Temazepam – Drug class, mechanism of action, uses, side effect, withdrawal

Temazepam - Drug class, mechanism of action, uses, side effect, withdrawal

What is temazepam?

Temazepam is a drug which belongs to the class of benzodiazepines. Benzodiazepines are the drugs which are used for the treatment of people who are unable to sleep. Likewise, temazepam is used for the treatment of people with sleep difficulties and those suffering from insomnia. The drug usually acts by altering the chemicals in the brain which are usually unbalanced in people who are suffering from insomnia.

Temazepam is a prescription drug and is only available on the prescription of a registered medical practitioner. The drug is an anti-anxiety medication and works by enhancing the effects of gamma-aminobutyric acid (GABA) in the brain. GABA is an inhibitory neurotransmitter that acts in the brain and inhibits some of its activities leading to a reduction in anxiety.

By reducing the anxiety, temazepam enhances the ability to fall as well as staying asleep and hence results in the treatment of insomnia. Temazepam is manufactured by various companies and is available under different brand names such as Restoril etc.

Temazepam description, IUPAC name, molecular formula, weight, structure and drug class

Temazepam is a drug which is recognized as a hypnotic drug since it is used for the treatment of insomnia and induces sleep in people who find it difficult to sleep. It belongs to the chemical class of benzodiazepines and is chemically described as 7-chloro-1,3-dihydro-3-hydroxy-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one.Temazepam binds to the benzodiazepine receptors in the brain and mediates the inhibitory effects of GABA. The drug is a controlled substance and has a high potential for abuse.

IUPAC name: 7-chloro-3-hydroxy-1-methyl-5-phenyl-3H-1,4-benzodiazepin-2-one

Molecular formula: C16H13ClN2O2

Molecular weight: 300.742 g/mol

Chemical structure:

Drug class: Temaepam belongs to the class of organic compounds known as 1,4-benzodiazepines which are organic compounds containing a benzene ring fused to a 1,4-azepine.

Temazepam identification

Temazepam is available in the form of a white solid which is crystalline in nature. The drug is only slightly soluble in water while it is sparingly soluble in alcohol. It is available in the form of capsules of varying strength which includes capsules of 7.5 mg, 15 mg, 22.5 mg, and 30 mg. This implies that the drug is administered orally to patients in the form of capsules.

What is the mechanism of action of temazepam?

Temazepam is classified as a benzodiazepine and acts primarily in the central nervous system (CNS). This drug has the ability to produce any level of CNS depression as may be required which includes sedation, hypnosis, skeletal muscle relaxation, and anticonvulsant activity. Benzodiazepines exert their effects by enhancing the activity of gamma-aminobutyric acid (GABA)-benzodiazepine receptor complex.

GABA is an inhibitory neurotransmitter which has a high affinity for GABA-A and GABA-B receptors and exerts its effects by binding to these receptors. GABA-A receptors are located primarily in the CNS and are coupled with specific benzodiazepine receptor subtypes. There are generally three types of benzodiazepine receptors which are present and are located in the CNS and other tissues.

These are BNZ1 receptors which are located in the cerebellum and cerebral cortex in the CNS, BNZ2 receptors which are located in the cerebral cortex and the spinal cord, and BNZ3 receptors which are located in the peripheral tissues. Out of these, BNZ1 receptors are involved in the regulation of sleep while BNZ2 receptors are associated with anticonvulsant activity, motor coordination, and muscle relaxation.

Benzodiazepines enhance the inhibitory effects of GABA by binding non-specifically to BNZ1 and BNZ2 receptors which increases the affinity of GABA for GABA receptors. As GABA binds to its receptor, this results in the opening of chloride ion channel producing a hyperpolarized cell membrane which prevents further excitation of the cell. Therefore, benzodiazepines are used for the treatment of insomnia as they increase the total sleep time through their effects on GABA.

What are the indications of temazepam?

Temazepam is a drug which is used primarily for the treatment of insomnia. It is used for the short-term treatment of insomnia and is used for 7 to 10 days.

Is Temazepam good for anxiety?

What are the pharmacokinetics of temazepam?

Temazepam is administered orally in the form of capsules. The drug is well absorbed upon oral administration and exhibits minimal first pass effect. Only about 8% of the drug is metabolized in the liver which implies that the drug has a bioavailability of more than 90%. The drug exerts its action within 30 to 60 mins. Temazepam is widely distributed and is extensively bound to plasma proteins.

It is 96 to 98% bound to plasma proteins. Temazepam undergoes hepatic metabolism and is completely metabolized by conjugation prior to excretion. The major metabolite which is formed as a result of metabolism is the O-conjugate of temazepam and accounts for about 90% of the drug. The other metabolite is the O-conjugate of N-desmethyl temazepam which is a minor metabolite and only 7% of the drug is present in the form of this metabolite.

