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Class: Barbiturates
VA Class: CN301
CAS Number: 50-06-6
Brands: Luminal

Medically reviewed by Last updated on Aug 25, 2020.


Barbiturate;a b c d anxiolytic, sedative, hypnotic, and anticonvulsant.a b f

Uses for Phenobarbital

Insomnia and Anxiety

Relief of anxiety, tension, and apprehension.c d However, barbiturates used infrequently for routine sedation, since there are few clinical situations in which oral barbiturates provide a safety or efficacy advantage over nonbarbiturate sedatives/hypnotics.f

Short-term treatment of insomnia.c d However, generally not used orally as a hypnotic because several hours are required to achieve maximal effectsa and barbiturates have decreased effectiveness for sleep induction and maintenance after 2 weeks.d

Drug Withdrawal

Withdrawal of barbiturate or nonbarbiturate hypnotics in patients who are physically dependent on these drugs.a


Preoperatively, to produce sedation and relieve anxiety.a c

Seizure Disorders

Management of tonic-clonic seizures and partial seizures; used alone (particularly in infants and young children) or, more commonly, in combination with phenytoin or other anticonvulsants.b

Prevention of febrile seizures in infants and young children.b

Second-line agent in the termination of status epilepticus; may be useful to prevent seizure recurrence after seizures are initially terminated with other anticonvulsants (e.g., diazepam, phenytoin) or for termination of status epilepticus that does not respond to initial therapy with other anticonvulsants.b c Usefulness of parenteral phenobarbital in terminating acute seizure episodes is limited by its slow onset of action.a b d

Prophylactic management of epilepsy.c d

Hyperbilirubinemia in Neonates

Prevention and treatment of hyperbilirubinemia in neonates.a


Has been used to reduce bilirubin concentrations in patients with congenital nonhemolytic unconjugated hyperbilirubinemia or chronic intrahepatic cholestasis.a

Has been used in the management of hyperlipemia associated with intrahepatic and extrahepatic cholestasis.a

Phenobarbital Dosage and Administration


  • Adjust dosage carefully and slowly according to individual requirements and response.a b

  • Following chronic administration, withdraw phenobarbital slowly to avoid the possibility of precipitating withdrawal symptoms if the patient is physically dependent on the drug.a d

  • To prevent rebound in rapid eye movement (REM) sleep, withdrawal of a single therapeutic dose over 5 or 6 days (e.g., reducing dosage from 3 to 2 doses daily for 1 week) has been recommended when barbiturates are discontinued following prolonged use.a


  • 2–3 weeks of therapy may be required to achieve full anticonvulsant effects.b

  • When transferring a patient to another anticonvulsant drug, reduce phenobarbital dosage gradually over 1 week while, at the same time, instituting therapy with a low dose of the replacement drug.b

  • Withdraw phenobarbital or reduce dosage slowly to avoid precipitating seizures or status epilepticus.b


  • Do not administer for periods >2 weeks.a


Administer orally or by IM or slow IV injection.a b c d Sub-Q injection not recommended.a d

Oral Administration

Frequently administered in 2 or 3 divided doses;a however, there is no advantage in dividing the daily dosage (because of the long half-life).a b

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Reserve IV administration for emergency treatment of acute seizure states; however, usefulness in these conditions is limited.a b (See Seizure Disorders under Uses.)

Patient should be hospitalized and under close supervision.a

To minimize the risk of irritation and thrombosis, do not use small veins (e.g., those on the dorsum of the hands or wrist).d

Avoid intra-arterial injection.b (See Intra-arterial Injection under Cautions.)

Rate of Administration

≤60 mg/minute.a b d

IM Administration

Maximum volume of single injections is 5 mL; administer deeply into a large muscle to avoid tissue irritation.d


Available as phenobarbital sodium; dosage expressed in terms of the salt.d

Pediatric Patients


6 mg/kg daily or 180 mg/m2 daily, in 3 equally divided doses.a c


1–3 mg/kg preoperatively.a d


16–100 mg administered 60–90 minutes before surgery;a alternatively, 1–3 mg/kg preoperatively.a d

Drug Withdrawal

Infants: 3–10 mg/kg daily.a After symptoms are relieved, decrease dosage gradually and withdraw drug completely over a 2-week period.a

