Diazepam

Diazepam is indicated for the short-term treatment of mild to moderate anxiety, excitation, agitation, fear, aggressiveness, etc. Anxiety reactions caused by stressed conditions, anxiety states with somatic expression, acute alcohol withdrawal, status epilepticus, premedication for surgical procedures, febrile convulsions, insomnia of hospitalized patients.

Benzodiazepine sedatives, Centrally acting Skeletal Muscle Relaxants, Primary anti-epileptic drugs

Diazepam attaches to the specific site on the GABA receptor and potentiates the effect of GABA, which acts by opening chloride ion channels into cells.

Diazepam is absorbed rapidly and completely after oral administration. Peak Plasma concentration reaches within 15-90 minutes. Mean plasma half-life is 30 hours. Plasma protein binding is 98-99%. Diazepam is metabolized in the liver with only traces of the unchanged drug excreted in urine. A very small proportion of the metabolites is excreted through the bile into the intestine and eliminated with the feces. After rectal administration in suppository form diazepam is significantly absorbed and peak concentration reaches within 1.5-2 hours.

Oral:

• Anxiety: 2 mg thrice daily, increased if necessary to 15-30 mg daily in divided doses. Elderly (or debilitated), half of the adult dose.
• Insomnia associated with anxiety: 5-15 mg at bedtime.
• Night terrors and somnambulism in Child: 1-5 mg at bedtime.

IM/slow IV injection (large vein, a rate below 5 mg/minute):

• For severe acute anxiety, control of acute panic attacks, and acute alcohol withdrawal: 10 mg repeated if necessary after not less than 4 hours.
• Febrile convulsion in children: Slow IV in a dose of 250 mcg/kg.

Rectal:

• In case of children- A dose of 500 mcg/kg (maximum 10 mg), repeated if necessary.

Diazepam is generally well tolerated. Higher doses may cause somnolence, dizziness, light headedness, confusion and ataxia.

Diazepam is contraindicated in myasthenia gravis, pulmonary insufficiency, respiratory depression and hypersensitivity to bezodiazepine.

Prolonged use and abrupt withdrawal should be avoided. Diazepam should be used with caution in respiratory disease, muscle weakness, history of drug or alcohol abuse, in hepatic or renal impairment.

Concomitant intake with alcohol is not recommended. Sedation may be increased due to concomitant use of neuroleptics (antipsychotics), hypnotics, sedative antihistamines and CNS depressants e.g., general anesthetics, narcotic analgesics or antidepressants. Diazepam clearance is increased by concomitant administration of phonobarbitone and is decreased by administration of cimetidine. Omeprazole and isoniazide inhibit diazepam metabolism.

Diazepam and its active metabolites cross the placental barrier and also pass into breast milk. So, it should be avoided if possible during pregnancy and lactation. US FDA pregnancy category D.

Sedation, muscle weakness, profound sleep or paradoxical excitation. In more severe cases symptoms may include ataxia, hypotonia, hypotension, respiratory depression and rarely coma and death.

Store in a cool (below 25˚C temperature) and dry place protected from light.