indication

For the treatment of all types of seizures except absence seizures.

pharmacology

Phenobarbital, the longest-acting barbiturate, is used for its anticonvulsant and sedative-hypnotic properties in the management of all seizure disorders except absence (petit mal).

mechanism of action

Phenobarbital acts on GABAA receptors, increasing synaptic inhibition. This has the effect of elevating seizure threshold and reducing the spread of seizure activity from a seizure focus. Phenobarbital may also inhibit calcium channels, resulting in a decrease in excitatory transmitter release. The sedative-hypnotic effects of phenobarbital are likely the result of its effect on the polysynaptic midbrain reticular formation, which controls CNS arousal.

toxicity

CNS and respiratory depression which may progress to Cheyne-Stokes respiration, areflexia, constriction of the pupils to a slight degree (though in severe poisoning they may wshow paralytic dilation), oliguria, tachycardia, hypotension, lowered body temperature, and coma. Typical shock syndrome (apnea, circulatory collapse, respiratory arrest, and death) may occur.

biotransformation

Hepatic (mostly via CYP2C19).

absorption

Absorbed in varying degrees following oral, rectal or parenteral administration. The salts are more rapidly absorbed than are the acids. The rate of absorption is increased if the sodium salt is ingested as a dilute solution or taken on an empty stomach.

half life

53 to 118 hours (mean 79 hours)

drug interactions

Acenocoumarol: The barbiturate, phenobarbital, decreases the anticoagulant effect of acenocoumarol.

Aminophylline: The barbiturate, phenobarbital, decreases the effect of aminophylline.

Anisindione: The barbiturate, phenobarbital, decreases the anticoagulant effect of anisindione.

Betamethasone: The barbiturate, phenobarbital, may decrease the effect of the corticosteroid, betamethasone.

Chlorotrianisene: The enzyme inducer, phenobarbital, decreases the effect of the hormone agent, chlorotrianisene.

Clomifene: The enzyme inducer, phenobarbital, decreases the effect of the hormone agent, clomifene.

Conjugated Estrogens: The enzyme inducer, phenobarbital, decreases the effect of the hormone agent, conjugated estrogens.

Cortisone acetate: The barbiturate, phenobarbital, may decrease the effect of the corticosteroid, cortisone acetate.

Cyclosporine: The barbiturate, phenobarbital, may decrease the therapeutic effect of cyclosporine by increasing its metabolism.

Dasatinib: Phenobarbital may decrease the serum level and efficacy of dasatinib.

Delavirdine: The anticonvulsant, phenobarbital, decreases the effect of delavirdine.

Dexamethasone: The barbiturate, phenobarbital, may decrease the effect of the corticosteroid, dexamethasone.

Dicumarol: The barbiturate, phenobarbital, decreases the anticoagulant effect, dicumarol.

Diethylstilbestrol: The enzyme inducer, phenobarbital, may decrease the therapeutic effect of diethylstilbestrol.

Disopyramide: Phenobarbital decreases levels of disopyramide

Doxycycline: The anticonvulsant, phenobarbital, may decrease the therapeutic effect of doxycycline.

Dyphylline: The barbiturate, phenobarbital, decreases the effect of dyphylline.

Estradiol: The enzyme inducer, phenobarbital, decreases the effect of the hormone agent, estradiol.

Estriol: The enzyme inducer, phenobarbital, decreases the effect of the hormone agent, estriol.

Estrone: The enzyme inducer, phenobarbital, decreases the effect of the hormone agent, estrone.

Estropipate: The enzyme inducer, phenobarbital, decreases the effect of the hormone agent, estropipate.

Ethinyl Estradiol: This product may cause a slight decrease of contraceptive effect

Felbamate: Felbamate increases the effect and toxicity of phenobarbital/primidone

Felodipine: The barbiturate, phenobarbital, decreases the effect of felodipine.

Fludrocortisone: The barbiturate, phenobarbital, may decrease the effect of the corticosteroid, fludrocortisone.

Folic Acid: Folic acid decreases the effect of anticonvulsant, phenobarbital.

Gefitinib: The CYP3A4 inducer, phenobarbital, may decrease the serum concentration and therapeutic effects of gefitinib.

Griseofulvin: The barbiturate, phenobarbital, decreases the effect of griseofulvin.

Hydrocortisone: The barbiturate, phenobarbital, may decrease the effect of the corticosteroid, hydrocortisone.

