Diazepam is a long-acting oral and parenteral benzodiazepine. Diazepam is similar to chlordiazepoxide and clorazepate in that all three generate the same active metabolite. Diazepam is used orally for the short-term management of anxiety dis
In addition to treating status epilepticus, diazepam has recently been shown effective in preventing recurrence of febrile seizures. Although diazepam has been the benzodiazepine of choice for status epilepticus, recent evidence indicates that lorazepam may be more beneficial because it provides longer control of seizures and produces less cardiorespiratory depression. Diazepam was approved by the FDA in November 1963. Phase III data for a rectal formulation of diazepam in the treatment of acute repetitive seizures was completed April 1995. The NDA for the rectal formulation (Diastat) is expected to be filed in 1995. Diazepam is a schedule IV controlled substance.
Diazepam is an anxiolytic-sedative drug useful in the symptomatic relief of anxiety and tension states. It has also adjunctive value in the relief of certain neurospastic conditions. Peak blood levels after oral administration of diazepam are reached within 1 to 2 hours after single oral dosing. The acute half-life is 6 to 8 hours with a slower decline thereafter, possibly due to tissue storage. However, after repeated doses, blood levels increase significantly over a period of 24 to 48 hours.
In humans, comparable blood levels of diazepam were obtained in maternal and cord blood indicating placental transfer of the drug.
The symptomatic management of mild to moderate degrees of anxiety in conditions dominated by tension, excitation, agitation, fear or aggressiveness, such as may occur in psychoneurosis, anxiety reactions due to stress conditions and anxiety states with somatic expression.
In acute alcoholic withdrawal, diazepam may be useful in the symptomatic relief of acute agitation, tremor and impending acute delirium tremens.
As an adjunct for the relief of skeletal muscle spasm due to reflex spasm to local pathology, such as inflammation of the muscle and joints or secondary to trauma; spasticity caused by upper motor neuron disorders, such as cerebral palsy and paraplegia; athetosis and the rare "stiff man syndrome".
Geriatrics: Elderly and debilitated patients or those with organic brain disorders have been found to be prone to CNS depression following even low doses. For these patients it is recommended that the dosage be limited to the smallest effective amount to preclude development of ataxia, oversedation or other possible adverse effects.
Emotional Disorders: Diazepam is not recommended in the treatment of psychotic or severely depressed patients. Precautions are indicated for severely depressed patients or those who show evidence of impending depression, particularly the recognition that suicidal tendencies may be present and protective measures may be necessary. Since excitement and other paradoxical reactions may result from the use of the drug in psychotic patients, it should not be used in ambulatory patients suspected of having psychotic tendencies.
Epileptic Patients: Careful consideration should be given if diazepam is to be used in patients with epilepsy as the possibility of an increase in the frequency and/or severity of grand mal seizures may require an increase in the doses of standard anticonvulsant medication. An abrupt withdrawal of diazepam is such cases may also be associated with the temporary increase in the frequency and/or severity of seizures.
Pregnancy: Diazepam should not be used during the first trimester of pregnancy except if absolutely necessary.
Potentiation of Drug Effects: Careful consideration should be given if diazepam is to be combined with other psychotropic agents, phenothiazines, barbiturates, MAO inhibitors and other antidepressants because the pharmacological action of these agents might potentiate the action of diazepam. Since diazepam has a CNS depressant effect, patients should be advised against the simultaneous ingestion of alcohol and other CNS depressant drugs during diazepam therapy.
Drug Dependence: Abrupt cessation of large doses of diazepam after prolonged periods may precipitate acute withdrawal symptoms and, in these cases, the drug should be discontinued gradually. Caution should be exercised when it is considered necessary to administer diazepam to addiction prone individuals.
General: Patients receiving diazepam should be advised to proceed cautiously wherever mental alertness and physical coordination are required.
The usual precautions in treating patients with impaired renal and hepatic functions should be observed. If diazepam is administered for protracted periods, periodic blood counts and liver function tests would be highly advisable.
The most common adverse effects reported are drowsiness and ataxia. Other reactions noted less frequently are fatigue, dizziness, nausea, blurred vision, diplopia, vertigo, headache, slurred speech, tremors, hypoactivity, dysarthria, euphoria, impairment of memory, confusion, depression, incontinence or urinary retention, constipation, skin rash, generalized exfoliative dermatitis, hypotension and changes in libido.
The more serious adverse reactions occasionally reported are leukopenia, jaundice, hypersensitivity and paradoxical reactions (such as hyperexcited states, anxiety, excitement, hallucinations, increased muscle spasticity, insomnia