II. Indications
- Insomnia
- Anxiety Disorder
- Alcohol Withdrawal
- Seizure Disorder (esp. Status Epilepticus)
- Musculoskeletal spasm
- Tetanus
III. Contraindications
- Acute Narrow Angle Glaucoma
- Untreated Open Angle Glaucoma
- Children under age 6 years
IV. Dosing: Adults for General Procedures
- See Status Epilepticus dosing below
-
Anxiety Disorder
- PO: 2 to 10 mg orally 2 to 4 times daily
- IV/IM: 2 to 10 mg orally every 3 to 4 hours as needed
- Maximum Daily Dose: 40 mg/day
- Acute Alcohol Withdrawal
- See Alcohol Withdrawal for extended protocol
- Oral
- First day: 10 mg orally 3 to 4 times daily
- Next days: 5 mg orally 3 to 4 times daily
- IV/IM
- Load 10 mg IV/IM, then 5-10 mg every 3-4 hours as needed
- In ED/ICU: 10 to 20 mg orally or 10 mg slow IV every 1 to 2 hours based on CIWA protocol until sedated
- Musculoskeletal spasm or spasticity (e.g. Cerebral Palsy, Paraplegia, Athetosis, Tetanus)
- PO: 2 to 10 mg orally 3 to 4 times daily
- IV/IM: 5 to 10 mg every 3 to 4 hours as needed
- Pre-procedure Anxiolysis and Sedation (e.g. endoscopy)
- Oral before minor procedure (e.g. Vasectomy): 10 mg orally take 2 hours before procedure
- IV (e.g. endoscopy): 10 to 20 mg IV 15 to 30 min prior to procedure
- Older patients or with comorbid condition
- Dose: 1 to 2.5 mg orally daily to twice daily
V. Dosing: Adults and Children for Status Epilepticus
- See Status Epilepticus
- IV: 0.1 to 0.3 mg/kg IV up to 8-10 mg/dose maximum (may repeat once in 5 minutes)
- Rectal: 0.2 to 0.5 mg/kg per Rectum up to maximum of 20 mg/day
- Instill via lubricated Feeding Tube inserted 4-5 cm into the Rectum OR
- Via tuberculin syringe (without needle) intra-rectally OR
- Using prefilled rectal gel (Diastat)
- Hold buttocks closed after instilling medication
- Diazepam is as effective as Lorazepam in Status Epilepticus
- Diazepam IM dosing is as effective as IV dosing
- Antiepileptic activity is short (5 to 15 minutes)
- Must be immediately followed with longer acting anticonvulsant (e.g. Fosphenytoin) due to short duration
VI. Dosing: Equivalent Doses of other Benzodiazepines
- Equivalents to 10 mg Diazepam (for withdrawal protocol)
- Alprazolam (Xanax) 1 mg
- Chlordiazepoxide (Librium) 25 mg
- Clonazepam (Klonopin) 4 mg
- Flurazepam (Dalmane) 15 mg
- Halazepam (Paxipam) 40 mg
- Lorazepam (Ativan) 2 mg
- Oxazepam (Serax) 10 mg
- Temazepam (Restoril) 10 mg
- Equivalents to 60 mg Diazepam (for withdrawal protocol)
- Alprazolam (Xanax) 6 mg
- Chlordiazepoxide (Librium) 150 mg
- Clonazepam (Klonopin) 24 mg
- Flurazepam (Dalmane) 90 mg
- Halazepam (Paxipam) 240 mg
- Lorazepam (Ativan) 12 mg
- Oxazepam (Serax) 60 mg
- Temazepam (Restoril) 60 mg
VII. Pharmacokinetics
- Half Life: 20-100 hours
- Half-Life may be extended to >100 hours in slow metabolizers (infants, elderly, severe liver disease)
- High lipid solubility (lipophilic)
- Despite long Half-Life, re-distributes quickly out of the CNS (where it is primarily active)
- Rapid onset of action (1-3 minutes IV)
- Most rapidly absorbed from the Gastrointestinal Tract (oral, rectal) of any Benzodiazepine
- Diazepam is metabolized by CYP3A4, CYP2C9, CYP2C19, CYP1A2 in the liver to active metabolites
VIII. Precautions
- Very long Half-Life may be even longer with more adverse effects in the elderly
- Avoid when requiring optimal mental status
- Driving
- Operating machinery
- Use caution if risk of cardiopulmonary depression
- Elderly
- Very ill patients
- Limited pulmonary reserve (e.g. COPD)
- Avoid use with other cardiopulmonary and CNS Depressants
- Alcohol
- Barbiturates
- Opioids (use only with caution)
- Intravenous Injection
- Inject intravenously slowly (1 ml per minute)
- Reduce dose to 70% when administering with Narcotic
IX. Adverse Effects
- Common General affects
- Drowsiness
- Fatigue
- Ataxia
- Benzodiazepine Dependence with withdrawal symptoms
- Local injection side affects (inject slowly)
- Venous thrombosis
- Phlebitis
- Less common, but serious reactions (esp. when combined with other CNS Depressants, such as Alcohol, Opioids, Barbiturates)
- Hypotension
- Respiratory depression
X. Safety
- Pregnancy Category D
- Avoid in Lactation
- Schedule IV Controlled Substance
XI. Drug Interactions
- Drug Interactions have a greater impact due to the very long half life of Diazepam
- Avoid use with Protease Inhibitors
- Drugs that increase Diazepam Levels
- Drugs that decrease Diazepam Levels
- Rifampin (increases Diazepam metabolism)
- Drugs whose levels are increased by Diazepam
XII. Resources
- Diazepam Tablet (DailyMed)
- Diazepam Injection (DailyMed)
XIII. References
- (2019) Med Lett Drugs Ther 61(1578): 121-6
- (2020) Presc Lett, Resource #361206, Appropriate Use of Benzodiazepines
- Olson (2020) Clinical Pharmacology, Medmaster Miami, p. 55
- Hamilton (2020) Tarascon Pocket Pharmacopoeia
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diazepam (on 12/20/2023 at Medicaid.Gov Survey of pharmacy drug pricing) | ||
DIAZEPAM 10 MG RECTAL GEL SYST | Generic | $252.48 each |
DIAZEPAM 10 MG TABLET | Generic | $0.03 each |
DIAZEPAM 2 MG TABLET | Generic | $0.02 each |
DIAZEPAM 20 MG RECTAL GEL SYST | Generic | $249.66 each |
DIAZEPAM 5 MG TABLET | Generic | $0.03 each |
DIAZEPAM 5 MG/5 ML SOLUTION | Generic | $0.10 per ml |