Pentobarbital (Monograph)

Brand name: Nembutal
Drug class: Barbiturates

Medically reviewed by Drugs.com on Jul 10, 2025. Written by ASHP.

Introduction

Short-acting barbiturate that has sedative-hypnotic properties and anticonvulsant activities at anesthetic doses.

Uses for Pentobarbital

Seizures

Used to control status epilepticus or acute seizure episodes resulting from other causes (e.g., meningitis, poisons, eclampsia, tetanus, or cholera).

Generally reserved for use in patients with status epilepticus refractory to other treatments (i.e., benzodiazepines and antiepileptic drugs such as phenytoin/fosphenytoin, valproate sodium, and levetiracetam).

Sedation

FDA-labeled for use as a sedative or preanesthetic medication; however, use has fallen out of favor, in part due to the unpredictable response and prolonged recovery time associated with its use in children.

Insomnia

FDA-labeled for use as a hypnotic for the short-term (<2 weeks) treatment of insomnia; however, other agents currently preferred.

Elevated Intracranial Pressure

Has been used in high doses to manage increased intracranial pressure^{† [off-label]} associated with head trauma.

Generally considered when patients are refractory to first-line treatments (i.e., CSF drainage, hyperosmolar therapy, additional analgesia/sedation, neuromuscular blockade).

Pentobarbital Dosage and Administration

General

Patient Monitoring

• When pentobarbital is administered IV, vital signs should be monitored; BP, respiration, and cardiac function should be maintained; and equipment for resuscitation and artificial ventilation should be readily available.

• After IM administration of large hypnotic doses, monitor vital signs.

• If therapy with pentobarbital is prolonged, the manufacturer recommends periodic monitoring of liver function, CBC, and chemistry profiles.

Dispensing and Administration Precautions

• The Institute for Safe Medication Practices (ISMP) includes PENTobarbital and PHENobarbital on their List of Confused Drug Names, and recommends using special safeguards to ensure the accuracy of prescriptions for these drugs.

Other General Considerations

• In patients taking excessive dosages of pentobarbital over long periods of time, the drug should be withdrawn slowly to avoid the possibility of precipitating withdrawal symptoms if the patient is physically dependent on the drug.

• 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. When procedures requiring the use of general anesthetics or sedation drugs are considered for young children or pregnant women, clinicians should take into consideration the benefits, risks (including potential risk of adverse neurodevelopmental effects), and appropriate timing and duration of the procedure.

Administration

Administer by IM or slow IV injection.

Also has been administered by continuous IV infusion^{† [off-label]} in the treatment of status epilepticus; administration by continuous IV infusion requires assisted ventilation and cardiovascular monitoring.

Reserve IV administration for acute treatment when other routes of administration are not feasible.

IV Administration

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.

Avoid intra-arterial and extravascular injection. If complaints of limb pain occur, stop the injection.

Standardize 4 Safety

Standardized concentrations for pentobarbital have been established through Standardize 4 Safety (S4S), a national patient safety initiative to reduce medication errors, especially during transitions of care. Because recommendations from the S4S panels may differ from the manufacturer’s prescribing information, caution is advised when using concentrations that differ from labeling, particularly when using rate information from the label. For additional information on S4S (including updates that may be available), see [Web].

Rate of Administration

Do not exceed rate of 50 mg/minute.

IM Administration

Administer by deep IM injection into a large muscle.

Do not exceed a maximum volume of 5 mL at any one site to avoid tissue irritation.

Dosage

Individualize dosage, taking into consideration patient age, weight, and condition.

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

Pediatric Patients

Seizures

IV

No average IV dosage available. Manufacturer states that a commonly used initial IV dose is 100 mg for a 70-kg adult, with additional small increments given if necessary up to a total of 200−500 mg; proportional dosage reduction should be made for pediatric patients. A time interval of >1 minute required to determine the full effect of an IV dose.

Refractory status epilepticus in mechanically ventilated patients receiving cardiovascular monitoring: Experts recommend initial dose of 5−15 mg/kg (administered no faster than 50 mg/minute), followed by an additional 5−10 mg/kg if necessary. Recommended dosage for continuous infusion is 0.5−5 mg/kg per hour; administer additional 5 mg/kg bolus doses for breakthrough seizures. May increase continuous infusion by 0.5−1 mg/kg per hour every 12 hours, titrated to EEG findings.

