(1989; 60 pages) [French]
Tablet: 2 mg, 5 mg
Injection: 5 mg/ml in 2-ml ampoule
Diazepam is a benzodiazepine with anxiolytic properties, a centrally mediated muscle-relaxant effect and, when used intravenously, an anticonvulsant action. It is metabolized in the liver to several active metabolites, which are mainly excreted in the urine as glucuronides.
The response, which persists for 12-24 hours, becomes evident 30-90 minutes after oral administration and 1-5 minutes after intravenous injection. The plasma half-life is 20-50 hours.
In general surgery:
• premedication before major or minor surgery
• to relieve anxiety and provide light sedation for endoscopic procedures and surgery under local anaesthesia
• in combination with pethidine, when other anaesthetic agents are not available, for emergency reduction of fractures.
Dosage and administration
Adults and children over 12 years: 5-10 mg orally 2 hours before surgery.
Anxiety relief and light sedation
Adults and children over 12 years: 200 micrograms/kg i.v. immediately before medical or surgical intervention.
In order to ensure stability, diazepam for injection should not be mixed with other drugs in syringes or infusion fluids, nor should it be diluted before use except in saline or glucose solution. Unused diazepam solutions should be discarded within 6 hours.
It should be administered directly into the cubital vein at a rate of no more than 1 ml/min to reduce the risk of thrombophlebitis. Preparations of diazepam in an oil-in-water emulsion are available which reduce the risk of thrombophlebitis after injection.
Accidental intra-arterial injection can cause severe local necrosis.
• Age less than 12 years.
• Known hypersensitivity to benzodiazepines.
• Parenteral administration is contraindicated in shocked or comatose patients.
Equipment for resuscitation should be immediately available.
Diazepam should be administered with particular caution to patients with myasthenia gravis. Patients with chronic obstructive airway disease are at particular risk of respiratory depression.
Diazepam should be used with great caution, in much reduced doses, and only when essential in elderly and debilitated patients, and in patients with chronic pulmonary insufficiency or chronic renal or hepatic disease.
Ambulatory patients should be warned that diazepam may impair their ability to drive or operate machinery for up to 24 hours.
Use in pregnancy
Use in pregnancy should be avoided whenever possible. An increased incidence of malformations has been reported in some studies among infants born to mothers who have received diazepam during the first trimester of pregnancy, although other, large-scale prospective studies have failed to confirm this.
Use of diazepam during labour can result in marked fetal sedation and hypotonia.
Paradoxical reactions including irritability, excitability, hallucinations, increased muscle spasticity and sleep disturbances have been reported, particularly in elderly patients and in children.
Rare but serious adverse reactions include leukopenia, jaundice and hypersensitivity reactions.
The effects of phenothiazines, barbiturates, monoamine oxidase inhibitors and other antidepressants may be potentiated.
Signs include somnolence, ataxia, dysarthria, diminished reflexes, confusion and coma. Paradoxical excitement may occur in children. Unless the specific benzodiazepine antagonist flumazenil is available, treatment should be symptomatic and directed to the management of respiratory depression and shock.
Diazepam should be stored in tightly closed containers protected from light.