Pronunciation:

(fee noe BAR bi tal)

U.S. Brand Names:

Synonyms:

Generic Available:

Canadian Brand Names:

Use:

Use - Unlabeled/Investigational:

Restrictions:

Pregnancy Risk Factor:

Pregnancy Implications:

Lactation:

Contraindications:

Warnings/Precautions:

Adverse Reactions:

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

Miscellaneous: Gangrene with inadvertent intra-arterial injection

Overdosage/Toxicology:

Drug Interactions:

Acetaminophen: Barbiturates may enhance the hepatotoxic potential of acetaminophen overdoses

Antiarrhythmics: Barbiturates may increase the metabolism of antiarrhythmics, decreasing their clinical effect; includes disopyramide, propafenone, and quinidine

Anticonvulsants: Barbiturates may increase the metabolism of anticonvulsants; includes ethosuximide, felbamate (possibly), lamotrigine, phenytoin, tiagabine, topiramate, and zonisamide; does not appear to affect gabapentin or levetiracetam

Antineoplastics: Limited evidence suggests that enzyme-inducing anticonvulsant therapy may reduce the effectiveness of some chemotherapy regimens (specifically in ALL); teniposide and methotrexate may be cleared more rapidly in these patients

Antipsychotics: Barbiturates may enhance the metabolism (decrease the efficacy) of antipsychotics; monitor for altered response; dose adjustment may be needed

Beta-blockers: Metabolism of beta-blockers may be increased and clinical effect decreased; atenolol and nadolol are unlikely to interact given their renal elimination

Calcium channel blockers: Barbiturates may enhance the metabolism of calcium channel blockers, decreasing their clinical effect

Chloramphenicol: Barbiturates may increase the metabolism of chloramphenicol and chloramphenicol may inhibit barbiturate metabolism; monitor for altered response

Cimetidine: Barbiturates may enhance the metabolism of cimetidine, decreasing its clinical effect

CNS depressants: Sedative effects and/or respiratory depression with barbiturates may be additive with other CNS depressants; monitor for increased effect; includes ethanol, sedatives, antidepressants, narcotic analgesics, and benzodiazepines

Corticosteroids: Barbiturates may enhance the metabolism of corticosteroids, decreasing their clinical effect

Cyclosporine: Levels may be decreased by barbiturates; monitor

CYP1A2 substrates: Phenobarbital may decrease the levels/effects of CYP1A2 substrates. Example substrates include aminophylline, estrogens, fluvoxamine, mirtazapine, ropinirole, and theophylline.

CYP2A6 substrates: Phenobarbital may decrease the levels/effects of CYP2A6 substrates. Example substrates include ifosfamide and rifampin.

CYP2B6 substrates: Phenobarbital may decrease the levels/effects of CYP2B6 substrates. Example substrates include bupropion, efavirenz, promethazine, selegiline, and sertraline.

CYP2C8/9 substrates: Phenobarbital may decrease the levels/effects of CYP2C8/9 substrates. Example substrates include amiodarone, fluoxetine, glimepiride, glipizide, losartan, nateglinide, phenytoin, pioglitazone, rosiglitazone, sertraline, sulfonamides, warfarin, and zafirlukast.

CYP2C19 inducers: May decrease the levels/effects of phenobarbital. Example inducers include aminoglutethimide, carbamazepine, phenytoin, and rifampin.

CYP2C19 inhibitors: May increase the levels/effects of phenobarbital. Example inhibitors include delavirdine, fluconazole, fluvoxamine, gemfibrozil, isoniazid, omeprazole, and ticlopidine.

CYP3A4 substrates: Phenobarbital may decrease the levels/effects of CYP3A4 substrates. Example substrates include benzodiazepines, calcium channel blockers, clarithromycin, cyclosporine, erythromycin, estrogens, mirtazapine, nateglinide, nefazodone, nevirapine, protease inhibitors, tacrolimus, and venlafaxine.

