Temazepam has very good bioavailability with 100% being absorbed from the gut. The drug is metabolized through conjugation and demethylation prior to excretion. Most of the drug is excreted in the urine, with about 20% appearing in the feces. The major metabolite was the O-conjugate of temazepam (90%); the O-conjugate of N-desmethyl temazepam was a minor metabolite (7%).
Temazepam is officially indicated for severe insomnia and other severe or disabling sleep disorders. The prescribing guidelines limit prescribing of hypnotics to two-four weeks due to concerns of tolerance and physical dependence.
The smallest possible effective dose should be used in elderly or very ill patients, as there is a risk of apnea and/or cardiac arrest. This risk is increased when temazepam is given concomitantly with other drugs that depress the central nervous system.
Before taking temazepam, one should ensure that at least 8 hours are available to dedicate to sleep. Failing to do so can increase the side effects of the drug.
The use of this drug in combination with alcohol potentiates the side effects, and can lead to toxicity and death. Though rare, residual 'hangover' effects after night time administration of temazepam such as sleepiness, impaired psychomotor and cognitive functions may persist into the next day, which may impair the ability of users to drive safely or may increase the risks of falls and hip fractures.
Unlike many benzodiazepines, pharmacokinetic interactions involving the P450 system have not been observed with temazepam. Temazepam shows no significant interaction with CYP3A4 inhibitors (e.g. itraconazole, erythromycin).
Chronic or excessive use of temazepam may cause drug tolerance, which can develop rapidly, so this drug is therefore not recommended for long-term use. In 1979 the Institute of Medicine (USA) and the National Institute on Drug Abuse stated that most hypnotics lose their sleep-inducing properties after about 3 to 14 days. In use longer than 1–2 weeks, tolerance will frequently develop towards the ability of temazepam to maintain sleep, so that the drug loses effectiveness. Some studies have observed tolerance to temazepam after as little as one week's use. Another study examined the short-term effects of the accumulation of temazepam over 7 days in elderly inpatients, and found that little tolerance developed during the accumulation of the drug. Other studies examined the use of temazepam over six days and saw no evidence of tolerance. A study in 11 young male subjects showed that significant tolerance occurs to temazepam's thermoregulatory effects and sleep inducing properties after 1 week of use of 30 mg temazepam. Body temperature is well correlated with the sleep inducing or insomnia promoting properties of drugs. In one study the drug sensitivity of people who had used temazepam for 1–20 years was no different from that of controls. In an additional study in which at least one of the authors is employed by multiple drug companies examined the efficacy of temazepam treatment on chronic insomnia over three months and saw no drug tolerance, with the authors even suggesting that the drug might become more effective over time. The Journal of Clinical Sleep Medicine published a paper which had carried out a systematic review of the medical literature concerning insomnia medications and raised concerns about benzodiazepine receptor agonist drugs, the benzodiazepines and the Z-drugs that are used as hypnotics in humans. The review found that almost all trials of sleep disorders and drugs are sponsored by the pharmaceutical industry. It was found that the odds ratio for finding results favorable to industry in industry-sponsored trials was 3.6 times higher than non-industry-sponsored studies and that 24% of authors did not disclose being funded by the drug companies in their published paper when they were funded by the drug companies. The paper found that there is little research into hypnotics that is independent from the drug manufacturers. Establishing continued efficacy beyond a few weeks can be complicated by the difficulty in distinguishing between the return of the original insomnia complaint and withdrawal or rebound related insomnia. Sleep EEG studies on hypnotic benzodiazepines show that tolerance tends to occur completely after one to four weeks with sleep EEG returning to pretreatment levels. The paper concluded that due to concerns about long term use both toxicity and tolerance and dependence as well as controversy over long term efficacy that wise prescribers should restrict benzodiazepines to a few weeks and avoid continuing prescriptions for months or years.
