FDA label 709452dc-4bb4-4e99-e053-2991aa0a67af

WARNINGS Diazepam is not recommended in the treatment of psychotic patients and should not be employed instead of appropriate treatment. Since diazepam has a central nervous system depressant effect, patients should be advised against the simultaneous ingestion of alcohol and other CNS-depressant drugs during diazepam therapy. As with other agents that have anticonvulsant activity, when diazepam 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 diazepam 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/m 2 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 diazepam 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 diazepam.

ADVERSE REACTIONS Side effects most commonly reported were drowsiness, fatigue, muscle weakness, and ataxia. The following have also been reported: Central Nervous System: confusion, depression, dysarthria, headache, slurred speech, tremor, vertigo Gastrointestinal System: constipation, nausea, gastrointestinal disturbances Special Senses: blurred vision, diplopia, dizziness Cardiovascular System: hypotension Psychiatric and Paradoxical Reactions: stimulation, restlessness, acute hyperexcited states, anxiety, agitation, aggressiveness, irritability, rage, hallucinations, psychoses, delusions, increased muscle spasticity, insomnia, sleep disturbances, and nightmares. Inappropriate behavior and other adverse behavioral effects have been reported when using benzodiazepines. Should these occur, use of the drug should be discontinued. They are more likely to occur in children and in the elderly. Urogenital System: incontinence, changes in libido, urinary retention Skin and Appendages: skin reactions Laboratories: elevated transaminases and alkaline phosphatase Other: changes in salivation, including dry mouth, hypersalivation Antegrade amnesia may occur using therapeutic dosages, the risk increasing at higher dosages. Amnestic effects may be associated with inappropriate behavior. Minor changes in EEG patterns, usually low-voltage fast activity, have been observed in patients during and after diazepam therapy and are of no known significance. Because of isolated reports of neutropenia and jaundice, periodic blood counts and liver function tests are advisable during long-term therapy. Postmarketing Experience Injury, Poisoning and Procedural Complications: There have been reports of falls and fractures in benzodiazepine users. The risk is increased in those taking concomitant sedatives (including alcohol), and in the elderly.