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

Images: Related links to external sites (from Bing)

Related Studies

Cost: Medications

phenobarbital (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
PHENOBARBITAL 100 MG TABLET Generic $0.32 each
PHENOBARBITAL 15 MG TABLET Generic $0.18 each
PHENOBARBITAL 16.2 MG TABLET Generic $0.18 each
PHENOBARBITAL 20 MG/5 ML ELIX Generic $0.06 per ml
PHENOBARBITAL 20 MG/5 ML SOLN Generic $0.06 per ml
PHENOBARBITAL 30 MG TABLET Generic $0.19 each
PHENOBARBITAL 32.4 MG TABLET Generic $0.23 each
PHENOBARBITAL 60 MG TABLET Generic $0.27 each
PHENOBARBITAL 64.8 MG TABLET Generic $0.29 each
PHENOBARBITAL 97.2 MG TABLET Generic $0.38 each

Ontology: Phenobarbital (C0031412)

Definition (CHV) a drug used for epilepsy and anxiety
Definition (CHV) a drug used for epilepsy and anxiety
Definition (NCI) A long-acting barbituric acid derivative with antipsychotic property. Phenobarbital binds to and activates the gamma-aminobutyric acid (GABA)-A receptor, thereby mimicking the inhibitory actions of GABA in the brain. The activation effects of the phenobarbital-receptor-ionophore complex include increased frequency of chloride channel openings, membrane hyperpolarization and ultimately synaptic inhibition and decreased neuronal excitability. In addition, this agent inhibits glutamate induced depolarization.
Definition (NCI_NCI-GLOSS) A drug that is used to treat seizures and as a sedative. It is being studied in the treatment of diarrhea and for its ability to increase the antitumor effect of other therapies. It belongs to the family of drugs called barbiturates.
Definition (MSH) A barbituric acid derivative that acts as a nonselective central nervous system depressant. It potentiates GAMMA-AMINOBUTYRIC ACID action on GABA-A RECEPTORS, and modulates chloride currents through receptor channels. It also inhibits glutamate induced depolarizations.
Definition (CSP) barbituric acid derivative that acts as a nonselective central nervous system depressant.
Definition (PDQ) A long-acting barbituric acid derivative with antipsychotic property. Phenobarbital binds to and activates the gamma-aminobutyric acid (GABA)-A receptor, thereby mimicking the inhibitory actions of GABA in the brain. The activation effects of the phenobarbital-receptor-ionophore complex include increased frequency of chloride channel openings, membrane hyperpolarization and ultimately synaptic inhibition and decreased neuronal excitability. In addition, this agent inhibits glutamate induced depolarization. Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=42405&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=42405&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C739" NCI Thesaurus)
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D010634
SnomedCT 255670005, 373505007, 51073002
LNC LP14729-5, MTHU003431
English Acid, Phenylethylbarbituric, Phenemal, Phenobarbital, Phenobarbitone, Phenylbarbital, Phenylethylbarbituric Acid, 2,4,6(1H,3H,5H)-Pyrimidinetrione, 5-ethyl-5-phenyl-, 5-Ethyl-5-phenyl-2,4,6(1H,3H,5H)-pyrimidinetrione, PHENO, phenobarbital (medication), Phenobarbitone - chemical, Phenobarbital [Chemical/Ingredient], PHENOBARBITAL, phenobarbitone, PHENobarbital, phenobarbital, Phenobarbitone - chemical (substance), Phenobarbitone product, Phenylethylmalonylurea, Phenobarbital (product), Phenobarbital (substance), Phenobarbital product
Swedish Fenobarbital
Czech fenobarbital
Finnish Fenemaali
Russian LIUMINAL, FENOBARBITAL, FENILBARBITAL, FENEMAL, FENOBARBITON, ЛЮМИНАЛ, ФЕНЕМАЛ, ФЕНИЛБАРБИТАЛ, ФЕНОБАРБИТАЛ, ФЕНОБАРБИТОН
Japanese フェネマール, フェニルエチルバルビツール酸, フェニルエチルマロニル尿素, エチルフェニルバルビツール酸, フェニルバルビトン, フェノバール, ワコビタール, フェノバルビタール, ルミナール, リナーセン, ルピアール, フェニルバルビタール, フェノバルビトン, ノーベルバール
Italian Acido feniletilbarbiturico, Fenilbarbital, Fenobarbitone, Fenobarbital
Croatian FENOBARBITAL
Polish Fenobarbital, Gardenal
Spanish fenobarbital - químico, fenobarbital - químico (sustancia), feniletilmalonilurea, fenobarbital (producto), fenobarbital (sustancia), fenobarbital, fenobarbitona, Fenobarbital, Fenemal, Fenilbarbital, Fenobarbitona
French Phénobarbital
German Phenemal, Phenobarbital, Phenobarbiton, Phenylbarbital
Portuguese Fenemal, Fenilbarbital, Fenobarbital, Fenobarbitona