pentobarbital sodium
Nembutal

Available forms
Available by prescription only
Capsules: 50 mg, 100 mg
Elixir: 18.2 mg/5 ml
Injection: 50 mg/ml, 1-ml and 2-ml disposable syringes; 2-ml, 20-ml, and 50-ml vials
Suppositories: 30 mg, 60 mg, 120 mg, 200 mg

Indications and dosages
 Sedation. Adults: 20 to 40 mg P.O. b.i.d., t.i.d., or q.i.d.
Children: 2 to 6 mg/kg P.O. daily in divided doses, to maximum of 100 mg/dose.
 Insomnia. Adults: 100 mg P.O. h.s. or 150 to 200 mg deep I.M.; 120 to 200 mg P.R.
Children: 2 to 6 mg/kg I.M., up to maximum of 100 mg/ dose. Or 30 mg P.R. (ages 2 months to 1 year), 30 to 60 mg P.R. (ages 1 to 4), 60 mg P.R. (ages 5 to 12), 60 to 120 mg P.R. (ages 12 to 14).
 Preanesthetic action. Adults: 150 to 200 mg I.M. or P.O. in two divided doses.
 Anticonvulsant action. Adults: Initially, 100 mg I.V.; after 1 minute additional doses may be given. Maximum dose is 500 mg.
Children: 50 mg initially; after 1 minute additional small doses may be given until desired effect is obtained.

Pharmacodynamics
Sedative-hypnotic action: Exact cellular site and mechanism of action unknown. Acts throughout the CNS as a nonselective depressant with a fast onset of action and short duration of action. Particularly sensitive to this drug is the reticular activating system, which controls CNS arousal. Pentobarbital decreases both presynaptic and postsynaptic membrane excitability by facilitating the action of gamma-aminobutyric acid (GABA).
Anticonvulsant action: Suppresses spread of seizure activity produced by epileptogenic foci in the cortex, thalamus, and limbic systems by enhancing the effect of GABA. Both presynaptic and postsynaptic excitability are decreased, and the seizure threshold is raised.

Pharmacokinetics
Absorption: Absorbed rapidly after oral or rectal administration. Serum levels needed for sedation and hypnosis are 1 to 5 mcg/ml and 5 to 15 mcg/ml, respectively.
Distribution: Distributed widely throughout body. About 35% to 45% protein-bound. Accumulates in fat with long-term use.
Metabolism: Metabolized in liver.
Excretion: 99% eliminated as glucuronide conjugates and other metabolites in urine. Terminal half-life ranges from 35 to 50 hours; duration of action 3 to 4 hours.

Contraindications and precautions
Contraindicated in patients hypersensitive to barbiturates and in those with porphyria or severe respiratory disease when dyspnea or obstruction is evident. Use cautiously in elderly or debilitated patients and in those with acute or chronic pain, mental depression, suicidal tendencies, history of drug abuse, or impaired hepatic function.

Interactions
Drug-drug. Antidepressants, antihistamines, narcotics, sedative-hypnotics, tranquilizers: Potentiates or causes additive CNS and respiratory depressant effects. Monitor patient closely.
Corticosteroids, digitoxin, doxycycline, hormonal contraceptives (and other estrogens), theophylline (and other xanthines): Enhances hepatic metabolism. Monitor patient for clinical effectiveness.
Disulfiram, MAO inhibitors, valproic acid: Decreases metabolism of pentobarbital. Monitor patient for toxicity.
Griseofulvin: Impairs effectiveness of this drug; decreases absorption from GI tract. Separate administration times.
Rifampin: Decreases pentobarbital levels; increases hepatic metabolism. Adjust dosage as needed.
Warfarin, other oral anticoagulants: Enhances enzymatic degradation of these drugs. Increased doses of anticoagulants may be needed.
Drug-lifestyle. Alcohol use: Potentiates or causes additive CNS and respiratory depressant effects. Discourage alcohol use.

Adverse reactions
CNS: drowsiness, lethargy, hangover, paradoxical excitement in elderly patients, somnolence, syncope, hallucinations, change in EEG patterns.
CV: bradycardia, hypotension.
GI: nausea, vomiting.
Hematologic: exacerbation of porphyria.
Respiratory: respiratory depression.
Skin: rash, urticaria, Stevens-Johnson syndrome.
Other: angioedema, physical and psychological dependence.

Effects on lab test results
None reported.

Overdose and treatment
Toxicity may cause unsteady gait, slurred speech, sustained nystagmus, somnolence, confusion, respiratory depression, pulmonary edema, areflexia, and coma. Typical shock syndrome with tachycardia and hypotension may occur. Jaundice, hypothermia, then fever and oliguria also may occur. Serum levels greater than 10 mcg/ml may produce profound coma; levels greater than 30 mcg/ml may be fatal.
 To treat, maintain and support ventilation and pulmonary function as needed; support cardiac function and circulation with vasopressors and I.V. fluids, as needed. If patient is conscious and gag reflex is intact, induce emesis (if ingestion was recent) by administering ipecac syrup. If emesis is contraindicated, perform gastric lavage while a cuffed endotracheal tube is in place to prevent aspiration. Follow with administration of activated charcoal or sodium chloride cathartic. Measure intake or output, vital sighs, and laboratory parameters. Maintain body temperature.
 Alkalinization of urine may be helpful in removing drug from body. Hemodialysis may be useful in severe overdose.

Special considerations
• Reserve I.V. injection for emergency treatment. Be prepared for emergency resuscitative measures.
• Avoid I.V. administration at a rate exceeding 50 mg/minute to prevent hypotension and respiratory depression.
• High-dose therapy for elevated intracranial pressure may require mechanically assisted ventilation.
• Administer I.M. dose deep into large muscle mass. Don’t administer more than 5 ml into any one site.
• Discard solution that is discolored or contains precipitate.
• Administration of full loading doses over short periods of time to treat status epilepticus will require ventilatory support in adults.
• To assure accuracy of dosage, don’t divide suppositories.
• Drug has no analgesic effect and may cause restlessness or delirium in patients with pain.
• Nembutal tablets contain tartrazine dye, which may cause allergic reactions in susceptible persons.
• To prevent rebound of rapid-eye-movement sleep after prolonged therapy, discontinue gradually over 5 to 6 days.
• Administer with caution in patients with a substance abuse history.
• Pentobarbital may cause a false-positive phentolamine test. Drug’s physiologic effects may impair the absorption of cyanocobalamin Co 57; it may decrease serum bilirubin levels in neonates, epileptic patients, and patients with congenital nonhemolytic unconjugated hyperbilirubinemia.
Pregnant patients
• Drug may be hazardous to fetus or neonate when taken late in pregnancy. Withdrawal symptoms can occur.
Breast-feeding patients
• Drug appears in breast milk. Don’t administer to breast-feeding women.
Pediatric patients
• Barbiturates may cause paradoxical excitement in children. Use cautiously.
Geriatric patients
• Elderly patients usually need lower doses because of increased susceptibility to CNS depressant effects of pentobarbital. Confusion, disorientation, and excitability may occur in elderly patients. Use cautiously.

Patient education
• Advise pregnant patient of potential hazard to fetus or neonate when drug is taken late in pregnancy and that withdrawal symptoms can occur.
• Tell patient not to take drug continuously for longer than 2 weeks.
• Instruct patient that drug may be habit forming and to take as directed.
• Emphasize the dangers of combining drug with alcohol. Tell him that an excessive depressant effect is possible even if drug is taken the evening before ingestion of alcohol.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use