Insomnia

IM

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

IV

No average IV dosage available. Manufacturer states that a commonly used initial IV dose is 100 mg for a 70-kg adult, with additional small doses administered if necessary up to a total of 200−500 mg; proportional dosage reduction should be made for pediatric patients.

When used for short-term treatment of insomnia, do not exceed 2 weeks of treatment. Withdrawal of a single therapeutic dose over 5 or 6 days recommended following prolonged use.

Sedation

IV

No average IV dosage available. Manufacturer states that a commonly used initial IV dosage is 100 mg for a 70-kg adult, with additional small doses administered if necessary up to a total of 200−500 mg; proportional dosage reduction should be made for pediatric patients.

Adults

Seizures

IV

No average IV dosage available. Manufacturer states that a commonly used initial IV dose is 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.

Refractory status epilepticus in mechanically ventilated patients receiving cardiovascular monitoring: Experts recommend initial dose of 5−15 mg/kg (administered no faster than 50 mg/minute), followed by an additional 5−10 mg/kg if necessary. Recommended dosage for continuous infusion is 0.5−5 mg/kg per hour; administer additional 5 mg/kg bolus doses for breakthrough seizures. May increase continuous infusion by 0.5−1 mg/kg/hour every 12 hours, titrated to EEG findings.

Insomnia

IM

Usual dose is 150–200 mg as a single dose.

IV

No average IV dosage available. 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.

Sedation

IV

No average IV dosage available. Initially, usually 100 mg for a 70-kg adult. After >1 minute, if necessary additional small doses can be administered up to a total of 200−500 mg.

Special Populations

Hepatic Impairment

Initial dosage reduction recommended. Avoid use in patients demonstrating premonitory signs of hepatic coma.

Renal Impairment

Dosage reduction recommended.

Geriatric Patients

Dosage reduction recommended.

Debilitated Patients

Dosage reduction recommended.

Cautions for Pentobarbital

Contraindications

• Known hypersensitivity to barbiturates.

• History of manifest or latent porphyria.

Warnings/Precautions

Tolerance and Dependence

Possible tolerance, psychological dependence, and physical dependence following prolonged use. Abrupt discontinuation after prolonged use in a dependent patient can result in withdrawal symptoms such as delirium, convulsions, and potentially death.

Administer with caution, if at all, to patients who are mentally depressed, have suicidal tendencies, or a history of drug abuse.

Withdraw gradually in patients receiving excessive dosages over extended periods of time.

Rapid Administration

Possible respiratory depression, apnea, laryngospasm, or vasodilation, and hypotension if pentobarbital is administered IV too rapidly. Rate of IV injection should not exceed 50 mg/minute. Carefully observe patient during administration. Equipment for resuscitation and artifical respiration should be readily available.

Patients with Acute or Chronic Pain

Potential for paradoxical excitement in patients with acute or chronic pain.

Use with caution in such patients; may mask important pain symptoms.

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm. 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 during the third trimester of pregnancy may result in adverse neurodevelopmental effects in the fetus.

Possible withdrawal symptoms in neonates exposed to barbiturates in utero. If used during pregnancy or if patient becomes pregnant, apprise of potential fetal hazard.

CNS Depression

Concurrent use of other CNS depressants may potentiate CNS depression.

Pediatric Neurotoxicity

Animal data indicate anesthetic and sedation drugs that block N-methyl-d-aspartic acid (NMDA) receptors and/or potentiate γ-aminobutyric acid (GABA) activity lead to increased neuronal apoptosis in the developing brain and results in long-term cognitive deficits when administered for >3 hours. Window of vulnerability for these changes thought to correlate with third trimester drug exposure through the first several months of life in humans, but may extend to approximately 3 years of age.

Similar deficits in cognition and behavior may occur in children following repeated or prolonged exposure to anesthesia early in life. Most studies to date have had substantial limitations; not clear whether adverse neurodevelopmental outcomes observed in children were drug-related or due to other factors (e.g., surgery, underlying illness).

When procedures requiring use of general anesthetics or sedation drugs are considered for young children or pregnant women, consider benefits, risks (including potential risk of adverse neurodevelopmental effects), and appropriate timing and duration of the procedure.

Specific Populations

Pregnancy

Animal data indicate repeated or prolonged use of general anesthetics and sedatives during the third trimester of pregnancy may result in adverse neurodevelopmental effects in the fetus. Clinical importance of these findings in humans not known.

Infants with long-term exposure to barbiturates in utero may exhibit an immediate or delayed onset of withdrawal symptoms (e.g., seizures, hyperirritability) up to 14 days after birth.

