FIORINAL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for FIORINAL (FIORINAL).
FIORINAL is a combination of butalbital (barbiturate), aspirin (NSAID), and caffeine. Butalbital potentiates GABA-A receptor activity, producing sedative-hypnotic effects. Aspirin inhibits cyclooxygenase (COX-1 and COX-2), reducing prostaglandin synthesis, which provides analgesic and antipyretic effects. Caffeine is a non-selective adenosine receptor antagonist, enhancing analgesic efficacy.
| Metabolism | Butalbital is extensively metabolized in the liver via hydroxylation and glucuronidation, primarily by CYP2C9 and CYP2C19. Aspirin is hydrolyzed to salicylic acid, then conjugated with glycine (salicyluric acid) and glucuronidated. Caffeine is metabolized by CYP1A2 to paraxanthine, theobromine, and theophylline. |
| Excretion | Renal: 60% butalbital (mostly unchanged), 10% aspirin (salicylates, majorly as metabolites), 3% caffeine (metabolites and unchanged). Fecal: <5% overall. |
| Half-life | Butalbital 35-50 hours, aspirin 15-20 minutes (salicylate 2-3 hours at low doses, >20 hours at high doses), caffeine 3-5 hours. Prolonged in hepatic/renal impairment. |
| Protein binding | Butalbital 20-40% (albumin), aspirin 80-90% (albumin, concentration-dependent), caffeine 25-36% (albumin). |
| Volume of Distribution | Butalbital 0.8 L/kg, aspirin 0.15-0.2 L/kg, caffeine 0.6-0.8 L/kg. Indicates extensive tissue distribution for butalbital and caffeine. |
| Bioavailability | Oral: butalbital ~100%, aspirin 50-75% (first-pass metabolism), caffeine ~100%. |
| Onset of Action | Oral: butalbital 30-60 min, aspirin 5-30 min, caffeine 15-45 min. |
| Duration of Action | Butalbital 4-6 hours (longer with high doses), aspirin 4-6 hours (antiplatelet effect lasts days), caffeine 4-6 hours. |
| Molecular Weight | 282.34 |
1-2 capsules (butalbital 50 mg, acetaminophen 300 mg, caffeine 40 mg) orally every 4 hours as needed, not exceeding 6 capsules per day.
| Dosage form | TABLET |
| Renal impairment | No specific guidelines; contraindicated in severe renal impairment (CrCl <30 mL/min) due to acetaminophen accumulation. Use with caution in moderate impairment. |
| Liver impairment | Contraindicated in severe hepatic impairment (Child-Pugh Class C). For mild to moderate (Child-Pugh A or B), reduce dose by 50% or extend dosing interval. |
| Pediatric use | Not recommended for pediatric use; safety and efficacy not established. |
| Geriatric use | Start at lowest effective dose (e.g., 1 capsule every 4 hours) due to increased sensitivity to butalbital (sedation, confusion) and risk of acetaminophen hepatotoxicity; maximum daily acetaminophen dose 2 g. |
| 1st trimester | Avoid; contains butalbital (barbiturate) and aspirin; both associated with teratogenic risk; aspirin linked to neural tube defects and cardiovascular malformations. |
| 2nd trimester | Avoid; aspirin may cause premature closure of ductus arteriosus and oligohydramnios; butalbital may cause neonatal withdrawal. |
| 3rd trimester | Contraindicated; aspirin increases risk of intracranial hemorrhage in neonate and premature closure of ductus arteriosus; butalbital can cause neonatal sedation and withdrawal. |
Clinical note
Comprehensive clinical and safety monograph for FIORINAL (FIORINAL).
| Placental transfer | Both aspirin and butalbital cross the placenta. Aspirin is detected in fetal serum; butalbital reaches fetal concentrations similar to maternal. |
| Breastfeeding | Both aspirin and butalbital are excreted into breast milk. Aspirin may cause Reye's syndrome in infants; butalbital may cause infant sedation. Avoid use during breastfeeding. If necessary, use lowest effective dose and monitor infant for drowsiness and poor feeding. |
■ FDA Black Box Warning
None.
| Serious Effects |
Hypersensitivity to any componentPorphyriaG6PD deficiency (due to aspirin)Pregnancy third trimesterSevere hepatic impairmentSevere renal impairmentBleeding disorders (e.g., hemophilia, von Willebrand disease)Concurrent use of NSAIDs or anticoagulants (increased bleeding risk)
| Precautions | Risk of Reye's syndrome in children with viral illness, Aspirin hypersensitivity (e.g., asthma, nasal polyps), Gastrointestinal bleeding and ulceration, Hepatic impairment due to butalbital metabolism, Caffeine overdose from excessive use, Dependence and withdrawal with prolonged butalbital use |
| Food/Dietary | Avoid excessive caffeine intake from coffee, tea, energy drinks, or chocolate as it may compound caffeine's stimulant effects and increase anxiety or insomnia. Alcohol should be strictly avoided due to additive CNS depression and increased GI bleeding risk with aspirin. No specific food restrictions besides moderation of caffeine-containing foods. |
Loading safety data…
| Lactation Rating | Avoid |
| Teratogenic Risk | First trimester: Butalbital is associated with neural tube defects, cleft palate; aspirin increases risk of gastroschisis, cardiac defects. Second trimester: Aspirin may cause premature closure of ductus arteriosus. Third trimester: Aspirin increases risk of intracranial hemorrhage, premature closure of ductus arteriosus; butalbital may cause neonatal withdrawal. Caffeine is not a major teratogen but high doses may increase miscarriage risk. |
| Fetal Monitoring | Fetal ultrasound for anomalies; ductus arteriosus Doppler in third trimester; maternal platelet count, coagulation profile; neonatal monitoring for withdrawal if chronic butalbital use. |
| Fertility Effects | High-dose aspirin may inhibit prostaglandin synthesis, potentially impair ovulation; butalbital may induce hepatic enzymes affecting hormonal contraception efficacy. |
| Clinical Pearls | FIORINAL (butalbital/aspirin/caffeine) is a barbiturate-containing combination analgesic. Due to butalbital's high abuse potential and risk of withdrawal, it is reserved for tension-type headaches refractory to non-barbiturate therapies. Monitor for signs of barbiturate dependence, and limit quantity dispensed. Avoid in patients with porphyria, severe hepatic impairment, or hemorrhagic disorders (aspirin component). Caffeine may exacerbate anxiety or insomnia. |
| Patient Advice | This medication contains butalbital, which can be habit-forming; do not exceed prescribed dose or duration. · Avoid alcohol and other CNS depressants (e.g., benzodiazepines, opioids) as they increase sedation and respiratory depression risk. · Do not drive or operate heavy machinery until you know how this drug affects you. · Take with food to reduce stomach upset; if you experience black or bloody stools, stop and seek immediate medical attention (signs of GI bleeding from aspirin). · Do not use more than directed; sudden discontinuation can cause withdrawal symptoms (anxiety, tremors, seizures). · Keep out of reach of children; overdose may be fatal. |