Section 01 · Monograph
Diazepam
Reviewed Nov 2026FDA label
Valium / DiastatBenzodiazepine
- Forms
- Tab: 2, 5, 10mg | Sol: 5mg/5mL | IV: 5mg/mL | Rectal gel: 2.5, 10, 20mg
- Dose
- status/rescue dosing, weight-based
- MOA
- ↑GABA-A Cl- channel frequency
Black Box Warning
- RISKS FROM CONCOMITANT USE WITH OPIOIDS: Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing for patients with inadequate alternative treatment options; limit dosages/durations to the minimum required; monitor for signs/symptoms of respiratory depression and sedation.
- ABUSE, MISUSE, AND ADDICTION: The use of benzodiazepines, including diazepam, exposes users to risks of abuse, misuse, and addiction, which can lead to overdose or death. Assess each patient's risk before prescribing and monitor for these behaviors during therapy.
- DEPENDENCE AND WITHDRAWAL REACTIONS: Continued use of benzodiazepines may lead to clinically significant physical dependence. Abrupt discontinuation or rapid dose reduction can precipitate acute withdrawal reactions (including seizures), which can be life-threatening. To reduce risk, use a gradual taper when discontinuing or reducing dose.
Indications
- Management of anxiety disorders and short-term relief of anxiety symptoms.FDA-labeled
- Adjunct for the relief of skeletal muscle spasm due to reflex spasm to local pathology (e.g., inflammation of muscles/joints, or secondary to trauma).FDA-labeled
- Spasticity caused by upper motor neuron disorders, such as cerebral palsy and paraplegia.FDA-labeled
- Athetosis.FDA-labeled
- Stiff-man syndrome.FDA-labeled
- Adjunct in status epilepticus and severe recurrent convulsive seizures (specific formulations); adjunctive therapy for convulsive disorders.FDA-labeled
- Acute treatment of intermittent, stereotypic episodes of frequent seizure activity (seizure clusters/acute repetitive seizures) distinct from a patient's usual seizure pattern, in patients with epilepsy 2 years of age and older (rectal gel, e.g., Diastat).FDA-labeled
- Management of symptoms of acute alcohol withdrawal (tremor, impending/acute delirium tremens, hallucinosis).FDA-labeled
- Preoperative sedation/anxiety relief (injectable formulation).FDA-labeled
Off-Label Uses
- Adjunct in tetanus-associated muscle spasm.Off-label
- Vestibular disorders/vertigo symptom management.Off-label
- Insomnia (short-term, off-label, not preferred given dependence risk).Off-label
- Procedural sedation adjunct.Off-label
- Restless legs syndrome (adjunctive, limited evidence).Off-label
Mechanism of Action
- Diazepam is a 1,4-benzodiazepine that exerts anxiolytic, sedative, skeletal muscle-relaxant, anticonvulsant, and amnestic effects.
- Acts by binding to a specific site on the GABA-A receptor complex, enhancing the effect of GABA by increasing the frequency of chloride channel opening; this potentiates GABAergic inhibitory neurotransmission at both supraspinal and spinal levels.
- Increased chloride influx hyperpolarizes the neuron, raising the threshold for seizure activity — the basis of its anticonvulsant effect in seizure clusters and status epilepticus.
- The antispastic effect is thought to result primarily from enhancement of GABAergic pre-synaptic inhibition at the spinal cord level, reducing excitatory reflex arcs and hyperexcitable motor neuron activity characteristic of upper motor neuron (spastic) syndromes.
- Distinguish from botulinum toxins (peripheral, focal chemodenervation) and baclofen (GABA-B receptor agonist) — diazepam acts centrally via GABA-A and produces more generalized (rather than focal) muscle relaxation and sedation.
Full Dosing
Adult / usual
- Spasticity (oral, adults): 2 mg to 10 mg orally, 3 to 4 times daily, as an adjunct to other spasticity management (physical therapy, other antispasmodics).
- Elderly or debilitated patients: initiate at 2 mg to 2.5 mg, 1 to 2 times daily; increase gradually as needed and tolerated, given increased sensitivity to sedative/CNS-depressant effects and fall risk.
- Seizure clusters — diazepam rectal gel (Diastat) dosing is age- and weight-based, rounded up to the nearest available unit dose (2.5, 5, 7.5, 10, 12.5, 15, 17.5, or 20 mg): ages 2-5 years approximately 0.5 mg/kg; ages 6-11 years approximately 0.3 mg/kg; ages 12 years and older approximately 0.2 mg/kg.
- A second rectal gel dose may be given 4-12 hours after the first if needed per protocol, but rectal gel should not be used to treat more than one episode every 5 days or more than 5 episodes per month.
- Taper gradually when discontinuing after regular/prolonged use to avoid precipitating withdrawal (which can include seizures); do not abruptly discontinue.
- Controlled substance: Schedule IV (C-IV) under the U.S. Controlled Substances Act.
