Temazepam

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# Overview
Temazepam is a benzodiazepines that is FDA approved for the treatment of insomnia (generally 7 to 10 days).   Common adverse reactions include anorexia, ataxia, equilibrium loss, tremor, increased dreaming, dyspnea, palpitations, vomiting, backache, hyperhidrosis, burning eyes, amnesia, hallucinations, horizontal nystagmus, and paradoxical reactions including restlessness, overstimulation and agitation were rare (less than 0.5%).

# Adult Indications and Dosage

## FDA-Labeled Indications and Dosage (Adult)
- It is indicated for the short-term treatment of insomnia (generally 7 to 10 days).
- For patients with short-term insomnia, instructions in the prescription should indicate that RestorilTM (temazepam) should be used for short periods of time (7 to 10 days).
- The clinical trials performed in support of efficacy were 2 weeks in duration with the final formal assessment of sleep latency performed at the end of treatment.
- While the recommended usual adult dose is 15 mg before retiring, 7.5 mg may be sufficient for some patients, and others may need 30 mg. In transient insomnia, a 7.5 mg dose may be sufficient to improve sleep latency. In elderly or debilitated patients, it is recommended that therapy be initiated with 7.5 mg until individual responses are determined.

## Off-Label Use and Dosage (Adult)

### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Temazepam in adult patients.

### NonGuideline-Supported Use
There is limited information regarding Off-Label NonGuideline-Supported Use of Temazepam in adult patients.

# Pediatric Indications and Dosage

## FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding Temazepam FDA-Labeled Indications and Dosage (Pediatric) in the drug label.

## Off-Label Use and Dosage (Pediatric)

### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Temazepam in pediatric patients.

### NonGuideline-Supported Use
There is limited information regarding Off-Label NonGuideline-Supported Use of Temazepam in pediatric patients.

# Contraindications
- Benzodiazepines may cause fetal harm when administered to a pregnant woman.
- An increased risk of congenital malformations associated with the use of diazepam and chlordiazepoxide during the first trimester of pregnancy has been suggested in several studies.
- Transplacental distribution has resulted in neonatal CNS depression following the ingestion of therapeutic doses of a benzodiazepine hypnotic during the last weeks of pregnancy.
- Reproduction studies in animals with temazepam were performed in rats and rabbits.
- In a perinatal-postnatal study in rats, oral doses of 60 mg/kg/day resulted in increasing nursling mortality.
- Teratology studies in rats demonstrated increased fetal resorptions at doses of 30 and 120 mg/kg in one study and increased occurrence of rudimentary ribs, which are considered skeletal variants, in a second study at doses of 240 mg/kg or higher.
- In rabbits, occasional abnormalities such as exencephaly and fusion or asymmetry of ribs were reported without dose relationship.
- Although these abnormalities were not found in the concurrent control group, they have been reported to occur randomly in historical controls.
- At doses of 40 mg/kg or higher, there was an increased incidence of the 13th rib variant when compared to the incidence in concurrent and historical controls.
- Restoril is contraindicated in women who are or may become pregnant. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. Patients should be instructed to discontinue the drug prior to becoming pregnant. The possibility that a woman of childbearing potential may be pregnant at the time of institution of therapy should be considered.

# 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 to 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.
- Because some of the worrisome adverse effects of benzodiazepines, including Restoril, appear to be dose related, it is important to use the lowest possible effective dose. Elderly patients are especially at risk.
- 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, and depersonalization. Complex behaviors such as sleep-driving (i.e., driving while not fully awake after ingestion of a sedative-hypnotic, with amnesia for the event) have been reported.
- These events can occur in sedative-hypnotic-naive as well as in sedative-hypnotic-experienced persons.
- Although behaviors such as sleep-driving may occur with Restoril alone at therapeutic doses, the use of alcohol and other CNS depressants with Restoril appears to increase the risk of such behaviors, as does the use of Restoril at doses exceeding the maximum recommended dose.
- Due to the risk to the patient and the community, discontinuation of Restoril should be strongly considered for patients who report a sleep-driving episode. Other complex behaviors (e.g., preparing and eating food, making phone calls, or having sex) have been reported in patients who are not fully awake after taking a sedative-hypnotic. As with sleep-driving, patients usually do not remember these events.
- Amnesia and other neuro-psychiatric symptoms may occur unpredictably. In primarily depressed patients, worsening of depression, including suicidal thinking has been reported in association with the use of sedative/hypnotics.
- 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.
- Withdrawal symptoms (of the barbiturate type) have occurred after the abrupt discontinuation of benzodiazepines.

