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Diazepam should be used with caution in patients with renal or hepatic dysfunction, circulatory insufficiency and myasthenia gravis (because of the pre-existing muscle weakness). 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.
Psychiatric and paradoxical reactions: Paradoxical reactions such as restlessness, agitation, irritability, aggressiveness, delusion, rages, nightmares, hallucinations, psychoses, inappropriate behaviour and other adverse behavioural effects are known to occur when using benzodiazepines. Should this occur, the use of the drug should be discontinued. They are more likely to occur in children and in the elderly.
Elderly and debilitated patients are particularly susceptible to the side effects and may require lower doses. Alertness and performance at skilled tasks may be impaired. Patients should be warned not to drive vehicles or operate machinery.
Alcohol may potentiate these effects.
Cross-senitivity and/or related problems: Patients sensitive to one of the benzodiazepines may be sensitive to the other benzodiazepines also.
Use in Pregnancy: Diazepam crosses the placenta.
First trimester: Diazepam has been reported to increase the risk of congenital malformations when used during the first trimester of pregnancy. Risk-benefit must be carefully considered. However, since the use of benzodiazepines (with the possible exception of anticonvulsant use) is rarely a matter of urgency, it should be avoided during pregnancy, especially during the first trimester.
When diazepam is used as anticonvulsant, risk-benefit must be considered since recent reports suggest an increased incidence of congenital abnormalities in children whose mothers used anticonvulsants during pregnancy: however, a definite cause and effect relationship has not been established.
Chronic usage of benzodiazepines during pregnancy may cause physical dependence with resulting withdrawal symptoms in the neonate.
Use of benzodiazepine hypnotics during the last weeks of pregnancy may result in neonatal CNS depression.
Labour: Use of benzodiazepines just prior to or during labour may cause neonatal flaccidity.
Delivery: When diazepam is administered in doses of more than 30 mg (especially, intramuscularly or intravenously) to women within 15 hours before delivery, the neonate may develop apnea, hypotonia, hypothermia, a reluctance to feed, and impaired metabolic response to cold stress.
Use in Lactation: Diazepam is distributed into breast milk.
Since neonates metabolise benzodiazepines more slowly than adults and accumulation of the benzodiazepine and/or its metabolites may occur, use by nursing mothers may cause sedation, and possibly feeding difficulties and weight loss in the infant.
Use in Children: Children, especially the very young, are usually more sensitive to the CNS effects of benzodiazepines. Prolonged CNS depression may be produced in the neonate because of inability to biotransform the benzodiazepine into inactive metabolites.
Use in Elderly: Geriatric patients are usually more sensitive to the CNS effects of benzodiazepines. It is recommended that dosage is limited to the smallest effective dose and increased gradually, if necessary, to decrease the possibility of development of ataxia, dizziness, and oversedation. A retrospective case-control study has shown that elderly patients receiving long-acting benzodiazepines are more likely than those receiving short-acting benzodiazepines to suffer falls and fall-related fractures.
However, both groups had an increased risk of these sequelae as compared to older patients who did not receive benzodiazepines or who received other short-acting sedative-hypnotics.
Parenteral administration of benzodiazepines may be more likely to cause apnea, hypotension, bradycardia, or cardiac arrest in geriatric patients.
