indication

Used in combination with acetaminophen or aspirin and caffeine for its sedative and relaxant effects in the treatment of tension headaches, migraines, and pain.

pharmacology

Butalbital is a short to intermediate-acting barbiturate. Barbiturates act as nonselective depressants of the central nervous system (CNS), capable of producing all levels of CNS mood alteration from excitation to mild sedation, hypnosis, and deep coma. In sufficiently high therapeutic doses, barbiturates induce anesthesia.

mechanism of action

Butalbital binds at a distinct binding site associated with a Cl^- ionopore at the GABA_A receptor, increasing the duration of time for which the Cl^- ionopore is open. The post-synaptic inhibitory effect of GABA in the thalamus is, therefore, prolonged.

toxicity

Symptoms of acute barbiturate poisoning include drowsiness, confusion, coma, respiratory depression, hypotension, and shock.

biotransformation

Hepatic, although most of the dose is eliminated via the kidney (59 to 88%). Urinary excretion products included parent drug (about 3.6% of the dose), 5-isobutyl-5-(2,3-dihydroxypropyl) barbituric acid (about 24% of the dose), 5-allyl-5(3-hydroxy-2-methyl-1-propyl) barbituric acid (about 4.8%).

absorption

Well absorbed from the gastrointestinal tract and is expected to distribute to most tissues in the body.

half life

35 hours

drug interactions

Acenocoumarol: Barbiturates such as butalbital may increase the metabolism of Vitamin K Antagonists such as acenocoumarol. Monitor for decreased therapeutic effects of oral anticoagulants if a barbiturate is initiated/dose increased (anticoagulant dosage increases of 30% to 60% may be needed based on monitored PT), or increased effects if a barbiturate is discontinued/dose decreased. An increased frequency of PT monitoring should be considered for the period immediately following barbiturate initiation/dosage changes.

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

Amitriptyline: Barbiturates such as butalbital may increase the metabolism of tricyclic antidepressants such as amitriptyline. Monitor for decreased therapeutic effects of tricyclic antidepressants if a barbiturate is initiated/dose increased, or increased effects if a barbiturate is discontinued/dose decreased. The tricyclic antidepressant dosage will likely need to be increased during concomitant barbiturate therapy, and reduced upon barbiturate discontinuation.

Amoxapine: Barbiturates such as butalbital may increase the metabolism of tricyclic antidepressants amoxapine. Monitor for decreased therapeutic effects of tricyclic antidepressants if a barbiturate is initiated/dose increased, or increased effects if a barbiturate is discontinued/dose decreased. The tricyclic antidepressant dosage will likely need to be increased during concomitant barbiturate therapy, and reduced upon barbiturate discontinuation.

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

Chloramphenicol: Barbiturates such as butalbital may increase the metabolism of Chloramphenicol. Chloramphenicol may decrease the metabolism of Barbiturates. Monitor for decreased serum concentrations/therapeutic effects of chloramphenicol if a barbiturate is initiated/dose increased, or increased effects if a barbiturate is discontinued/dose decreased. In addition, monitor for increased effects of barbiturates if chloramphenicol is initiated/dose increased, or decreased effects if chloramphenicol is discontinued/dose decreased.

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

Clomipramine: Barbiturates such as butalbital may increase the metabolism of tricyclic antidepressants such as clomipramine. Monitor for decreased therapeutic effects of tricyclic antidepressants if a barbiturate is initiated/dose increased, or increased effects if a barbiturate is discontinued/dose decreased. The tricyclic antidepressant dosage will likely need to be increased during concomitant barbiturate therapy, and reduced upon barbiturate discontinuation.

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

Cyclosporine: The barbiturate, butalbital, increases the effect of cyclosporine.

Desipramine: Barbiturates such as butalbital may increase the metabolism of tricyclic antidepressants such as desipramine. Monitor for decreased therapeutic effects of tricyclic antidepressants if a barbiturate is initiated/dose increased, or increased effects if a barbiturate is discontinued/dose decreased. The tricyclic antidepressant dosage will likely need to be increased during concomitant barbiturate therapy, and reduced upon barbiturate discontinuation.

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

Diethylstilbestrol: The enzyme inducer, butalbital, decreases the effect of the hormone agent, diethylstilbestrol.

Doxepin: Barbiturates such as butalbital may increase the metabolism of tricyclic antidepressants such as doxepin. Monitor for decreased therapeutic effects of tricyclic antidepressants if a barbiturate is initiated/dose increased, or increased effects if a barbiturate is discontinued/dose decreased. The tricyclic antidepressant dosage will likely need to be increased during concomitant barbiturate therapy, and reduced upon barbiturate discontinuation.

Doxycycline: The anticonvulsant, butalbital, decreases the effect of doxycycline.

Droperidol: Droperidol may enhance the CNS depressant effect of CNS depressants such as butalbital. Consider dose reductions of droperidol or of other CNS agents (e.g., opioids, barbiturates) with concomitant use.

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

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

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

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

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

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

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

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

Hydroxyzine: Hydroxyzine may enhance the CNS depressant effect of barbiturates such as butalbital. Consider a decrease in the barbiturate dose, as appropriate, when used together with hydroxyzine. With concurrent use, monitor patients closely for excessive response to the combination.

Imipramine: Barbiturates such as butalbital may increase the metabolism of tricyclic antidepressants such as imipramine. Monitor for decreased therapeutic effects of tricyclic antidepressants if a barbiturate is initiated/dose increased, or increased effects if a barbiturate is discontinued/dose decreased. The tricyclic antidepressant dosage will likely need to be increased during concomitant barbiturate therapy, and reduced upon barbiturate discontinuation.

Lamotrigine: Barbiturates such as butalbital may decrease the serum concentration of lamotrigine. There are separate management guidelines for patients age 12 and under and for patients older than 12 years of age. Please refer to the current approved prescribing information for additional information. Monitor for decreased serum concentrations/therapeutic effects of lamotrigine if a barbiturate is initiated/dose increased, or increased effects if a barbiturate is discontinued/dose decreased.

Levonorgestrel: Phenobarbital decreases the effect of levonorgestrel

Medroxyprogesterone: The enzyme inducer, butalbital, decreases the effect of the hormone agent, medroxyprogesterone.

Megestrol: The enzyme inducer, butalbital, decreases the effect of the hormone agent, megestrol.

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

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

Nifedipine: The barbiturate, butalbital, decreases the effect of the calcium channel blocker, nifedipine.

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

Nortriptyline: Barbiturates such as butalbital may increase the metabolism of tricyclic antidepressants such as nortriptyline. Monitor for decreased therapeutic effects of tricyclic antidepressants if a barbiturate is initiated/dose increased, or increased effects if a barbiturate is discontinued/dose decreased. The tricyclic antidepressant dosage will likely need to be increased during concomitant barbiturate therapy, and reduced upon barbiturate discontinuation.

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

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

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

Protriptyline: Barbiturates such as butalbital may increase the metabolism of tricyclic antidepressants such as protriptyline. Monitor for decreased therapeutic effects of tricyclic antidepressants if a barbiturate is initiated/dose increased, or increased effects if a barbiturate is discontinued/dose decreased. The tricyclic antidepressant dosage will likely need to be increased during concomitant barbiturate therapy, and reduced upon barbiturate discontinuation.

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

Teniposide: Barbiturates such as butalbital may decrease the serum concentration of teniposide. Consider alternatives to combined treatment with barbiturates and teniposide due to the potential for decreased teniposide concentrations. If the combination cannot be avoided, monitor teniposide response closely.

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

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

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

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

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

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

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