Valium - Drug Monograph

Introduction

Valium (diazepam) is a benzodiazepine medication first synthesized in 1959 and approved by the FDA in 1963. It remains one of the most widely prescribed anxiolytic medications worldwide. As a Schedule IV controlled substance, Valium possesses significant therapeutic benefits but also carries risks of dependence, abuse, and potentially severe withdrawal symptoms.

Mechanism of Action

Valium exerts its pharmacological effects primarily through potentiation of gamma-aminobutyric acid (GABA) neurotransmission. It binds to specific sites on the GABA-A receptor complex, enhancing GABA's inhibitory effects by increasing chloride ion conductance through the receptor channel. This hyperpolarizes neuronal membranes and reduces neuronal excitability throughout the central nervous system, resulting in anxiolytic, sedative, hypnotic, anticonvulsant, muscle relaxant, and amnestic effects.

Indications

FDA-approved indications:

• Anxiety disorders
• Acute alcohol withdrawal symptoms
• Adjunctive therapy for skeletal muscle spasm
• Adjunctive therapy for convulsive disorders
• Preoperative anxiety and amnesia

Off-label uses:

• Panic disorder
• Restless legs syndrome
• Agitation in critical care settings
• Status epilepticus (IV formulation)

Dosage and Administration

• Anxiety: 2-10 mg PO 2-4 times daily
• Alcohol withdrawal: 10 mg PO 3-4 times first 24 hours, then 5 mg 3-4 times daily
• Muscle spasm: 2-10 mg PO 3-4 times daily
• Seizure disorders: 2-10 mg PO 2-4 times daily

• Oral tablets: May be administered with or without food
• Injectable: For IM or IV administration (IV administration requires slow injection)
• Rectal gel: For acute repetitive seizures

• Hepatic impairment: Reduce dose by 50% or avoid
• Renal impairment: Use with caution
• Pregnancy: Category D - avoid unless clearly needed

Pharmacokinetics

Contraindications

• Hypersensitivity to diazepam or other benzodiazepines
• Acute narrow-angle glaucoma
• Severe respiratory depression
• Severe hepatic impairment
• Myasthenia gravis
• Sleep apnea syndrome
• Concurrent use with strong CYP3A4 inhibitors in patients with impaired CYP2C19 function

Warnings and Precautions

• Use with extreme caution in patients with respiratory compromise
• Elderly patients at increased risk of sedation, falls, and cognitive impairment
• Potential for paradoxical reactions (excitation, agitation)
• Not recommended during pregnancy (risk of neonatal withdrawal syndrome)
• Avoid abrupt discontinuation (risk of withdrawal seizures)
• Impaired alertness affecting driving or operating machinery

Drug Interactions

• Opioids: Increased CNS and respiratory depression
• Alcohol: Additive CNS depression
• Other sedatives/hypnotics: Enhanced sedative effects

• CYP3A4 inhibitors (ketoconazole, clarithromycin): Increased diazepam levels
• CYP3A4 inducers (rifampin, carbamazepine): Decreased diazepam levels
• CYP2C19 inhibitors (omeprazole, fluvoxamine): Increased diazepam levels

• Levodopa: May decrease efficacy
• Neuromuscular blocking agents: Enhanced effects

Adverse Effects

• Drowsiness, fatigue
• Ataxia, dizziness
• Muscle weakness
• Headache
• Blurred vision

• Respiratory depression
• Dependence and withdrawal syndrome
• Paradoxical reactions (agitation, aggression)
• Suicidal ideation
• Blood dyscrasias
• Jaundice
• Severe hypotension (with IV administration)

Monitoring Parameters

• Efficacy: Anxiety symptoms, seizure frequency, muscle spasm severity
• Safety: Respiratory rate, oxygen saturation (especially with IV administration)
• CNS effects: Sedation, cognitive impairment, coordination
• Signs of misuse or dependence
• Liver function tests (periodically with long-term use)
• Complete blood count (with prolonged therapy)
• Withdrawal symptoms during dose reduction

Patient Education

• Take exactly as prescribed; do not increase dose without medical supervision
• Avoid alcohol and other CNS depressants
• Do not abruptly stop medication
• May cause drowsiness - avoid driving or hazardous activities until effect known
• Use effective contraception; notify provider if pregnancy planned or suspected
• Store securely to prevent misuse by others
• Report any signs of worsening anxiety, depression, or suicidal thoughts
• Keep all follow-up appointments for monitoring
• Do not share medication with others

References

1. FDA Prescribing Information: Valium (diazepam) tablets. Revised 2016. 2. Griffiths RR, Johnson MW. Relative abuse liability of hypnotic drugs: a conceptual framework and algorithm for differentiating among compounds. J Clin Psychiatry. 2005;66 Suppl 9:31-41. 3. Lader M. Benzodiazepines revisited—will we ever learn? Addiction. 2011;106(12):2086-2109. 4. Soyka M. Treatment of Benzodiazepine Dependence. N Engl J Med. 2017;376(12):1147-1157. 5. Brett J, Murnion B. Management of benzodiazepine misuse and dependence. Aust Prescr. 2015;38(5):152-155. 6. Goodman & Gilman's The Pharmacological Basis of Therapeutics, 13th Edition. 7. Lexicomp Online, Diazepam Drug Information.