Diazepam is a long-acting benzodiazepine derivative with potent anxiolytic, sedative, hypnotic, muscle relaxant, and anticonvulsant properties. It acts centrally by enhancing the effect of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) at the GABA-A receptor. In the Indian context, it is a widely prescribed but strictly controlled Schedule H1 drug due to its high potential for dependence and abuse.
Adult: Anxiety: 2-10 mg, 2-4 times daily. Muscle spasm: 2-10 mg, 3-4 times daily. Alcohol withdrawal: 10 mg, 3-4 times in first 24 hours, then reduce to 5 mg, 3-4 times daily as needed. Seizures: 2-10 mg, 2-4 times daily. Geriatric/debilitated: 2-2.5 mg, 1-2 times daily initially.
Note: Take with or without food. For oral tablets, swallow whole with water. Avoid grapefruit juice. Do not crush or chew. For IV administration: Administer slowly (max 5 mg/min) to avoid respiratory depression/apnea. IM route is painful and absorption erratic; avoid. Taper dose gradually to discontinue; do not stop abruptly.
Diazepam potentiates the inhibitory effects of GABA, the major inhibitory neurotransmitter in the central nervous system. It binds to a specific site (the benzodiazepine binding site) on the GABA-A receptor complex, which is a ligand-gated chloride channel. This binding increases the frequency of chloride channel opening events in response to GABA, leading to hyperpolarization of the neuronal membrane and reduced neuronal excitability.
Pregnancy: Pregnancy Category D (US FDA). Evidence of human fetal risk. Benzodiazepines cross the placenta. Use in first trimester associated with increased risk of congenital malformations (cleft lip/palate). Use in late pregnancy can cause fetal sedation, neonatal flaccidity (floppy infant syndrome), and withdrawal symptoms in the neonate. AVOID USE, especially in first trimester and near term.
Driving: SEVERELY IMPAIRS alertness, reaction time, and motor coordination. Patients must NOT drive or operate heavy machinery, especially during initial therapy and dose changes.
| Alcohol | Profound additive CNS depression, respiratory depression, risk of death | Contraindicated |
| Opioids (e.g., Codeine, Tramadol, Morphine) | Additive CNS depression, profound sedation, respiratory depression, coma, death | Major - Requires extreme caution, dose adjustment, and monitoring |
| Other CNS Depressants (Barbiturates, Antipsychotics, Antihistamines) | Increased sedative effects and impaired psychomotor performance | Major |
| CYP3A4 Inhibitors (e.g., Ketoconazole, Itraconazole, Clarithromycin, Ritonavir) | Increased diazepam plasma levels, enhanced effects and toxicity | Major |
| CYP3A4/CYP2C19 Inducers (e.g., Rifampicin, Carbamazepine, Phenytoin, Phenobarbital) | Decreased diazepam plasma levels, reduced efficacy | Moderate |
| Cimetidine | Inhibits metabolism, increases diazepam levels | Moderate |
| Levodopa | Diazepam may decrease efficacy of levodopa in Parkinson's disease | Moderate |
| Theophylline | May antagonize the sedative effects of diazepam | Moderate |