Composition of Butalbital
Butalbital is a short- to intermediate-acting barbiturate (5-allyl-5-isobutylbarbituric acid) that is never prescribed alone but only available in combination products, most commonly with acetaminophen (325 mg), caffeine (40 mg), and sometimes aspirin or codeine. 1
Chemical Structure and Properties
- Butalbital itself is a white, odorless, slightly bitter crystalline powder with the chemical name 5-allyl-5-isobutylbarbituric acid and a molecular weight of approximately 220-232 Da 2, 1
- The standard formulation contains 50 mg of butalbital per capsule or tablet, which carries a warning that it "may be habit-forming" 1
Common Combination Products
The typical butalbital-containing product includes three active ingredients 1:
- Butalbital 50 mg (the barbiturate component)
- Acetaminophen 325 mg (the analgesic/antipyretic component)
- Caffeine 40 mg (the CNS stimulant component)
Alternative formulations may substitute aspirin for acetaminophen or add codeine (as in Fiorinal with Codeine) 3
Mechanism of Action
- Butalbital works via gamma-aminobutyric acid (GABA) receptors in the central nervous system, producing sedation, anxiolytic effects, and hypnotic properties 2, 4
- The medication is primarily metabolized in the liver through the cytochrome P450 enzyme system and acts as a CYP enzyme inducer, potentially affecting metabolism of other medications 2, 5
- Approximately 20-25% of long-acting barbiturates are excreted unchanged in urine, though butalbital (as a short-acting agent) has less renal excretion than phenobarbital 2
Pharmacokinetic Properties
- Protein binding: 26-35% 2, 3
- Volume of distribution: 0.5-1.0 L/kg 2, 3
- Elimination half-life: 15-48 hours (short- to intermediate-acting) 2
- Duration of action: 3-4 hours 2
Critical Safety Profile
Butalbital carries the same clinical risks as Schedule III controlled barbiturates, including habit formation, tolerance, physical dependence, and withdrawal seizures with chronic use 2, 6, 5
Key Clinical Risks:
- Medication-overuse headache develops when used more than twice weekly, creating a vicious cycle of increasing headache frequency 6, 7
- Additive CNS and respiratory depression when combined with other depressants (alcohol, opioids, benzodiazepines, anesthetics) can be life-threatening 2, 5
- Abrupt discontinuation after long-term use can cause intractable seizures, visual/auditory hallucinations, delirium, and potentially fatal withdrawal 2
- Hepatotoxicity risk from the acetaminophen component when total daily intake exceeds 4000 mg from all sources 6
Prescribing Recommendations
- Limit use to no more than twice weekly to prevent medication-overuse headache and dependence 6, 5, 7
- Use only as backup medication when NSAIDs, triptans, and other first-line agents are contraindicated or have failed 6
- Daily use indicates treatment failure and warrants immediate therapy adjustment 6, 4
- For perioperative management: ideally wean slowly over 2 weeks prior to surgery; if unable to wean, continue the medication to avoid perioperative withdrawal 2, 5