Diazepam

Tablets: 2 mg, 5 mg, 10 mg
Oral Concentrate (Intensol): 5 ml/ml
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

See Status Epilepticus dosing below
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
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
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
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
Older patients or with comorbid condition
1. Dose: 1 to 2.5 mg orally daily to twice daily

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
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)
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
Diazepam is as effective as Lorazepam in Status Epilepticus
1. Chamberlain (2014) JAMA 311(16): 1652-60 [PubMed]
Diazepam IM dosing is as effective as IV dosing
1. Silbergleit (2012) N Engl J Med 366:591-600 [PubMed]
Antiepileptic activity is short (5 to 15 minutes)
1. Must be immediately followed with longer acting anticonvulsant (e.g. Fosphenytoin) due to short duration

Half Life: 20-100 hours
1. Half-Life may be extended to >100 hours in slow metabolizers (infants, elderly, severe liver disease)
High lipid solubility (lipophilic)
1. 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
1. Metabolized primarily to the active agent desmethyldiazepam
2. Also metabolized to other active agents to a lesser extent including Temazepam and Oxazepam

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

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

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
1. Rifampin (increases Diazepam metabolism)
Drugs whose levels are increased by Diazepam
1. Digoxin
2. Phenytoin