Seizure Disorders

15–50 mg 2 or 3 times daily.c Alternatively, 3–5 mg/kg or 125 mg/m2 daily.b

IV or IM

4–6 mg/kg daily for 7–10 days to reach therapeutic blood concentrations; alternatively, 10–15 mg/kg daily.d

Prevention of Febrile Seizures

3–4 mg/kg daily.b

Status Epilepticus
IV or IM

15–20 mg/kg IV over 10–15 minutes.d Alternatively 100–400 mg IM or IV; allow up to 30 minutes for maximum anticonvulsant effect before administering additional doses (to prevent overdosage).b

Hyperbilirubinemia in Neonates†

7 mg/kg per day from the first to fifth day of life.a

IM, then Oral

5 mg/kg IM on the first day of life, followed by 5 mg/kg orally on the second to seventh day.a


Children <12 years of age: Dosages of 3–12 mg/kg daily in 2 or 3 divided doses have been used.a


Insomnia and Anxiety

30–120 mg daily.c


100–320 mg.c


100–320 mg.c d

Drug Withdrawal

30-mg dose for each 100- to 200-mg dose of the barbiturate or nonbarbiturate hypnotic that the patient has been taking daily, administered in 3 or 4 divided doses.a If the patient shows signs of withdrawal on the first day, a loading dose of 100–200 mg of phenobarbital sodium may be administered IM in addition to the oral dose.a

After stabilization on phenobarbital sodium, decrease the total daily dose of phenobarbital sodium by 30 mg per day.a After withdrawal symptoms are relieved, gradually decrease dosage and withdraw completely over a 2-week period.a


100–200 mg given 60–90 minutes before surgery.a d

Seizure Disorders

100–300 mg daily,b c usually at bedtime.b

Status Epilepticus
IV or IM

20–320 mg; repeat in 6 hours, if necessary.d Alternatively, 200–600 mg; allow up to 30 minutes for maximum anticonvulsant effect before administering additional doses (to prevent overdosage).b

Some clinicians administer phenobarbital sodium IV until seizures stop or a total dose of 20 mg/kg has been given.a b Discontinue IV injections as soon as the desired effect is obtained.b


Dosages of 90–180 mg daily in 2 or 3 divided doses have been used.a

Special Populations

Hepatic Impairment

Dosage reduction recommended in patients with hepatic impairment;c d e avoid use in patients with marked hepatic impairment.c d

Renal Impairment

Dosage reduction recommended.d e

Geriatric Patients

Dosage reduction recommended.d e f

Cautions for Phenobarbital


  • Known hypersensitivity to any barbiturates.c d

  • Respiratory disease in which dyspnea or obstruction is evident.c d

  • Marked impairment of hepatic function.c d

  • History of manifest or latent porphyriac d (due to potential for exacerbation of acute intermittent porphyria or porphyria variegata).f

  • Previous addiction to sedative and/or hypnotic drugs.c d



Pain Reaction

Potential for paradoxical excitement and/or euphoria, restlessness, or delirium in patients with severe pain.f Barbiturates could mask important symptoms in patients with acute or chronic pain.d f Use with caution in such patients.d f Should not be used to relieve pain or to produce sedation or sleep in the presence of uncontrolled pain.c f

Abuse Potential

Possible tolerance, psychologic dependence, and physical dependence.c d (See Contraindications under Cautions.)

Withdrawal Effects

Abrupt cessation after prolonged use in dependent individuals may result in withdrawal symptoms (e.g., delirium, convulsions) and potentially be fatal.c d Drug must be withdrawn gradually in patients receiving excessive dosages over extended periods of time.d

CNS Depression

Performance of activities requiring mental alertness and physical coordination may be impaired.c d

Concurrent use of other CNS depressants may potentiate CNS depression.c d (See Specific Drugs under Interactions.)

