listed here. It is advisable to ask your doctor or pharmacist for more information.

What special dietary precautions should I follow?

  • It is generally recommended to continue with the normal diet, unless and until suggested by your doctor.

What special precautions should I follow/ What should I avoid while using Fondaparinux?

  • Do not use the medicine if you are hypersensitive or allergic to any of the ingredients.
  • Before taking Fondaparinux, tell your doctor about your medical history preferentially if you have bleeding ulcer, low platelet count, high blood pressure, kidney disease, bleeding problems, diabetic retinopathy, heart infection, seizures, stroke, recent surgery, low body weight (less than 110 pounds/50 kilograms.
  • Consumption of alcohol should be avoided while taking Fondaparinux as it increases stomach bleeding.
  • During pregnancy this medication is recommended only when it is essential and under doctor or pharmacist supervision.
  • Since the information about excretion of drug in milk is not explored consult your doctor before breast feeding to your child.
  • Consult with your doctor and pharmacist if you are taking any prescription and nonprescription medications, and herbal products.
  • Do not share this medication with other persons having the similar kind of problems. Consult your doctor for more details.
  • The drug should be used with high caution in older people.
  • It is generally recommended to avoid activities that lead to increased risk of bleeding or injury. Extra precaution should be taken to prevent bleeding while brushing or shaving.

What are the possible side effects of this drug?

Fondaparinux may bring forth some side effects in the patients. However, not all the patients show the side effects. The side effects can be common and severe. If the common side effects persist for a longer duration and become troublesome consult your doctor. The common side effects include:

  • Irritation
  • Trouble sleeping
  • Mild bleeding
  • Rashes
  • Itching at the injection site

In some cases side effects can be serious and needs immediate medical attention and emergency help. These are as follows:

  • Yellow eyes or skin
  • Chest pain
  • Pale skin
  • Loss of appetite
  • Difficulty walking
  • Fainting
  • Swelling in hands, feet, or ankles
  • Bloody, black, tarry stools
  • Tingling or numbness in the legs and feet
  • Reddish or pinkish, or dark urine
  • Persistent or severe headache or dizziness
  • Severe or persistent weakness, nausea, tiredness, or vomiting
  • Slurred speech
  • Fever
  • Muscle weakness
  • Severe bruising or bleeding
  • Confusion
  • Irregular heart beat
  • Increased oozing from a wound;
  • Nosebleed
  • Weakness on one-side
  • Vomit that looks like coffee grounds
  • Severe allergic reactions associated with the drug are as follows: swelling of the mouth, face, lips, or tongue; itching; chest tightness; hives; rashes; and difficulty breathing. Contact your doctor for any query or medical advice regarding the side effects mentioned and also for the other side effects not mentioned in the list.

What should I do in case of overdose?

Try to avoid taking the overdose of the drug. Symptoms include excessive bleeding and bruising.

  • In case you or some other person has taken overdose of this medication contact your local poison control centre at 1-800-222-1222 or emergency room immediately.
  • Consult your doctor or pharmacist for symptomatic and supportive measures in any case of overdose.

What should I do in case of missed a dose?

  • In case of missed dosage, take it as soon as you remember and maintain a regular dosing schedule.
  • Skip the missed dose if it is almost time for your next scheduled dose. Keep in mind to not use a double dose to make up a missed dose.

Does Fondaparinux have any interaction with other drugs?

Co-administration of Fondaparinux with other medicines can alter the working of either this or the other medicines. Hence, when taken together they can result in harmful side effects. It is always advisable to consult your doctor in case you are taking:

  • Aspirin and other salicylates such as Tricosal, Kaopectate, Pamprin Cramp Formula, Knee Relief, Nuprin Backache Caplet, Pepto-Bismol, and Trilisate etc.
  • Medicines that bring about in reduction in the blood clot formation chances such as warfarin (Coumadin), cilostazol (Pletal), dabigatran (Pradaxa), ticagrelor (Brilinta), dipyridamole (Aggrenox, Persantine), rivaroxaban (Xarelto), heparin, abciximab (ReoPro), enoxaparin (Lovenox), apixaban (Eliquis), fondaparinux (Arixtra), clopidogrel (Plavix), prasugrel (Effient), anagrelide (Agrylin), and dalteparin (Fragmin)
  • Medicines that dissolve blood clots like tenecteplase (TNKase), reteplase (Retavase), and alteplase (Activase)
  • Pentoxifylline and Deferasirox (Exjade).
  • Medicines for treatment of cancer such as tositumomab (Bexxar), ibritumomab (Zevalin), and dasatinib (Sprycel)
  • Nonsteroidal anti-inflammatory medicines (NSAIDs) including ibuprofen (Advil, Motrin, Motrin IB), naproxen (Naprelan, Anaprox, Naprosyn, Aleve), piroxicam (Feldene), oxaprozin (Daypro), celecoxib (Celebrex), indomethacin (Indocin), diclofenac (Cataflam, Voltaren), sulindac (Clinoril), and ketorolac, nabumetone, ketoprofen (Relafen)
  • Selective Serotinin Reuptake Inhibitors (SSRI) and antidepressants such as fluoxetine (Prozac, Sarafem), sertraline (Zoloft), fluvoxamine (Luvox CR), citalopram (Celexa), paroxetine (Paxil), and escitalopram (Lexapro).
Fondaparinux : Drug Interaction.

Fondaparinux : Drug Interaction.

Does Fondaparinux have any interaction with diseases?

  • It has been suggested that Fondaparinuc is primarily eliminated by urinary excretion and hence, the exposure to Fondaparinuc in patients with renal impairment is significantly higher than the normal individuals.
  • Patients of severe hepatic impairment show increased risk of bleeding and therefore, Fondaparinux should be used with caution.
  • Fondaparinux should be used with high caution in patients with increased risk of bleeding such as in case of congenital or acquired bleeding disorders, ulcerative gastrointestinal disease, and intracranial haemorrhage.

Where can I get more information?

Your pharmacist or health care provider can provide more information about Fondaparinux.

Clinical research and current scenario of the drug

  • Clinical studies indicate the effectiveness of Fondaparinux as per the comparators in the studies regarding the prevention of Venous Thromboembolic Events and treatment of Deep Vein Thrombosis and Pulmonary Embolism. The frequency of thrombotic events decreased significantly in patients undergoing leg surgery and treated with Fondaparinux in comparison to placebo or enoxaparin.
  • Studies indicate the effectiveness of Fondaparinux in decreasing the overall occurrence of Venous Thromboembolic Events or death in patients with superficial vein thrombosis as compared to placebo. Results indicate only one Venous Thromboembolic Events or death for every 100 patients who took Fondaparinux as against six for every hundred taking placebo.
  • Fondaparinux was also as effective as enoxaparin in preventing death or an ischaemic event in patients with unstable angina or myocardial infarction without ST segment elevation.
  • Studies in patients of myocardial infarction with ST segment elevation showed the effectiveness of Fondaparinux in lowering the death risk or heart attack by 14% after 30 days compared to standard care.

References from chemical, biological and toxicological databases.

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Atazanavir

Jun 25 2015 Published by under Medicines

What is Atazanavir

  • Atazanavir is a drug that is in the  treatment of human immunodeficiency virus (HIV) infection which can cause the acquired immunodeficiency syndrome (AIDS).

Atazanavir brand name

  • The drug is available under generic name Atazanavir, Atazanavir sulfate and marketed by Bristol Myers, (formerly known as BMS-232632) under brand name Reyataz.
  • The drug has been placed in the World Health Organization’s List of Essential Medicines, a list of the most important medication needed in a basic health system.

What is the source of the drug (natural or synthetic)

  • Atazanavir is a synthetic (man-made) protease inhibitor (PI) class of antiretroviral drug.

What is Atazanavir used for

  • Atazanavir is an antiretroviral protease inhibitor class of drug that plays a key role in the treatment of HIV-1 infection in combination therapy with other drug such as Ritonavir.
  • The drug is also used in combination of other retroviral drugs for postexposure prophylaxis of HIV infection in individuals who have had occupational or nonoccupational exposure to HIV-1.
  • However, this drug does not cure the infection of Human Immunodeficiency Virus. It may reduce the possibility of the development of AIDS and also diminish the occurrence of other infections or cancer.
  • Atazanavir inhibits the enzyme activity of protease by binding to its active site and lowering the quantity of virus in the infected person’s blood.
  • Pharmacokinetics of Atazanavir has allowed once-daily dosing, and it is not associated with significant PI-associated dyslipidemia, lipodystrophy and elevated cholesterol levels.
  • The drugs also showed no cross-resistant when boosted with other protease inhibitors.

Pharmacophore structure: Information about the chemical structure of the drug

Atazanavir chemically belongs to the class of synthetic pharmaceutical organic compounds which are known as Phenylpyridines. Phenylpyridines are characterized by the presence of benzene ring linked to a pyridine ring through a CC or CN bond. The detailed chemical classification of Atazanavir is described below:

  Kingdom Organic compounds 
Super Class Organoheterocyclic compounds
Class Pyridine and derivatives
Sub Class Phenylpyridines
Direct Parent Phenylpyridines

Chemical information of the drug

  • Atazanavir is available as a sulfate salt which selectively brings about the inhibition of the processing of viral polyprotein precursors (Gag and Gag-Pol polyprotein) in cells infected with HIV-1 virus.
  • Atazanavir is a synthetic pharmaceutical aromatic heteromonocyclic compound with a molecular formula C38H52N6O7 and molecular weight of 704.389 Da.
  • The Atazanavir is chemically named as methyl N-[(1S)-1-{[(2S,3S)-3-hydroxy-4-[(2S)-2-[(methoxycarbonyl)amino]-3,3-dimethyl-N’-{[4-(pyridin-2-yl)phenyl]methyl}butanehydrazido]-1-phenylbutan-2-yl]carbamoyl}-2,2-dimethylpropyl]carbamate.
  • Atazanavir is available as free base or as sulfate (Atazanavir sulfate). Atazanavir sulfate is white to pale-yellow crystalline powder.
  • The drug is slightly soluble in water and has water solubility of 4-5 mg/mL.
  • The melting point of Atazanavir is 214°C -216 °C.

Atazanavir strengths

  • Atazanavir is available in powder and capsule form for oral administration.
  • Atazanavir capsule is available in different dosage of 150, 200 and 300 mg/capsule and contains crospovidone, magnesium stearate and lactose monohydrate as inactive ingredients.
  • The shells of capsule contain titanium dioxide, gelatine, red black & yellow iron oxides and FD&C Blue No.2.
  • Shell of capsule of 150 mg labelled with “150” mg & “3624” and capule of 200 mg labelled with “200” mg & “3631” while capsule of 300 mg is labelled with “300” mg & “3622” and all type of capsule are labelled with “BMS”.
  • The ink used for printing on shell contains titanium dioxide, isopropyl alcohol, ammonium hydroxide, propylene glycol, simethicone, n-butyl alcohol, shellac and FD&C Blue No.2.
  • Atazanavir powder is available in strength of 50 mg Atazanavir in 1.5 gm of powder.
  • The Atazanavir powder is off white to pale yellow in color and contains aspartame, sucrose and orange-vanilla flavour as inactive ingredients.

How does Atazanavir work

  • Atazanavir is a HIV-1 protease inhibitor (PI) class of drug, which shows potent activity against Human Immunodeficiency Virus Type 1 (HIV-1).
  • Chemically Atazanavir is an azapeptide, which is a peptide analogue in which one or more of the amino residues is replaced by a semicarbazide.
  • The mode of action of Atazanavir is similar to that of other drugs used for the treatment of retroviral infection.
  • Atazanavir works similar to other protease inhibitor drug by inhibiting the HIV-1 protease enzyme.
  • HIV-1 protease is an HIV-1 enzyme that is involved in the formation of infectious viral functional proteins (by proteolytic cleavage) from the viral polyprotein precursors.
  • Atazanavir inhibits the activity of HIV-1 protease enzyme by binding to its active site. As a result of Atazanavir binding, HIV-1 protease is unable to cleave viral polyproteins precursors and development of mature infectious viral particles.
  • Due to the inhibition of HIV-1 protease enzyme, processing of viral Gag and Gag-Pol polyprotein stops, which results into the formation of immature non-infectious viral particles.
  • Apart from this, Atazanavir also plays an important role in increasing the number of CD4 (T) cells and help immune system to fight against HIV infection.
Atazanavir : Mode of Action

Atazanavir : Mode of Action

Atazanavir dose

  • The recommended dose of the drug for adults with HIV infection is usually 400 mg once a day.
  • In combination therapy with the Ritonavir, the recommended dose of the drug is 300 mg once a day.
  • In case of children from 6 years to less than 18 years, the recommended doses are based on the body weight and are as follows:
    • 15 to less than 20 kg (33 to less than 44 lbs): 150 mg Atazanavir + 100 mg Ritonavir once a day
    • 20 to less than 40 kg (44 to less than 88 lbs): 200 mg Atazanavir + 100 mg Ritonavir once a day
    • 40 or more than 40 kg (88 or more than 88 lbs): 300 mg Atazanavir + 100 mg Ritonavir once a day
  • In case of hepatic and renal impairment, the dosing recommendations are as follows:
    • Dose in hepatic impairment: no dose adjustment required, take dose as prescribed by pharmacist or doctor.
    • Dose in renal impairment: no need to alter the doses but in case of Haemodialysis 300 mg Atazanavir with 100 mg of Ritonavir should be recommended.
  • Atazanavir powder is recommended for infants older than 3 months with Ritonvir. It should not be used alone.

When should I discontinue, withhold or modify the dose of Atazanavir

  • The usual dosing of the drug (i.e. 400 mg Atazanavir or 300 mg Atazanavir + 100 mg Ritonavir per day) may vary depending upon the efficiency and side effects of the drug in a particular individual.
  • No dosage adjustment is necessary in patients with hepatic impairment and renal impairment but in case of haemodialysis dose should be adjusted.
  • The drug is contraindicated in case of hypersensitive response to any component of the drug.
  • Atazanavir should be contraindicated with the medication of Triazolam, Dihydroergotamine, Ergotamine, Ergonovine, Midazolam and Pimozide.
  • Atazanavir is not recommended for children younger than 6 year old.
  • Dose adjustment is required during the medication with antacids, Didanosine or buffered Aspirin.
  • Patient with phenylketonuria should use Atazanavir oral powder with aspartame.

What are the pharmacokinetic properties of Atazanavir

  • Pharmacokinetic studies suggested that after oral administration, Atazanavir is rapidly absorbed and has a bio-availability of approximately 60-68 %.
  • When Atazanavir is taken with food, it decreases the pharmacokinetic variability and increases the bioavailability.
  • It has been observed that following a 400 mg dose,  maximum (or peak) plasma concentration is achieved in 150 minutes (2.5 hour) in the fasted state.
  • Following absorption the majority (86%) of the drug is bound to serum proteins such as albumin and alpha-1-acid glycoprotein.
  • The drug is primarily metabolized by liver through major (monooxygenation and dioxygenation) and some minor (oxygenation, hydrolysis, dehydrogenation, glucuronidation and N-dealkylation) pathways.
  • Studies with human liver microsomes also suggested that Atazanavir is extensively metabolised by hepatic cyotochrome P450, primarily the CYP3A4/ CYP3A5 isoenzymes.
  • The average median half-life of Atazanavir is 7 hours except 12.1 hours in hepatically impaired patients.
  • Atazanavir is mainly excreted in the feces (approximately 79%) in the form of metabolites and very little amount in the urine (13%).
  • Uncharged drug account for 27% of total administered dose and excreted through feces (20%) and urine (7%).