### Severe Anaphylactic and Anaphylactoid Reactions
- Rare cases of angioedema involving the tongue, glottis or larynx have been reported in patients after taking the first or subsequent doses of sedative-hypnotics, including Restoril.
- Some patients have had additional symptoms such as dyspnea, throat closing, or nausea and vomiting that suggest anaphylaxis. Some patients have required medical therapy in the emergency department.
- If angioedema involves the tongue, glottis or larynx, airway obstruction may occur and be fatal. Patients who develop angioedema after treatment with Restoril should not be rechallenged with the drug.

# Adverse Reactions

## Clinical Trials Experience
There is limited information regarding Temazepam Clinical Trials Experience in the drug label.

## Postmarketing Experience
- The following adverse events have been reported less frequently (0.5% to 0.9%):

### Central Nervous System
- Anorexia, ataxia, equilibrium loss, tremor, increased dreaming

### Cardiovascular
- Dyspnea, palpitations

### Gastrointestinal
- Vomiting

### Musculoskeletal
- Backache

### Special Senses
- Hyperhidrosis, burning eyes

### Psychological
- Amnesia, hallucinations, horizontal nystagmus, and paradoxical reactions including restlessness, overstimulation and agitation were rare (less than 0.5%).

# Drug Interactions
There is limited information regarding Temazepam Drug Interactions in the drug label.

# Use in Specific Populations

### Pregnancy
Pregnancy Category (FDA): 
There is no FDA guidance on usage of Temazepam in women who are pregnant.
Pregnancy Category (AUS):
- Australian Drug Evaluation Committee (ADEC) Pregnancy Category
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Temazepam in women who are pregnant.

### Labor and Delivery
There is no FDA guidance on use of Temazepam during labor and delivery.

### Nursing Mothers
There is no FDA guidance on the use of Temazepam with respect to nursing mothers.

### Pediatric Use
There is no FDA guidance on the use of Temazepam with respect to pediatric patients.

### Geriatic Use
There is no FDA guidance on the use of Temazepam with respect to geriatric patients.

### Gender
There is no FDA guidance on the use of Temazepam with respect to specific gender populations.

### Race
There is no FDA guidance on the use of Temazepam with respect to specific racial populations.

### Renal Impairment
There is no FDA guidance on the use of Temazepam in patients with renal impairment.

### Hepatic Impairment
There is no FDA guidance on the use of Temazepam in patients with hepatic impairment.

### Females of Reproductive Potential and Males
There is no FDA guidance on the use of Temazepam in women of reproductive potentials and males.

### Immunocompromised Patients
There is no FDA guidance one the use of Temazepam in patients who are immunocompromised.

# Administration and Monitoring

### Administration
- While the recommended usual adult dose is 15 mg before retiring, 7.5 mg may be sufficient for some patients, and others may need 30 mg. In transient insomnia, a 7.5 mg dose may be sufficient to improve sleep latency. In elderly or debilitated patients, it is recommended that therapy be initiated with 7.5 mg until individual responses are determined.

### Monitoring
There is limited information regarding Temazepam Monitoring in the drug label.

# IV Compatibility
- Intravenous

# Overdosage
- Manifestations of acute overdosage of Restoril can be expected to reflect the CNS effects of the drug and include somnolence, confusion, and coma, with reduced or absent reflexes, respiratory depression, and hypotension.
- The oral LD50 of Restoril was 1963 mg/kg in mice, 1833 mg/kg in rats, and >2400 mg/kg in rabbits.

### Treatment
- If the patient is conscious, vomiting should be induced mechanically or with emetics.
- Gastric lavage should be employed utilizing concurrently a cuffed endotracheal tube if the patient is unconscious to prevent aspiration and pulmonary complications.
- Maintenance of adequate pulmonary ventilation is essential. The use of pressor agents intravenously may be necessary to combat hypotension.
- Fluids should be administered intravenously to encourage diuresis. The value of dialysis has not been determined. If excitation occurs, barbiturates should not be used.
- It should be borne in mind that multiple agents may have been ingested. Flumazenil (Romazicon)*, a specific benzodiazepine receptor antagonist, is indicated for the complete or partial reversal of the sedative effects of benzodiazepines and may be used in situations when an overdose with a benzodiazepine is known or suspected.
- Prior to the administration of flumazenil, necessary measures should be instituted to secure airway, ventilation, and intravenous access.
- Flumazenil is intended as an adjunct to, not as a substitute for, proper management of benzodiazepine overdose.
- Patients treated with flumazenil should be monitored for re-sedation, respiratory depression, and other residual benzodiazepine effects for an appropriate period after treatment.
- The prescriber should be aware of a risk of seizure in association with flumazenil treatment, particularly in long-term benzodiazepine users and in cyclic antidepressant overdose.
- Up-to-date information about the treatment of overdose can often be obtained from a certified Regional Poison Control Center. Telephone numbers of certified Regional Poison Control Centers are listed in the Physicians.

### DOSAGE AND ADMINISTRATION
- While the recommended usual adult dose is 15 mg before retiring, 7.5 mg may be sufficient for some patients, and others may need 30 mg. In transient insomnia, a 7.5 mg dose may be sufficient to improve sleep latency.
- In elderly or debilitated patients, it is recommended that therapy be initiated with 7.5 mg until individual responses are determined.

# Pharmacology

## Mechanism of Action
There is limited information regarding Temazepam Mechanism of Action in the drug label.

## Structure
There is limited information regarding Temazepam Structure in the drug label.

## Pharmacodynamics
There is limited information regarding Pharmacodynamics of Temazepam in the drug label.

## Pharmacokinetics
- In a single and multiple dose absorption, distribution, metabolism, and excretion (ADME) study, using 3H labeled drug, Restoril was well absorbed and found to have minimal (8%) first pass metabolism. There were no active metabolites formed and the only significant metabolite present in blood was the O-conjugate.
- The unchanged drug was 96% bound to plasma proteins. The blood level decline of the parent drug was biphasic with the short half-life ranging from 0.4 to 0.6 hours and the terminal half-life from 3.5 to 18.4 hours (mean 8.8 hours), depending on the study population and method of determination.
- Metabolites were formed with a half-life of 10 hours and excreted with a half-life of approximately 2 hours. Thus, formation of the major metabolite is the rate limiting step in the biodisposition of temazepam.
- There is no accumulation of metabolites. A dose-proportional relationship has been established for the area under the plasma concentration/time curve over the 15 to 30 mg dose range.
- Temazepam was completely metabolized through conjugation prior to excretion; 80% to 90% of the dose appeared in the urine. The major metabolite was the O-conjugate of temazepam (90%); the O-conjugate of N-desmethyl temazepam was a minor metabolite (7%).

### Bioavailability, Induction, and Plasma Levels
- Following ingestion of a 30 mg Restoril capsule, measurable plasma concentrations were achieved 10 to 20 minutes after dosing with peak plasma levels ranging from 666 to 982 ng/mL (mean 865 ng/mL) occurring approximately 1.2 to 1.6 hours (mean 1.5 hours) after dosing.
- In a 7 day study, in which subjects were given a 30 mg Restoril capsule 1 hour before retiring, steady-state (as measured by the attainment of maximal trough concentrations) was achieved by the third dose. Mean plasma levels of temazepam (for days 2 to 7) were 260210 ng/mL at 9 hours and 7580 ng/mL at 24 hours after dosing. A slight trend toward declining 24 hour plasma levels was seen after day 4 in the study, however, the 24 hour plasma levels were quite variable.
- At a dose of 30 mg once-a-day for 8 weeks, no evidence of enzyme induction was found in man.
- Elimination Rate of Benzodiazepine Hypnotics and Profile of Common Untoward Effects
- The type and duration of hypnotic effects and the profile of unwanted effects during administration of benzodiazepine hypnotics may be influenced by the biologic half-life of the administered drug and for some hypnotics, the half-life of any active metabolites formed. Benzodiazepine hypnotics have a spectrum of half-lives from short (20 hours).
- When half-lives are long, drug (and for some drugs their active metabolites) may accumulate during periods of nightly administration and be associated with impairments of cognitive and/or motor performance during waking hours; the possibility of interaction with other psychoactive drugs or alcohol will be enhanced. In contrast, if half-lives are shorter, drug (and, where appropriate, its active metabolites) will be cleared before the next dose is ingested, and carry-over effects related to excessive sedation or CNS depression should be minimal or absent. However, during nightly use for an extended period, pharmacodynamic tolerance or adaptation to some effects of benzodiazepine hypnotics may develop.
- If the drug has a short elimination half-life, it is possible that a relative deficiency of the drug, or, if appropriate, its active metabolites (i.e., in relationship to the receptor site) may occur at some point in the interval between each night's use. This sequence of events may account for 2 clinical findings reported to occur after several weeks of nightly use of rapidly eliminated benzodiazepine hypnotics, namely, increased wakefulness during the last third of the night, and the appearance of increased signs of daytime anxiety.

