The symptoms of diazepam overdose are mainly an intensification of the therapeutic effects (ataxia, drowsiness, dysarthria, sedation, muscle weakness, profound sleep, hypotension, bradycardia, nystagmus) or paradoxical excitation F3157, F3160, L5188. In most cases only observation of vital functions is required F3157, F3160, L5188.

Extreme overdosage may lead to coma, areflexia, cardio-respiratory depression and apnoea, requiring appropriate countermeasures (ventilation, cardiovascular support) F3157, F3160, L5188.

Benzodiazepine respiratory depressant effects are more serious in patients with severe chronic obstructive airways disease F3157, F3160, L5188. Severe effects in overdose also include rhabdomyolysis and hypothermia ^L5188. Overdose of benzodiazepines in combination with other CNS depressants (including alcohol) may be fatal and should be closely monitored ^F3157.

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 ^F3157. The possibility that a woman of childbearing potential may be pregnant at the time of institution of therapy should be considered ^F3157. 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 ^F3157. 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 ^F3157.

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 ^F3157. 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) ^F3157.

Diazepam passes into breast milk ^F3157. Breastfeeding is therefore not recommended in patients receiving diazepam ^F3157.

Safety and effectiveness in pediatric patients below the age of 6 months have not been established ^F3157.

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) ^F3157. 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 ^F3157. 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 ^F3157.

Decreases in clearance and protein binding, and increases in volume of distribution and half-life has been reported in patients with cirrhosis ^F3157. In such patients, a 2- to 5- fold increase in mean half-life has been reported ^F3157. Delayed elimination has also been reported for the active metabolite desmethyldiazepam ^F3157. Benzodiazepines are commonly implicated in hepatic encephalopathy ^F3157. Increases in half-life have also been reported in hepatic fibrosis and in both acute and chronic hepatitis ^F3157.