Which pregnancy category (A; B; C; D; X) has been assigned to Atazanavir

  • The Atazanavir is classified by US FDA pregnancy category: B
  • Atazanavir is used for only those pregnant women who are infected with HIV-1 strain and prescribed for Atazanavir.
  • Due to lack of adequate and well-controlled studies the use of Atazanavir in pregnant women is contraindicated and recommended only when benefit justifies the risk.
  • Laboratory animal studies have shown no adverse effect of Atazanavir on fetus.
  • Studies support the excretion of the drug into animal milk. However, no adequate data is available on excretion of Atazanavir into human breast milk.
  • HIV infected women and women who use the medication of Atazanavir should not breastfeed the baby.
  • Despite these facts caution should be exercised when taking Atazanavir.

How to take Atazanavir

  • Atazanavir is available in capsule form for oral administration by mouth and usually recommended once a day with snacks or food.
  • It is usually recommended not to chew or open or split the capsule.
  • Atazanavir is also available in the powder form and used always with the combination of Ritonavir. Do not take the Atazanavir powder without Ritonavir.
  • The powder of Atazanavir can be taken with food products (such as applesauce or yogurt) or liquids such as water, or milk.
  • Precautions should be taken to mix the powder well and to take full dose of the drug.
  • While taking or mixing the Atazanavir in water it is usually prescribed to take snacks or meal immediately after the consumption of powder mix.
  • In case of infants Atazanavir powder can be mixed in infant formula and can be given using dropper or oral dosing syringe. Avoid mixing or use of baby bottle for  the powder dosing.
  • It is usually recommended to take the drug at the same time daily and the time duration between the drug uses should be at least 24 hours.
  • Atazanavir is taken with water (one glass or more) at same time each day.
  • It is advisable to take Atazanavir exactly as directed and not to take more than one capsule daily.
  • Follow the instructions carefully as directed on prescription leaflet and ask your pharmacist for any information or any part you are unable to understand.
  • Do not change the dose of the drug as prescribed by your doctor, since the dosage is based on patient medical condition, treatment responses and usage with other drugs.

How to store the drug

  • Atazanavir is stored at 25°C (77°F) and excursion permitted to 15-30°C (59-86°F).
  • The container should be tightly closed and kept away from excessive heat, direct sun light and reach of children.
  • Do not freeze or store the medicine at extreme cold temperature.
  • Medicine should not be stored in the bathroom.

How to dispose the medicine

  • Throw away unused and opened, outdated or no longer used container.
  • Also dispose the old medicine after the expiration date.
  • Atazanavir should not be disposed in the household garbage, sink or in wastewater.

Does Atazanavir has approval from government / FDA /or any other related agencies

  • The drug has received it official approval for the treatment of infection of human immunodeficiency virus (HIV) on 20 June 2003 by U.S. Food and Drug Administration.
  • The drug was first protease inhibitors approved for once-daily dosing (rather than multiple dosing) and do not cross-resistant with other protease inhibitors (used for boosting the effect of Atazanavir).
  • In year 2009, the US FDA issued a warning regarding use of Atazanavir with proton-pump inhibitors i.e. Asomeprazole (Prilosec), Rabeprazole (Aciphex) or Esomeprazole (Nexium). According to US FDA the concomitant use of Atazanavir with proton pump inhibitors significantly reduces the absorption and effects of Atazanavir.

Other uses of the drug

  • Atazanavir may also be used for preventing the infection of HIV in peoples who are accidentally exposed.
  • Atazanavir may also be used for other cases not mentioned here. It is advisable to ask your doctor or pharmacist for more information.

What special dietary precautions should I follow

  • Alcoholic beverages, grapefruit, or grapefruit juice should be avoided.
  • Alcohol consumption can also enhance some side effects of the drug.

What precautions should I follow while using Atazanavir?

  • Do not use the medicine if you are hypersensitive or allergic to any of the ingredients. Consult with your doctor and pharmacist if you are taking any prescription and non-prescription medications or herbal products.
  • Before taking Atazanavir, tell your doctor about your medical history preferentially if you have any kind of liver disease, renal disorder, heart disease, eye disorders, bleeding disorders, or blood pressure problems.
  • During the treatment of Atazanavir, if the symptoms of other infections develop, consult to your doctor immediately.
  • Avoid sharing razors, toothbrushes, medicine needles and unprotected sex.
  • Use of Atazanavir may increase the body weight. Consult your doctor in case of any query.

Atazanavir side effects

In addition to the associated benefits, Atazanavir administration  is accompanied with some side effects few of them are more common, others less common whereas some are more serious. It is always recommended to consult a doctor if you encounter any of the side effects.

Some common side effects of Atazanavir are as follows. If these symptoms persist tell to your doctor:

  • Fever
  • Nausea
  • Diarrhea
  • Vomiting
  • Mild rash
  • Headache
  • Depression
  • Muscle pain
  • Stomach pain
  • Difficulty falling asleep or staying asleep
  • Numbness, burning, pain, or tingling of hands or feet

Atazanavir may cause serious side effects. On appearing of these symptoms immediately contact to your doctor and get emergency treatment:

  • Blood in urine or dark colored urine
  • Dizziness
  • Erection that lasts longer than 4 hours
  • Irregular heartbeat
  • Light-colored bowel movements
  • Loss of appetite
  • Pain in your back or side
  • Pain or burning with urination
  • Vision changes
  • Vomiting
  • Yellowing of skin or eyes (especially in newborn infants)

Stop taking the Atazanavir if following side-effects are observed:

  • Development of severe rashes with other symptoms like fever, blisters or peeling skin, mouth sores, red or swollen eyes, muscle or joint aches, swelling of your face or neck.
  • ‘Flu-like’ symptoms, painful, warm, or red lump under your skin.
  • Symptoms of kidney stone like blood in urine or pain in your side.
  • Symptoms of Lactic acidosis such as unusual muscle pain, stomach pain with vomiting and nausea, irregular heartbeats or unusual weakness.

Atazanavir overdose

  • Symptoms of overdose of Atazanavir include yellowing of eyes or skin.
  • Overdose usually occurs when someone by mistake or deliberately takes more than the prescribed limit of this medication.
  • If you overdose the drug contact immediately with your doctor or pharmacist for symptomatic and supportive measures.
  • Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Atazanavir missed dose

  • In case of missed dosage, take it as soon as you remember and maintain a regular dosing schedule. Keep in mind to take the missed dose only on an empty stomach.
  • Skip the missed dose if it is almost time for your next scheduled dose. Keep in mind to not use a double dose to make up a missed dose

Atazanavir drug interactions

It has been observed that Atazanavir may interact with or increase or decrease the effect of following drugs. Caution should be taken when co administrating Atazanavir with one of the following drugs.

  • Insulin or oral diabetes medication
  • Drugs that weaken the immune system, such as Tacrolimus (Prograf), Sirolimus (Rapamune), or Cyclosporine (Neoral, Sandimmune, Gengraf)
  • Telaprevir (Incivek)
  • Antifungal or antibiotic medication
  • Antidepressant
  • Buprenorphine (Suboxone, Subutex, Buprenex)
  • Rosuvastatin (Crestor)
  • Other HIV/AIDS medicine such as Saquinavir (Invirase), Tenofovir (Viread), or Efavirenz (Sustiva)
  • Salmeterol (Advair, Serevent)
  • Medicines for treatment of erectile dysfunction, such as Vardenafil (Levitra), Tadalafil (Cialis, Adcirca), or Sildenafil (Viagra)
  • A blood thinner such as warfarin (Jantoven, Coumadin)
  • Heart rhythm or blood pressure medication
  • Stomach acid reducers such as Famotidine (Pepcid),Omeprazole (Prilosec), Lansoprazole (Prevacid), Cimetidine (Tagamet), Esomeprazole (Nexium), Ranitidine (Zantac), and others.

Atazanavir should not be concomitantly used with Ritonavir (Norvir) in case you are also taking a steroid medicine called Fluticasone (Flovent, Flonase, Advair). Consult your doctor for a different HIV drug, or using another treatment for allergic reaction.

This list is not complete and there can be many more drugs that can interact with Atazanavir.

Does Atazanavir have any interaction with diseases

It has been observed that following medical conditions (disease) may interact with Atazanavir:

  • Heart block:
    • Use of Atazanavir should be done very cautiously in such patients (HIV patients or heart patients) suffering with conduction abnormalities.
    • Atazanavir extends the PR interval (atrioventricular (AV) conduction time or interval from where the P wave         begins until the beginning of the QRS complex in the electrocardiogram) in some patients and causes conduction abnormalities.
  • Nephrolithiasis (kidney stones in urinary tract):
    • Some cases of nephrolithiasis may result in acute interstitial nephritis, renal failure, and/or hospitalization upon receiving Atazanavir therapy.
    • Atazanavir should be used very cautiously in patients with renal and/or hepatic insufficiency or past history of nephrolithiasis.
    • Therapy should be withheld or discontinued temporary under such situations.
  • Haemophilia:
    • Types A and B hemophiliac patients show an increased bleeding including spontaneous skin hematomas (collection of blood under the skin) and hemarthrosis (bleeding into joints spaces) on treatment with Atazanavir.
    • Atazanavir therapy is interrupted and then reintroduced in hemophiliac patients.
    • Patients of haemophilia and with other coagulation defects should be monitored closely for bleeding during Atazanavir therapy.
  • Liver Disease:
    • Patients who are suffering with hepatitis B or C viral infections or have noticeable increase in transaminases before Atazanavir treatment are more prone to further transaminase elevations or hepatic decompensation during use of Atazanavir.
    • Besides, Atazanavir may get accumulated in patients with moderate or severe hepatic insufficiency as it is primarily metabolized by the liver.
  • Hyperglycemia (high glucose levels):
    • HIV patients treated with Atazanavir show an onset or increased severity of already existing glucose intolerance, hyperglycemia, and diabetes mellitus.
    • Insulin resistance may be accompanied with HIV-associated lipodystrophy syndrome characterized by fat redistribution and serum lipid elevations.
    • Adjustments in dose for insulin or oral hypoglycemic drugs may be necessary in patients with diabetes.
  • Hyperlipidemia (high lipid levels):
    • Patients treated with Atazanavir are associated with hyperlipidemia.
    • Severe hyperlipidemia can occasionally lead to pancreatitis.
    • Some patients receiving Atazanavir therapy may develop symptomatic atherosclerosis and coronary artery disease.

It is usually recommended to discuss any medical condition or allergies you have before you start taking Atazanavir.

Atazanavir disease interaction.

Atazanavir disease interaction.

Clinical research and current scenario of the drug

  • An open-label, multicenter clinical studies indicated the safety profile of Atazanavir in pediatric patients comparable to that in adults.
  • The clinical studies with Atazanavir indicated that pharmacokinetic of Atazanavir did not showed any differences due to age or gender.
  • Clinical studies prescribed the concomitant use of Atazanavir and Lopinavir (HIV protease inhibitors) during pregnancy.
  • Pharmacokinetic study with Atazanavir (400 mg once a day) and diltiazem (180 mg once a day) indicated a 2-fold increase in the diltiazem plasma concentration and an additive effect on the PR interval.
  • No additive effect of Atazanavir and atenolol on the PR interval is observed in clinical study between Atazanavir (400 mg once a day) and atenolol (50 mg once a day).
  • In vivo studies indicated that Atazanavir neither induce its own metabolism nor increase the bio-transformation of substrates of CYP3A.
References from chemical, biological and toxicological databases

Where can I get more information

Your pharmacist or health care provider can provide more information about Atazanavir.

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Clopidogrel

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Esomeprazole

Jun 18 2015 Published by under Medicines

What is Esomeprazole

  • Esomeprazole is a drug that is used for the treatment of gastroesophageal reflux disease (GERD).

What is the generic and brand name of the drug

  • The drug is available under generic name Esomeprazole and brand names Nexium® and many others worldwide.
  • The drug is marketed in by Astra Zeneca Lp. and STAT Rx USA

What is the source of the drug (natural or synthetic)

  • Esomeprazole is a synthetic (man-made) pharmaceutical proton pump inhibitor of gastric parietal cells.

Waht does Esomeprazole do

  • Esomeprazole is used to inhibit gastric acid secretion and formation of excessive stomach acid.
  • The drug is generally used to treat symptoms of gastroesophageal reflux disease (GERD). The disease is characterized by backward flow of stomach acid (gastric reflux) into oesophagus (tube lining the throat and stomach). It results in heart burn,  mucosal damage and chronic injury to esophagus.
  • Besides GERD, Esomeprazole is also recommended to treat peptic ulcer disease, dyspepsia, and Zollinger-Ellison syndrome (condition in which stomach produces large amount of acid).
  • Esomeprazole is used in combination with other drugs for treatment peptic ulcer caused by consumption of nonsteroidal anti-inflammatory drugs (NSAIDs) or by a certain type of bacteria ( pylori).
  • The drug reduced formation of excessive stomach acid by inhibiting H+ / K+ ATPase (membrane transporter) in the parietal cells of the stomach. This results in prevention of further damage and allows healing of damage esophagus.
Clinical uses of Esomeprazol.

Clinical uses of Esomeprazol.

Pharmacophore structure: Information about the chemical structure of the drug

Esomeprazole chemically belongs to the class of organic compounds which are known as sulfinylbenzimidazoles. The sulfinylbenzimidazoles are chemically characterize as polycyclic aromatic compounds containing a sulfinyl group attached to benzimidazole moiety.The detailed chemical classification of  Esomeprazole  is described below:

Kingdom Organic compounds
Super Class Organic heterocyclic compounds
Class Benzimidazoles
Sub Class Sulfinylbenzimidazoles
Direct Parent Sulfinylbenzimidazoles

Chemical information of the drug.

  • Esomeprazole is a synthetic pharmaceutical organic compound named as 5-methoxy-2-[(S)-(4-methoxy-3,5-dimethylpyridin-2-yl)methanesulfinyl]-1H-1,3-benzodiazole.
  • The compound has molecular formula C17H19N3O3and the molecular weight of 461 Da.
  • The melting point of Esomeprazole is 155 °C.
  • It is slightly soluble in water with a maximum solubility of 0.353mg/ml.