Doxycycline: Barbiturates may enhance the metabolism of doxycycline, decreasing its clinical effect; higher dosages may be required

Estrogens: Barbiturates may increase the metabolism of estrogens and reduce their efficacy

Felbamate may inhibit the metabolism of barbiturates and barbiturates may increase the metabolism of felbamate

Griseofulvin: Barbiturates may impair the absorption of griseofulvin, and griseofulvin metabolism may be increased by barbiturates, decreasing clinical effect

Guanfacine: Effect may be decreased by barbiturates

Immunosuppressants: Barbiturates may enhance the metabolism of immunosuppressants, decreasing its clinical effect; includes both cyclosporine and tacrolimus

Loop diuretics: Metabolism may be increased and clinical effects decreased; established for furosemide, effect with other loop diuretics not established

MAO inhibitors: Metabolism of barbiturates may be inhibited, increasing clinical effect or toxicity of the barbiturates

Methadone: Barbiturates may enhance the metabolism of methadone resulting in methadone withdrawal

Methoxyflurane: Barbiturates may enhance the nephrotoxic effects of methoxyflurane

Oral contraceptives: Barbiturates may enhance the metabolism of oral contraceptives, decreasing their clinical effect; an alternative method of contraception should be considered

Theophylline: Barbiturates may increase metabolism of theophylline derivatives and decrease their clinical effect

Tricyclic antidepressants: Barbiturates may increase metabolism of tricyclic antidepressants and decrease their clinical effect; sedative effects may be additive

Valproic acid: Metabolism of barbiturates may be inhibited by valproic acid; monitor for excessive sedation; a dose reduction may be needed

Warfarin: Barbiturates inhibit the hypoprothrombinemic effects of oral anticoagulants via increased metabolism; this combination should generally be avoided

Ethanol/Nutrition/Herb Interactions:

Ethanol: Avoid ethanol (may increase CNS depression).

Food: May cause decrease in vitamin D and calcium.

Herb/Nutraceutical: Avoid evening primrose (seizure threshold decreased). Avoid valerian, St John's wort, kava kava, gotu kola (may increase CNS depression).

Stability:

Compatibility:

Y-site administration: Compatible: Enalaprilat, fosphenytoin, gatifloxacin, levofloxacin, linezolid, meropenem, propofol, sufentanil. Incompatible: Amphotericin B cholesteryl sulfate complex, hydromorphone

Compatibility in syringe: Compatible: Heparin. Incompatible: Hydromorphone, pentazocine, ranitidine, sufentanil

Compatibility when admixed: Compatible: Amikacin, aminophylline, calcium chloride, calcium gluconate, colistimethate, dimenhydrinate, meropenem, polymyxin B sulfate, sodium bicarbonate, thiopental, verapamil. Incompatible: Chlorpromazine, cimetidine, clindamycin, dimenhydrinate, diphenhydramine, droperidol, ephedrine, hydralazine, hydrocortisone sodium succinate, hydroxyzine, insulin (regular), kanamycin, levorphanol, meperidine, morphine, norepinephrine, pancuronium, penicillin G, pentazocine, phenytoin, procaine, prochlorperazine edisylate, prochlorperazine mesylate, promazine, promethazine, streptomycin, succinylcholine, vancomycin. Variable (consult detailed reference): Isoproterenol, metaraminol, methyldopate, norepinephrine

Mechanism of Action:

Pharmacodynamics/Kinetics:

Onset of action: Oral: Hypnosis: 20-60 minutes; I.V.: ~5 minutes

Peak effect: I.V.: ~30 minutes

Duration: Oral: 6-10 hours; I.V.: 4-10 hours

Absorption: Oral: 70% to 90%

Protein binding: 20% to 45%; decreased in neonates

Metabolism: Hepatic via hydroxylation and glucuronide conjugation

Half-life elimination: Neonates: 45-500 hours; Infants: 20-133 hours; Children: 37-73 hours; Adults: 53-140 hours

Time to peak, serum: Oral: 1-6 hours

Excretion: Urine (20% to 50% as unchanged drug)

Dosage:

Children:

Sedation: Oral: 2 mg/kg 3 times/day

Hypnotic: I.M., I.V., SubQ: 3-5 mg/kg at bedtime

Preoperative sedation: Oral, I.M., I.V.: 1-3 mg/kg 1-1.5 hours before procedure

Adults:

Sedation: Oral, I.M.: 30-120 mg/day in 2-3 divided doses

Hypnotic: Oral, I.M., I.V., SubQ: 100-320 mg at bedtime

Preoperative sedation: I.M.: 100-200 mg 1-1.5 hours before procedure

Anticonvulsant: Status epilepticus: Loading dose: I.V.:

Infants and Children: 10-20 mg/kg in a single or divided dose; in select patients may administer additional 5 mg/kg/dose every 15-30 minutes until seizure is controlled or a total dose of 40 mg/kg is reached

Adults: 300-800 mg initially followed by 120-240 mg/dose at 20-minute intervals until seizures are controlled or a total dose of 1-2 g

Anticonvulsant maintenance dose: Oral, I.V.:

Infants: 5-8 mg/kg/day in 1-2 divided doses

Children:

1-5 years: 6-8 mg/kg/day in 1-2 divided doses

5-12 years: 4-6 mg/kg/day in 1-2 divided doses

Children >12 years and Adults: 1-3 mg/kg/day in divided doses or 50-100 mg 2-3 times/day

Sedative/hypnotic withdrawal (unlabeled use): Initial daily requirement is determined by substituting phenobarbital 30 mg for every 100 mg pentobarbital used during tolerance testing; then daily requirement is decreased by 10% of initial dose

Dosing interval in renal impairment: Clcr<10 mL/minute: Administer every 12-16 hours

Hemodialysis: Moderately dialyzable (20% to 50%)

Dosing adjustment/comments in hepatic disease: Increased side effects may occur in severe liver disease; monitor plasma levels and adjust dose accordingly

Administration:

Monitoring Parameters:

Reference Range:

Therapeutic:

Infants and children: 15-30 mcg/mL (SI: 65-129 mol/L)

Adults: 20-40 mcg/mL (SI: 86-172 mol/L)

Toxic: >40 mcg/mL (SI: >172 mol/L)

Toxic concentration: Slowness, ataxia, nystagmus: 35-80 mcg/mL (SI: 150-344 mol/L)

Coma with reflexes: 65-117 mcg/mL (SI: 279-502 mol/L)

Coma without reflexes: >100 mcg/mL (SI: >430 mol/L)

Test Interactions:

Dietary Considerations:

Patient Education:

Additional Information:

Anesthesia and Critical Care Concerns/Other Considerations:

Status Epilepticus: A randomized, double-blind trial (Treiman D, 1998) evaluated the efficacy of four treatments in overt status epilepticus. Treatment arms were designed based upon accepted practices of North American neurologists. The treatments were: 1) lorazepam 0.1 mg/kg, 2) diazepam 0.15 mg/kg followed by phenytoin 18 mg/kg, 3) phenytoin 18 mg/kg alone, and 4) phenobarbital 15 mg/kg. Treatment was considered successful if the seizures were terminated (clinically and by EEG) within 20 minutes of start of therapy without seizure recurrence within 60 minutes from the start of therapy. Patients who failed the first treatment received a second and a third, if necessary. Patients did not receive randomized treatments after the first one but the treating physician remained blinded. Treatment success: Lorazepam 64.9%, phenobarbital 58.2%, diazepam/phenytoin 55.8%, and phenytoin alone 43.6%. Using an "intention-to-treat" analysis, there was no statistical difference between the groups. Results of subsequent treatments in patients who failed the first therapy indicated that response rate significantly dropped regardless of treatment. Aggregate response rate to the second treatment was 7.0% and third treatment 2.3%.

Dental Health: Effects on Dental Treatment:

Dental Health: Vasoconstrictor/Local Anesthetic Precautions:

Dosage Forms:

Elixir: 20 mg/5 mL (5 mL, 7.5 mL, 15 mL, 473 mL, 946 mL, 4000 mL) [contains alcohol]

Injection, solution, as sodium: 60 mg/mL (1 mL); 130 mg/mL (1 mL) [contains alcohol]

Luminal® Sodium: 60 mg/mL (1 mL); 130 mg/mL (1 mL) [contains alcohol 10%]

Tablet: 15 mg, 30 mg, 32 mg, 60 mg, 65 mg, 100 mg

International Brand Names: