temazepam

TEMAZEPAM INDICATIONS AND USAGE

Temazepam Capsules, USP are 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 Temazepam Capsules 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.

TEMAZEPAM 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 perinatalpostnatal 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.

Temazepam 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 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.

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 sedativehypnotic, with amnesia for the event) have been reported. These events can occur in sedative-hypnoticnaive as well as in sedative-hypnotic-experienced persons. Although behaviors such as sleep-driving may occur with temazepam alone at therapeutic doses, the use of alcohol and other CNS depressants with temazepam appears to increase the risk of such behaviors, as does the use of temazepam at doses exceeding the maximum recommended dose. Due to the risk to the patient and the community, discontinuation of temazepam 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 sleepdriving, 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 (see DRUG ABUSE AND DEPENDENCE ).

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 temazepam. 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 temazepam should not be rechallenged with the drug.

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 temazepam is recommended as the initial dosage for such patients.

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 temazepam is to be combined with other drugs having known hypnotic properties or CNS-depressant; and effects, consideration should be given to potential additive effects.

The possibility of a synergistic effect exists with the co-administration of temazepam and diphenhydramine. One case of stillbirth at term has been reported 8 hours after a pregnant patient received temazepam and diphenhydramine. A cause and effect relationship has not yet been determined (see CONTRAINDICATIONS ).

Information for Patients

The text of a patient Medication Guide is printed at the end of this insert. To assure safe and effective use of temazepam, the information and instructions provided in this patient Medication Guide should be discussed with patients.

Special Concerns

"Sleep-Driving" and Other Complex Behaviors - There have been reports of people getting out of bed after taking a sedative-hypnotic and driving their cars while not fully awake, often with no memory of the event. If a patient experiences such an episode, it should be reported to his or her doctor immediately, since "sleep-driving" can be dangerous. This behavior is more likely to occur when temazepam is taken with alcohol or other central nervous system depressants (see WARNINGS ). 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.

Laboratory Test

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 doses 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 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 temazepam is administered to a nursing woman.

Pediatric Use
Safety and effectiveness in pediatric patients have not been established.

TEMAZEPAM ADVERSE REACTIONS

During controlled clinical studies in which 1076 patients received temazepam at bedtime, the drug was well tolerated. Side effects were usually mild and transient. Adverse reactions occurring in 1% or more of patients are presented in the following table:

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

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

DRUG ABUSE AND DEPENDENCE

Abuse and addiction are separate and distinct from physical dependence and tolerance. Abuse is characterized by misuse of the drug for non-medical purposes, often in combination with other psychoactive substances. Physical dependence is a state of adaptation that is manifested by a specific withdrawal syndrome that can be produced by abrupt cessation, rapid dose reduction, decreasing blood level of the drug and/or administration of an antagonist. Tolerance is a state of adaptation in which exposure to a drug induces changes that result in a diminution of one or more of the drug's effects over time. Tolerance may occur to both the desired and undesired effects of drugs and may develop at different rates for different effects.

Addiction is a primary, chronic, neurobiological disease with genetic, psychosocial, and environmental factors influencing its development and manifestations. It is characterized by behaviors that include one or more of the following: impaired control over drug use, compulsive use, continued use despite harm, and craving. Drug addiction is a treatable disease, utilizing a multidisciplinary approach, but relapse is common.

Controlled Substance
Temazepam is a controlled substance in Schedule IV.

Abuse and Dependence

Withdrawal symptoms, similar in character to those noted with barbiturates and alcohol (convulsions, tremor, abdominal, and muscle cramps, vomiting, and sweating), have occurred following abrupt discontinuance of benzodiazepines. The more severe withdrawal symptoms have usually been limited to those patients who received excessive doses over an extended period of time. Generally milder withdrawal symptoms (e.g., dysphoria and insomnia) have been reported following abrupt discontinuance of benzodiazepines taken continuously at therapeutic levels for several months. Consequently, after extended therapy at doses higher than 15 mg, abrupt discontinuation should generally be avoided and a gradual dosage tapering schedule followed. As with any hypnotic, caution must be exercised in administering temazepam to individuals known to be addiction-prone or to those whose history suggests they may increase the dosage on their own initiative. It is desirable to limit repeated prescriptions without adequate medical supervision.

OVERDOSAGE

Manifestations of acute overdosage of temazepam 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 temazepam 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 (Romazicorn® )*, 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. The complete flumazenil package insert including CONTRAINDICATIONS, WARNINGS, and PRECAUTIONS should be consulted prior to use.

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’ Desk References®**

TEMAZEPAM 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.

HOW SUPPLIED

Temazepam Capsules USP

15 mg
Blue opaque cap and white opaque body, imprinted “15 mg” on cap and “Novel 121” on the body in black ink.

Bottle of 100........NDC 67877-146-01
Bottle of 500........NDC 67877-146-05

30 mg
White opaque cap and body, imprinted “30 mg” on cap and “Novel 123” on the body in black ink.
Bottle of 100........NDC 67877-147-01
Bottle of 500........NDC 67877-147-05

Dispense in a well-closed, light-resistant container with a child-resistant closure.

Storage: Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].

*Romazicon is the registered trademark of Hoffman-LaRoche Inc.
**Trademark of Medical Economics Company, Inc.

Manufactured by:                                          Distributed by:
Novel Laboratories, Inc.                                 ASCEND Laboratories, LLC
Somerset, NJ 08873                                      Montvale, NJ 07645

MEDICATION GUIDE

What is TEMAZEPAM?

TEMAZEPAM is a federally controlled substance (C-IV) because it can be abused or lead to dependence. Keep TEMAZEPAM in a safe place to prevent misuse and abuse. Selling or giving away TEMAZEPAM may harm others, and is against the law. Tell your doctor if you have ever abused or been dependent on alcohol, prescription medicines or street drugs.

Who should not take TEMAZEPAM?

Do not take TEMAZEPAM if you are pregnant or planning to become pregnant.

TEMAZEPAM may not be right for you. Before starting TEMAZEPAM, tell your doctor about all of your health conditions, including if you:






Do not take TEMAZEPAM with other medicines that can make you sleepy.



How should I take TEMAZEPAM?

Take TEMAZEPAM right before you get into bed.
Do not take TEMAZEPAM unless you are able to get a full night’s sleep before you must be active again.
Call your doctor if your insomnia worsens or is not better within 7 to 10 days.


What are the possible side effects of TEMAZEPAM?

Possible serious side effects of TEMAZEPAM include:
getting out of bed while not being fully awake and do an activity that you do not know you are doing.
abnormal thoughts and behavior.
memory loss
anxiety
severe allergic reactions.

Call your doctor right away if you have any of the above side effects or any other side effects that worry you while using TEMAZEPAM.

The most common side effects of TEMAZEPAM are:







Do not drive or do other dangerous activities after taking TEMAZEPAM until you feel fully awake.







How should I store TEMAZEPAM?

Keep TEMAZEPAM and all medicines out of reach of children.

General Information about TEMAZEPAM






What are the ingredients in TEMAZEPAM?

15mg and 30mg Capsules



15 mg Capsules

Inactive Ingredients:

May also include:

30 mg Capsules
Inactive Ingredients:

May also include:

TEMAZEPAM CIV
Capsules, USP

30 mg

Rx only

temazepam temazepam CAPSULE Product Information Product Type Human prescription drug label Item Code (Source) NDC:55289-660(NDC:67877-147) Route of Administration ORAL DEA Schedule Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength temazepam TEMAZEPAM 30 mg Inactive Ingredients Ingredient Name Strength STARCH, CORN ANHYDROUS LACTOSE MAGNESIUM STEARATE SODIUM LAURYL SULFATE GELATIN titanium dioxide SODIUM LAURYL SULFATE AMMONIA ALCOHOL ISOPROPYL ALCOHOL BUTYL ALCOHOL SHELLAC POTASSIUM HYDROXIDE propylene glycol FERROSOFERRIC OXIDE Product Characteristics Color Size Imprint Code Shape white 19 mm 30mg;Novel123 CAPSULE Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:55289-660-30 30 in 1 BOTTLE, PLASTIC Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA071457 1987-04-21