Temazepam like other benzodiazepine drugs can cause physical dependence and addiction. Withdrawal from temazepam or other benzodiazepines after regular use often leads to a benzodiazepine withdrawal syndrome, which resembles symptoms during alcohol and barbiturate withdrawal. The higher the dose and the longer the drug is taken for, the greater the risk of experiencing unpleasant withdrawal symptoms. Withdrawal symptoms can also occur from standard dosages and after short term use. Abrupt withdrawal from therapeutic doses of temazepam after long term use may result in a severe benzodiazepine withdrawal syndrome. Gradual and careful reduction of the dosage, preferably with a long-acting benzodiazepine with long half life active metabolites such as chlordiazepoxide or diazepam is recommended, to prevent severe withdrawal syndromes from developing. Other hypnotic benzodiazepines are not recommended. There are rare reports in the medical literature of psychotic states developing after abrupt withdrawal from benzodiazepines, even from therapeutic doses. Antipsychotics increase the severity of benzodiazepine withdrawal effects with an increase in the intensity and severity of convulsions. Patients who were treated in the hospital with temazepam or nitrazepam have continued taking these after leaving the hospital. It was recommended that hypnotics in the hospital be limited to 5 nights use only, to avoid the development of withdrawal symptoms like insomnia.
Temazepam has the highest rate of drug intoxication, including overdose, among the common benzodiazepines. Temazepam and nitrazepam were the two benzodiazepines most commonly detected in overdose-related deaths in an Australian study of drug deaths. The two benzodiazepines were found to be the sole cause of death in one third of cases. A 1993 British study found temazepam to have the highest number of deaths per million prescriptions among medications commonly prescribed in the 1980s (11.9, versus 5.9 for benzodiazepines overall, taken with or without alcohol). A 1995 Australian study of patients admitted to hospital after benzodiazepine overdose corroborated these results, and found temazepam overdose much more likely to lead to coma in comparison to other benzodiazepines (odds ratio 1.86). The authors note that several factors—such as differences in potency, receptor affinity, and rate of absorption between benzodiazepines—could explain this relatively higher toxicity.
Although benzodiazepines have a relatively high therapeutic index, temazepam is one of the more dangerous of this group of drugs.
In 2003 and 2004, temazepam was the most frequently encountered benzodiazepine in drug-related deaths according to reports from US poison control centers. In 2005, a total of 67,593 benzodiazepine exposures were reported to US poison control centers, of which 3018 (4.46%) resulted in major toxicity and 243 (0.35%) resulted in death. Temazepam was the most frequently encountered benzodiazepine in the cases which resulted in death. Temazepam was also one of two benzodiazepines most frequently encountered in the cases which resulted in major toxicity.
In Canada, temazepam is a Schedule IV controlled substance requiring a doctors prescription.
In Ireland, temazepam is a Schedule 3 controlled substance with strict restrictions.
In Norway, temazepam is a "narcotic" drug (According to the norwegian narcotics list), all benzodiazepine derivates and analogues are considered narcotic and temazepam is not available by prescription. Small amounts are punishable with a fine.
In Sweden, temazepam is a "narcotic" drug under the Narcotics Drugs Act (1968). Temazepam is banned in Sweden and possession and distribution of even small amounts is punishable by a prison sentence and a fine.
In Singapore, temazepam is a Class A-Schedule I controlled drug, along with one other benzodiazepine: Nimetazepam. The clandestine manufacture and illegal distribution of temazepam may be punishable by death. Possession of the drug without a valid prescription from a registered medical doctor is illegal and punishable by extremely long prison terms.
In Australia, temazepam is only available in tablet form and is designated a Schedule 8 controlled drug, requiring a medical doctor's prescription.
In South Africa, temazepam is a Schedule 6 drug, requiring a prescription, and restricted to 10–20 mg doses.
In Hong Kong, temazepam is regulated under Schedule 1 of Hong Kong's Chapter 134 Dangerous Drugs Ordinance. Temazepam can only be used legally by health professionals and for university research purposes. The substance can be given by pharmacists under a prescription. Anyone who supplies the substance without prescription can be fined $10000 (HKD). The penalty for trafficking or manufacturing the substance is a $5,000,000 (HKD) fine and life imprisonment. Possession of the substance for consumption without license from the Department of Health is illegal with a $1,000,000 (HKD) fine and/or 7 years of jail time.
Internationally, temazepam is a Schedule IV drug under the Convention on Psychotropic Substances. Penalties for its possession and/or trafficking in some countries are more severe than for most other benzodiazepines.