Pentobarbital

Class: Barbiturates
VA Class: CN301
CAS Number: 76-74-4
Brands: Nembutal

Introduction

Barbiturate; anxiolytic, sedative, hypnotic, and anticonvulsant.^{a b}

Uses for Pentobarbital

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Insomnia

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

Has been used for routine sedation.^{a b} 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.^e

Surgery and Preanesthesia

Preoperatively, to produce sedation and relieve anxiety.^b

Provide basal hypnosis for general, spinal, or regional anesthesia, or to facilitate intubation procedures.^{a b}

Seizure Disorders

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

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

Drug Withdrawal

Withdrawal of barbiturate or nonbarbiturate hypnotics in physically dependent patients.^b

Agitated Behavior

Has been used to control acute episodes of agitated behavior in psychoses†; however, little value in long-term management of psychoses.^b

Coma Induction

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

Has been used to ameliorate or prevent sequelae associated with cerebral ischemia during neurosurgical procedures† that require long periods of cerebral hypoxia.^b

Pentobarbital Dosage and Administration

General

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

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

• 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

Insomnia

• Do not administer for periods >2 weeks.^{a b e}

Administration

Administer by IM or slow IV injection.^{a b}

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.^b (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 A time interval of ≥1 minute is required to determine the full effect of an IV dose.^{a b}

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.^{a b} (See Respiratory and Cardiovascular Effects under Cautions.)

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

Rate of Administration

Do not exceed 50 mg/minute.^{a b} (See Respiratory and Cardiovascular Effects under Cautions.)

IM Administration

Administer by deep IM injection into a large muscle.^{a b}

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

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

Dosage

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

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

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

A time interval of >1 minute required to determine the full effect of an IV dose.^{a b}

Pediatric Patients

Insomnia

IM

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

Surgery and Preanesthesia

IM

Usually, approximately 5 mg/kg. ^b

IV

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

Seizure Disorders

IV

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

Agitated Behavior†

IV

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

Adults

Insomnia

IM

150–200 mg as a single dose.^{a b}

IV

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

Surgery and Preanesthesia

IM

150–200 mg as a single dose.^{a b}

Seizures

IV

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

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

Drug Withdrawal

IM

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

Agitated Behavior†

IV

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

Prescribing Limits

Pediatric Patients

Insomnia

IM

Maximum 100 mg daily.^{a b}

Adults

IV

Maximum 200–500 mg.^{a b}

Special Populations

Hepatic Impairment

Dosage reduction recommended. ^{a b e}

Renal Impairment

Dosage reduction recommended.^a

Geriatric Patients

Dosage reduction recommended.^{a b e}

Debilitated Patients

Dosage reduction recommended.^{a b e}

Cautions for Pentobarbital

Contraindications

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

• Known hypersensitivity to any barbiturates.^a

• History of manifest or latent porphyria.^{a e} (See Porphyria under Cautions.)

• Bronchopneumonia or other severe pulmonary insufficiency.^e

Warnings/Precautions

Warnings

Pain Reaction

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

Abuse Potential

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

Withdrawal Effects

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

CNS Depression

Performance of activities requiring mental alertness or physical coordination may be impaired.^{a e}

Concurrent use of other CNS depressants may potentiate CNS depression.^a (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. ^{a e} Administer slowly; personnel and equipment should be readily available for administration of artificial respiration.^{a b}

Fetal/Neonatal Morbidity

May cause fetal harm.^{a e} If used during pregnancy or if patient becomes pregnant, apprise of potential fetal hazard.^{a e}

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

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

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

Porphyria

Potential exacerbation of acute intermittent porphyria or porphyria variegata.^e (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.^h

Sensitivity Reactions

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

Dermatologic Effects and Hypersensitivity Reactions

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

General Precautions

Intra-arterial Injection

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

Discontinue injection if the patient complains of pain in limb.^a

Suicide

Use with caution, if at all, in patients with depression or suicidal tendencies.^{a e}

Concomitant Diseases

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

Specific Populations

Pregnancy

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

Lactation

Distributed into milk;^{a e} use with caution.^a

Geriatric Use

Possible increased sensitivity to barbiturates.^a Geriatric patients may frequently react to barbiturates with excitement, confusion, or depression.^{a e}

Debilitated Patients

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

Hepatic Impairment

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

Common Adverse Effects

Residual sedation,^e drowsiness,^{a e} lethargy,^e vertigo,^{a e} nausea,^{a e} vomiting,^{a e} headache.^{a e}

Interactions for Pentobarbital

Metabolized by hepatic microsomal enzymes.^a Induces hepatic microsomal enzymes.^a

Specific Drugs

Pentobarbital Pharmacokinetics

Absorption

Onset

Following IV administration, onset occurs within 1 minute.^{a b e}

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

Duration

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

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.^b

Distribution

Extent

Rapidly distributed to all tissues and fluids,^{a e} with high concentrations in the brain, liver, and kidneys.^{a e}

Crosses the placenta and is distributed into milk.^{a e}

Plasma Protein Binding

Approximately 35–45%.^b

Elimination

Metabolism

Metabolized primarily by hepatic microsomal enzymes.^{a b e}

Elimination Route

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

Half-life

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

Stability

Storage

Parenteral

Solution for Injection

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

Do not use if discoloration or precipitation occurs.^a

Compatibility

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

Parenteral

Solution Compatibility^HID

Drug Compatibility

Actions

• 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 GABA_A receptors.^e

• Capable of producing all levels of CNS depression—from mild sedation to hypnosis to deep coma to death.^{a e}

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

• 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.^e

Advice to Patients

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

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

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

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

• Importance of informing patients of other important precautionary information.^a (See Cautions.)

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) drugs.^b

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