Esomeprazole strength

  • The medication is supplied as a delayed-release capsule or suspension for oral administration that means the drug is directly release in intestine rather than stomach to prevent its breakdown by stomach acids.
  • Esomeprazole capsule is available in two strengths (20 mg and 40 mg) and as a delayed release oral suspension in three strength (2.5mg, 5mg, 10 mg, 20 mg and 40 mg).
  • Each 20 mg and 40 mg capsule of Esomeprazole contains 22.3 mg, or 44.5 mg Esomeprazole magnesium trihydrate in the form ofenteric-coated
  • Besides Esomeprazole, other ingredients of capsule includes hypromellose, magnesium stearate, glyceryl monostearate 40-55, hydroxypropyl cellulose, methacrylic acid copolymer type C, polysorbate 80, sugar spheres, talc, and triethyl citrate.
  • The capsule is usually swallowed as a whole or open and mix with water or applesauce to take by mouth or or emptied into a syringe for administration through a feeding tube.
  • The drug is usually recommended once a day and at least 1 hour prior to meal.

How does Esomeprazole work

  • The mode of action of Esomeprazole is similar to the working of other proton pump inhibitors.
  • Proton pump inhibitors bind their respective proton pump and blocks their function.
  • Esomeprazole brings about inhibition of the H+/K+-ATPase in the stomach or gastric parietal cells responsible for the production of the acid.
  • This interferes with the final step in the production of the acid, thereby decreasing the gastric acidity.
Esomeprazol : Mode of action.

Esomeprazol : Mode of action.

What are the recommended doses of Esomeprazole

The prescribed dose of Esomeprazole varies depending upon the age and the diseased state.

  • For the treatment of gastroesophageal reflux disease (GERD) and reflux esophagitis:
    • The recommended dose of Esomeprazole is 40 mg per day for a period of 4 to 8 weeks. The dose that follows this period is 20 mg per day.
  • Treatment of reflux esophagitis in children:
    • Age group of 12 months to 11 years: a daily dose of 10-20 mg as per the body weight for a period of 8 weeks.
    • Age group of 11years to 17 years: a daily dose of 20-40 mg for a period of 4 to 8 weeks.
  • Treatment of Non-erosive relux disease (NERD) comprising heartburn and reflux in children:
    • Age group of 12 months to 11 years: a daily dose of 10 mg for a period of 8 weeks.
    • Age group of 11years to 17 years: a daily dose of 20 mg for a period of 2 to 4 weeks.
  • Treatment of Zollinger-Ellison syndrome characterized by the production of more acid as compared to normal requires a dose of 40 mg twice a day
  • NERD or heartburn in case of adults requires the prescribed dosage of 20 mg once a day for the time duration ranging from 2 to 4 weeks.
  • For the treatment of duodenal ulcers caused by H. pylori, a dosage of 20 mg twice or 40 mg once a day along with amoxicillin and clarithromycin for a period of 7-10 days.
  • The prescribed dosage for prevention of NSAID (nonsteroidal anti-inflammatory drugs) induced ulcers is 20 to 40 mg per day for duration of 6 months. The treatment requires a daily dosage of 20 mg for a period of 4-8 weeks.

When should I discontinue, withhold or modify the dose of Esomeprazole

  • The usual dosing of the drug (i.e. 10 mg per day) may vary depending upon the efficiency and side effects of the drug in a particular individual. The health care provider will determine dosage based on the patient’s age, weight and diagnosis.
  • No dosage adjustment is necessary in mild to moderate hepatic impairment In case of severe cases, the drug dose should not be exceeded above 20 mg.
  • The drug is contraindicated in case of pregnancy, breastfeeding or hypersensitive response to any component of the drug.
  • Esomeprazole oral suspension is not prescribed in children less than one year old.
  • It has been observed that patients taking higher doses of Esomeprazole are the risk for fractures, therefore it is advisable to take higher dose of medicine under surveillance of health care providers and try to recommend or prescribe a lower dose if possible.
  • Dosage adjustments are required in case of geriatric population.
  • Esomeprazole use is contraindicated in patients with known hypersensitivity to proton pump inhibitors e.g.,angioedema and anaphylactic shock.

What are the pharmacokinetic properties of the drug

  • Pharmacokinetic studies suggest that after oral administration, Esomeprazole is rapidly absorbed and shows bioavailability ranging from 50 – 90 %.
  • It has been observed that following a single 20mg to 40mg oral dose of Esomeprazole peak plasma concentrations of 0.5-1.0 mg/l is achieved within 1–4 hours.
  • Following absorption the majority (97%) of the drug is bound to plasma proteins.
  • The drug is mainly metabolized mainly by the hepatic system.
  • The drug is eliminated mainly in urine as metabolites (about 80%) and the remaining 20% as feces.
  • The average median half-life of Esomeprazole 1 to 1.5 hours.
  • The average steady state volume of distribution of Esomeprazole is approximately 16 liters.

Which pregnancy category (A; B; C; D; X) has been assigned to Esomeprazole

  • The Esomeprazole is classified by US FDA pregnancy category: C
  • Due to lack of adequate and well-controlled studies the use of Esomeprazole in pregnant women is contraindicated and recommended only when benefit justifies the risk.
  • Laboratory animal studies have shown adverse effects on the fetus toxicity.
  • No adequate data is available on excretion of Esomeprazole into human breast milk.
  • Despite these facts caution should be exercised when taking Esomeprazole.

How to take Esomeprazole

  • Esomeprazole is available as delayed release capsule or in granule form for oral administration by mouth
  • The capsules should be swallowed and not chewed or crushed.
  • The drug is taken only once per day and should be taken at least 1 hour prior to food consumption.
  • Try to take the medicine at the same time every day.
  • Follow the instructions carefully as directed on prescription leaflet and take Esomeprazole exactly as directed.
  • Antacid may be co-administered with the drug if necessary but requires consuming Esomeprazole at least 30 minutes prior to the antacid.
  • Take the medication regularly, even if you feel well.
  • Do not change the dose of the drug as prescribed by your doctor. Since, the dosage is based on patient medical condition and treatment responses.

How to store the drug

  • Esomeprazole is stored at at room temperature between 68°F to77°F (20°C to 25°C).
  • The container should be tightly closed and away from excess heat, direct sun light and reach of children.
  • Do not freeze or store the medicine at extreme cold too.

How to dispose the medicine

  • Throw away unused and opened, outdated or no longer used container.
  • Also dispose the old medicine after the expiration date.
  • Consult your pharmacist for the proper disposal of the drug.

Does Esomeprazole has approval from government / FDA /or any other related agencies

  • Esomeprazole has received its official approval from US Food and Drug Administration (FDA) in February 2001.
  • The drug also received official approval from FDA to treat heartburn and other symptoms associated with gastroesophageal reflux disease (GERD).
  • The FDA also approved Esomeprazole for treatment of healing of erosive esophagitis. The drug is also recommended to use in combination with amoxicillin and clarithromycin, for the treatment/eradication ofduodenal /peptidic ulcer disease caused by Helicobacter pylori
  • Esomeprazole capsules are also approved to treat the gastric ulcers associated with use of nonsteroidal anti-inflammatory drugs (NSAIDs) and Zollinger-Ellison syndrome.

Other uses of the drug

  • Esomeprazole may also be used for other uses not listed here. It is advisable to ask your doctor or pharmacist for more information.

What special dietary precautions should I follow

  • It is generally recommended to continue with the normal diet unless and until asked by your doctor.

Esomeprazole precautions

  • Do not use the medicine if you are hypersensitive or allergic to any of the ingredients.
  • Before taking Esomeprazole, tell your doctor about your medical history preferentially if you have any kind of Liver disease or low levels of magnesium in the blood.
  • During pregnancy this medication is recommended only when it is essential and under doctor or pharmacist supervision.
  • Since the information about excretion of drug in milk is not explored consult your doctor before breast feeding to your child.
  • Consult with your doctor and pharmacist if you are taking any prescription and nonprescription medications, nutritional supplements, vitamins and herbal products such as some antifungals like ketoconazole, mediators for HIV, anticoagulants like Warfarin, iron supplements, diuretics etc.
  • Do not share this medication with other persons having the similar kind of problems. Consult your doctor for more details.

Esomeprazole side effects

Esomeprazole may provide relief from the acidic conditions but may be associated with a number of serious side effects which are as follows:

  • Diarrhea: The chances of acquiring severe diarrhea caused due to intestinal infection by Clostridium difficile.
  • Bone fractures: People who are on multiple doses of Esomeprazole for a longer duration pose increased risk of spine, hip or wrist fracture.
  • Atrophic Gastritis: Prolonged uptake of Esomeprazole increases the chances of chronic inflammation of the stomach lining.
  • Low body magnesium concentration: Magnesium level goes down in people who are on Esomeprazole medication for a period of at least 3 months and may show the following symptoms: seizures; tremors; muscle ache, cramps or weakness; fast heart beat; hands and feet spasm, and dizziness.

The most commonly occurring side effects associated with Esomeprazole may include:

  • Gas
  • Constipation
  • Headache
  • Abdominal pain
  • Drowsiness
  • Diarrhea
  • Dry mouth
  • Nausea

Serious allergic reactions: Some people may develop following allergic reactions on consuming proton pump inhibitors (such as Esomeprazole)

  • Difficulty breathing
  • Rash
  • Face swelling
  • Throat tightness

Other adverse side effects are also reported by the body system and include:

  • Body as a Whole: Chest pain, fatigue, pain, enlarged abdomen, flu-like disorder, back pain, chest pain, facial and peripheral edema, leg edema, fever, asthenia, generalized edema, and rigors.
  • Hearing: Tinnitus,
  • Visual: Conjunctivitis, abnormal vision.
  • Gastrointestinal: Constipation, duodenitis, eructation, bowel irregularity, gastroenteritis, esophageal stricture, esophagitis, dysphagia, epigastric pain, esophageal disorder, GI hemorrhage, dysplasia GI, frequent stools, ulcerative stomatitis, esophageal ulceration, vomiting, esophageal varices, gastric ulcer .
  • Hematologic: Anemia hypochromic, epistaxis, anemia, cervical lymphadenopathy, leukopenia, leukocytosis, thrombocytopenia.
  • Nervous System/Psychiatric: Confusion, nervousness, visual field defect, vertigo, tremor, sleep disorder, apathy, impotence, migraine, hypertonia, hypoesthesia, paresthesia, insomnia, increased appetite, dizziness, depression.
  • Hepatic: Abnormal hepatic function, increased SGOT and SGPT, bilirubinemia.
  • Cardiovascular: tachycardia, flushing, hypertension.
  • Urogenital: Micturition frequency, moniliasis, fungal infection, genital moniliasis, albuminuria, hematuria, polyuria, abnormal urine, dysuria, cystitis.
  • Respiratory: sinusitis, larynx edema, pharyngitis, dyspnea, asthma, coughing, rhinitis.
  • Reproductive: Vaginitis, change in menstrual cycle, dysmenorrhea.
  • Endocrine:
  • Metabolic/Nutritional: Increased alkaline phosphatase, thirst, weight gain or loss, vitamin B12 deficiency, hyperuricemia, glycosuria, hyponatremia.
  • Special Senses: Taste loss, parosmia, otitis media, taste perversion.
  • Skin and Appendages: Dermatitis, increased sweating, urticaria, skin inflammation, acne, angioedema, rash, rash maculo-papular, rash erythematous.
  • Musculoskeletal: Arthropathy, cramps, fibromyalgia syndrome, aggravated arthritis, polymyalgia rheumatica, hernia.

Esomeprazole overdose

What happens if you overdose on Nexium?

Try to avoid taking the overdose of the drug. Symptoms include extreme sweating, blurred vision, confusion, or extremely fast heartbeat.

  • In case you or some other person has taken overdose of this medication contact your local poison control centre at 1-800-222-1222 or emergency room immediately.
  • Consult your doctor or pharmacist for symptomatic and supportive measures in any case of overdose.

Esomeprazole missed dose

  • In case of missed dosage, take it as soon as you remember and maintain a regular dosing schedule.
  • Skip the missed dose if it is almost time for your next scheduled dose. Keep in mind to not use a double dose to make up a missed dose.

Esomeprazole drug interactions

Controlled clinical studies suggested that Esomeprazole may interact with one of the following drugs. Care should be taken when you are taking these medications together.

  • Digoxin: Esomeprazole raises the serum concentration of digoxin but usually may not be clinically important
  • Rifampin: Esomeprazole plasma concentration reduces along with its pharmacologic effects.
  • Clopidogrel: Esomeprazole brings about an inhibition in the anti-platelet activity of clopidogrel.
  • Antifungals (such as voriconazole, ketoconazole, and itraconazole): Co-administration with voriconazole increases the exposure of Esomeprazole and with itraconazole and ketoconazole lowers their bioavailability.
  • Warfarin: Use of Esomeprazole enhances the chances of bleeding.
  • Clarithromycin: This drug brings about an increase in the plasma levels of Esomeprazole and thereby its pharmacologic effects and side effects.
  • Benzodiazepines (eg, diazepam): Coadministration with diazepam may increase its CNS effects (eg, sedation, ataxia).
  • Nilotinib, dasatinib, erlotinib: Try avoiding these drugs along with Esomeprazole as their absorption is greatly hampered in its presence.
  • Fluvoxamine: It elevates the plasma levels as well as adverse effects of Esomeprazole.
  • Rilpivirine: Esomeprazole causes an elevation in the plasma levels and reduced pharmacologic effects and virologic resistance of rilpivirine.
  • Cilostazol: Esomeprazole enhances the concentration of cilostazol along with its active metabolite (i.e. 3,4-dihydrocilostazol) and hence requires lowering of this drug dose when given in combination with Esomeprazole.
  • Tacrolimus: Esomeprazole elevates the plasma levels of tacrolimus thereby affecting its pharmacologic and adverse effects.
  • Calcium salts: The uptake of calcium by gastro-intestinal tract may be impeded by the use of drug to lower the acid secretion.
  • Methotrexate: Esomeprazole causes an increase in the concentration and side effects of methotrexate by lowering its excretion by renal pathway.
  • Clozapine: Esomeprazole causes an increase in the plasma concentration and hence pharmacologic and adverse effects of clozapine.
  • Iron salts (such as ferrous sulfate): Esomeprazole consumption interferes with the uptake of iron salts.
  • Protease inhibitors (like atazanavir, indinavir, nelfinavir, saquinavir): Plasma level of these inhibitors gets affected in presence of Esomeprazole. Saquinavir plasma levels get increased. Try to avoid coadministration of atazanavir or nelfinavir with Esomeprazole.
  • Mycophenolate: The plasma levels of mycophenolate and its pharmacologic effects get decreased in presence of Esomeprazole.
  • Tolterodine: Esomeprazole causes an elevation in the release of tolterodine from the ER and its pharmacologic and adverse effects.

Does Esomeprazole have any interaction with Diseases

  • It has been suggested that Esomeprazole is primarily metabolized in liver, therefore, the exposure to Esomeprazole in patients with mild, moderate or severe hepatic impairment is significantly higher than the normal individuals.
  • It is suggested that little amount of Esomeprazole can accumulate in Child Pugh Class A and B  following once-daily, multiple-dose administration.
  • Esomeprazole plasma concentration was increased substantially in patients with severe hepatic impairment (Child Pugh Class C) in comparison to healthy individuals. Thus, the drug is recommended a maximum dosage of 20 mg once daily in patients with severe liver disease.

