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Pentobarbital (Monograph)

Brand name: Nembutal
Drug class: Barbiturates
VA class: CN301
CAS number: 76-74-4

Medically reviewed by on Mar 3, 2022. Written by ASHP.


Special Alerts:

A standardized concentration for this drug has been established through Standardize 4 Safety (S4S), a national patient safety initiative to reduce medication errors, especially during transitions of care. The drug is included in a standard concentration list which may apply to an IV or oral compounded liquid formulation. For additional information, see the ASHP website [Web].


Barbiturate; anxiolytic, sedative, hypnotic, and anticonvulsant.

Uses for Pentobarbital


Short-term treatment of insomnia (i.e., ≤2 weeks duration); decreased effectiveness for sleep induction and maintenance after 2 weeks.

Has been used for routine sedation. However, barbiturates used infrequently for this indication since there are few clinical situations in which oral barbiturates provide a safety or efficacy advantage over nonbarbiturate sedatives/hypnotics.

Surgery and Preanesthesia

Preoperatively, to produce sedation and relieve anxiety.

Provide basal hypnosis for general, spinal, or regional anesthesia, or to facilitate intubation procedures.

Seizure Disorders

Alternate therapy to control status epilepticus or acute seizure episodes resulting from meningitis, poisons, eclampsia, alcohol withdrawal, tetanus, or chorea.

IV diazepam generally considered drug of choice for termination of status epilepticus.

Drug Withdrawal

Withdrawal of barbiturate or nonbarbiturate hypnotics in physically dependent patients.

Agitated Behavior

Has been used to control acute episodes of agitated behavior in psychoses [off-label]; however, little value in long-term management of psychoses.

Coma Induction

Has been used in high doses to induce coma in the management of cerebral ischemia [off-label] and increased intracranial pressure [off-label] associated with head trauma, stroke, Reye’s syndrome, cardiac arrest, asphyxiation, or drowning.

Has been used to ameliorate or prevent sequelae associated with cerebral ischemia during neurosurgical procedures [off-label] that require long periods of cerebral hypoxia.

Pentobarbital Dosage and Administration


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

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

  • 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.


  • Do not administer for periods >2 weeks.


Administer by IM or slow IV injection.

IV Administration

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

Reserve IV administration for inducing anesthesia or emergency treatment of acute seizure episodes or acute episodes of agitated behavior in psychoses. (See Seizure Disordersand also Agitated Behavior under Uses.)

Usually administered in a concentration of 50 mg/mL.

Must be administered by slow IV injection and in fractional doses to allow for adequate time for pentobarbital to distribute into CNS. A time interval of ≥1 minute is required to determine the full effect of an IV dose.

Administer under close supervision and in a setting where vital signs can be monitored; BP, respiration, and cardiac function maintained; and equipment for resuscitation and artificial ventilation are readily available. (See Respiratory and Cardiovascular Effects under Cautions.)

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

Rate of Administration

Do not exceed 50 mg/minute. (See Respiratory and Cardiovascular Effects under Cautions.)

IM Administration

Administer by deep IM injection into a large muscle.

Administer a maximum volume of 5 mL at any one site to avoid tissue irritation.

After administration of large hypnotic doses, observe patient closely for 20–30 minutes and monitor vital signs to ensure narcosis will not be excessive.


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

IV dosage generally determined by patient’s reaction to slow administration of the drug.

A time interval of >1 minute required to determine the full effect of an IV dose.

Pediatric Patients


2–6 mg/kg or 125 mg/m2 as a single dose (maximum 100 mg).

Surgery and Preanesthesia

Usually, approximately 5 mg/kg.


Initially, usually 50 mg. If necessary, administer subsequent doses after >1 minute.

Seizure Disorders

Initially, usually 50 mg. If necessary, administer subsequent doses after >1 minute.

Agitated Behavior† [off-label]

Initially, usually 50 mg. If necessary, administer subsequent doses after >1 minute.



150–200 mg as a single dose.


Initially, usually 100 mg for an adult weighing 70 kg. After >1 minute, if necessary, administer additional small doses up to a total of 200–500 mg.

Surgery and Preanesthesia

150–200 mg as a single dose.


Initially, usually 100 mg. After >1 minute, if necessary, administer additional small doses up to a total of 200–500 mg.

Administer minimum dosage to avoid compounding the CNS and respiratory depression which may follow seizures. (See CNS Depression and also Respiratory and Cardiovascular Effects, under Cautions.)

Drug Withdrawal

Establish a stabilizing dose (generally adminstered at 6-hour intervals), then decrease the daily dose by no more than 100 mg per day. Severely dependent patients can usually be withdrawn from barbiturates in 14–21 days.

