What is the half-life of Valium (diazepam)?

Valium (Diazepam) Half-Life

Diazepam has an elimination half-life of 20-120 hours in adults, with the terminal elimination phase extending up to 48 hours, and its active metabolite N-desmethyldiazepam has an even longer half-life of up to 100 hours. 1

Age-Specific Half-Life Variations

The half-life of diazepam varies significantly across different age groups:

Adults

• Young adults (20 years): Baseline half-life of approximately 20 hours 1
• Age-related increase: The elimination half-life increases by approximately 1 hour for each year of age after 20 years 1
• General adult range: 20-120 hours, with the terminal elimination phase up to 48 hours 2

Pediatric Populations

• Children (3-8 years): Mean half-life of 18 hours 2
• Children (2-12 years): 15-21 hours 2
• Adolescents (12-16 years): 18-20 hours 2
• Infants (1 month-2 years): 40-50 hours 2

Neonates

• Full-term newborns: Approximately 30 hours 1
• Premature infants (28-34 weeks gestational age): Average of 54 hours, with a range of 50-95 hours 2, 1
• The prolonged half-life in neonates is due to incomplete maturation of metabolic pathways 1

Active Metabolite Considerations

A critical clinical point: Diazepam's active metabolite desmethyldiazepam (N-desmethyldiazepam) has a prolonged half-life that can extend beyond the parent compound. 2, 1

• Desmethyldiazepam half-life: Up to 100 hours 1
• This active metabolite contributes significantly to the drug's prolonged clinical effects 2
• The metabolite shows evidence of continued accumulation, particularly in premature and full-term infants compared to children 1

Special Population Considerations

Elderly Patients

• The elimination half-life increases progressively with age due to increased volume of distribution and decreased clearance 1
• Elderly patients may have lower peak concentrations but higher trough concentrations with multiple dosing 1
• Time to reach steady-state is prolonged in this population 1

Hepatic Impairment

• Mild to moderate cirrhosis: Average half-life increases 2-5 fold, with individual half-lives exceeding 500 hours reported 1
• Hepatic fibrosis: Mean half-life of 90 hours (range 66-104 hours) 1
• Chronic active hepatitis: Mean half-life of 60 hours (range 26-76 hours), with clearance decreased by almost half 1
• Acute viral hepatitis: Mean half-life of 74 hours (range 49-129 hours) 1

Clinical Implications

Drug Accumulation

• Diazepam accumulates upon multiple dosing, and the terminal elimination half-life is slightly prolonged with repeated administration 1
• The long half-life results in a gradual, self-tapering decline in drug levels, producing smoother withdrawal with lower incidence of breakthrough symptoms and rebound phenomena 3

Timing Considerations for Brain Death Determination

• When diazepam is used in critically ill pediatric patients, specific waiting periods are required before brain death examination 2
• Drug levels should be obtained to ensure levels are in low to mid-therapeutic range prior to neurologic examination 2
• Metabolism may be affected by organ dysfunction and hypothermia 2

Breastfeeding Context

• Due to the prolonged half-life of both diazepam and its active metabolite desmethyldiazepam, the drug is known to transfer into breast milk at significant levels 2
• Use may be considered as a one-off dose before a procedure, but is not preferred for routine use in breastfeeding women 2

Classification

Diazepam is classified as a long-acting benzodiazepine with a half-life exceeding 24 hours. 4 This classification is based on its pharmacologically active metabolites (particularly desmethyldiazepam), extensive accumulation during multiple dosing, and potentially impaired clearance in elderly patients and those with liver disease 4