Where can I get more information

Your pharmacist or health care provider can provide more information about Esomeprazole.

Clinical research and current scenario of the drug

  • Esomeprazole reduces gastric acid secretion by inhibiting protom pump in the gastric parietal cells. It blocks the final step in the gastric acid production.
  • In controlled clinical trials it has been observed that Esomeprazole administration elevated the serum gastrin (is a peptide hormone that stimulates secretion of gastric acid ) which returned to baseline levels following discontinuation of therapy.
  • Clinical studies using oral doses of 20 mg and 40 mg Esomeprazole suggested no effects on thyroid and parathyroid functions.
  • Esomeprazole reduces the gastric acidity which results increases gastric counts of bacteria normally present in the gastrointestinal tract. It has been observed that long term treatment with proton pump inhibitors may lead to increased risk of gastrointestinal infections such as Salmonella, Campylobacter and Clostridium difficile.
  • Animal studies using RAT and rabbit model suggested that Esomeprazole at oral doses up to 280 mg/kg/day and 86 mg/kg/day showed no evidence of impaired fertility or harm to the fetus.
References from chemical, biological and toxicological databases

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Vardenafil, uses, strength, side effects, mechanism of action
Fondaparilux, uses, strength, side effects, mechanism of action

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Vardenafil

Jun 18 2015 Published by under Medicines

What is Vardenafil

  • Vardenafil is a drug that is used for the treatment of erectile dysfunction (inability to attain penile erection during sexual activity).

Vardenafil brand name

  • The drug is available under generic name Vardenafil and brand names Levitra, Staxyn ODT, and Vivanza.
  • Initially three pharmaceutical companies were responsible for the co-marketing of Vardenafil namely, Shering Plouh (now owned by Merck and Co), Bayer, and GlaxoSmithKline (GSK).
  • Bare Health Care Pharmaceuticals is responsible for its manufacture and is distributed by

What is the source of the drug (natural or synthetic)

  • Vardenafil is a synthetic (man-made) pharmaceutical anti-impotence medication.

What does Vardenafil do

Why is this medication prescribed?

  • Vardenafil plays a key role in the treatment of complications related to the sexual activitye., erectile dysfunction or impotence.
  • However, this drug does not provide any protection against sexually transmitted diseases like syphilis, HIV, hepatitis B etc.
  • Vardenafil acts by enhancing blood flow to the male penis and helps in attaining and keeping erection.

Pharmacophore structure: Information about the chemical structure of the drug

Vardenafil chemically belongs to the class of organic compounds which are known as benzenesulphonamides characterized by a sulphonamide group that is S-linked to the benzene ring.

The detailed chemical classification of Vardenafil is described below:

  Kingdom Organic compounds 
Super Class Benzenoids
Class Benzene and substituted derivatives
Sub Class Benzenesulphonamides
Direct Parent Benzenesulphonamides

Chemical information of the drug

  • Vardenafil is available as monohydrochloride salt which selectively brings about the inhibition of cyclic guanosine monophosphate (cGMP) specific phosphodiesterase type (PDE5).
  • It is a synthetic pharmaceutical compound with a molecular formula C23H32N6O4S.
  • The molecular weight of the compound is 488.603 Da.
  • Chemically, Vardenafil is known as 2-{2-ethoxy-5-[(4-ethylpiperazin-1-yl)sulfonyl]phenyl}-5-methyl-7-propyl-1H,4H-imidazo[4,3-f][1,2,4]triazin-4-one.
  • Vardenafil is nearly colorless, solid in texture and has a water solubility of 0.11 mg/mL.
  • Vardenafil is slightly soluble in acetone, soluble in ethanol and freely soluble in methanol.
  • The melting point of Vardenafil is 192 °C.

Vardenafil strengths

  • Vardenafil is available in tablet form for oral administration: regular tablets and orally disintegrating tablets.
  • It is available in different dosage strength of 2.5, 5, 10 and 20 mg/tablet.
  • The tablet is orange in colour, film coated and round with “2.5”, “5”, “10”, and “20” on one side corresponding to the different doses of the drug respectively and “BAYER” cross debossed on other side.
  • Each tablet contains active Vardenafil HCl and inactive ingredients such as yellow ferric oxide, colloidal silicon dioxide, titanium dioxide, polyethylene glycol, microcrystalline cellulose, red ferric oxide, magnesium stearate, hypromellose, and crospovidone.

Vardenafil uses

How the medicine works (mode of action)?

  • The mode of action of Vardenafil is same as that of other drugs used for the treatment of erectile dysfunction such as viagra and cialis.
  • Penile erection occurs by rushing of the blood in the penis via enlargement of the blood vessels responsible for delivering blood to the penis and decrease in the size of blood vessels taking blood away from the penis.
  • During sexual stimulation, nitric oxide is released in the penis responsible for activating the enzyme, guanylate cyclase that produces cyclic guanosine monophosphate (cGMP).
  • The cGMP plays an important role in the amount of blood flow in the penis during stimulation due to its action in increasing or decreasing the size of blood vessels bringing or carrying away blood in the penis.
  • Vardenafil maintains the levels of cGMP by inactivating the cGMP specific enzyme known as phosphodiesterase-5 (PDE-5) and thus enhances the penile erection.
Vardenafil: Mode of action.

Vardenafil: Mode of action.

What are the recommended doses of Vardenafil

  • The recommended dose of the drug for adult with erectile dysfunction is usually 10 mg once a day which has to be taken 60 minutes before the sexual intercourse.
  • However, the dose may be increased to a maximum of 20 mg or decreased to 5 mg depending upon the efficiency or the side effects of the drug.
  • The drug can be taken orally either in presence or absence of food.
  • In case of orally disintegrating tablet (ODT), only one tablet is recommended per day 60 minutes prior to the sexual activity.
  • ODT should not be swallowed with water but kept on tongue until it disintegrates.
  • In case of specific population and in cases where the individual is continuously on this medication, the dosing recommendations are as follows:
  • Geriatric dose (patients 65 years or older): An initial dose of 5 mg
  • Children dose: not recommended in children upto 16 years
  • Dose in patients of stable alpha blocker therapy: An initial dose of 5 mg. In case of concomitant use with some CYP3A4 inhibitors, the recommended doses may vary from 2.5 to 5 mg as directed:
  • ritonavir- a single maximum dose of 2.5 mg in 72 hours
  • itraconazole: 400 mg daily; ketoconazole, saquinavir, indinavir, atazanavir: 400 mg daily; and clarithromycin –a single maximum dose of 2.5 mg in 24 hours
  • intraconazole: 200 mg daily; ketoconazole: 200 mg daily; and erythromycin –a single maximum dose of 5 mg in 24 hours
  • Dose in hepatic impairment: mild cases- no dose adjustment required; moderate cases- an initial dose of 5 mg and maximum of 10 mg; severe cases-not evaluated
  • Dose in renal impairment – in mild, moderate and severe cases there is no need to adjust the doses. No evaluation done in case of renal dialysis

When should I discontinue, withhold or modify the dose of Vardenafil

  • The usual dosing of the drug (i.e. 10 mg per day) may vary depending upon the efficiency and side effects of the drug in a particular individual.
  • Dosage adjustment is required in case of geriatric population.
  • No dosage adjustment is necessary in renal impairment (mild, moderate or severe) patients and patients with mild hepatic impairment.
  • The drug is contraindicated in case of pregnancy, breastfeeding or hypersensitive response to any component of the drug.
  • Vardenafil use should be withheld in case of sudden vision loss.
  • Co-administration of Vardenafil with nitrates and nitric oxide donors is contraindicated.
  • The dosage of the drug has to be adjusted in case you are taking inhibitors of CYP4503A4.

What are the pharmacokinetic properties of the drug

  • Pharmacokinetic studies suggested that after oral administration, Vardenafil is rapidly absorbed and has a bio-availability of approximately 15%.
  • It has been observed that following a 20 mg dose of maximum (or peak) plasma concentration is achieved in 30 to 120 minutes in the fasted state.
  • Following absorption the majority (95%) of the drug is bound to plasma proteins.
  • The drug is mainly metabolized by the hepatic enzyme CYP3A4along with two other isoforms, namely, CYP3A5 and CYP2C.
  • The average median half-life of Vardenafil is 4-5 hours.
  • Vardenafil is mainly excreted in the feces (approximately 91-95%) in the form of metabolites and very little amount in the urine (2-6%).
  • The average steady state volume of distribution of the drug is 208 litres.

Which pregnancy category (A; B; C; D; X) has been assigned to Vardenafil

  • The Vardenafil is classified by US FDA pregnancy category: B
  • Due to lack of adequate and well-controlled studies the use of Vardenafil in pregnant women is contraindicated and recommended only when benefit justifies the risk.
  • Laboratory animal studies have shown increased frequency of the fetus damage.
  • Studies support the excretion of the drug into animal milk. However, no adequate data is available on excretion of Vardenafil into human breast milk.
  • Despite these facts caution should be exercised when taking Vardenafil.

How to take Vardenafil

  • Vardenafil is available in tablet form for oral administration by mouth with or without food.
  • Follow the instructions carefully as directed on prescription leaflet and take Vardenafil exactly as directed.
  • It is also recommended to take drug about 1 hour before sexual intercourse.
  • It is advisable not to take more than one tablet daily.
  • The time duration between the drug uses should be at least 24 hours.
  • Do not change the dose of the drug as prescribed by your doctor. Since, the dosage is based on patient medical condition, treatment responses and usage with other drugs.

How to store the drug

  • Vardenafil is stored at 25°C (77°F) and excursion permitted to 15-30°C (59-86°F).
  • Store the medicine away from light and moisture.
  • Medicine should not be stored in the bathroom.
  • The drug should be kept away from children and pets.

How to dispose the medicine

  • Throw away unused and opened, outdated or no longer used container.
  • Also dispose the old medicine after the expiration date.

Does Vardenafil has approval from government / FDA /or any other related agencies

  • Vardenafil has received its official approval from US Food and Drug Administration (FDA) in August 2003 for the treatment of erectile dysfunction.

Other uses of the drug

  • Vardenafil may also be used for the treatment ofpremature ejaculation.

What special dietary precautions should I follow

  • Grapes and its juice are known to interact with Vardenafil and increased its adverse effects via increasing the levels of the drug in the blood.
  • Consult your doctor regarding the use of grapefruit products with your doctor or pharmacist.
  • Alcohol consumption can also enhance some side effects of the drug.

What precautions should I follow while using Vardenafil

  • Do not use the medicine if you are hypersensitive or allergic to any of the ingredients.
  • Before taking Vardenafil, tell your doctor about your medical history preferentially if you have any kind of liver disease, heart disease, kidney disease, eye disorders, bleeding disorders, or blood pressure problems.
  • Alcoholic beverages, grapefruit, or grapefruit juice should be avoided.
  • It is usually recommended to avoid driving, use of machinery or any chore requiring alertness or clear vision.
  • Consult with your doctor and pharmacist if you are taking any prescription and non-prescription medications or herbal products.
  • Consult your doctor in case of any query.
  • Avoid use of other drugs used for the treatment of impotence.

Vardenafil side effects

In addition to the associated benefits, Vardenafil also is accompanied with the side effects some of which are more common, others less common whereas some that fade away with time while you take the drug. It is always recommended to consult a doctor if you encounter any of the side effects.

Some of the less commonly occurring side effects but requiring medical attention is outlined as:

  • Blurred or decreased vision or blindness
  • Hives and itching
  • Chills
  • Pain or discomfort in the neck, jaw, back, or arms
  • Difficulty with swallowing or breathing
  • Sweating
  • Eye pain
  • Fainting
  • Slow or fast heartbeat
  • Chest tightness, pain, heaviness, or discomfort
  • Dizziness
  • Unusual tiredness
  • Confusion
  • Nausea and vomiting
  • Swelling of the face, eyelids, lips, around the eyes, or tongue
  • Skin rashes

In some cases the incidence are rarely known such as hearing loss. There are some adverse effects that disappear while consuming the drug with time. But, if any of them keep on persisting, consult your doctor.

More common side effects include:

  • stuffy nose
  • redness of the neck, face, upper chest, and arms
  • sneezing

Less commonly occurring side effects include:

  • Diarrhea
  • Pain in stomach, back or eye
  • Congestion
  • Ejaculation problem
  • Fast heartbeat
  • Dry or sore mouth or throat
  • Face swelling
  • Muscle stiffness or pain in joints
  • Itching skin
  • Acid or sour stomach or chest
  • Loss of appetite
  • Sleeplessness and drowsiness
  • Shivering, cough or fever
  • Feeling of discomfort
  • Stomach discomfort
  • Swollen joints
  • Changes in vision or dim vision

Besides these, Vardenafil may also be associated with some long term effects. These include:

  • Hypersensitivity effects: allergic reactions.
  • Nervous system effects: sleep disorder, headache, amnesia, dizziness, seizure.
  • Genitourinary effects: hematospermia, penile hemorrhage, increased erection.
  • Ocular effects: eye discomfort, photophobia, visual color distortions or disturbances including vision loss, eye pain, increase in intraocular pressure, conjunctivitis.
  • Cardiovascular effects: myocardial infarction, ischemic attack, hypertension, tachycardia, sudden cardiac death, cerebrovascular hemorrhage, palpitation.
  • Respiratory effects: sinusitis, rhinitis, sinus or nasal congestion
    Dermatologic effects: photosensitivity reaction, erythema, angioedema, rashes, allergic edema.
  • Renal effects: increase in the levels of creatinine kinase.
    Hepatic effects: Increase in transaminases, and gamma-glutamyl-transferase.
  • Gastrointestinal effects: nausea, diarrhea, dyspepsia, abdominal and gastrointestinal pain, dry mouth.
  • Musculoskeletal effects: back pain, increased muscle cramping and tone.

Vardenafil overdose

  • If you overdose the drug contact with your doctor or pharmacist for symptomatic and supportive measures.
  • The symptoms of overdose include back or muscle pain, abnormal vision.

Vardenafil missed dose

  • It is not applicable in this case.

Does Vardenafil have any interaction with other drugs

Vardenafil may interact with one of the following drugs. Care should be taken when you are taking these medications together.