- Injectable and rectal gel formulations exist for acute seizure/status epilepticus management but are not typically used for chronic spasticity management (oral tablets are standard for spasticity).
Renal
- Renal impairment: use with caution; dose adjustment may be needed as metabolites are renally excreted.
Hepatic
- Hepatic impairment: use with caution/lower doses given reliance on hepatic metabolism; contraindicated in severe hepatic insufficiency.
Pediatric
- Pediatric spasticity/muscle spasm dosing should be individualized per current labeling and specialist guidance; diazepam is contraindicated under 6 months of age (oral formulation).
Contraindications
- Known hypersensitivity to diazepam or any component of the formulation.
- Pediatric patients under 6 months of age (oral formulation).
- Myasthenia gravis.
- Severe respiratory insufficiency (except when used for the management of seizures).
- Severe hepatic insufficiency/hepatic impairment.
- Sleep apnea syndrome.
- Acute narrow-angle glaucoma (may be used in open-angle glaucoma if patients are receiving appropriate therapy).
Drug Interactions
- Opioids: markedly increased risk of profound sedation, respiratory depression, coma, and death (boxed warning) — avoid unless alternatives are inadequate.
- Other CNS depressants (alcohol, barbiturates, other sedative-hypnotics, general anesthetics, other muscle relaxants, sedating antihistamines, phenothiazines, MAO inhibitors): additive CNS/respiratory depression.
- Strong CYP3A4/CYP2C19 inhibitors (e.g., cimetidine, ketoconazole, fluconazole, fluvoxamine, fluoxetine, omeprazole, protease inhibitors): may increase diazepam plasma concentrations and prolong sedative effect.
- CYP450 inducers (e.g., rifampin, carbamazepine, phenytoin, phenobarbital): may reduce diazepam plasma levels/efficacy.
- Phenytoin: diazepam may alter phenytoin metabolism/levels — monitor phenytoin levels with co-administration.
- Valproate may potentiate CNS depressant effects.
- Oral contraceptives: may decrease diazepam clearance, potentiating its effect.
- Concomitant use with other muscle relaxants or antispasticity agents (baclofen, tizanidine) may produce additive sedation and hypotonia — monitor closely when combining for refractory spasticity.
Adverse Effects
- Very common/common: drowsiness/somnolence, fatigue, muscle weakness, ataxia, incoordination, dizziness, hypotonia.
- CNS: confusion, memory impairment/anterograde amnesia, slurred speech, headache.
- Paradoxical reactions (more common in children and the elderly): stimulation, restlessness, acute hyperexcited states, anxiety, hallucinations, psychosis, rage/aggressive or hostile behavior, sleep disturbances.
- Respiratory: respiratory depression, especially with concomitant opioids/CNS depressants or in patients with pulmonary disease.
- Falls and fractures, particularly in elderly patients.
- Tolerance and physical/psychological dependence with prolonged use; withdrawal syndrome on abrupt discontinuation, including risk of seizures; abuse/misuse potential.
- Other: blurred vision, constipation/GI upset, hypotension (with IV use), injection-site reactions (with parenteral formulations).
Monitoring Parameters
- Assess baseline and periodically for abuse/misuse risk, particularly with long-term therapy.
- Monitor respiratory status and level of sedation closely if co-prescribed with opioids or other CNS depressants.
- Distinguish the patient's characteristic seizure cluster from their usual seizure pattern before administering rescue therapy; ensure caregivers are educated on proper rectal gel administration and recognition of when to seek emergency care.
- Periodic complete blood counts and liver function tests are recommended during long-term therapy.
- Monitor for signs of tolerance, dependence, and withdrawal; use gradual tapering schedules when discontinuing.
- Assess fall risk and cognitive/psychomotor function, especially in elderly patients.
- Monitor renal and hepatic function periodically, particularly with long-term use or in patients with baseline impairment.
- Screen for paradoxical reactions, particularly in pediatric and elderly patients.
- Monitor neonates exposed late in pregnancy for sedation, respiratory depression, and withdrawal.
Pregnancy & Lactation
- Pregnancy: Benzodiazepines, including diazepam, are associated with an increased risk of congenital malformations when used during the first trimester (historically classified FDA Pregnancy Category D). Use late in pregnancy can cause neonatal flaccidity ('floppy infant syndrome'), respiratory and feeding difficulties, hypothermia, and a neonatal withdrawal syndrome (hyperreflexia, irritability, tremor, feeding difficulty). Avoid use in pregnancy unless clearly necessary.
- Encourage enrollment in the North American Antiepileptic Drug (NAAED) Pregnancy Registry (1-888-233-2334) for patients treated for epilepsy.
- Lactation: Diazepam and its active metabolites pass into breast milk and can accumulate in the nursing infant (sedation, poor feeding, weight loss have been reported). Breastfeeding is generally not recommended during Valium/diazepam therapy.