BUTALBITAL AND ACETAMINOPHEN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for BUTALBITAL AND ACETAMINOPHEN (BUTALBITAL AND ACETAMINOPHEN).
Butalbital is a barbiturate that enhances GABA-A receptor activity, producing sedation. Acetaminophen inhibits cyclooxygenase (COX) enzymes in the CNS, reducing pain and fever.
| Metabolism | Butalbital: hepatic via CYP2C19 and other CYP enzymes. Acetaminophen: hepatic via glucuronidation (UGT1A1, UGT1A6), sulfation, and CYP2E1 (minor pathway). |
| Excretion | Acetaminophen: renal excretion of metabolites (glucuronide ~55%, sulfate ~30%, cysteine ~3%, unchanged ~4%). Butalbital: renal excretion of metabolites (unchanged <3%, 5-15% as hydroxylated metabolites). Total renal elimination >90% combined; biliary/fecal <10%. |
| Half-life | Acetaminophen: 2-3 hours (adults), prolonged in hepatic impairment. Butalbital: 35-50 hours (terminal), indicating potential accumulation with repeated dosing. |
| Protein binding | Acetaminophen: 10-25% (albumin). Butalbital: 20-30% (albumin). |
| Volume of Distribution | Acetaminophen: 0.9-1.5 L/kg (distributes into most body fluids). Butalbital: 0.5-1.0 L/kg (moderate distribution). |
| Bioavailability | Oral: Acetaminophen ~88%, Butalbital ~100% (assuming no first-pass). |
| Onset of Action | Oral: 30-60 minutes for analgesic effect; 30-60 minutes for sedative effect. |
| Duration of Action | Analgesia: 4-6 hours. Sedation: butalbital may cause residual sedation lasting up to 12 hours due to long half-life. |
1-2 capsules (50 mg butalbital/300 mg acetaminophen per capsule) orally every 4 hours as needed, not to exceed 6 capsules per day.
| Dosage form | TABLET |
| Renal impairment | GFR 30-89 mL/min: No adjustment. GFR 10-29 mL/min: Avoid or extend dosing interval to every 6-8 hours. GFR <10 mL/min: Avoid use. |
| Liver impairment | Child-Pugh A: No adjustment. Child-Pugh B: Reduce dose by 50% or extend interval. Child-Pugh C: Avoid use. |
| Pediatric use | Children ≥12 years: 1 capsule (50 mg butalbital/300 mg acetaminophen) orally every 4 hours as needed, not to exceed 6 capsules per day. Children <12 years: Not recommended. |
| Geriatric use | Start with 1 capsule orally every 4 hours as needed, not to exceed 6 capsules per day. Caution due to increased sensitivity to butalbital (sedation, confusion) and acetaminophen hepatotoxicity. Monitor renal and hepatic function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for BUTALBITAL AND ACETAMINOPHEN (BUTALBITAL AND ACETAMINOPHEN).
| Breastfeeding | Butalbital and acetaminophen are excreted into breast milk. Acetaminophen M/P ratio approximately 1.0; butalbital M/P ratio unknown but barbiturates pass into milk. At maternal therapeutic doses, effects on infant are unlikely; however, high doses of butalbital may cause sedation or poor feeding. Caution is advised; monitor infant for drowsiness. |
| Teratogenic Risk | Pregnancy Category C. First trimester: butalbital (barbiturate) may be associated with oral clefts and neural tube defects; acetaminophen is generally considered low risk but high doses may be associated with adverse outcomes. Second and third trimesters: butalbital may cause neonatal withdrawal, sedation, and respiratory depression; acetaminophen is considered safe at therapeutic doses. Chronic use of butalbital in third trimester may lead to neonatal dependence. |
■ FDA Black Box Warning
None
| Serious Effects |
["Hypersensitivity to butalbital, acetaminophen, or any component","Porphyria","Severe hepatic impairment"]
| Precautions | ["Hepatotoxicity with acetaminophen overdose","Risk of barbiturate dependence and withdrawal","CNS depression with alcohol or other depressants","Acetaminophen may cause severe skin reactions (SJS, TEN, AGEP)"] |
| Food/Dietary | Avoid excessive consumption of alcohol-containing foods or beverages due to risk of hepatotoxicity and CNS depression. No significant food interactions. |
| Clinical Pearls |
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| Fetal Monitoring | Monitor maternal liver function, renal function, and signs of butalbital dependence or withdrawal. Monitor fetal growth and wellbeing by ultrasound in cases of chronic use. In third trimester, monitor for neonatal withdrawal syndrome (irritability, tremors, seizures) after delivery. Assess infant for respiratory depression if used near term. |
| Fertility Effects | Limited data. Acetaminophen may affect male and female fertility at high doses (e.g., altered hormone levels). Butalbital may induce hepatic enzymes and affect hormone metabolism, potentially impacting menstrual cycle and fertility. Clinical significance uncertain. |
| Butalbital is a barbiturate that potentiates acetaminophen's analgesic effect; combination carries risk of barbiturate dependence and withdrawal. Maximum adult acetaminophen dose is 4 g/day; avoid in severe hepatic impairment or active liver disease. Monitor for respiratory depression, especially with alcohol or other CNS depressants. Abrupt discontinuation after prolonged use may cause withdrawal symptoms. Not recommended for children under 12. |
| Patient Advice | Take exactly as prescribed; do not exceed 6 tablets per day. · Avoid alcohol and other sedatives; may cause dizziness or drowsiness. · Do not use with other acetaminophen-containing products to avoid liver damage. · Do not stop suddenly if taken for more than 5 days; withdrawal possible. · May impair ability to drive or operate machinery. · Contact provider if signs of liver injury: yellow skin/eyes, dark urine, abdominal pain. · Keep out of reach of children; overdose can be fatal. |