  • Drugs for the treatment of chest pain (e.g. nitrates such as isosorbide, nitroglucerin)
  • Recreational drugs called “poppers” consisting of amyl or butyl nitrite
  • Drugs to treat high blood pressure or a prostate disorder (alpha blocker medication) including terazosin (Hytrin), prazosin (Minipress), doxazosin (Cardura), alfuzosin (Uroxatral),  tamsulosin  (Flomax)
  • Drugs for treating erectile dysfunction-ED or pulmonary hypertension (such as tadalafil, sildenafil)
  • Drugs for treatment of tuberculosis i.e., isoniazid
  • Antidepressant medications like nefazodone
  • Antibiotic such as erythromycin (Erythrocin, Pediazole), telithromycin (Ketek), dalfopristin/quinupristin (Synercid), or clarithromycin (Biaxin)
  • Antifungal medication such as ketoconazole (Nizoral), itraconazole (Sporanox), or voriconazole (Vfend); miconazole (Oravig),
  • Drugs for high blood pressure or a prostate disorder, including prazosin (Minipress), terazosin (Hytrin), doxazosin (Cardura), alfuzosin (Uroxatral), tamsulosin (Flomax)
  • Heart or blood pressure medication such as verapamil (Covera, Calan, Verelan, Isoptin), nicardipine (Cardene), or diltiazem (Dilacor, Tiazac, Cardizem)
  • Drugs that alter hyeart rhythm such as quinidine (Quin-G), amiodarone (Pacerone, Cordarone), procainamide (Pronestyl, Procan), or sotalol (Betapace)
  • Drugs for HIV/AIDS including such as saquinavir (Invirase), delavirdine (Rescriptor), indinavir (Crixivan), atazanavir (Reyataz), fosamprenavir (Lexiva), or ritonavir (Kaletra, Norvir)

This list of drugs interacting with Vardenafil is not complete and other drugs may also interact with it. Always consult your doctor about the medications you use.

Does Vardenafil have any interaction with diseases

It has been suggested that Vardenafil should be administered in certain diseases very cautiously due to its interaction with the diseased state. These are as follows:

  • Vardenafil should not be used in cases when the sexual activity is not recommended due to underlying cardiovascular status.
  • The drug should be used very cautiously by patients having deformed penis or by patients suffering from conditions that predispose them to multiple myeloma, sickle cell anemia, or leukemia.
  • Vardenafil use is prohibited in patients with known retinal disorders, including retinitis pigmentosa.
  • The use of Vardenafil is not recommended in patients with severe hepatic insufficiency.
  • Avoid use of Vardenafil in patients on renal dialysis.
  • Patients with underlying NAION (non-arteritic anterior ischemic optic neuropathy, a rare condition that causes decreased vision, and even permanent loss of vision) risk factors could be adversely affected by use of Vardenafil.
  • Vardenafil provides no protection against sexually transmitted diseases and hence proper counselling of patients required.
  • Combination therapy of Vardenafil with other erectile dysfunction therapies is usually contraindicated.
  • Concomitant use of Vardenafil with alpha-blockers can drastically lower the blood pressure (hypotension) and hence should be avoided.
Vardenafil disease interaction.

Vardenafil disease interaction.

Where can I get more information

Your pharmacist or health care provider can provide more information about Ezetimibe.

Clinical research and current scenario of the drug

  • Placebo-controlled studies have suggested a dose effect in the occurence of some adverse reactions (dyspepsia, headache, nausea, flushing, and rhinitis) over the 5 mg, 10 mg, and 20 mg doses of Vardenafil.
  • Double-blind, placebo-controlled studies of patients with diabetes mellitus have demonstrated significant improvement in erectile function in aprospective-dose (10 and 20 mg Vardenafil).
  • In some patients the use of the drug is not recommended due to lack of controlled clinical data on the safety or efficacy:
  • Renal disease requiring dialysis
  • Retinal disorders, including retinitis pigmentosa
  • Severe cardiac failure
  • Unstable angina; hypertension; hypotension; recent history of stroke, or arrhythmia
  • Severe hepatic impairment
  • Myocardial infarction
References from chemical, biological and toxicological databases

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Filgrastim, drug class, uses, strength, side effects, mechanism of action
Esomeprazole, drug class, uses, strength, side effects, mechanism of action

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Filgrastim

Jun 13 2015 Published by under Medicines

What is Filgrastim 

  • Filgrastim is a synthetic pharmaceutical analogue of naturally occurring granulocyte colony-stimulating factor(G-CSF).

Generic and brand name of Filgrastim

  • The drug is available under generic name Filgrastim and brand names Filcad, Imumax, Neukine, Neupogen, Grafeel, Emgrast, Religrast, Zarzio or Zarxio and Nufil.
  • The Filgrastim is marketed in by Cadila Pharmaceuticals, Abbott Laboratories, Dr. Reddys Laboratories, Intas pharmaceuticals, Novartis, Biocon etc.

What is the source of drug (natural or synthetic)

  • Filgrastim is a synthetic (man-made) pharmaceutical antineutropenic and hematopoietic agents.

What does Filgrastim do

Why is this medication prescribed?

  • Filgrastim is a granulocyte colony-stimulating factor (G-CSF) analogue, which is principally used to enhance the growth, differentiation and proliferation of granulocytes by stem cells.
  • Granulocytes (neutophils, PMN, mast cells, eosinophils and basophils) are key cells of immune system and help to protect body against diseases and foreign invaders.
  • Filgrastim is generally used in cancer patients (acute myeloid leukaemia) who are receiving chemotherapy, or in patients undergoing bone marrow transplants or in patients under condition of severe chronic neutropenia (low number of neutrophils in the blood).
  • Since chemotherapy weakens the patient immune system and decrease the number of neutrophils thus increases the chances of infections. Filgrastim works by helping the body by stimulating the proliferation and differentiation of granulocytes (including neutrophils), thus protect the body from infections.
  • The drug is also used to increase the number of stem cells as well as to treat low white blood cells count in case of patients undergoing bone marrow transplants or under condition of severe chronic neutropenia.
  • The drug is also used for blood preparation for leukapheresis, (a process whereby white blood cells are removed from the blood in the body and returned back following chemotherapy).
  • Filgrastim is also used to enhance the survival in patients undergoing or receiving radiation therapy.
Clinical Uses of Filgrastim.

Clinical Uses of Filgrastim.

Pharmacophore structure: Information about the chemical structure of the drug

  • Filgrastim chemically belongs to the class of organic compounds known as carboxylic acid derivative. The detailed chemical classification of Filgrastim is as follows.
Kingdom Organic compounds 
Super Class Organic Acids
Class Carboxylic Acids and Derivatives
Sub Class Amino Acids, Proteins , Peptides, and Analogues
Direct Parent Peptides/Proteins

 Chemical information of the drug

  • Filgrastim is a synthetic pharmaceutical recombinant protein of 175 amino acid (non-pegylated human granulocyte colony stimulating factor analogue).
  • The sequence of Filgrastim is identical to its natural sequence as predicted from DNA, except N-terminal methionine which is needed for its expression in bacterial host.
  • It is synthesized using recombinantDNA technology in bacterial strain of E. coli.
  • The compound has molecular formula C845H1343N223O243S9 and the molecular weight of 18.8 Da.
  • The melting point of Filgrastim is 60°C.
  • The hydrophobicity and isoelectric point of Filgrastim is 209 and 5.65, respectively.

Filgrastim strengths

What is the available strength of the drug?

  • Filgrastim is available in solution (liquid) form in vials and pre filled syringes for intravenous and subcutaneous administration.
  • The drug can be injected directly into the skin or into a vein.
  • Filgrastim is available in different dosage strength of 300 µg/ 0.5 ml or ml and 480 µg/0.8 ml or 1.6 ml.

How does Filgrastim work

How the medicine works (mode of action)?

  • Filgrastim is an antineutropenic and hematopoietic agent that enhances the production of granulocytes.
  • It acts on hematopoietic cells as an analogue of granulocyte colony-stimulating factor(G-CSF) and binds to specific cell surface receptors.
  • Following binding Filgrastim stimulates the proliferation, differentiation and maturation of committed progenitor cells.
  • It also stimulates the release and maturation of neutrophils from storage pool of bone marrow cells.
  • Apart from this, Filgrastim also enhances the phagocytic activity of mature adult neutrophils.
  • In patients receiving chemotherapy or radiation therapy Filgrastim reduces the duration of neutropenic state by enhancing the neutrophils recovery.
Filgrastim: Mode of action.

Filgrastim: Mode of action.

Recommended doses of Filgrastim

The Filgrastim is available in ready to use solution form and the dosage varies depending upon the diseases status.

  • The initial usual dose of Filgrastim for adult patient with Neutropenia Associated with Chemotherapy is 5 mcg/kg/day either as subcutaneous infusion / or short intravenous infusion (15 to 30 minutes)/or subcutaneous or intravenous infusion.
  • The initial usual dose of Filgrastim for adult patient with Bone Marrow Transplantation is10 mcg/kg/day either as an intravenous infusion of 4 or 24 hours, or continuous 24 hour subcutaneous infusion.
  • The initial usual dose of Filgrastim for adult patient with Peripheral Progenitor Cell Transplantation is 10 mcg/kg/day either as subcutaneous infusion or as a bolus or a continuous infusion, for a minimum period of 4 days. The treatment begins before the first leukapheresis procedure and scheduled until the last leukapheresis.
  • The initial usual doses of Filgrastim for adult patient with Congenital Neutropenia are 6 mcg/kg subcutaneously (twice a day), while 5 mcg/kg subcutaneously once a day in case of Idiopathic or Cyclic Neutropenia.
  • The initial usual dose of Filgrastim for pediatric use in patients with Congenital Neutropenia are 6 mcg/kg subcutaneously (twice a day), while 5mcg/kg subcutaneously once a day in case of Idiopathic or Cyclic Neutropenia.
  • The initial usual dose of Filgrastim for pediatric use for Neutropenia Associated with Chemotherapy is 5 mcg/kg/day either as subcutaneous bolus injection, or short intravenous infusion (15 to 30 minutes) or by continuous subcutaneous or intravenous infusion.

It is recommended that Filgrastim should not be administered earlier than 24 hours following cytotoxic chemotherapy.

A complete blood count (CBC) and platelet count should be monitored before instituting therapy, during the therapy.

Bone marrow and cytogenetic evaluations should also be performed throughout the duration of treatment, particularly in case of congenital neutropenia.

However, the represented dose schedule can vary according to patient response and can change on the basis of CBC count or other routine tests. Treatment should continue until disease progression or unacceptable toxicity occurs.

When should I discontinue, withhold or modify the dose of Filgrastim

  • The dose of Filgrastim should be adjusted based on the patient’s clinical status, course and absolute neutrophil count (ANC).
  • The data for use of Filgrastim is contraindicated in case of severe renal impairment as well as patient undergoing dialysis.
  • The drug is also not recommended in patients with active liver disease or persistent liver dysfunction or abnormal function.
  • The use of the drug is also restricted in patients who are hypersensitive to the Filgrastim.
  • In case of pre-existing gallbladder disease, the Filgrastim use is not recommended.
  • The use of Filgrastim has not been evaluated in case of hepatic impairment; however it is necessary that the condition should be monitored very cautiously while using higher dosage.

What are the pharmacokinetic properties of the drug

  • Following administration, Filgrastim does not accumulate and follows first order absorption pharmacokinetic without apparent concentration dependence.
  • It has been observed that following subcutaneous injection of 3.45 mcg/kg and 11.5 mcg/kg of Filgrastim the maximum serum concentration is 4 and 49 ng/mL.
  • The peak plasma concentration of Filgrastim is achieved within 2 to 8 hours.
  • The absolute bioavailability of Filgrastim is approximately 62% and 71% for 375 mcg and 750 mcg doses respectively.
  • Pharmacokinetic studies with Filgrastim have shown that following administration is primarily eliminated by the kidney.
  • Besides kidney, the drug is also eliminated by neutrophils/neutrophils precursors. This route of elimination involves binding of the growth factor receptor, internalization, and subsequent degradation inside the cells.
  • The peak plasma level of drug is appeared within 6-8 hours following administration of the drug.
  • The bioavailability of Filgrastim is increased significantly to 35% under fed conditions as compared to fasting.
  • The details regarding protein binding, metabolism and toxicity of drug was not reported.
  • Filgrastim is primarily eliminated by the kidney and neutrophils/neutrophils precursors. The latter presumably involves binding of the growth factor to the G-CSF receptor on the cell surface, internalization of the growth factor-receptor complexes via endocytosis, and subsequent degradation inside the cells.
  • Following absorption the majority (~90%) of the drug is protein bound to plasma.
  • The distribution volume of the drug in healthy people and cancer patients is 150 mL/kg.
  • The average elimination half-life of Filgrastim in healthy subjects and cancer patients is near 3.5 hours.
  • No significant relationships were observed between the drug absorbance and clearance to patient age, body weight or gender.

Which pregnancy category (A; B; C; D; X) has been assigned to Filgrastim

  • The Filgrastim is classified by US FDA pregnancy category: C
  • Due to lack of adequate and well-controlled studies the use and safety of Filgrastim in pregnant women is contraindicated and recommended only when potential benefit justifies the risk.
  • No adequate data is available on excretion of Filgrastim into human breast milk. However, the use of drug is not recommended in nursing mothers.

Due these facts caution should be exercised when taking Filgrastim during pregnancy.

How to take Filgrastim

  • Follow the instructions carefully as directed on prescription leaflet and take Filgrastim exactly as directed or exactly directed by your health care professional.
  • Do not change the dose of the drug as prescribed by your doctor.
  • It is also recommended to take drug at almost the same time every day.
  • If you have any queries about the drug immediately consult to your doctor to explain any part you do not understand.       
  • If you use Filgrastim at home, ask your doctor beforehand about the technique of using it.
  • Filgrastim should be removed from the refrigerator and kept at room temperature for 30 minutes prior to its use.
  • Shaking the vial or syringe of Filgrastim is not recommended due to the formation of foam.
  • Discoloured, particulate or cloudy solution of Filgrastim should not be used.
  • Damaged or cracked vials/syringes of Filgrastim should be disposed off.
  • Only disposable syringes and needles should be used for the injection of Filgrastim.

How to store the drug

  • Filgrastim is stored in the refrigerator at 2° to 8°C (36° to 46°F).
  • Do not freeze or store the medicine at extreme cold too.
  • The drug should be thawed in the refrigerator if it gets frozen. Repeated freezing should not be allowed.
  • Discard Filgrastim if exposed to room temperature for more than 24 hours.

How to dispose the medicine

  • Throw away outdated or no longer used medicine.
  • Also dispose the old medicine after the expiration date.
  • Talk to your pharmacist about the proper disposal of your medication.

Does Filgrastim has approval from government / FDA /or any other related agencies

  • Filgrastim has received its official approval from US Food and Drug Administration (FDA) in February 1991 to treat neutropenia (low white blood cells).

Other uses of the drug

  • Filgrastim may also be used for reducing the chances of infection in HIV infected individuals.
  • It also decreases infection in the people who are on medications that lowers the neutrophils count.
  • Filgrastim is also prescribed for the treatment of cancer of white blood cells (acute myeloid leukemia).
  • Filgrastim is also sometimes recommended for the treatment of myelodysplastic syndrome wherein blood cells are either poorly formed or are dysfunctional.
  • Filgrastim may also be used for other cases not mentioned here. It is advisable to ask your doctor or pharmacist for more information.

What special dietary precautions should I follow

  • It is generally recommended to continue with the normal diet unless and until asked by your doctor.

