Diazepam

Aka: Diazepam, Valium, Diastat, Valtoco

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II. Indications

  1. Insomnia
  2. Anxiety Disorder
  3. Alcohol Withdrawal
  4. Seizure Disorder (esp. Status Epilepticus)
  5. Musculoskeletal spasm
  6. Tetanus

III. Contraindications

  1. Acute Narrow Angle Glaucoma
  2. Untreated Open Angle Glaucoma
  3. Children under age 6 years

IV. Mechanism

  1. See Benzodiazepine

V. Medications

  1. Tablets: 2 mg, 5 mg, 10 mg
  2. Oral Concentrate (Intensol): 5 ml/ml
  3. Agents for Status Epilepticus (for home rescue)
    1. Rectal Gel (Diastat): 10 mg, 20 mg
    2. Diastat AcuDial Syringes: 10 mg (in 2.5 mg increments) or 20 mg (in 2.5 mg increments)
    3. Intranasal Diazepam (Valtoco) in 5, 10, 15 or 20 mg

VI. Dosing: Adults for General Procedures

  1. See Status Epilepticus dosing below
  2. Anxiety Disorder
    1. PO: 2 to 10 mg orally 2 to 4 times daily
    2. IV/IM: 2 to 10 mg orally every 3 to 4 hours as needed
    3. Maximum Daily Dose: 40 mg/day
  3. Acute Alcohol Withdrawal
    1. See Alcohol Withdrawal for extended protocol
    2. Oral
      1. First day: 10 mg orally 3 to 4 times daily
      2. Next days: 5 mg orally 3 to 4 times daily
    3. IV/IM
      1. Load 10 mg IV/IM, then 5-10 mg every 3-4 hours as needed
      2. In ED/ICU: 10 to 20 mg orally or 10 mg slow IV every 1 to 2 hours based on CIWA protocol until sedated
  4. Musculoskeletal spasm or spasticity (e.g. Cerebral Palsy, Paraplegia, Athetosis, Tetanus)
    1. PO: 2 to 10 mg orally 3 to 4 times daily
    2. IV/IM: 5 to 10 mg every 3 to 4 hours as needed
  5. Pre-procedure Anxiolysis and Sedation (e.g. endoscopy)
    1. Oral before minor procedure (e.g. Vasectomy): 10 mg orally take 2 hours before procedure
    2. IV (e.g. endoscopy): 10 to 20 mg IV 15 to 30 min prior to procedure
  6. Older patients or with comorbid condition
    1. Dose: 1 to 2.5 mg orally daily to twice daily

VII. Dosing: Adults and Children for Status Epilepticus

  1. See Status Epilepticus
  2. IV: 0.1 to 0.3 mg/kg IV up to 8-10 mg/dose maximum (may repeat once in 5 minutes)
  3. Rectal
    1. Dose: 0.2 to 0.5 mg/kg per Rectum up to maximum of 20 mg/day (use closest available dose)
      1. Ages 2 to 5 years: 0.5 mg/kg
      2. Ages 6 to 11 years: 0.3 mg/kg
      3. Ages 12 years and older: 0.2 mg/kg
    2. Technique: Hold buttocks closed after instilling medication
      1. Instill via lubricated Feeding Tube inserted 4-5 cm into the Rectum OR
      2. Via tuberculin syringe (without needle) intra-rectally OR
      3. Using prefilled rectal gel (Diastat or Diastat AcuDial)
  4. Intranasal (Valtoco)
    1. Age 6 to 11 years (0.3 mg/kg)
      1. Weight 10 to 18 kg: Dose 5 mg
      2. Weight 19 to 37 kg: Dose 10 mg
      3. Weight 38 to 55 kg: Dose 15 mg
      4. Weight 56 to 74 kg: Dose 20 mg
    2. Age 12 and older including adults (0.2 mg/kg)
      1. Weight 14 to 27 kg: Dose 5 mg
      2. Weight 28 to 50 kg: Dose 10 mg
      3. Weight 51 to 75 kg: Dose 15 mg
      4. Weight >=76 kg: Dose 20 mg
  5. Diazepam is as effective as Lorazepam in Status Epilepticus
    1. Chamberlain (2014) JAMA 311(16): 1652-60 [PubMed]
  6. Diazepam IM dosing is as effective as IV dosing
    1. Silbergleit (2012) N Engl J Med 366:591-600 [PubMed]
  7. Antiepileptic activity is short (5 to 15 minutes)
    1. Must be immediately followed with longer acting anticonvulsant (e.g. Fosphenytoin) due to short duration

