Yes

Anticonvulsant, Barbiturate; Barbiturate

Sedative/hypnotic; preanesthetic; high-dose barbiturate coma for treatment of increased intracranial pressure or status epilepticus unresponsive to other therapy

C-II (capsules, injection); C-III (suppositories)

D

Hypersensitivity to barbiturates or any component of the formulation; marked hepatic impairment; dyspnea or airway obstruction; porphyria

Tolerance to hypnotic effect can occur; do not use for >2 weeks to treat insomnia. Potential for drug dependency exists, abrupt cessation may precipitate withdrawal, including status epilepticus in epileptic patients. Do not administer to patients in acute pain. Use caution in elderly, debilitated, renally impaired, hepatic dysfunction, or pediatric patients. May cause paradoxical responses, including agitation and hyperactivity, particularly in acute pain and pediatric patients. Use with caution in patients with depression or suicidal tendencies, or in patients with a history of drug abuse. Tolerance, psychological and physical dependence may occur with prolonged use.

May cause respiratory depression or hypotension, particularly when administered intravenously. Use with caution in hemodynamically unstable patients or patients with respiratory disease. High doses (loading doses of 15-35 mg/kg given over 1-2 hours) have been utilized to induce pentobarbital coma, but these higher doses often cause hypotension requiring vasopressor therapy.

Cardiovascular: Bradycardia, hypotension, syncope

Central nervous system: Drowsiness, lethargy, CNS excitation or depression, impaired judgment, "hangover" effect, confusion, somnolence, agitation, hyperkinesia, ataxia, nervousness, headache, insomnia, nightmares, hallucinations, anxiety, dizziness

Dermatologic: Rash, exfoliative dermatitis, Stevens-Johnson syndrome

Gastrointestinal: Nausea, vomiting, constipation

Hematologic: Agranulocytosis, thrombocytopenia, megaloblastic anemia

Local: Pain at injection site, thrombophlebitis with I.V. use

Renal: Oliguria

Respiratory: Laryngospasm, respiratory depression, apnea (especially with rapid I.V. use), hypoventilation, apnea

Miscellaneous: Gangrene with inadvertent intra-arterial injection

Symptoms of overdose include unsteady gait, slurred speech, confusion, jaundice, hypothermia, hypotension, respiratory depression, coma

If hypotension occurs, administer I.V. fluids and place the patient in the Trendelenburg position. If unresponsive, an I.V. vasopressor (eg, dopamine, epinephrine) may be required. Forced alkaline diuresis is of no value in the treatment of intoxications with short-acting barbiturates. Charcoal hemoperfusion or hemodialysis may be useful in the harder to treat intoxications, especially in the presence of very high serum barbiturate levels when the patient is in a coma, shock, or renal failure.

Barbiturates are enzyme inducers. Patients should be monitored when these drugs are started or stopped for a decreased or increased therapeutic effect respectively.

Increased toxicity when combined with other CNS depressants, benzodiazepines, valproic acid, chloramphenicol, or antidepressants; respiratory and CNS depression may be additive. MAOIs may prolong the effect of pentobarbital; barbiturates stimulate the metabolism of beta-blockers and decrease their serum concentrations. Consider a renally-eliminated beta-blocker (atenolol, nadolol). Barbiturates may enhance the hepatotoxic potential of acetaminophen via an increased formation of toxic metabolites. Barbiturates may increase chloramphenicol metabolism and chloramphenicol may inhibit the metabolism of barbiturates. Barbiturates may increase the metabolism of corticosteroids, cyclosporine, disopyramide, griseofulvin, nifedipine, oral contraceptives, phenytoin, propafenone, quinidine, verapamil; dosage adjustments may be useful. Barbiturates may enhance the metabolism of methadone resulting in methadone withdrawal.

Protect from freezing; aqueous solutions are not stable, commercially available vehicle (containing propylene glycol) is more stable; low pH may cause precipitate; use only clear solution

Short-acting barbiturate with sedative, hypnotic, and anticonvulsant properties. Barbiturates depress the sensory cortex, decrease motor activity, alter cerebellar function, and produce drowsiness, sedation, and hypnosis. In high doses, barbiturates exhibit anticonvulsant activity; barbiturates produce dose-dependent respiratory depression.

Onset of action: Oral, rectal: 15-60 minutes; I.M.: Within 10-15 minutes; I.V.: Within 1 minute

Duration: Oral, rectal: 1-4 hours; I.V.: 15 minutes

Distribution: V_d: Children: 0.8 L/kg; Adults: 1 L/kg

Protein binding: 35% to 55%

Metabolism: Extensively in liver via hydroxylation and oxidation pathways

Half-life, terminal: Children: 25 hours; Adults, normal: 22 hours; range: 35-50 hours

Elimination: <1% excreted unchanged renally

Children:

Sedative: Oral: 2-6 mg/kg/day divided in 3 doses; maximum: 100 mg/day

Hypnotic: I.M.: 2-6 mg/kg; maximum: 100 mg/dose

Rectal:

2 months to 1 year (10-20 lb): 30 mg

1-4 years (20-40 lb): 30-60 mg

5-12 years (40-80 lb): 60 mg

12-14 years (80-110 lb): 60-120 mg

or

<4 years: 3-6 mg/kg/dose

>4 years: 1.5-3 mg/kg/dose

Preoperative/preprocedure sedation: greater than or equal to 6 months:

Oral, I.M., rectal: 2-6 mg/kg; maximum: 100 mg/dose

I.V.: 1-3 mg/kg to a maximum of 100 mg until asleep

Children 5-12 years: Conscious sedation prior to a procedure: I.V.: 2 mg/kg 5-10 minutes before procedures, may repeat one time

Adolescents: Conscious sedation: Oral, I.V.: 100 mg prior to a procedure

Adults:

Hypnotic:

Oral: 100-200 mg at bedtime or 20 mg 3-4 times/day for daytime sedation

I.M.: 150-200 mg

I.V.: Initial: 100 mg, may repeat every 1-3 minutes up to 200-500 mg total dose

Rectal: 120-200 mg at bedtime

Preoperative sedation: I.M.: 150-200 mg

Children and Adults: Barbiturate coma in head injury patients: I.V.: Loading dose: 5-10 mg/kg given slowly over 1-2 hours; monitor blood pressure and respiratory rate; Maintenance infusion: Initial: 1 mg/kg/hour; may increase to 2-3 mg/kg/hour; maintain burst suppression on EEG

Tolerance testing: 200 mg every 2 hours until signs of intoxication are exhibited at any time during the 2 hours after the dose; maximum dose: 1000 mg

Dosing adjustment in hepatic impairment: Reduce dosage in patients with severe liver dysfunction

Alcohol: Additive CNS effect, avoid use

Respiratory status (for conscious sedation, includes pulse oximetry), cardiovascular status, CNS status; cardiac monitor and blood pressure monitor required

Therapeutic:

Hypnotic: 1-5 mg/mL (SI: 4-22 mmol/L)

Coma: 10-50 mg/mL (SI: 88-221 mmol/L)

Toxic: >10 mg/mL (SI: >44 mmol/L)

ammonia (B); bilirubin (S)

No information available to require special precautions

No effects or complications reported

I.V./I.M.: Patient instructions and information are determined by patient condition and therapeutic purpose. If self-administered, use exactly as directed (do not increase dose or frequency); may cause physical and/or psychological dependence. While using this medication, do not use alcohol and other prescription or OTC medications (especially pain medications, sedatives, antihistamines, or hypnotics) without consulting prescriber. Maintain adequate hydration (2-3 L/day of fluids unless instructed to restrict fluid intake). You may experience drowsiness, dizziness, or blurred vision (use caution when driving or engaging in tasks requiring alertness until response to drug is known); nausea, vomiting, or loss of appetite (small frequent meals, frequent mouth care, chewing gum, or sucking lozenges may help); constipation (increased exercise, fluids, or dietary fruit and fiber may help). Report skin rash or irritation; CNS changes (confusion, depression, increased sedation, excitation, headache, insomnia, or nightmares); difficulty breathing or shortness of breath; changes in urinary pattern or menstrual pattern; muscle weakness or tremors; or difficulty swallowing or feeling of tightness in throat. Pregnancy/breast-feeding precautions: Do not get pregnant; use appropriate contraceptive measures to prevent possible harm to the fetus. Do not breast-feed.

Avoid extravasation; institute safety measures to avoid injuries; has many incompatibilities when given I.V.

Capsule, as sodium (C-II): 50 mg, 100 mg

Elixir (C-II): 18.2 mg/5 mL (473 mL, 4000 mL)

Injection, as sodium (C-II): 50 mg/mL (1 mL, 2 mL, 20 mL, 50 mL)

Suppository, rectal (C-III): 30 mg, 60 mg, 120 mg, 200 mg

Fischer JH and Raineri DL, "Pentobarbital Anesthesia for Status Epilepticus," Clin Pharm, 1987, 6(8):601-2.

Hubbard AM, Markowitz RI, Kimmel B, et al, "Sedation for Pediatric Patients Undergoing CT and MRI," J Comput Assist Tomogr, 1992, 16(1):3-6.

McCarron MM, Schulze BW, Walberg CB, et al, "Short-Acting Barbiturate Overdosage. Correlation of Intoxication Score With Serum Barbiturate Concentration," JAMA, 1982, 248(1):55-61.

Pereira JK, Burrows PE, Richards HM, et al, "Comparison of Sedation Regimens for Pediatric Outpatient CT," Pediatr Radiol, 1993, 23(5):341-4.

Schaible DH, Cupit GC, Swedlow DB, et al, "High-Dose Pentobarbital Pharmacokinetics in Hypothermic Brain-Injured Children," J Pediatr, 1982, 100(4):655-60.

Tobias JD, Deshpande JK, Pietsch JB, et al, "Pentobarbital Sedation for Patients in the Pediatric Intensive Care Unit," South Med J, 1995, 88(3):290-4.

Wermeling D, Record K, Bell R, et al, "Hemodialysis Clearance of Pentobarbital During Continuous Infusion," Ther Drug Monit, 1985, 7(4):485-7.

Zeltzer LK, Altman A, Cohen D, et al, "American Academy of Pediatrics Report of the Subcommittee on the Management of Pain Associated With Procedures in Children With Cancer," Pediatrics, 1990, 86(5 Pt 2):826-31.