What special precautions should I follow?/ What should I avoid while using Filgrastim

  • First of all inform your doctor if you are allergic to Filgrastim products or any of the ingredients present in the Filgrastim product or any medication made from coli  bacteria. Ask your pharmacist or check the prescription leaflet carefully for a list of the ingredients.
  • It is advisable to discuss with your doctor and pharmacist about what prescription and non-prescription medications, vitamins, and nutritional supplements you are taking or plan to take.
  • Tell your doctor if you are being treated or have recently been treated with radiation therapy.
  • Inform your doctor if you are pregnant or plan to become pregnant. Tell your doctor if you are breastfeeding.
  • Inform your doctor if you are having surgery, including dental surgery.
  • It is generally recommended to avoid vaccination while you are on Filgrastim medication.

Filgrastim side effects

  • Filgrastim may be associated with a number of side effects. Some of the effects can be more serious and others less severe. A person may not show all the side effects but may be one or a few.
  • Some people may develop allergic reactions on taking Filgrastim.
  • A person should get the emergency help immediately if he shows any sign of allergic reaction. These may include
  • Swelling on the body parts including throat, lips, tongue and face
  • Hives
  • Difficulty in breathing

In case of serious side effects, the use of drug should be withdrawn instantaneously. Side effects that may be serious are as follows:

  • Fever
  • Sore throat
  • Chill
  • Bleeding in nose and gums
  • Abdominal or stomach pain
  • Nausea
  • Vomiting
  • Extreme weakness
  • Rapid breathing
  • Sore in the mouth
  • Loss of appetite
  • Difficulty in breathing
  • Headache
  • Signs of flu
  • Dizziness
  • Paralysis
  • Prolonged bleeding in the cuts or wounds
  • Difficulty in urination
  • Blood during cough

Some of the effects may be less serious and include:

  • Swelling or redness at the place of injection
  • >Headache
  • Constipation
  • Itching
  • Skin rashes
  • Feeling of tiredness
  • Diarrhea
  • Pain in bones
  • Hair loss
  • Body or muscle ache

This list of side effects is not complete. Other side effects may also occur. In some cases side effects vanish during treatment and need no medical care. Your doctor would suggest you the ways to lessen the side effects. Consult your doctor in case of any query or if the side effects continues.

Filgrastim overdose

What should I do in case of overdose?

  • Overdose usually occurs when someone by mistake or deliberately takes more than the prescribed limit of this medication.
  • There is no specific treatment for Filgrastim overdose.
  • In case of overdose, contact with your doctor or emergency room immediately.
  • Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Filgrastim missed dose

What should I do in case of missed a dose?

  • In case of missed dosage, take it as soon as you remember and maintain a regular dosing schedule.
  • Skip the missed dose if it is almost time for your next scheduled dose. Keep in mind not to use a double dose to make up a missed dose.

Does Filgrastim have any interaction with drugs

  • Due to lack of controlled trial studies of Filgrastim interactions, no formal data is available. However, it has been suggested that precautions should be taken while taking any of the drug that can stimulate release, activation or proliferation of neutrophils. Therefore, caution should be taken when co administrating the Filgrastim with one of the following drugs.
  • It has been observed that enhanced hematopoietic activity of bone marrow may be associated with transient positive bone imaging changes with transient positive bone imaging changes. This fact should be kept in mind when interpreting bone imaging results of patients taking Filgrastim.
  • This information is not complete  and  if you start any new medication, first consult your doctor or pharmacist.

Does Filgrastim have any interaction with Diseases

It has been observed that Filgrastim consumption may potentiate or initiate the following medical complications (disease):

  • Acute Respiratory Distress Syndrome (ARDS): It has been observed that continuous use of Filgrastim can cause Acute respiratory distress syndrome (ARDS). It is advisable to discontinue Filgrastim in patients with ARDS or if patient develop respiratory distress, fever and lung infiltrates should be monitored for ARDS.
  • Splenic Rupture: Filgrastim consumption may also cause splenic rupture and fatal cases can occur. Patients treated with Filgrastim should be discontinue and diagnose properly if feeling upper abdominal or shoulder pain.
  • Tumor Growth Stimulatory Effects on Malignant Cells: Clinical studies with Filgrastim suggested that Filgrastim acts on tumor cell lines, thus can acts as a growth factor for any tumor type i.e. Myeloid malignancies and myelodysplasia.
  • Allergic Reactions: It has been observed that Filgrastim administration can cause serious allergic reactions including anaphylaxis. It can occur on either initial exposure or during subsequent treatment. It bis generally recommended to permanently discontinuing Filgrastim in patients with serious allergic reactions.
  • Use in Patients with Sickle Cell Disease: Filgrastim use in Sickle Cell Disease may cause severe and sometimes fatal sickle cell crises. It is advisable to keep the potential risks and benefits into consideration prior to the administration of Filgrastim.

Where can I get more information

Your pharmacist can provide more information about Filgrastim.

Clinical research and current scenario of the drug

  • Randomized, placebo-controlled, double-blind experiment in patients suffering from nonmyeloid malignancies has shown the efficacy and safety of Filgrastim in lowering the chances of infection.
  • Randomized, multi-center, placebo-controlled, double-blind experiments in patients of acute myeloid leukaemia(AML) have revealed role of Filgrastim in decreasing the fever, neutrophils recovery time after chemotherapy of patients.
  • The effectiveness of Filgrastim in diminishing the extent of neutropenia in patients inflicted with nonmyeloid malignancies has been established in randomized control experiments.
  • Studies have also indicated the role of Filgrastim in mobilization of peripheral blood progenitor cells that can be collected in a procedure wherein white blood cells are separated from the sample of blood.

 References from chemical, biological and toxicological database

Warfarin, uses, strength, side effects, mechanism of action
Vardenafil, uses, strength, side effects, mechanism of action

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Warfarin

Jun 13 2015 Published by under Medicines

What is Warfarin

  • Warfarin is a drug that is used for the treatment of existing blood clots and to prevent new blood clots formation inside the body.
Warfarin : Structure and chemical information.

Warfarin : Structure and chemical information.

What is the generic and brand name of the drug

  • The drug is available under generic name Warfarin or Warfarin sodium and brand names Jantoven, CoumadinUniwarfin,

What is the source of the drug (natural or synthetic)

  • Warfarin is a synthetic (man-made) pharmaceutical anticoagulant that acts by inhibiting vitamin K-dependent coagulation factors.

What does Warfarin do

  • Warfarin is used to treat or prevent venous thrombosis (swelling and blood clot in a vein) to exclude chances of further spreading of the clot
  • The drug is also prescribed for patients suffering from pulmonary embolism (a blood clot in the lung) to lower the risk of further embolism.
  • Warfarin is also recommended for people with irregular and rapid heartbeat (atrial fibrillation) or artificial heart valves to minimize the risk factor of strokes, and also for people who have had a heart attack.
  • The drug also is helpful in some of the orthopedic surgeries like replacement of hip or knee to prevent formation of blood clots.
  • During the treatment of coronary heart disease, the drug find application in preventing closure of coronary artery stents ( tube-shaped device placed in the coronary arteries supplying blood to the heart, to keep the arteries open) due to clotting.

Pharmacophore structure: Information about the chemical structure of the drug

Warfarin chemically belongs to the class of organic synthetic compounds known as 4-hydroxycoumarins that contain one or more hydroxyl groups at C4-position in the coumarin skeleton. The detailed chemical classification of Warfarin is as follows.

Kingdom Organic compounds 
Super Class Phenylpropanoids and polyketides 
Class Coumarins and derivatives 
Sub Class Hydroxycoumarins 
Direct Parent 4-hydroxycoumarins 

Chemical information of the drug

  • Warfarin sodium (Coumadin) is a synthetic pharmaceutical class of organic compound known as 4-hydroxycoumarins.
  • It is chemically known as 3-(α-acetonylbenzyl)-4- hydroxycoumarin.
  • It is available as sodium salt with a molecular formula C19H15NaO
  • Molecular weight of Warfarin sodium is 330.31 g/mol and melting point is 161°C.
  • Warfarin sodium occurs as a white, odorless, crystalline powder
  • It is very soluble in water, freely soluble in alcohol, and very slightly soluble in chloroform and ether.
  • It has a pKa (the number that denotes the pH) of 5. 08.

Warfarin available strength

  • Warfarin is available for oral administration in tablet form or in the form of injections.
  • Warfarin tablets are available in different dosage strength which contain different dosage of Warfarin sodium (1 mg, 2 mg, 2.5 mg, 3 mg, 4 mg, 5 mg, 6 mg, 7.5 mg and 10 mg) respectively.
  • The Warfarin tablets contain a very small amount of colour additives for product identification.
  • Each tablet shows strength imprinted on one side, and is scored so that it can be broken easily in two halves to adjust the dose as directed by the doctor.
  • Each strength of tablet is depicted by different colour to differentiate between them: 0.5 mg tablets are white, 1 mg tablets are brown, 3 mg tablets are blue and 5 mg tablets are pink.
  • The formulation contains Warfarin Sodium as the active ingredient and Lactose, starch, and magnesium stearate as the inactive ingredients.
  • Powder for injection is also available as 5 mg/vial.

How does Warfarin work?

  • Warfarin acts by antagonizing vitamin K and reduction of the factors involved directly or indirectly in blood clotting.
  • Warfarin brings about the inhibition of vitamin K reductase enzyme, which results in decrease pool of reduced form of vitamin K.
  • Reduction in vitamin K (reduced) lowers down the glutamate residues carboxylation in the N-terminal regions of coagulant proteins.
  • This inhibits the synthesis of vitamin K-dependent coagulation factors (factors II, VII, IX, and X) and anticoagulant proteins (regulatory factors) C and S by the liver.
  • Decrease in the coagulation factors causes lowering in the prothrombin levels.
  • Reduce prothrombin affects production of thrombin and fibrin bound thrombin,which ultimately reduces blood clotting.
Warfarin : Mode of action.

Warfarin : Mode of action.

Warfarin recommended doses

  • Warfarin may be taken along with or without food.
  • Warfarin dosage in patients suffering from liver and kidney dysfunction need to be lowered as it may affect its metabolism by the liver and excretion by the kidneys.
  • Regular blood tests (International Normalized Ratio (INR) or prothrombin time (PT)) have to be performed to determine the effect of Warfarin and to adjust dosing.
  • The dosage and administration of the drug has to be individualized for each patient according to the patient’s INR response to the drug.
  • The drug treatment initially is started at 2 to 5 mg dosage per day and then adjusted on the basis of INR tests and the diseased state.

Congestive Heart Failure:

  • Initial: 2 to 5 mg orally or intravenously per day for 1 to 2 days, then adjusted according to results of the INR or PT.
    Maintenance: 2 to 10 mg orally or intravenously once a day.

Myocardial Infarction:

  • Initial: 2 to 5 mg orally or intravenously per day for 1 to 2 days, then adjusted according to results of the INR or PT.
    Maintenance: 2 to 10 mg orally or intravenously once a day.

Pulmonary Embolism — First Event:

  • Initial: 2 to 5 mg orally or intravenously per day for 1 to 2 days, then adjusted according to results of the INR or PT.
    Maintenance: 2 to 10 mg orally or intravenously once a day.

Pulmonary Embolism — Recurrent Event:

  • Initial: 2 to 5 mg orally or intravenously per day for 1 to 2 days, then adjusted according to results of the INR or PT.
    Maintenance: 2 to 10 mg orally or intravenously once a day.

Atrial Fibrillation:

  • Initial: 2 to 5 mg orally or intravenously per day for 1 to 2 days, then adjusted according to results of the INR or PT.
    Maintenance: 2 to 10 mg orally or intravenously once a day.

Deep Vein Thrombosis — First Event:

  • Initial: 2 to 5 mg orally or intravenously per day for 1 to 2 days, then adjusted according to results of the INR or PT.
    Maintenance: 2 to 10 mg orally or intravenously once a day.

Deep Vein Thrombosis — Recurrent Event:

  • Initial: 2 to 5 mg orally or intravenously per day for 1 to 2 days, then adjusted according to results of the INR or PT.

Deep Vein Thrombosis Prophylaxis after Hip Replacement Surgery:

  • Initial: 2 to 5 mg orally or intravenously per day for 1 to 2 days, then adjusted according to results of the INR or PT.
    Maintenance: 2 to 10 mg orally or intravenously once a day.
  • Maintenance: 2 to 10 mg orally or intravenously once a day.

Deep Vein Thrombosis Prophylaxis after Knee Replacement Surgery:

  • Initial: 2 to 5 mg orally or intravenously per day for 1 to 2 days, then adjusted according to results of the INR or PT.
    Maintenance: 2 to 10 mg orally or intravenously once a day.

Thromboembolic Stroke Prophylaxis:

  • Initial: 2 to 5 mg orally or intravenously per day for 1 to 2 days, then adjusted according to results of the INR or PT.
    Maintenance: 2 to 10 mg orally or intravenously once a day.

Chronic Central Venous Catheterization:

  • 1 mg orally or intravenously per day with initiation of therapy three days prior to the insertion of the catheter.

Prosthetic Heart Valves — Mechanical Valves:

  • Initial: 2 to 5 mg orally or intravenously per day for 1 to 2 days, then adjusted according to results of the INR or PT.
  • Maintenance: 2 to 10 mg orally or intravenously once a day.

Prosthetic Heart Valves – Tissue Valves:

  • Initial: 2 to 5 mg orally or intravenously per day for 1 to 2 days, then adjusted according to results of the INR or PT.
  • Maintenance: 2 to 10 mg orally or intravenously once a day.
  • The duration of therapy to be continued depends on individual patient. However, the drug therapy should be continued until the risk of thrombosis and embolism has passed.

When should I discontinue, withhold or modify the dose of Warfarin

  • Warfarin therapy should be discontinued or modified in some of the dental and surgical procedures.
  • Warfarin is contraindicated in pregnant women except in cases of pregnant women who have mechanical heart valves and are prone to thromboembolism.
  • Avoid Warfarin as initial therapy in patients with heparin-induced thrombocytopenia or thrombocytopenia.
  • Avoid Warfarin under following health conditions, including:
  • High blood pressure
  • Hypersensitivity
  • Bleeding disorder, such ashaemophilia
  • Increased risk of bleeding inside the body such as in peptic ulcer, CNS haemorrhage, dissecting aorta, or over bleeding of the gastrointestinal, genitourinary or respiratory tracts;
  • Threatened abortion
  • Patients with conditions such as dementia, alcoholism, psychosis
  • Hemorrhagic tendencies
  • Spinal puncture and other diagnostic or therapeutic procedures with potential for uncontrollable bleeding

What are the pharmacokinetic properties of the drug

  • Pharmacokinetic studies suggested that after oral administration, Warfarin is rapidly absorbed with considerable inter-individual variations.
  • The elimination of Warfarin is almost entirely by metabolism. Very little Warfarin is excreted unchanged in urine. The metabolites are principally excreted into the urine; and to a lesser extent into the bile.
  • Warfarin is stereo-selectively metabolized by hepatic cytochrome P-450 (CYP450) microsomal enzymes to inactive hydroxylated metabolites (predominant route) and by reductases to reduced metabolites (Warfarin alcohols)
  • Warfarin distributes into a relatively small apparent volume of distribution of about 0.14 L/kg.
  • The bioavailability of the drug ranges from 79-100% (oral).
  • It has been observed that following a dose of Warfarin maximum (or peak) serum concentration is achieved within the first 4 hours.
  • Following absorption the majority (99%) of the drug is bound to plasma proteins (primarily to albumin).
  • The average median plasma half-life of Warfarin is approximately 40 hours.