### Controlled Trials Supporting Efficacy
- Restoril improved sleep parameters in clinical studies. Residual medication effects (hangover) were essentially absent. Early morning awakening, a particular problem in the geriatric patient, was significantly reduced.
- Patients with chronic insomnia were evaluated in 2 week, placebo controlled sleep laboratory studies with Restoril at doses of 7.5 mg, 15 mg, and 30 mg, given 30 minutes prior to bedtime. There was a linear dose-response improvement in total sleep time and sleep latency, with significant drug-placebo differences at 2 weeks occurring only for total sleep time at the 2 higher doses, and for sleep latency only at the highest dose.
- In these sleep laboratory studies, REM sleep was essentially unchanged and slow wave sleep was decreased. No measurable effects on daytime alertness or performance occurred following Restoril treatment or during the withdrawal period, even though a transient sleep disturbance in some sleep parameters was observed following withdrawal of the higher doses.
- There was no evidence of tolerance development in the sleep laboratory parameters when patients were given Restoril nightly for at least 2 weeks.
- In addition, normal subjects with transient insomnia associated with first night adaptation to the sleep laboratory were evaluated in 24 hour, placebo controlled sleep laboratory studies with Restoril at doses of 7.5 mg, 15 mg, and 30 mg, given 30 minutes prior to bedtime.
- There was a linear dose-response improvement in total sleep time, sleep latency and number of awakenings, with significant drug-placebo differences occurring for sleep latency at all doses, for total sleep time at the 2 higher doses and for number of awakenings only at the 30 mg dose.

## Nonclinical Toxicology
There is limited information regarding Temazepam Nonclinical Toxicology in the drug label.

# Clinical Studies
There is limited information regarding Clinical Studies of Temazepam in the drug label.

# How Supplied
- RestorilTM (temazepam) Capsules USP
7.5 mg
- Blue and pink capsules, with the pink body imprinted FOR SLEEP on one side and Boxed M on the other side in red, and a blue cap imprinted RESTORIL 7.5 mg twice in red.
Bottle of 30-NDC 0406-9915-03
Bottle of 100-NDC 0406-9915-01
15 mg
- Maroon and pink capsules, with the pink body imprinted FOR SLEEP on one side and Boxed M on the other side in red, and a maroon cap imprinted RESTORIL 15 mg twice in white.
Bottle of 100-NDC 0406-9916-01
22.5 mg
- Opaque blue capsules, with the opaque blue body imprinted FOR SLEEP on one side and Boxed M on the other side in red, and an opaque blue cap imprinted RESTORIL 22.5 mg twice in red.
Bottle of 30-NDC 0406-9914-03
30 mg
- Maroon and blue capsules, with the blue body imprinted FOR SLEEP on one side and Boxed M on the other side in red, and a maroon cap imprinted RESTORIL 30 mg twice in white.
Bottle of 100-NDC 0406-9917-01
- Dispense in a well-closed, light-resistant container with a child-resistant closure.

## Storage
- Storage: Store at 20 to 25C (68 to 77F).

# Images

## Drug Images

## Package and Label Display Panel

# Patient Counseling Information
There is limited information regarding Temazepam Patient Counseling Information in the drug label.

# Precautions with Alcohol
Alcohol-Temazepam interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

# Brand Names
There is limited information regarding Temazepam Brand Names in the drug label.

# Look-Alike Drug Names
There is limited information regarding Temazepam Look-Alike Drug Names in the drug label.

# Drug Shortage Status

# Price