Agitated Behavior†

Initially, usually 100 mg. After >1 minute, if necessary, administer additional small doses up to a total of 200–500 mg.

Prescribing Limits

Pediatric Patients


Maximum 100 mg daily.



Maximum 200–500 mg.

Special Populations

Hepatic Impairment

Dosage reduction recommended.

Renal Impairment

Dosage reduction recommended.

Geriatric Patients

Dosage reduction recommended.

Debilitated Patients

Dosage reduction recommended.

Cautions for Pentobarbital


  • Known hypersensitivity to any barbiturates.

  • History of manifest or latent porphyria. (See Porphyria under Cautions.)

  • Bronchopneumonia or other severe pulmonary insufficiency.



Pain Reaction

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

Abuse Potential

Possible tolerance, psychological dependence, and physical dependence following prolonged administration.

Withdrawal Effects

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

CNS Depression

Performance of activities requiring mental alertness or physical coordination may be impaired.

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

Respiratory and Cardiovascular Effects

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

Fetal/Neonatal Morbidity

May cause fetal harm. If used during pregnancy or if patient becomes pregnant, apprise of potential fetal hazard.

Retrospective, case-controlled studies indicate an association between maternal ingestion of barbiturates and a higher than expected incidence of fetal abnormalities.

Based on animal data, repeated or prolonged use of general anesthetics and sedation drugs, including pentobarbital, during the third trimester of pregnancy may result in adverse neurodevelopmental effects in the fetus. (See Pediatric Use under Cautions and also see Advice to Patients.)

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

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


Potential exacerbation of acute intermittent porphyria or porphyria variegata. (See Contraindications under Cautions.)

Complex Sleep-related Behaviors

Potential risk of complex sleep-related behaviors such as sleep-driving (i.e., driving while not fully awake after ingesting a sedative-hypnotic drug, with no memory of the event), making phone calls, or preparing and eating food, while asleep.

Sensitivity Reactions

Potential risk of anaphylaxis and angioedema; may occur as early as with the first dose of drug.

Dermatologic Effects and Hypersensitivity Reactions

Exfoliative dermatitis (e.g., Stevens-Johnson syndrome), sometimes fatal, reported rarely. Because skin eruptions can precede potentially fatal reactions, discontinue pentobarbital whenever dermatologic reactions occur.

General Precautions

Intra-arterial Injection

Inadvertent intra-arterial administration can cause local reactions varying in severity from transient pain to gangrene. Inadvertent extravascular injection may cause local tissue damage and result in necrosis.

Discontinue injection if the patient complains of pain in limb.


Use with caution, if at all, in patients with depression or suicidal tendencies.

Concomitant Diseases

Use parenterally with caution in patients with hypertension, hypotension, pulmonary or cardiovascular disease, or shock.

Specific Populations


Category D. (See Fetal/Neonatal Morbidity under Cautions.)


Distributed into milk; use with caution.

Pediatric Use

Repeated or prolonged use of general anesthetics and sedation drugs, including pentobarbital, in children <3 years of age or during the third trimester of pregnancy may adversely affect neurodevelopment. In animals, use for >3 hours of anesthetic and sedation drugs that block N-methyl-d-aspartic acid (NMDA) receptors and/or potentiate GABA activity leads to widespread neuronal apoptosis in the brain and long-term deficits in cognition and behavior; clinical relevance to humans is unknown.

Some evidence suggests similar deficits may occur in children following repeated or prolonged exposure to anesthesia early in life. Some evidence also indicates that a single, relatively brief exposure to general anesthesia in generally healthy children is unlikely to cause clinically detectable deficits in global cognitive function or serious behavioral disorders. Most studies to date have substantial limitations; further research needed to fully characterize effects, particularly for prolonged or repeated exposures and in more vulnerable populations (e.g., less healthy children).

Consider benefits and potential risks when determining the timing of elective procedures requiring anesthesia. FDA states that medically necessary procedures should not be delayed or avoided. (See Advice to Patients.)

Geriatric Use

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

Debilitated Patients

Possible increased sensitivity to barbiturates. Debilitated patients may frequently react to barbiturates with excitement, confusion, or depression.

Hepatic Impairment

Use with caution; should not be used in patients with marked hepatic impairment, including patients with premonitory signs of hepatic coma.

Common Adverse Effects

Residual sedation, drowsiness, lethargy, vertigo, nausea, vomiting, headache.

Interactions for Pentobarbital

Metabolized by hepatic microsomal enzymes. Induces hepatic microsomal enzymes.