Respiratory and Cardiovascular Effects

Possible respiratory depression, apnea, laryngospasm, hypertension, or vasodilation and hypotension, particularly if phenobarbital is administered IV too rapidly.d f Administer slowly; personnel and equipment should be readily available for administration of artificial respiration.d f

Sensitivity Reactions

Dermatologic Effects and Hypersensitivity Reactions

Exfoliative dermatitis (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis), sometimes fatal, reported rarely.b c d Because skin eruptions can precede potentially fatal reactions, discontinue phenobarbital whenever dermatologic reactions occur.d f

Hypersensitivity reactions (e.g., localized swelling, particularly of the eyelids, cheeks, or lips; erythematous dermatitis) may occur, particularly in patients with a history of asthma, urticaria, or angioedema.c

General Precautions

Intra-arterial Injection

Inadvertent intra-arterial administration can cause spasm and severe pain along the affected artery, resulting in local reactions varying in severity from transient pain to gangrene.d

Discontinue injection if the patient complains of pain or if signs of inadvertent intra-arterial injection (e.g., patches of discolored skin, a white hand with cyanosed skin, delayed onset of action) occur.b d Appropriate therapy for such inadvertent injection has not been fully established; consult manufacturers’ labeling for current recommendations.b d


Use with caution, if at all, in depressed patients; potential for suicidal tendencies.c d f Prescribe drug in the smallest feasible quantity.c

Concomitant Diseases

Use parenterally with extreme caution in debilitated patients or patients with severe hepatic impairment, pulmonary or cardiac disease, status asthmaticus, uremia, or shock.d f

Specific Populations


Tablets: Category B.c Injection: Category D.d

Barbiturates have caused postpartum hemorrhage and hemorrhagic disease in neonates; readily reversible with vitamin K therapy.f i

Possible withdrawal symptoms in neonates born to women who received barbiturates throughout the last trimester of pregnancy.f Premature neonates are particularly susceptible to the depressant effects of barbiturates.f


Distributed into milk; use with caution.c d

Pediatric Use

May produce paradoxical excitement and hyperactivity or exacerbate existing hyperactivity; if severe, substitute another barbiturate or therapeutic agent.b

Possible behavioral (e.g., hyperactivity, fussiness, lethargy, disturbed sleep, irritability, disobedience, stubbornness, depressive symptoms) or cognitive effects (e.g., deficits on neuropsychiatric tests, impaired short-term memory and memory concentration tasks) associated with anticonvulsant use.d i If such changes occur and alternative causes are not readily evident, consider the possibility that anticonvulsant therapy may be responsible and the need for dosage reduction or substitution of alternative anticonvulsant(s).i

Phenobarbital sodium injection contains benzyl alcohol.d Manufacturer does not recommend use in neonates;d AAP states that the presence of small amounts of this preservative in a commercially available injection should not proscribe its use when indicated in neonates.h

Geriatric Use

Possible increased sensitivity to barbiturates.d Geriatric patients may frequently react to barbiturates with excitement, confusion, or depression.c f

Hepatic Impairment

Use with caution; should not be used in patients with marked hepatic impairment.c d (See Contraindications under Cautions.)

Renal Impairment

Use with extreme caution in patients with nephritis.b d Use parenterally with extreme caution in patients with uremia.d f

Common Adverse Effects

Residual sedation, drowsiness, lethargy, vertigo, nausea, vomiting, headache.c d f

Interactions for Phenobarbital

Metabolized by hepatic microsomal enzymes.d Induces hepatic microsomal enzymes.c d

Specific Drugs




Anticoagulants, oral (e.g., warfarin)

Possible decreased plasma warfarin concentrationsc d

Monitor PT; adjust anticoagulant dosage as necessary, especially with initiation or discontinuance of phenobarbitalc f

Antidepressants, tricyclics

Antidepressant may precipitate seizures, resulting in decreased seizure controli

Potentiation of respiratory depression following toxic doses of tricyclic antidepressantsi

Monitor epileptic patients for decreased seizure control following initiation of antidepressant therapy; adjust phenobarbital dosage, if necessaryi

CNS depressants (e.g., sedatives, hypnotics, antihistamines, tranquilizers, alcohol)

Possible additive depressant effectsc d

Contraceptives, oral

Possible enhanced metabolism of estrogenic and progestinic components; potential for decreased oral contraceptive effectiveness and increased risk of pregnancy with phenobarbital pretreatment or concurrent therapyd

Consider alternate methods of contraceptiond


Possible increased corticosteroid metabolismd

Dosage adjustment of corticosteroid may be required;d closely monitor asthmatics receiving corticosteroids when phenobarbital is initiatedi


Possible decreased half-life of doxycycline; effect may persist up to 2 weeks after discontinuance of phenobarbitald

