WARNINGS
Sleep disturbance may be the presenting manifestation of an underlying physical and/or psychiatric disorder. Consequently, a decision to initiate symptomatic treatment of insomnia should only be made after the patient has been carefully evaluated.
The failure of insomnia to remit after 7-10 days of treatment may indicate the presence of a primary psychiatric and/or medical illness that should be evaluated.
Worsening of insomnia may be the consequence of an unrecognized psychiatric or physical disorder as may the emergence of new abnormalities of thinking or behavior. Such abnormalities have also been reported to occur in association with the use of drugs with central nervous system depressant activity, including those of the benzodiazepine class. Some of these changes may be characterized by decreased inhibition, e.g., aggressiveness and extroversion that seem out of character, similar to that seen with alcohol. Other kinds of behavioral changes can also occur, for example, bizarre behavior, agitation, hallucinations, depersonalization, and, in primarily depressed patients, the worsening of depression, including suicidal thinking. In controlled clinical trials involving 1076 patients on Restoril® (temazepam) and 783 patients on placebo, reports of hallucinations, agitation, and overstimulation occurred at rates less than 1 in 100 patients. Hallucinations were reported in 2 Restoril® (temazepam) patients and 1 placebo patient; agitation was reported in 1 Restoril® (temazepam) patient; 2 Restoril® (temazepam) patients reported overstimulation. There were no reports of worsening of depression or suicidal ideation, aggressiveness, extroversion, bizarre behavior or depersonalization in these controlled clinical trials.
It can rarely be determined with certainty whether a particular instance of the abnormal behaviors listed above is drug induced, spontaneous in origin, or a result of an underlying psychiatric or physical disorder. Nonetheless, the emergence of any new behavioral sign or symptom of concern requires careful and immediate evaluation.
Because some of the worrisome adverse effects of benzodiazepines, including Restoril® (temazepam), appear to be dose related (See PRECAUTIONS and DOSAGE AND ADMINISTRATION), it is important to use the lowest possible effective dose. Elderly patients are especially at risk. Patients receiving Restoril® (temazepam) should be cautioned about possible combined effects with alcohol and other CNS depressants.
Withdrawal symptoms (of the barbiturate type) have occurred after the abrupt discontinuation of benzodiazepines (See DRUG ABUSE AND DEPENDENCE).
PRECAUTIONS
General
Since the risk of the development of oversedation, dizziness, confusion, and/or ataxia increases substantially with larger doses of benzodiazepines in elderly and debilitated patients, 7.5 mg of Restoril® (temazepam) is recommended as the initial dosage for such patients.
Restoril® (temazepam) should be administered with caution in severely depressed patients or those in whom there is any evidence of latent depression; it should be recognized that suicidal tendencies may be present and protective measures may be necessary.
The usual precautions should be observed in patients with impaired renal or hepatic function and in patients with chronic pulmonary insufficiency.
If Restoril® (temazepam) is to be combined with other drugs having known hypnotic properties or CNS-depressant effects, consideration should be given to potential additive effects.
The possibility of a synergistic effect exists with the co-administration of Restoril® (temazepam) and diphenhydramine. One case of stillbirth at term has been reported 8 hours after a pregnant patient received Restoril® (temazepam) and diphenhydramine. A cause and effect relationship has not yet been determined. (See CONTRAINDICATIONS)
Information for Patients
The text of a patient package insert is printed at the end of this insert. To assure safe and effective use of Restoril® (temazepam), the information and instructions provided in this patient package insert should be discussed with patients.
Laboratory Tests
The usual precautions should be observed in patients with impaired renal or hepatic function and in patients with chronic pulmonary insufficiency. Abnormal liver function tests as well as blood dyscrasias have been reported with benzodiazepines.
Drug Interactions
The pharmacokinetic profile of temazepam does not appear to be altered by orally administered cimetidine dosed according to labeling.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenicity studies were conducted in rats at dietary temazepam doses up to 160 mg/kg/day for 24 months and in mice at dietary dose of 160 mg/kg/day for 18 months. No evidence of carcinogenicity was observed although hyperplastic liver nodules were observed in female mice exposed to the highest dose. The clinical significance of this finding is not known.
Fertility in male and female rats was not adversely affected by Restoril® (temazepam).
No mutagenicity tests have been done with temazepam.
Pregnancy
Pregnancy Category X (See CONTRAINDICATIONS).
Nursing Mothers
It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Restoril® (temazepam) is administered to a nursing woman.
Pediatric Use
Safety and effectiveness in pediatric patients have not been established.
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