VIII. Dosing: Equivalent Doses of other Benzodiazepines

  1. Equivalents to 10 mg Diazepam (for withdrawal protocol)
    1. Alprazolam (Xanax) 1 mg
    2. Chlordiazepoxide (Librium) 25 mg
    3. Clonazepam (Klonopin) 4 mg
    4. Flurazepam (Dalmane) 15 mg
    5. Halazepam (Paxipam) 40 mg
    6. Lorazepam (Ativan) 2 mg
    7. Oxazepam (Serax) 10 mg
    8. Temazepam (Restoril) 10 mg
  2. Equivalents to 60 mg Diazepam (for withdrawal protocol)
    1. Alprazolam (Xanax) 6 mg
    2. Chlordiazepoxide (Librium) 150 mg
    3. Clonazepam (Klonopin) 24 mg
    4. Flurazepam (Dalmane) 90 mg
    5. Halazepam (Paxipam) 240 mg
    6. Lorazepam (Ativan) 12 mg
    7. Oxazepam (Serax) 60 mg
    8. Temazepam (Restoril) 60 mg

IX. Pharmacokinetics

  1. Half Life: 20-100 hours
    1. Half-Life may be extended to >100 hours in slow metabolizers (infants, elderly, severe liver disease)
  2. High lipid solubility (lipophilic)
    1. Despite long Half-Life, re-distributes quickly out of the CNS (where it is primarily active)
  3. Rapid onset of action (1-3 minutes IV)
  4. Most rapidly absorbed from the Gastrointestinal Tract (oral, rectal) of any Benzodiazepine
  5. Diazepam is metabolized by CYP3A4, CYP2C9, CYP2C19, CYP1A2 in the liver to active metabolites
    1. Metabolized primarily to the active agent desmethyldiazepam
    2. Also metabolized to other active agents to a lesser extent including Temazepam and Oxazepam

X. Precautions

  1. Very long Half-Life may be even longer with more adverse effects in the elderly
  2. Avoid when requiring optimal mental status
    1. Driving
    2. Operating machinery
  3. Use caution if risk of cardiopulmonary depression
    1. Elderly
    2. Very ill patients
    3. Limited pulmonary reserve (e.g. COPD)
  4. Avoid use with other cardiopulmonary and CNS Depressants
    1. Alcohol
    2. Barbiturates
    3. Opioids (use only with caution)
  5. Intravenous Injection
    1. Inject intravenously slowly (1 ml per minute)
    2. Reduce dose to 70% when administering with Narcotic

XI. Adverse Effects

  1. Common General affects
    1. Drowsiness
    2. Fatigue
    3. Ataxia
    4. Benzodiazepine Dependence with withdrawal symptoms
  2. Local injection side affects (inject slowly)
    1. Venous thrombosis
    2. Phlebitis
  3. Less common, but serious reactions (esp. when combined with other CNS Depressants, such as Alcohol, Opioids, Barbiturates)
    1. Hypotension
    2. Respiratory depression

XII. Safety

  1. Pregnancy Category D
  2. Avoid in Lactation
  3. Schedule IV Controlled Substance

XIII. Drug Interactions

  1. Drug Interactions have a greater impact due to the very long half life of Diazepam
  2. Avoid use with Protease Inhibitors
  3. Drugs that increase Diazepam Levels
    1. Cimetidine
    2. Oral Contraceptives
    3. Disulfiram
    4. Fluoxetine
    5. Isoniazide
    6. Ketoconazole
    7. Metoprolol
    8. Propranolol
    9. Valproic Acid
  4. Drugs that decrease Diazepam Levels
    1. Rifampin (increases Diazepam metabolism)
  5. Drugs whose levels are increased by Diazepam
    1. Digoxin
    2. Phenytoin

XIV. Resources

  1. Diazepam Tablet (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=554baee5-b171-4452-a50a-41a0946f956c
  2. Diazepam Injection (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=7e7dd743-a87b-4ab3-b6ae-f116cd0c8b0f

XV. References

  1. (2019) Med Lett Drugs Ther 61(1578): 121-6
  2. (2020) Presc Lett, Resource #361206, Appropriate Use of Benzodiazepines
  3. Olson (2020) Clinical Pharmacology, Medmaster Miami, p. 55
  4. Hamilton (2020) Tarascon Pocket Pharmacopoeia

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Related Studies

Cost: Medications

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
diastat (on 5/18/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
DIASTAT ACUDIAL 5-7.5-10 MG KT Generic $252.48 each
valtoco (on 1/1/2023 at Medicaid.Gov Survey of pharmacy drug pricing)
VALTOCO 10 MG NASAL SPRAY $316.89 each
VALTOCO 15 MG NASAL SPRAY $317.79 each
VALTOCO 20 MG NASAL SPRAY $316.91 each
VALTOCO 5 MG NASAL SPRAY $316.99 each
FPNotebook does not benefit financially from showing this medication data or their pharmacy links. This information is provided only to help medical providers and their patients see relative costs. Insurance plans negotiate lower medication prices with suppliers. Prices shown here are out of pocket, non-negotiated rates. See Needy Meds for financial assistance information. GoodRx is another tool for finding lower drug prices.

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