Which pregnancy category (A; B; C; D; X) has been assigned to Warfarin

  • The Warfarin is classified by US FDA pregnancy category: D for women with mechanical heart valves and prone to thromboembolism; category X in case of other pregnant populations
  • Warfarin intake during pregnancy results in congenital malformations such as fetal haemorrhage, Warfarin embryopathy, spontaneous abortion and fetal mortality.
  • No studies have been done to evaluate the reproductive or developmental effects of Warfarin in animals.
  • No studies indicate the excretion of Warfarin in human breast milk.

How to take Warfarin

  • Warfarin is available in tablet form for oral administration by mouth with or without food usually once a day. .
  • Follow the instructions carefully as directed on prescription leaflet and take Warfarin exactly as directed. Take the medication regularly, even if you feel well until the time prescribed by your doctor.
  • Dose should not be changed even in case of skipping the dose two or more days continuously.
  • Do not change the dose as prescribed by your doctor, or stop abruptly as the dosage is based on your health condition, laboratory tests (such as INR), and treatment response.
  • A regular and balanced diet is recommended while consuming Warfarin.
  • Avoid any modification in the food habits especially related to vitamin k as it may affect the working of the drug as well as treatment and dose.
  • Consult with the doctor in case you plan to diet.
  • It is also recommended to take drug at almost the same time every day.

The dose and schedule of Warfarin depends on various factors, including health conditions, medical background and associated diseases.

How to store Warfarin

  • Warfarin is stored at room temperature between 59 and 86 ° F (15 and 30 ° C).
  • The container should be tightly closed and away from excess heat, direct sun light and dampness.
  • Do not freeze or store the medicine at extreme cold too.
  • The medication should be kept out of the reach of children.

How to dispose Warfarin

  • Throw away unused and opened, outdated or no longer used container.
  • Also dispose the old medicine after the expiration date.
  • Talk to your pharmacist or waste disposal company about the proper disposal of your medication.
  • Do not pour the drug in the drain or flush it.

Does Warfarin has approval from government / FDA /or any other related agencies

  • Warfarin has received its official approval from US Food and Drug Administration (FDA) in June 1954.

Other uses of the drug

  • Warfarin may also be used for other uses not listed here. It is advisable to ask your doctor or pharmacist for more information.

What special dietary precautions should I follow

  • It is generally recommended to eat green leafy vegetables while you are on Warfarin medication.
  • However, enormous consumption of green leafy vegetables and certain vegetable oils which are rich source of vitamin K should be avoided as it interferes with the action of Warfarin.
  • Foods rich in vitamin K should not be removed entirely from the diet.
  • Follow a normal routine diet with similar levels of food every week to maintain the INR constant.
  • Consult your doctor about eating grapefruit and drinking grapefruit juice while taking Warfarin.
  • Do not make any change in the food habit without bringing it focus to your dietician.

What special precautions should I follow / What should I avoid while using Warfarin

It has been observed that person to person response or Warfarin is different and primarily dependent on their heredity or genetic make-up. Therefore, it is advisable that Warfarin prescription/administration should be taken under the guidance of your health care provider.Some common precautions which should be followed before taking Warfarin are as follows.

  • Do not use the medicine if you are hypersensitive to any of the ingredients. Ask your pharmacist or check the Medication leaflet or Guidance book for complete list of the ingredients.
  • It is advisable to discuss with your doctor and pharmacist about what prescription and nonprescription medications, vitamins, and nutritional and natural supplements you are taking or plan to take.
  • Talk with your doctor or pharmacist about what herbal or botanical products you are taking, especially St. John’s wort, coenzyme Q10 (Ubidecarenone), Ginkgo biloba, goldenseal, garlic, ginseng, and), 
  • Tell your doctor if you have or have ever had history of stomach or intestinal bleeding , low blood count or cancer ,diabetes, history of stroke, or “mini-stroke”, serious heart disease and kidney problems.
  • Tell your doctor if you are taking or plan to take any other medicines that increase your risk of bleeding, other medicines to prevent or treat blood clots and NSAIDs.
  • Tell your doctor if you are being treated or have recently been treated with chemotherapy or radiation therapy.
  • Inform your doctor if you are breastfeeding or pregnant or plan to become pregnant. Warfarin do not recommended for pregnant women (may harm the fetus).unless they have a mechanical heart valve.
  • Inform your doctor if you are taking birth control pills while taking Warfarin.
  • Inform your doctor having surgery, including dental surgery.
  • Avoid using tobacco products; smoking can significantly reduce the Warfarin effect.
  • Keep regular and timely visit with your doctor and routinely undergo for blood test like prothrombin test (reported as international normalized ratio) to check your body’s response to Warfarin.

When you start taking Warfarin, regularly refill your prescription , read the information carefully and discuss all your queries with your doctor or health care provider. For more details you can also visit Food and Drug Administration (FDA) website (http://www.fda.gov/downloads/Drugs/DrugSafety/ucm088578.pdf).

Warfarin side effects

The common side effects of Warfarin are as follows.

  • Abdominal or stomach pain, cramping and gas
  • Taste change
  • Dizziness
  • Chills or cold
  • Hair loss
  • Bloating etc.

If symptoms persist and become more severe consult your doctor immediately.

If you experience any of these symptoms, call your health care provider immediately

Some of the common signs that need to be addressed immediately to your health care provider comprise:

  • Allergy i.e. hives, rashes, itching.
  • Breathing/ swallowing difficulty
  • Severe chest pain or pressure
  • Swelling of the face, the hands, lower legs, throat, tongue, lips, ankles and eyes
  • Lack of energy/extreme tiredness
  • Nausea/vomiting
  • Flu like symptom and fever
  • Hoarseness
  • Infections
  • Yellowing of the skin or eyes
  • Loss of appetite
  • Ulcer etc

Warfarin Overdose

What should I do in case of overdose?

Some common symptoms of Warfarin overdose are as follows:

  • Spitting or coughing up blood. Coffee color stool
  • Continued oozing or bleeding from minor cuts or injuries
  • Yellowish eyes, pink, red, or dark brown urine.
  • Bloody or red, or tarry bowel movements
  • Excessive bleeding during menstrual period
  • Small, flat, round red spots under the skin
  • Unusual large bruising or bleeding
  • Try to avoid taking the overdose of the drug. If you overdose the drug contact with your doctor or pharmacist for symptomatic and supportive measures.
  • In case you or some other person has taken overdose of this medication contact your local poison control centre at 1-800-222-1222 or emergency room immediately.
  • Call local emergency services at 911 in case a patient collapses or faces difficulty in breathing.

Warfarin missed dose

What should I do in case of missed a dose?

  • In case of missed dosage, take it as soon as you remember and maintain a regular dosing schedule.
  • Skip the missed dose if it is almost time for your next scheduled dose. Keep in mind to not use a double dose to make up a missed dose

Warfarin interactions with other drugs

The Warfarin may interact with one of the following drugs. Care should be taken when you are taking these medications together.

  • Medications for asthma such as zafirlukast, montelukast and zileuton .
  • Medications for cholesterol such as atorvastatin and fluvastatin
  • Medications for narcolepsy such as armodafinil and modafinil
  • Medications for seizures such as phenobarbital, carbamazepine , phenytoin  and rufinamide Medications to treat tuberculosis such as rifampin and isoniazid
  • Medications used to treat cancer such as imatinib, capecitabine , , and nilotinib
  • Serotonin reuptake inhibitors (SSRIs) or selective serotonin and norepinephrine reuptake inhibitors (SNRIs).
  • Medications for digestive disorders such as famotidine, cimetidine , and ranitidine.
  • Medications for human immunodeficiency virus (HIV) infection such as fosamprenavir , amprenavir, atazanavir , efavirenz , etravirine, lopinavir/ritonavir, ,indinavir , nelfinavir etc.
  • Acyclovir , allopurinol , alprazolam etc
  • Antibiotics such as ciprofloxacin, norfloxacin sulfinpyrazone, erythromycin , clarithromycin , nafcillin, and tigecycline
  • Anticoagulants such as argatroban , bivalirudin , dabigatran , heparin, desirudin
  • Antifungals such as fluconazole , ketoconazole , posaconazole , terbinafine ,  miconazole ,  voriconazole
  • Antiplatelet medications such as cilostazol , , prasugrel, clopidogrel , dipyridamole and ticlopidine
  • Aspirin or aspirin-containing products and other nonsteroidal anti-inflammatory drugs such as diclofenac, celecoxib , diflunisal, fenoprofen , ibuprofen , indomethacin, mefenamic acid oxaprozin and sulindac
  • Antiarrhythmic medications such as amiodarone , propafenone and mexiletine.
  • Calcium channel blocking medications such as amlodipine, verapamil and diltiazem

This list do not comprises all the drugs that interact with Warfarin and there are many other drugs that can interact with Warfarin. If you start any new medication, first consult your doctor or pharmacist

Does Warfarin have any interaction with Diseases

It has been observed that some medical conditions (disease state) may also interact with Warfarin such as:

Diabetes: Diabetes predisposes the patient to increased hemorrhage in presence of Warfarin.

Warfarin : Structure and chemical information.

Warfarin : Structure and chemical information.

  • Bleeding: Patients with hemorrhagic diathesis (an inherited predisposition to abnormalities characterized by excessive bleeding), risks for bleeding, active ulceration, active bleeding, threatened abortion, cerebrovascular hemorrhage, deficiency in vitamin c and k, malnutrition, etc. are more prone to uncontrollable hemorrhage or bleeding complications during Warfarin therapy.
  • Liver diseases: Patients with hepatic impairment shows heightened response to Warfarin owing to decreased metabolism and defective hemostasis by impaired clotting factors synthesis via liver.
  • Hypertension: Patients of hypertension (malignant or severe, uncontrolled) are more prone to cerebral hemorrhage. 
  • Protein C Deficiency: It has been observed that Warfarin consumption may interfere with familial, hereditary,or clinical deficiencies of protein C . Since protein C deficiency may be associated with a hyper-coagulable state and an increased risk of the complication.
  • Renal dysfunction: It has been suggested that person suffered from renal impairment may demonstrate platelet defects and may be at increased risk for bleeding.
  • Decreased Response: Patients with edema, hypothyroidism, hereditary coumarin resistance, hyperlipidemia, or nephrotic syndrome may exhibit lower than expected hypo-prothrombinemic response to Warfarin.
  • Increased Response: Patients with a collagen vascular disease (e.g., systemic lupus erythematosus, rheumatoid arthritis, and scleroderma), congestive heart failure (especially decompensated disease), severe or prolonged diarrhea, fever, hyperthyroidism, malabsorption, or steatorrhea may exhibit greater than expected hypoprothrombinemic response to Warfarin.

Where can I get more information

Your pharmacist or health care provider can provide more information about Warfarin.

Clinical research and current scenario of the drug

  • Efficacy of Warfarin in reducing the risk of systemic thromboembo­lism has been shown in some randomized controlled clinical trials in patients of non-rheumatic Atrial Fibrillation (AF).
  • Clinical trials in patients suffering with both mitral stenosis and atrial fibrillation have shown them to be benefited from the use of Warfarin.
  • Randomized, open-label clinical trial of Warfarin in providing the thromboembolic-free interval in patients with mechanical prosthetic heart valves was more significant as compared with aspirin/ pentoxifylline and aspirin / dipyridamole -treated patients.
  • Open label clinical study has shown similar frequency of thromboembolism in patients with mechanical prosthetic heart valves receiving moderate or high Warfarin therapies with major bleeding in case of high intensity.
  • Randomized study with higher or lower intensities of Warfarin therapy has shown same frequency of thromboembolism in different groups of test patients with major haemorrhages in the higher intensity group compared to zero in the lower intensity group.
  • The Warfarin Re-Infarction Study has shown major bleeding episodes in patients receiving Warfarin than those receiving aspirin alone. Frequency of major bleeding reduced drastically in patients receiving aspirin and Warfarin while frequency of minor bleeding episodes was higher in the combined therapy group.

 References from chemical, biological and toxicological databases

Other medicines,
Fenofibrate, drug class, uses, strength, side effects, mechanism of action
Filgrastim, drug class, uses, strength, side effects, mechanism of action

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Fenofibrate

Jun 13 2015 Published by under Medicines

What is Fenofibrate

  • Fenofibrate is a synthetic compound, which aids to reduce blood cholesterol and triglycerides (fatty acids) levels.

Fenofibrate brand name

  • The drug is available under generic name Fenofibrate and brand names TriCor, Antara, Lofibra, and Lipofen.
  • The Fenofibrate is marketed by Lupin Pharma, Teva Pharmaceuticals, Northwind Pharmaceuticals, H2 Pharma and Carilion Material Management.

What is the source of the drug (natural or synthetic)

  • Fenofibrate is a synthetic (man-made) pharmaceutical antihyperlipidemic agent.

What does Fenofibrate do

Why is this medication prescribed?

  • Fenofibrate is an anti-hyperlipidemic class of drug, which means it reduces the amount of fatty or lipid substances such as cholesterol and triglycerides.
  • Usually, Fenofibrate is used in combination of low fat diet or exercise or other drugs as adjunctive therapy to reduce elevated total cholesterol, LDL cholesterol, apolipoprotein B, total triglycerides and triglyceride rich lipoprotein (VLDL) ( types of fatty acids which increase the risk of heart diseases) and to increase the amount of HDL (high-density lipoprotein; a type of fatty substance that decreases the risk of heart disease) in the blood.
  • The drug is usually prescribed for adult patients with primary hypercholesterolemia or mixed dyslipidemia (Fredrickson Types IIa and IIb) and hypertriglyceridemia (Fredrickson Types IV and V hyperlipidemia).
  • Fenofibric acid is the active metabolite ingredient of Fenofibrate responsible for enhancing the natural processes that expel cholesterol from the body.
Therapeutic effects of Fenofibrate.

Therapeutic effects of Fenofibrate.

Pharmacophore structure: Information about the chemical structure of the drug

Fenofibrate chemically belongs to the class of organic compounds known as benzophenones, a heterocyclic aromatic molecule which contains ketone attached to two phenyl groups. The detailed chemical classification of Fenofibrate is as follows.