Specific Drugs




Anticoagulants, oral (e.g., warfarin)

Possible decreased plasma warfarin concentrations

Adjust anticoagulant dosage as necessary, especially upon initiation or discontinuance of pentobarbital

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

Possible additive depressant effects

Contraceptives, oral

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

Consider alternate methods of contraception


Possible increased corticosteroid metabolism

Dosage adjustment of corticosteroid may be required; closely monitor patients (especially asthmatics) receiving corticosteroids when pentobarbital is initiated


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

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


Possible decreased griseofulvin absorption, resulting in decreased blood concentrations

Avoid concomitant administration; if concomitant therapy is necessary, administration of griseofulvin in 3 divided doses daily may improve absorption

Monitor blood griseofulvin concentrations and increase dosage, if necessary

MAO inhibitors

Possible prolongation of pentobarbital effects

Dose adjustment of pentobarbital may be required


Increased, decreased, or no change in plasma phenytoin concentrations reported

Monitor plasma concentrations of phenytoin and pentobarbital; adjust dosages as necessary

Valproic acid

Possible increased plasma pentobarbital concentrations

Monitor plasma pentobarbital concentrations and adjust dosage as needed

Pentobarbital Pharmacokinetics



Following IV administration, onset occurs within 1 minute.

Following IM administration, onset occurs within 10–25 minutes.


Variable; patient-dependent and may vary occasionally within same patient. About 15 minutes following IV administration.

Plasma Concentrations

Plasma concentrations of 1–5 mcg/mL generally produce sedation and plasma concentrations of 5–15 mcg/mL generally produce sleep; however, plasma concentrations >10 mcg/mL may produce deep coma and those >30 mcg/mL are potentially lethal.



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

Crosses the placenta and is distributed into milk.

Plasma Protein Binding

Approximately 35–45%.



Metabolized primarily by hepatic microsomal enzymes.

Elimination Route

Excreted principally in urine, mostly as metabolites; excreted less commonly in the feces.


Biphasic; terminal half-life is 35–50 hours.




Solution for Injection

30°C (brief exposure up to 40°C permitted). Protect from freezing and avoid excessive heat.

Do not use if discoloration or precipitation occurs.


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


Solution CompatibilityHID


Dextran 6% in dextrose 5%

Dextran 6% in sodium chloride 0.9%

Dextrose–Ringer’s injection combinations

Dextrose–Ringer’s injection, lactated, combinations

Dextrose–saline combinations

Dextrose 2½ or 10% in water

Fructose 10% in sodium chloride 0.9%

Fructose 10% in water

Invert sugar 5 and 10% in sodium chloride 0.9%

Invert sugar 5 and 10% in water

Ionosol products

Ringer’s injection

Ringer’s injection, lactated

Sodium chloride 0.45%

Sodium lactate 1/6 M


Dextrose 5% in water (depends on pentobarbital concentration)

Sodium chloride 0.9% (depends on pentobarbital concentration)

Drug Compatibility
Admixture CompatibilityHID


Amikacin sulfate


Calcium chloride

Chloramphenicol sodium succinate


Erythromycin lactobionate

Lidocaine HCl

Thiopental sodium

Verapamil HCl


Chlorpheniramine maleate

Ephedrine sulfate

Hydrocortisone sodium succinate

Hydroxyzine HCl

Norepinephrine bitartrate

Penicillin G potassium

Pentazocine lactate

Phenytoin sodium

Promazine HCl

Promethazine HCl

Sodium bicarbonate

Streptomycin sulfate

Succinylcholine chloride

Vancomycin HCl

Y-Site CompatibilityHID


Acyclovir sodium





Amphotericin B cholesteryl sulfate complex

Fenoldopam mesylate



  • 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, by altering inhibitory synaptic transmissions that are mediated by GABAA receptors.

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

  • Anticonvulsant effects of barbiturates are multiple and rather nonselective. 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.

  • 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.

Advice to Patients

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

  • When procedures requiring general anesthetics or sedation drugs, including pentobarbital, are considered for young children or pregnant women, importance of discussing with the patient, parent, or caregiver the benefits, risks (including potential risk of adverse neurodevelopmental effects), and appropriate timing and duration of the procedure.

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

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

  • Importance of informing patients of other important precautionary information. (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 II (C-II) drug.

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

PENTobarbital Sodium


Dosage Forms


Brand Names




50 mg/mL*

Nembutal Sodium Solution ( C-II)


AHFS DI Essentials™. © Copyright 2023, Selected Revisions March 3, 2022. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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

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