If possible, avoid concomitant administration;f if administered concomitantly, monitor clinical response to doxycyclined


Possible decreased griseofulvin absorption, resulting in decreased blood concentrationsd

Avoid concomitant administration;d if concomitant therapy is necessary, administration of griseofulvin in 3 divided daily doses may improve absorption.f Monitor blood griseofulvin concentrations and increase dosage, if necessaryf

MAO inhibitors

Possible prolongation of phenobarbital effectsd

Dosage adjustment of phenobarbital may be requiredf


Increased, decreased, or no change in plasma phenytoin concentrations reportedd i

Monitor plasma concentrations of phenytoin and phenobarbital; adjust dosages as necessaryd i

Valproic acid

Possible increased plasma phenobarbital concentrationsd

Monitor plasma phenobarbital concentrations and adjust dosage as neededd

Phenobarbital Pharmacokinetics



Slowly absorbed from GI tract following oral administration,b with peak plasma concentrations usually attained within 8–12 hours and peak brain concentrations in 10–15 hours.b

Following IV administration, ≥15 minutes may be required to reach peak brain concentrations.d


Following oral administration, onset occurs within 30 minutes.c

Following IV administration, onset occurs within 5 minutes, with maximum CNS depression occurring ≥15 minutes after administration.b d Onset is slower following IM administration.b d


About 5–6 hoursc or 4–6 hoursd following oral or parenteral administration, respectively.

Plasma Concentrations

Plasma concentrations of 10–25 mcg/mL associated with anticonvulsant activity in most patients.d Concentrations >50 mcg/mL may produce coma; concentrations >80 mcg/mL are potentially lethal.b



Rapidly distributed to all tissues and fluids, with high concentrations in the brain, liver, and kidneys.d

Crosses the placenta and is distributed into milk.d

Plasma Protein Binding




Metabolized primarily by hepatic microsomal enzymes.d

Elimination Route

Excreted principally in urine (25–50% as unchanged drug).d


Adults: 53–118 hours.d

Children and neonates: 60–180 hours.d





Tight, light-resistant containers at 15–30°C.c Protect from moisture.c


Tight containers at 20–25°C.e





For information on systemic interactions resulting from concomitant use, see Interactions.


Solution CompatibilityHID


Dextrose–Ringer’s injection combinations

Dextrose–Ringer’s injection, lactated, combinations

Dextrose–saline combinations

Dextrose 2.5, 5, or 10% in water

Ionosol products

Ringer’s injection

Ringer’s injection, lactated

Sodium chloride 0.45 or 0.9%

Sodium lactate 1/6 M

Drug Compatibility
Admixture CompatibilityHID


Amikacin sulfate


Calcium chloride

Calcium gluconate

Colistimethate sodium



Polymyxin B sulfate

Verapamil HCl


Chlorpromazine HCl

Ephedrine sulfate

Hydralazine HCl

Hydrocortisone sodium succinate

Hydroxyzine HCl

Pentazocine lactate

Prochlorperazine mesylate

Promethazine HCl

Succinylcholine chloride

Y-site CompatibilityHID



Doxapram HCl


Fentanyl citrate

Fosphenytoin sodium




Methadone HCl

Morphine sulfate



Amphotericin B cholesteryl sulfate complex


Hydromorphone HCl


  • CNS effects appear to be related, at least partially, to the drug’s ability to enhance activity of GABA, the principal inhibitory neurotransmitter in the CNS,104 105 106 107 108 by altering inhibitory synaptic transmissions that are mediated by GABAA receptors.105 106 108

  • Capable of producing all levels of CNS depression—from mild sedation to hypnosis to deep coma to death.c d

  • Anticonvulsant effects of barbiturates are multiple and rather nonselective.i Principal mechanism of action appears to be reduction of monosynaptic and polysynaptic transmission resulting in decreased excitability of the entire nerve cell; barbiturates also increase the threshold for electrical stimulation of the motor cortex.i

  • Barbiturates lower serum bilirubin concentrations in neonates and patients with congenital nonhemolytic unconjugated hyperbilirubinemia, presumably by induction of glucuronyl transferase, the enzyme that conjugates bilirubin.f

Advice to Patients

  • Potential for phenobarbital to impair mental alertness or physical coordination; do not drive or operate machinery until effects on individual are known.c d

  • Importance of taking exactly as prescribed; do not exceed the recommended dosage.c d

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and alcohol consumption.c d Importance of avoiding alcohol while taking the drug.c d

  • Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.c d

  • Importance of advising patients of other important precautionary information.c d (See Cautions.)


Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Subject to control under the Federal Controlled Substances Act of 1970 as schedule IV (C-IV) drugs.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name



Dosage Forms


Brand Names




20 mg/5 mL C-IV*


15 mg*

16 mg C-IV*

30 mg C-IV*

32 mg C-IV*

60 mg C-IV*

65 mg C-IV*

100 mg C-IV*

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

PHENobarbital Sodium


Dosage Forms


Brand Names




30 mg/mL*

Phenobarbital Sodium Injection (C-IV)


60 mg/mL*

Phenobarbital Sodium Injection (C-IV)


65 mg/mL*

Phenobarbital Sodium Injection (C-IV)


130 mg/mL*

Luminal Sodium (C-IV)


PHENobarbital Sodium Injection (C-IV)


Phenobarbital Sodium Injection (C-IV)


AHFS DI Essentials™. © Copyright 2021, Selected Revisions September 4, 2013. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.


Only references cited for selected revisions after 1984 are available electronically.

100. Jones-Pharma. Brevital sodium (methohexital sodium) for injection prescribing information (dated 2001 Mar 28). In: Physicians’ desk reference. 56th ed. Montvale, NJ: Medical Economics Company Inc; 2002:1815-17.

103. Abbott. Pentothal thiopental sodium for injection prescribing information. North Chicago, IL; 1993 Nov.

104. Carmichael FJ, Haas DA. General Anesthetics. In: Kalant H and Roschlau WHE, eds. Principles of Medical Pharmacology. 6th edition. New York: Oxford University Press; 1998:278-92.

105. Evers AS, Crowder CM. General Anesthetics. In: Hardman JG, Gilman AG, Limbird LE, eds Goodman and Gilman’s The pharmacological basis of therapeutics. 10th ed. McGraw-Hill; 2001: 337-44.

106. Donnelly AJ, Shafer AL. Perioperative care. In: Young LL, Koda-Kimble MA, eds. Applied Therapeutics: The clinical use of drugs. 6th ed. Vancouver WA: Applied Therapeutics, Inc.; 1995:8-1-8-24.

107. Tanelian DL, Kosek P, Mody I et al. The role of the GABAA receptor/chloride channel complex in anesthesia. Anesthesiology. 1993; 78:757-76.

108. Hales TG, Olsen RW. Basic pharmacology of intravenous induction agents. In: Bowdle TA, Horita A, Kharasch ED, eds. The pharmacologic basis of anesthesiology. New York: Churchill Livingstone; 1994:295-306.

a. AHFS Drug Information 2004. McEvoy GK, ed. Phenobarbital . Bethesda, MD: American Society of Health-System Pharmacists; 2004:2370-1.

b. AHFS Drug Information 2004. McEvoy GK, ed. Phenobarbital. Bethesda, MD: American Society of Health-System Pharmacists; 2004:2108-9.

c. West-ward Pharmaceutical Corp. Phenobarbital tablets prescribing information. Eatontown, NJ; 2001 Jan.

d. Elkins-Sinn, Inc. Phenobarbital Sodium injection prescribing information. Cherry Hill, NJ; 2002 Apr.

e. Pharmaceutical Associates, Inc. Phenobarb elixir prescribing information. Greenville, NC; 2000 Apr.

f. AHFS Drug Information 2004. McEvoy GK, ed. Barbiturate general statement . Bethesda, MD: American Society of Health-System Pharmacists; 2004:2363-6.

HID. Trissel LA. Handbook on injectable drugs. 17th ed. Bethesda, MD: American Society of Health-System Pharmacists; 2013:935-8.

h. American Academy of Pediatrics Committee on Fetus and Newborn and Committee on Drugs. Benzyl alcohol: toxic agent in neonatal units. Pediatrics. 1983; 72:356 8.

i. AHFS Drug Information 2004. McEvoy GK, ed. Anticonvulsants general statement . Bethesda, MD: American Society of Health-System Pharmacists; 2004:2102-7.