Imatinib: Phenobarbital decreases levels of imatinib

Itraconazole: The barbiturate, phenobarbital, decreases the effect of itraconazole.

Levonorgestrel: Phenobarbital decreases the effect of levonorgestrel

Medroxyprogesterone: The enzyme inducer, phenobarbital, may decrease the effect of the hormone, medroxyprogesterone.

Megestrol: The enzyme inducer, phenobarbital, may decrease the effect of the hormone, megestrol.

Mestranol: This product may cause a slight decrease of contraceptive effect

Methadone: The barbiturate, phenobarbital, decreases the effect of methadone.

Methoxyflurane: The barbiturate, phenobarbital, increases the renal toxicity of methoxyflurane.

Methylprednisolone: The barbiturate, phenobarbital, may decrease the effect of the corticosteroid, methylprednisolone.

Metoprolol: The barbiturate decreases the effect of the metabolized beta-blocker

Metronidazole: The barbiturate, phenobarbital, decreases the effect of metronidazole.

Nifedipine: The barbiturate, phenobarbital, may decrease the effect of the calcium channel blocker, nifedipine.

Norethindrone: This product may cause a slight decrease of contraceptive effect

Oxtriphylline: The barbiturate, phenobarbital, decreases the effect of oxtriphylline.

Paramethasone: The barbiturate, phenobarbital, may decrease the effect of the corticosteroid, paramethasone.

Prednisolone: The barbiturate, phenobarbital, may decrease the effect of the corticosteroid, prednisolone.

Prednisone: The barbiturate, phenobarbital, may decrease the effect of the corticosteroid, prednisone.

Propranolol: The barbiturate decreases the effect of the metabolized beta-blocker

Quinestrol: The enzyme inducer, phenobarbital, decreases the effect of the hormone agent, quinestrol.

Quinidine: The anticonvulsant, phenobarbital, decreases the effect of quinidine.

Sunitinib: Possible decrease in sunitinib levels

Tacrolimus: Phenobarbital may decrease the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Phenobarbital therapy is initiated, discontinued or altered.

Telithromycin: Phenobarbital may decrease the plasma concentration of Telithromycin. Consider alternate therapy.

Temsirolimus: Phenobarbital may increase the metabolism of Temsirolimus decreasing its efficacy. Concomitant therapy should be avoided.

Theophylline: The barbiturate, phenobarbital, decreases the effect of theophylline.

Ticlopidine: Ticlopidine may decrease the metabolism and clearance of Phenobarbital. Consider alternate therapy or monitor for adverse/toxic effects of Phenobarbital if Ticlopidine is initiated, discontinued or dose changed.

Tipranavir: Phenobarbial decreases the concentration of Tipranavir. Monitor for decreased Tipranavir efficacy.

Tramadol: Phenobarbital may decrease the effect of Tramadol by increasing Tramadol metabolism and clearance.

Trazodone: The CYP3A4 inducer, Phenobarbital, may decrease Trazodone efficacy by increasing Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Phenobarbital is initiated, discontinued or dose changed.

Tretinoin: The strong CYP2C8 inducer, Phenobarbital, may increase the metabolism and clearance of oral Tretinoin. Consider alternate therapy to avoid failure of Tretinoin therapy or monitor for changes in Tretinoin effectiveness and adverse/toxic effects if Phenobarbital is initiated, discontinued or dose changed.

Triamcinolone: The barbiturate, phenobarbital, may decrease the effect of the corticosteroid, triamcinolone.

Trimipramine: The barbiturate, Phenobarbital, may increase the metabolism and clearance of Trimipramine. Monitor for changes in the therapeutics and adverse effects of Trimipramine if Phenobarbital is initiated, discontinued or dose changed. Dose adjustments of Trimipramine may be required.

Triprolidine: The CNS depressants, Triprolidine and Phenobarbital, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.

Verapamil: Phenobarbital, a CYP3A4 inducer, may increase the serum concentration of Verapamil, a CYP3A4 substrate. Monitor for changes in the therapeutic/adverse effects of Verapamil if Phenobarbital is initiated, discontinued or dose changed.

Voriconazole: Phenobarbital may reduce serum concentrations and efficacy of voriconazole. Concomitant voriconazole and long-acting barbiturates therapy is contraindicated.

Warfarin: Phenobarbital may decrease the serum concentration of warfarin by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of warfarin if phenobarbital is initiated, discontinued or dose changed.