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Valium (diazepam tablets) is not recommended in the treatment of psychotic patients and should not be employed instead of appropriate treatment.

Since Valium (diazepam tablets) has a central nervous system depressant effect, patients should be advised against the simultaneous ingestion of alcohol and other CNS-depressant drugs during Valium (diazepam tablets) therapy.

As with other agents that have anticonvulsant activity, when Valium (diazepam tablets) is used as an adjunct in treating convulsive disorders, the possibility of an increase in the frequency and/or severity of grand mal seizures may require an increase in the dosage of standard anticonvulsant medication. Abrupt withdrawal of Valium (diazepam tablets) in such cases may also be associated with a temporary increase in the frequency and/or severity of seizures.

Pregnancy

An increased risk of congenital malformations and other developmental abnormalities associated with the use of benzodiazepine drugs during pregnancy has been suggested. There may also be non-teratogenic risks associated with the use of benzodiazepines during pregnancy. There have been reports of neonatal flaccidity, respiratory and feeding difficulties, and hypothermia in children born to mothers who have been receiving benzodiazepines late in pregnancy. In addition, children born to mothers receiving benzodiazepines on a regular basis late in pregnancy may be at some risk of experiencing withdrawal symptoms during the postnatal period.

Diazepam has been shown to be teratogenic in mice and hamsters when given orally at daily doses of 100 mg/kg or greater (approximately eight times the maximum recommended human dose [MRHD=1 mg/kg/day] or greater on a mg/m² basis). Cleft palate and encephalopathy are the most common and consistently reported malformations produced in these species by administration of high, maternally toxic doses of diazepam during organogenesis. Rodent studies have indicated that prenatal exposure to diazepam doses similar to those used clinically can produce long-term changes in cellular immune responses, brain neurochemistry, and behavior.

In general, the use of diazepam in women of childbearing potential, and more specifically during known pregnancy, should be considered only when the clinical situation warrants the risk to the fetus. The possibility that a woman of childbearing potential may be pregnant at the time of institution of therapy should be considered. 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 also be advised that if they become pregnant during therapy or intend to become pregnant they should communicate with their physician about the desirability of discontinuing the drug.

Labor and Delivery

Special care must be taken when Valium (diazepam tablets) is used during labor and delivery, as high single doses may produce irregularities in the fetal heart rate and hypotonia, poor sucking, hypothermia, and moderate respiratory depression in the neonates. With newborn infants it must be remembered that the enzyme system involved in the breakdown of the drug is not yet fully developed (especially in premature infants).

Nursing Mothers

Diazepam passes into breast milk. Breastfeeding is therefore not recommended in patients receiving Valium (diazepam tablets) .

General

If Valium (diazepam tablets) is to be combined with other psychotropic agents or anticonvulsant drugs, careful consideration should be given to the pharmacology of the agents to be employed - particularly with known compounds that may potentiate the action of diazepam, such as phenothiazines, narcotics, barbiturates, MAO inhibitors and other antidepressants (see DRUG INTERACTIONS).

The usual precautions are indicated for severely depressed patients or those in whom there is any evidence of latent depression or anxiety associated with depression, particularly the recognition that suicidal tendencies may be present and protective measures may be necessary.

Psychiatric and paradoxical reactions are known to occur when using benzodiazepines (see ADVERSE REACTIONS). Should this occur, use of the drug should be discontinued. These reactions are more likely to occur in children and the elderly.

A lower dose is recommended for patients with chronic respiratory insufficiency, due to the risk of respiratory depression.

Benzodiazepines should be used with extreme caution in patients with a history of alcohol or drug abuse (see Drug Abuse And Dependence).

In debilitated patients, it is recommended that the dosage be limited to the smallest effective amount to preclude the development of ataxia or oversedation (2 mg to 2.5 mg once or twice daily, initially, to be increased gradually as needed and tolerated).

Some loss of response to the effects of benzodiazepines may develop after repeated use of Valium (diazepam tablets) for a prolonged time.

Carcinogenesis, Mutagenesis, Impairment of Fertility

In studies in which mice and rats were administered diazepam in the diet at a dose of 75 mg/kg/day (approximately 6 and 12 times, respectively, the maximum recommended human dose [MRHD=1 mg/kg/day] on a mg/m² basis) for 80 and 104 weeks, respectively, an increased incidence of liver tumors was observed in males of both species. The data currently available are inadequate to determine the mutagenic potential of diazepam. Reproduction studies in rats showed decreases in the number of pregnancies and in the number of surviving offspring following administration of an oral dose of 100 mg/kg/day (approximately 16 times the MRHD on a mg/m² basis) prior to and during mating and throughout gestation and lactation. No adverse effects on fertility or offspring viability were noted at a dose of 80 mg/kg/day (approximately 13 times the MRHD on a mg/m² basis).

Pregnancy

Category D (see WARNINGS: Pregnancy).

Pediatric Use

Safety and effectiveness in pediatric patients below the age of 6 months have not been established.

Geriatric Use

In elderly patients, it is recommended that the dosage be limited to the smallest effective amount to preclude the development of ataxia or oversedation (2 mg to 2.5 mg once or twice daily, initially to be increased gradually as needed and tolerated).

Extensive accumulation of diazepam and its major metabolite, desmethyldiazepam, has been noted following chronic administration of diazepam in healthy elderly male subjects. Metabolites of this drug are known to be substantially excreted by the kidney, and the risk of toxic reactions may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

Hepatic Insufficiency

Decreases in clearance and protein binding, and increases in volume of distribution and half-life has been reported in patients with cirrhosis. In such patients, a 2- to 5- fold increase in mean half-life has been reported. Delayed elimination has also been reported for the active metabolite desmethyldiazepam. Benzodiazepines are commonly implicated in hepatic encephalopathy. Increases in half-life have also been reported in hepatic fibrosis and in both acute and chronic hepatitis (see CLINICAL PHARMACOLOGY: Pharmacokinetics in Special Populations: Hepatic Insufficiency).

Last reviewed on RxList: 10/25/2010
This monograph has been modified to include the generic and brand name in many instances.