Temazepam has a biological half-life of about 10 to 20 hours. The metabolites of temazepam are formed with a half-life of 10 hours while they are excreted with a half-life of about 2 hours. The drug is excreted primarily in the urine and about 80 to 90% of the dose is excreted in urine as a result of conjugation.

What is the recommended dosage for temazepam?

Temazepam is administered only to adult patients in the treatment of insomnia. However, the dose varies according to the age of the patient.

  • In adults: the normal recommended dose is 15 mg PO given just before bedtime. In some cases, the dose can be increased up to 30 mg PO just before bedtime.
  • In geriatric adults: the lowest effective dose of about 7.5 mg should be administered PO just before bedtime. Depending upon the clinical requirement and tolerability level of the patient the dose can be raised up to 30 mg. When high doses of benzodiazepines are administered to elderly patient, close monitoring should be done to check as the risk of over-sedation, confusion, dizziness and ataxia increases.

What are the warnings associated with temazepam?

  • Temazepam is used primarily for the treatment of insomnia but the drug should only be used for the symptomatic treatment of insomnia after the condition of the patient has been properly evaluated. If the drug fails to remit the symptoms of insomnia within a period of 7 to 10 days so this might be indicative of an underlying psychiatric or medical illness, therefore, such condition should be carefully evaluated. The use of central nervous system depressant drugs including temazepam in patients with unrecognized psychiatric or physical disorder may worsen the symptoms of insomnia and also result in abnormalities of thinking or behaviour. Since benzodiazepines can cause some serious side effects, therefore, treatment with such drugs should be started with the lowest possible effective dose. The risk of side effects is increased in elderly patients.
  • The drug can lead to behavioural changes which include bizarre behaviour, hallucinations, agitation, and depersonalization. The drug can also cause aggressiveness and extroversion which may also be observed with the use of alcohol. Temazepam can also cause complex behaviours such as “sleep-driving” followed by amnesia. This condition is associated with the use of sedative-hypnotics and indicates that a person is driving while not being fully awake and then does not even remember these events. The risk of such behaviours may be increased if temazepam is used concomitantly with alcohol or other CNS depressant drugs, however, these events may also occur at normal therapeutic doses of the drug. The use of temazepam should be immediately discontinued if the patient experiences an episode of “sleep-driving” because the patient usually does not remember such events due to amnesia. The drug may also worsen the depressive state of depressed patients leading to an increase in suicidal thinking.
  • Benzodiazepines have a high potential for abuse and can cause physical dependence, therefore, the use of the drug should not be discontinued abruptly as this may lead to withdrawal symptoms. The dose of the drug should be gradually decreased to avoid the occurrence of a withdrawal state.
  • The drug may also cause a severe anaphylactic reaction, therefore, it should be used with caution in patients. This may lead to severe angioedema involving the tongue, larynx or glottis while additional symptoms may also appear in some patients such as dyspnea, throat closing, or nausea and vomiting. Those patients who develop angioedema of the tongue, larynx or glottis might require emergency treatment as it may cause airway obstruction which could be fatal.

Temazepam dependence

Temazepam has been held accountable for causing physical and psychological dependence in some of the patients especially those who are taking this for prolonged periods or using this drug in high doses. Great care is required while prescribing the drug to such patients who have a suspected or known history of drug abuse. In such patients tolerance to sedative effects of temazepam is developed quickly.

When temazepam is abruptly discontinued after using for a prolonged period, withdrawal symptoms are reported to occur. These include seizures and status epilepticus. In patients who are already using anti-epileptics for the purpose of lowering seizure threshold, on abrupt discontinuation of temazepam has increased the chance of precipitating seizures. It is suggested to gradually decrease the dose of benzodiazepine and then stop the medicine.

Temazepam withdrawal

People who take temazepam or any other benzodiazepines in large doses during long-term period can develop a dependence on the substance, which can lead to withdrawal symptoms. Although these symptoms can be easily managed, patients can develop benzodiazepine withdrawal syndrome, which can be physically dangerous if not monitored by a medical professional. Symptoms of this syndrome may include:

  • Extreme anxiety and panic
  • Paranoia
  • Rebound insomnia
  • Changes in perception, including tinnitus and tingling or numbness in the limbs
  • Muscle pain and weakness
  • Painful tremors
  • Abdominal cramps or diarrhea
  • Sweating
  • Hallucinations
  • Seizures

This condition can last for weeks or months, and psychological withdrawal symptoms can last for years. As a result, medical detox is always required for benzodiazepine withdrawal.

The physical and psychological dangers associated with nonmedical use of Restoril, or Restoril abuse, mean that it is very important to seek medical help as soon as possible. Medical professionals can help with the detox process, work with the individual on polydrug abuse issues, and help them overcome abuse and addiction problems.

Temazepam use in geriatric patients

Elderly patients have weak body systems. Elimination and clearance of majority of the drugs is decreased to a great extent. An interruption in the normal elimination can either exaggerate or extend the actions of the drugs including both the wanted and unwanted effects. Usually, geriatric patients are given the smallest effective dose for the shortest possible time and regular monitoring for any impairment in motor or cognitive function is done.

The drug remains in the body for longer period increasing the possibility of developing over-sedation, ataxia, dizziness and confusion. It is thus recommended to use instead of temazepam, a benzodiazepine which does not generate active metabolites. This reduces the chances of drug accumulation and lessens the risk of toxicity. Toxicity with temazepam is characterized by delirium, falls, fractures and cognitive impairment.

Temazepam use in neonates and children

Although benzodiazepines are in extreme cases given to children for inducing sleep or controlling hyperactivity, so far the safety and efficacy profile for temazepam is not been established. Due to this fact this drug should be avoided in neonates, infants, and children below 18 years of age. Benzodiazepines are more likely to cause CNS related effects due to greater penetration of the drug.

Use of temazepam in pregnancy and breastfeeding

Temazepam is not recommended to be used by pregnant women as the risks clearly outweigh the benefits. The drug is included in US Food and Drug Administration Category X. This implies that the drug has been reported to cause fetal abnormalities when administered to pregnant women and the risks of the drug outweigh the benefits.

The child may experience withdrawal symptoms if born to a mother taking benzodiazepines. The patient should be warned about the risks associated with the use of the drug during pregnancy and should be advised to discontinue the drug prior to becoming pregnant as it may be harmful to the fetus. The drug may cause congenital malformations if used during the first trimester of pregnancy.

Temazepam is excreted into breast milk but in very low concentration. However, caution is recommended when the drug is used by mothers who are feeding their young ones. The drug has a short half-life, therefore, the amount of drug ingested by infant does not necessarily cause any adverse events. The patients are usually advised to take the bedtime dose after the infant’s last feeding of the day as it may minimize the dose received by the infant.

What are the side effects associated with temazepam?

Temazepam can cause a variety of side effects. It can cause common as well as serious side effects. Some common side effects which occur by the use of temazepam includes:

  • Daytime drowsiness (or during hours when you do not normally sleep)
  • Amnesia or forgetfulness
  • Muscle weakness
  • Lack of balance or coordination
  • Numbness
  • Burning, pain
  • Tingling feeling
  • Headache
  • Blurred vision
  • Depressed mood
  • Feeling nervous, excited, or irritable
  • Nausea
  • Vomiting
  • Stomach discomfort
  • Dry mouth
  • Increased thirst

The drug may also cause some serious side effects including:

  • Weak or shallow breathing
  • Fast or pounding heartbeats
  • Confusion
  • Slurred speech
  • Unusual thoughts or behaviour
  • Hallucinations
  • Agitation, aggression
  • Thoughts of suicide or hurting yourself
  • Restless muscle movements especially in the eyes, jaw, tongue, or neck
  • Pale skin
  • Easy bruising or bleeding
  • Unusual weakness
  • Fever, chills, body aches
  • Flu symptoms
  • Problems with urination
  • Loss of appetite
  • Dark urine
  • Clay-coloured stools
  • Jaundice (yellowing of eyes or skin)

In what conditions is temazepam contraindicated

In some of the conditions, temazepam is contraindicated and its use should be restricted in such conditions. These conditions are as below:

  • Pain

Benzodiazepines such as temazepam are reported to worsen up the severe pain. It decreases the pain threshold and does not provide analgesic, antipsychotic or antidepressant effect.

  • Chronic obstructive pulmonary disorder (COPD) and other respiratory problems:

Temazepam usually causes the depression of respiratory system and central nervous system. Temazepam, unlike other benzodiazepines, should be avoided in patients who are already suffering from any illness of respiratory system. It will further depress the system and ultimately lead to failure and hence the death of the patient.

  • CNS depression or sleep apnea

Patients who are already suffering from CNS depression should not be recommended to use temazepam as it will further cause depression of the central nervous system. The patient goes into the coma and eventually, death occurs. Besides the effect on the CNS system, low blood pressure and other symptoms associated with hypotension occur.

What if I overdose temazepam?

If the drug has overdosed, it does not cause any significant threat to the life of the patient unless combined with drugs possessing CNS depressant activity such as alcohol. Symptoms of overdose may include drowsiness, ataxia, dysarthria, and nystagmus. Coma, respiratory depression, and hypotension occur less frequently if these drugs are taken alone. If coma occurs, it usually lasts for a few hours while respiratory depression may be more serious if it occurs in patients with severe obstructive airway disease.

These symptoms are less likely to develop in patients who remain asymptomatic for 4 hours or more. This condition can be managed by inducing vomiting if the patient is conscious, however, if the patient is unconscious then gastric lavage can be done while protecting the airways. The patient can also be given activated charcoal to reduce absorption of the drug. If the drug is not mixed with other drugs then flumazenil can be given as an antidote for the treatment of overdose.

What if I miss a dose of temazepam?

Temazepam is a prescription drug which is used by patients who have sleeping difficulties. The drug is usually taken by patients as needed and there isn’t any proper dosing schedule which the patients need to follow. This implies that even if a dose is missed then it is of least importance. The drug should only be used if the patient needs to sleep for 7 to 8 hours.

How should I take temazepam?

  1. Temazepam should be taken exactly in the same dose and directions as prescribed by the doctor.
  2. It is better to ingest the medicine just before the bedtime.
  3. It is not recommended to take temazepam unless the patient is able to take a proper sleep before he becomes active again.
  4. Report the doctor if on using temazepam insomnia worsens up within 7 – 9 days. If such a situation arises, insomnia is probably due to some other medical illness.

Can I take temazepam with safinamide?

A moderate degree of drug interaction takes place when safinamide is given concomitantly with temazepam. Safinamide is a dopaminergic medicine, which acts as an external source of L-dopa. When these two drugs are given together, it brings out a sudden commencement of somnolence. This has been a major cause of motor vehicle accidents.

Usually, patients do not recognize any of the side effects including excessive drowsiness or they may report any unusual feeling just before the adverse event takes place. Due to the additive effects of both of the sedating agents are not usually given together.

Can I take temazepam with probenecid?

The interaction between temazepam and probenecid is classified as a major interaction. Probenecid is reported to stop or decrease the metabolism of the majority of the benzodiazepines including temazepam. As a result of which the clearance of temazepam is decreased by 50% and hence increase in its elimination half-life is observed.

Moreover, patients who have been already treated with probenecid, the induction time of benzodiazepines is shortened by approximately 85 to 109 seconds.

Can I take temazepam with remifentanil?

Benzodiazepines and opioids, when used concomitantly, have produced a severe degree of interactions. When co-administered, these produce respiratory depression hypotension, intense sedation and in some cases death.

It is necessary to limit the dose of opioid medication and keeping the minimum course duration when benzodiazepines are already being administered and when the opioids are already being administered the dose, the benzodiazepines are given at the lowest effective dose. About 75% of the dose of benzodiazepine is reduced when given concomitantly with remifentanil.

Can I take temazepam with alcohol?

Using temazepam together with ethanol can increase nervous system side effects such as dizziness, drowsiness, and difficulty concentrating. Acute ethanol ingestion may potentiate the CNS effects of many benzodiazepines. Tolerance may develop with chronic ethanol use. The mechanism may be decreased clearance of the benzodiazepines because of CYP450 hepatic enzyme inhibition.

Also, it has been suggested that the cognitive deficits induced by benzodiazepines may be increased in patients who chronically consume large amounts of alcohol.

Some people may also experience impairment in thinking and judgment. You should avoid or limit the use of alcohol while being treated with temazepam. Do not use more than the recommended dose of temazepam, and avoid activities requiring mental alertness such as driving or operating hazardous machinery until you know how the medication affects you.

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

Temazepam use in obese patients

The plasma half-lives of benzodiazepines may be prolonged in obese patients, presumably due to increased distribution into fat. Marked increases in distribution (> 100%) have been reported for diazepam and midazolam, and moderate increases (25% to 100%) for alprazolam, lorazepam, and oxazepam.

Therapy with benzodiazepines should be administered cautiously in obese patients, with careful monitoring of CNS status. Longer dosing intervals may be appropriate. When dosing by weight, loading doses should be based on actual body weight, while maintenance dose should be based on ideal body weight to avoid toxicity.

Temazepam and respiratory depression

Benzodiazepines may cause respiratory depression and apnea, usually when given in high dosages and/or by intravenous administration. However, some patients may be susceptible at commonly used dosages, including the elderly, debilitated or severely ill patients, those receiving other CNS depressants, and those with limited ventilatory reserve, chronic pulmonary insufficiency or other respiratory disorders.

Therapy with benzodiazepines should be administered cautiously in these patients. Appropriate monitoring and individualization of dosage are particularly important, and equipment for resuscitation should be immediately available if the parenteral route is used. Benzodiazepines, especially injectable formulations, should generally be avoided in patients with sleep apnea, severe respiratory insufficiency, or hypoxia.

How should temazepam be stored?

The drug should be stored ideally at room temperature from68° to 77°F (20° to 25°C). it should not be stored in the washroom as it can get contaminated and should also be protected from excessive moisture and heat. The drug should be kept in a safe place to keep it out of the reach of children as it may lead to poisoning if they consume it.

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About Miljan Krcobic 363 Articles
Miljan Krčobić. has bachelor degree in Pharmacy.