Kingdom Organic compounds 
Super Class Benzenoids
Class Benzene and substituted derivatives
Sub Class Benzophenones
Direct Parent Benzophenones

Chemical information of the drug

  • Fenofibrate is a synthetic pharmaceutical benzophenones compound named as propan-2-yl 2-[4-(4-chlorobenzoyl)phenoxy]-2-methylpropanoate.
  • The compound has molecular formula C20H21ClO4 and the molecular weight of 360.83 g/mol.
  • The melting point of Fenofibrate is 79-82°C.
  • Fenofibrate is a white solid; granular or powder and practically insoluble in water.
  • It is slightly soluble in ethanol and methanol, while soluble in acetone, ether, benzene and chloroform.
  • The maximal solubility of Fenofibrate in water is ~ 0.42 mg/L at 25 °C. It is synthesized from 4-chloro-4-hydroxybenzophenone.

Fenofibrate dosage strengths

  • Fenofibrate is available for oral administration in tablet or a delayed release (long lasting) capsule form.
  • Fenofibrate is available in two dosage strength of 48 mg and 145 mg.
  • 48 mg tablet is yellow in colour and stamped with the “a” logo and code letter “FI”, while 145 mg tablet is imprinted with the “a” logo and code letter “FO”.
  • Each tablet contains sodium lauryl sulfate, sucrose, lactose monohydrate, silicified microcrystalline cellulose colloidal silicon dioxide, crospovidone, lecithin, microcrystalline cellulose, polyvinyl alcohol, sodium stearyl fumarate, titanium dioxide, talc, lecithin, and xanthan gum.

How does Fenofibrate work

How the medicine works (mode of action)?

Chemically Fenofibrate is made up of fenofibric acid linked to an isopropyl ester. The active moiety or component of Fenofibrate is fenofibric acid.

  • Laboratory studies with animal models suggested that Fenofibrate acts through activation of a key protein known as peroxisome proliferator activated receptor α (PPARα).
  • Peroxisome proliferator activated receptor α (PPARα) principally regulates the fatty acid and lipoprotein metabolism.
  • Fenofibrate lowers the blood cholesterol and other lipid levels by activating PPARα, which in turn activates lipoprotein lipase and reduces apoprotein C3.
  • Active lipoprotein lipase and reduced apoprotein C3 cause dramatic degradation (lipolysis) and elimination of triglyceride-rich particles from plasma.
  • Activation of PPARα also reduces very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) containing apoprotein B.
  • Apart from this PPARα also enhances the synthesis of apoproteins AI, AII, and high-density lipoprotein (HDL).
Fenofibrate: Mode of Action.

Fenofibrate: Mode of Action.

What are the recommended doses of Fenofibrate

The Fenofibrate is available in tablet form and the dosage varies depending upon the diseases status.

The usual doses of Fenofibrate for adult patient with Hyperlipoproteinemia Type IIa (Elevated LDL) are as follows.

  • Tricor (R): 145 mg (oral) once a day.
  • Antara (R): 130 mg (oral) once a day.
  • Lofibra (R) and others: 160 mg to 200 mg (oral) once a day with food
  • Lipofen (R): 150 mg (oral) once a day with food
  • Triglide (R): 160 mg (oral) once a day.
  • Fenoglide (R): 120 mg (oral) once a day with food
  • The usual doses of Fenofibrate for adult patient with Hyperlipoproteinemia Type IIb (Elevated LDL + VLDL) are as follows.
  • Tricor (R): 145 mg (oral) once a day.
  • Lofibra (R) and others: 160 mg to 200 mg (oral) once a day with food.
  • Antara (R): 130 mg (oral) once a day.
  • Triglide (R): 160 mg (oral) once a day.
  • Lipofen (R): 150 mg (oral) once a day with food.
  • Fenoglide (R): 120 mg (oral) once a day with food.

The usual doses of Fenofibrate for adult patient with Hyperlipoproteinemia Type IV (Elevated VLDL) are as follows.

  • Tricor (R): 48 to 145 mg (oral) once a day.
  • Lofibra (R) and others: 54 mg to 200 mg (oral) once a day with food.
  • Antara (R): 43 mg to 130 mg (oral) once a day.
  • Triglide (R): 50 mg to 160 mg (oral) once a day.
  • Lipofen (R): 50 mg to 150 mg (oral) once a day with food.
  • Fenoglide (R): 40 mg to 120 mg (oral) once a day with food.
  • The usual doses of Fenofibrate for adult patient with Hyperlipoproteinemia Type V (Elevated Chylomicrons + VLDL) are as follows.
  • Tricor (R): 48 to 145 mg (oral) once a day.
  • Lofibra (R) and others: 54 mg to 200 mg (oral) once a day with food.
  • Antara (R): 43 mg to 130 mg (oral) once a day.
  • Triglide (R): 50 mg to 160 mg (oral) once a day.
  • Lipofen (R): 50 mg to 150 mg (oral) once a day with food.
  • Fenoglide (R): 40 mg to 120 mg (oral) once a day with food.

However, the represented dose schedule can vary according to patient response and can be changed on the basis of repeated lipid levels determination at 4 to 8 weeks interval. Treatment should continue until disease progression or unacceptable toxicity occurs.

When should I discontinue, withhold or modify the dose of Fenofibrate

  • The use of Fenofibrate is contraindicated in case of severe renal impairment as well as patient undergoing dialysis.
  • The drug is also not recommended in patients with active liver disease or persistent liver dysfunction or abnormal function.
  • The use of the drug is also restricted in patients who are hypersensitive to the Fenofibrate or fenofibric acid.
  • In case of pre-existing gallbladder disease the Fenofibrate use is not recommended.
  • The use of Fenofibrate has not been evaluated in case of hepatic impairment; however, it is necessary that the condition should be monitored very cautiously while using higher dosage.

What are the pharmacokinetic properties of the drug

  • Fenofibrate is a prodrug, whose active chemical moiety is finofibric acid.
  • Following consumption, Fenofibrate is converted into fenofibric acid (active constituent of Fenofibrate computable in thecirculation) by acid hydrolysis.
  • Fenofibrate is well absorbed from the gastrointestinal.  However, due to insoluble nature the absolute bioavailability of fenofibrate cannot be determined.
  • Following administration the Fenofibrate is rapidly converted to fenofibric, which is subsequently conjugated with glucuronic acid.
  • Pharmacokinetic studies with Fenofibrate have shown that following oral administration about 60 % of the drug appeared in the urine, while 25% was excreted in the feces.  
  • The peak plasma level of the drug appears within 6-8 hours following administration of the drug.
  • The bioavaility of Fenofibrate is increased significantly to 35% under fed conditions as compared to fasting.
  • The peak plasma level of drug is observed after 4 hours of drug administration allowing once daily dosing.
  • Following absorption the majority (~90%) of the drug is protein bound to plasma.

Which pregnancy category (A; B; C; D; X) has been assigned to Fenofibrate

  • The Fenofibrate is classified by US FDA pregnancy category: C.
  • Due to lack of adequate and well-controlled studies, the use and safety of Fenofibrate in pregnant women is contraindicated and recommended only when potential benefit justifies the risk.
  • Laboratory animal studies have shown maternal toxicity of Fenofibrate at higher doses.
  • No adequate data is available on excretion of Fenofibrate into human breast milk. However, the use of drug is not recommended in nursing mothers.

Due these facts caution should be exercised when taking Fenofibrate during pregnancy.

How to take Fenofibrate

  • Fenofibrate is available in delayed/sustained release capsule form (long lasting action) for oral administration by mouth.
  • Fenofibrate sold under brand names Fenoglide, Lipofen, and Lofibra are prescribed with a meal, while other brands like Fibricor, antara, Tricor, Triglide, and Trilipix are usually prescribed with or without food.
  • Since food significantly increases drug absorption it is usually recommended on an empty stomach (at least 1 hour before or 2 hours after eating a meal or snack) once a day.
  • It is also recommended to take drug at almost the same time every day
  • Follow the instructions carefully as directed on prescription leaflet and take Fenofibrate exactly as directed on leaflet or by your health care professional.
  • Do not change the dose of the drug as prescribed by your doctor. Since, your doctor may decrease the dose of Fenofibrate depending upon adverse side effects or medication response.
  • If you have any queries about the drug immediately consult to your doctor to explain any part you do not understand.

How to store the drug

  • Fenofibrate is stored at room temperature 20° to 25°C (68° to 77°F).
  • The container should be tightly closed and away from excess heat, direct sun light and reach of children.
  • Do not freeze or store the medicine at extreme cold too.

How to dispose Fenofibrate

  • Throw away unused and opened, outdated or no longer used container.
  • Also dispose the old medicine after the expiration date.
  • Talk to your pharmacist about the proper disposal of your medication.

Does Fenofibrate has approval from government / FDA /or any other related agencies

  • Fenofibrate has received its official approval from US Food and Drug Administration (FDA) to treat medical complications such as primary hypercholesterolemia or mixed dyslipidemia (Fredrickson Types IIa and IIb) and hypertriglyceridemia (Fredrickson Types IV and V hyperlipidemia).

Other uses of the drug

  • Fenofibrate may also be used for other uses not listed here. It is advisable to ask your doctor or pharmacist for more detailed information regarding its use.

What special dietary precautions should I follow

  • It is generally recommended to avoid high fat/cholesterol diet and follow a routinely exercise regimen.
  • Follow a routine diet as prescribed by your dietician and avoid spicy foods.
  • For more details for additional dietary information please visit National Cholesterol Education Program (NCEP) website (http://www.nhlbi.nih.gov/health/public/heart/chol/chol_tlc.pdf.).

What special precautions should I follow/ What should I avoid while using Fenofibrate

  • First of all inform your doctor if you are allergic to any fenofibrate products or any of the ingredients present in the fenofibrate product. Ask your pharmacist or check the prescription leaflet carefully for a list of the ingredients.
  • It is advisable to discuss with your doctor and pharmacist about what prescription and nonprescription medications, vitamins, and nutritional supplements you are taking or plan to take.
  • Tell your doctor if you are being treated or have recently been treated with kidney, liver, or gall bladder disease.
  • Inform your doctor if you are alcoholic and have diabetes or hypothyroidism.
  • Inform your doctor if you are breastfeeding or pregnant or plan to become pregnant. Tell your doctor if you are breastfeeding.
  • Inform your doctor about the surgery you have undergone, including dental surgery.

Fenofibrate side effects

Long term controlled clinical trial studies with Fenofibrate suggested that it can cause side effects, which include:

  • Mild stomach pain /constipation/ diarrhea
  • Back pain, pain in arm and legs
  • Headache
  • Heartburn

Call immediately to your doctor in case of allergic reaction or if any of these symptoms are severe or do not go away.

If case you experience any of these symptoms, consult your health care provider instantly.

Fenofibrate rarely can cause breakdown of skeletal muscles, which can cause kidney failure. If you are feeling symptoms like weakness, muscles pain, unusual tiredness, dark coloured urine and fever call immediately your physician. Other serious side effects that may be serious are as follows.

  • Rashes, and hives
  • pain in the upper back between the shoulder blades or under the right shoulder
  • Stomach pain, particularly in the upper right part of the stomach
  • Breathing problems like shortness of breath or pain while breathing
  • Nausea and vomitting
  • Blood in cough
  • Peeling skin, swelling and redness

Stop taking medicine immediately if you are feeling such symptoms.

Fenofibrate overdose

  • Overdose usually occurs when someone by mistake or deliberately takes more than the prescribed limit of this medication.
  • There is no specific treatment for Fenofibrate overdose. In case of overdose, contact with your doctor or emergency room immediately. Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Fenofibrate missed dose

What should I do in case of missed a dose?

  • In case of missed dosage, take it as soon as you remember and maintain a regular dosing schedule. Keep in mind to take the missed dose only on an empty stomach.
  • Skip the missed dose if it is almost time for your next scheduled dose. Keep in mind to not use a double dose to make up a missed dose.

Fenofibrate drug interactions

It has been observed that Fenofibrate may interact with or increase or decrease the effect of following drugs. Caution should be taken when co administrating the Fenofibrate with one of the following drugs.

  • Anticoagulants (Coumarin): It has been observed that Fenofibrate potentiate the effectiveness of coumarin-type anticoagulant as measured by PT/INR test (prothrombin time test, used to monitor the effectiveness of the anticoagulant). Caution should be given when Fenofibrate is given in conjunction with coumarin anticoagulants. It is usually advisable to keep low dosage of anticoagulants to maintain the PT/INR at the desired level. Since high PT/INR may cause unexpected bleeding complications.
  • Immunosuppressants: The primary route of Fenofibrate elimination from body is renal excretion. Therefore, it is not recommended for patients suffering from moderate to severe renal problems. Immunosuppessants (such as cyclosporine and tacrolimus) generally potentiate nephrotoxicity and decreases serum creatinine clearance. As a consequence, serum creatinine level rises and can cause deterioration of renal function. The benefits and risks of using Fenofibrate tablets in conjunction with immunosuppressants and other potentially nephrotoxic agents should be carefully considered under the professional supervision.
  • Bile Acid Binding Resins: Bile acid binding resins bind with other drugs and thus impede the absorption of the drug, if used simultaneously. To avoid it, it is usually recommended to take Fenofibrate at least 1 hour before or 4 to 6 hours after a bile acid binding resin consumption.
  • Control trial and case studies suggests that co-administration of Fenofibrate with colchicines may cause myopathy, including rhabdomyolysis, therefore caution should be taken when prescribing Fenofibrate with colchicine.
  • Besides this, a large number of other drugs such as diuretics (water pills), hormonal contraceptives ( patches,birth control pills, implants, and injections), beta blockers, HMG-CoA reductase inhibitors (cholesterol-lowering agents) can also interact with Fenofibrate.
  • This list do not comprises all the drugs that interact with Fenofibrate and there are many other drugs that can interact with Fenofibrate. If you start any new medication, first consult your doctor or pharmacist.

Does Fenofibrate have any interaction with diseases

It has been observed that following medical conditions (disease) may also interact with Fenofibrate:

  • Hepatotoxicity, (biochemical abnormalities of liver function)
  • Hepatitis (Hepatocellular, chronic active, as well as cholestatic) and, rarely, cirrhosis
  • Liver disease or unexplained, persistent elevations of serum transaminases

Where can I get more information

Your pharmacist can provide more information about Fenofibrate.

Clinical research and current scenario of the drug
  • Fenofibrate is a PPAR-alpha agonist widely recommended for treatment of hypercholesterolemia, lipid abnormalities in patients with cardiovascular disease, including Type 2 diabetes and/or metabolic syndromes.
  • Studies with Fenofibrate revealed that it reduces postprandial VLDL and LDL particle concentrations, oxidative stress and inflammatory response.
  • Fenofibrate has very effective and promising results in preventing progression of diabetes-related microvascular complications as observed in Intervention for Event Lowering in Diabetes (FIELD) study.
  • Recent studies have shown a growing interest in use of Fenofibrate in the management of non-alcoholic fatty liver disease (NAFLD).
  • The combination therapy involving the use of Fenofibrate/ Statin for optimising reduction in the risk of cardiovascular disease in patients suffering with type 2 diabetes and metabolic syndrome is undergoing. Data are also awaited from the ongoing Action to Control Cardiovascular Risk in Diabetes (ACCORD) study to assess the outcome benefits of this approach.
 References from chemical, biological and toxicological databases

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