III. Pharmacology

  1. Mechanism
    1. GABA A Receptor Agonist
    2. See Barbiturates for more detalied mechanism description
  2. Pharmacokinetics
    1. Half-Life: 53 to 140 hours (very long, self tapering in withdrawal)
    2. Onset (IV): 5 minutes
    3. Peak Effect (IV): 30 minutes

IV. Safety

  1. Pregnancy Category D
  2. Lactation: Not safe
  3. FDA Controlled Substance IV
  4. Therapeutic level: 15-40 mg/ml
  5. May be less addictive than Valium in outpatient withdrawal protocols

V. Metabolism

  1. Liver Metabolism
  2. Renal Dosing: Decrease to twice daily for moderate to severe Renal Insufficiency

VI. Adverse Effects

  1. Serious
    1. Respiratory depression or apnea
      1. Intravenous dosing is higher risk for respiratory depression
      2. Avoid combining with Benzodiazepines or Opioids (see below)
    2. Withdrawal
      1. Avoid abruptly stopping
    3. Stevens-Johnson Syndrome
    4. Angioedema
    5. Suicidality
    6. Blood dyscrasias (Megaloblastic Anemia, Thrombocytopenia)
  2. Common
    1. Somnolence
    2. Bradycardia
    3. Nausea or Vomiting
    4. Dizziness, Nystagmus or Ataxia
    5. Decreased cognitive function

VII. Drug Interactions

  1. CNS Depressants (Benzodiazepines, Opioids)
    1. Risk of respiratory depression or apnea

VIII. Dosing: General

  1. Precautions
    1. Avoid IV infusion >60 mg/min
  2. Status Epilepticus
    1. Phenobarbital 20-30 mg/kg IV (infusion rate <=100 mg/min)
      1. Repeat dosing at 10 mg/kg every 1 hour as needed for refractory Seizures
  3. Epilepsy
    1. Phenobarbital 3 to 6 mg/kg/day divided 2-3 times daily, up to 50-100 mg orally twice to three times daily

IX. Dosing: Alcohol Withdrawal

  1. General Dosing
    1. Phenobarbital 5-10 mg/kg IBW up to 130 to 260 mg every 20-30 minutes titrating to light sedation
  2. Phenobarbital Single Agent Alcohol Withdrawal Protocol
    1. Indicated in Alcohol Withdrawal without use of Benzodiazepines or other CNS Depressants and neurologically intact
    2. Contraindicated with other CNS Depressants (e.g. Benzodiazepines)
    3. Protocol continued until patient is awake and calm
    4. IV Phenobarbital Load
      1. Phenobarbital 10 mg/kg Ideal Body Weight (IBW) over 30 minutes
      2. Wait 30 minutes before any additional Phenobarbital given
    5. IV Phenobarbital Titration
      1. Up to every 30 minutes give one of the 2 following doses as needed (no maximum, titrate to effect)
      2. Mild Symptoms: 130 mg IV over 3 minutes every 30 minutes as needed
      3. Severe symptoms 260 mg IV over 5 minutes every 30 minutes as needed
    6. Oral or IM Phenobarbital Maintenance (non-ED or ICU setting)
      1. Up to every 60 minutes give one of the 2 following doses as needed
      2. Mild Symptoms: 100 mg oral or IM every 60 minutes as needed
      3. Severe symptoms 200 mg oral or IM every 60 minutes as needed
  3. References
    1. Nisavic (2019) Psychosomatics 60(5):458-67 [PubMed]
    2. Nelson (2019) Am J Emerg Med 37(4):733-6 [PubMed]
    3. Tidwell (2018) Am J Crit Care 27(6):454-60 [PubMed]

XI. References

  1. (2020) Pharmacopeia, Tarascon, accessed on IOS 4/9/2021
  2. Cunningham and LoVecchio (2021) Crit Dec Emerg Med 35(4): 28

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phenobarbital (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
PHENOBARBITAL 100 MG TABLET Generic $0.32 each
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PHENOBARBITAL 20 MG/5 ML SOLN Generic $0.06 per ml
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