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

Lactation

Distributed into human milk; use with caution.

Females and Males of Reproductive Potential

May decrease efficacy of oral hormonal contraceptives when pentobarbital is used concomitantly or as pretreatment; use alternative contraceptive method.

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 NMDA receptors and/or potentiate GABA activity leads to increased neuronal apoptosis in the brain and long-term deficits in cognition and behavior; clinical importance to humans unknown.

Some evidence suggests similar deficits may occur in children following repeated or prolonged exposure to anesthesia early in life. Most studies to date have substantial limitations; unclear whether adverse outcomes related to the drug or other factors (e.g., surgery, underlying illness).

Consider benefits, potential risks, and appropriate timing and duration of elective procedures requiring anesthesia.

Geriatric Use

Possible increased sensitivity to barbiturates. May frequently react to barbiturates with excitement, confusion, or depression.

Debilitated Patients

Possible increased sensitivity to barbiturates. May react to barbiturates with excitement, confusion, or depression.

Hepatic Impairment

Use with caution; avoid use in patients with premonitory signs of hepatic coma.

Renal Impairment

Pharmacokinetics not studied; however, dosage reduction recommended.

Common Adverse Effects

Somnolence reported in up to 3% of patients; less common adverse effects reported in <1% of patients include agitation, confusion, hyperkinesia, ataxia, CNS depression, nightmares, nervousness, psychiatric disturbance, hallucinations, insomnia, anxiety, dizziness, thinking abnormalities, hypoventilation, apnea, bradycardia, hypotension, syncope, nausea and vomiting, constipation, headache, injection site reactions, hypersensitivity reactions (angioedema, skin rash, exfoliative dermatitis), fever, liver damage, megaloblastic anemia (following chronic use).

Drug Interactions

Metabolized by hepatic microsomal enzymes. Induces hepatic microsomal enzymes.

Specific Drugs

Pentobarbital Pharmacokinetics

Absorption

Onset

Following IV administration, onset occurs within 1 minute.

Plasma levels in therapeutic range of 0.5−3 mcg/mL generally produce sedation and calm; levels of 10−15 mcg/mL produce significant respiratory depression and coma; levels >15 mcg/mL potentially lethal.

Duration

Variable; patient-dependent and may vary occasionally within same patient. Maximal CNS depression may not occur until about 15 minutes following IV administration.

Distribution

Extent

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

Crosses the placenta; distributed into human milk.

Elimination

Metabolism

Metabolized primarily by hepatic microsomal enzymes.

Elimination Route

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

Half-life

Dose-dependent; 15–50 hours.

Stability

Storage

Parenteral

Solution for Injection

20–25°C (excursions permitted from 15–30°C). Protect from freezing and avoid excessive heat.

Do not use if discoloration or precipitation occurs.

Actions

• CNS effects appear to be related to the drug's ability to enhance activity of GABA and block N-methyl-d-aspartic acid (NMDA) receptors.

• Depresses sensory cortex, decreases motor activity, and alters cerebellar function to produce drowsiness, sedation, and hypnosis.

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

• Little analgesic activity at lower dosages; paradoxically may increase reaction to painful stimuli.

• Results in dose-dependent respiratory depression.

Advice to Patients

• Inform patients of the risk of psychological and/or physical dependence with use of barbiturates such as pentobarbital. Advise patients to not increase the dose of the drug without first consulting a prescriber.

• Inform patients that barbiturates such as pentobarbital can potentially impair the mental and/or physical abilities required to perform hazardous tasks such as driving or operating heavy machinery.

• Inform patients to avoid consuming alcohol while taking barbiturates such as pentobarbital. Concomitant use of barbiturates with CNS depressants such as alcohol, narcotics, tranquilizers, or antihistamines can result in additive CNS depressant effects.

• Inform patients that studies in young animals and children suggest that repeated or prolonged use of general anesthetics or sedation drugs in children <3 years of age may have detrimental effects on brain development. The risks and benefits, timing, and duration of surgery or procedures requiring anesthetic or sedation drugs should be discussed with the patient or caregiver.

• Stress importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.

• Advise patients to inform clinicians if they are or plan to become pregnant or plan to breast-feed. The window of vulnerability during the third trimester and the risks, benefits, timing, and duration of surgery or procedures requiring anesthetics or sedation should be discussed with pregnant women.

• Inform women receiving oral hormonal (estrogen or progestin-containing) contraceptives that an alternative contraceptive method should be used during pentobarbital therapy.

• Inform patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

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

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