butalbital/acetaminophen/caffeine (Fioricet, Orbivan, Alagesic LQ, Dolgic Plus, Esgic Plus, Margesic, Zebutal)
Classes: Analgesics, Barbiturate Combos
Dosing and uses of Fioricet, Orbivan (butalbital/acetaminophen/caffeine)
Adult dosage forms and strengths
tablet
- butalbital/acetaminophen/caffeine
- 50mg/325mg/40mg (Fioricet, Esgic)
- 50mg/500mg/40mg (Esgic-Plus)
- 50mg/750mg/40mg (Dolgic Plus)
capsule
- butalbital/acetaminophen/caffeine
- 50mg/300mg/40mg (Orbivan)
- 50mg/325mg/40mg (Esgic, Margesic)
- 50mg/500mg/40mg (Esgic-Plus, Zebutal)
liquid, oraL
- butalbital/acetaminophen/caffeine
- (50mg/325mg/40mg)15mL (Alagesic LQ)
Tension Headache
50 mg/300-325 mg/40 mg: 2 tablets or capsules PO q4hr; not to exceed 6 tablets or capsules/day
50 mg/500 mg/40 mg: 1 tablet/capsule PO q4hr; not to exceed 6 tablets or capsules/day
50 mg/750 mg/40 mg: 1 tablet/capsule PO q4hr; not to exceed 5 tablets or capsules/day
15-30 mL solution PO q4hr; not to exceed 180 mL solution/day
Not to exceed 4 g/day of acetaminophen for any dosage form or regimen
Dosing Modifications
Renal impairment: Not studied; use caution and reduce dosing if necessary in severe renal impairment
Hepatic impairment: Not studied; use caution and reduce dosing if necessary in severe hepatic impairment
Pediatric dosage forms and strengths
tablet
- butalbital/acetaminophen/caffeine
- 50mg/325mg/40mg (Fioricet, Esgic)
- 50mg/500mg/40mg (Esgic-Plus)
- 50mg/750mg/40mg (Dolgic Plus)
capsule
- butalbital/acetaminophen/caffeine
- 50mg/300mg/40mg (Orbivan)
- 50mg/325mg/40mg (Esgic, Margesic)
- 50mg/500mg/40mg (Esgic-Plus, Zebutal)
liquid, oraL
- butalbital/acetaminophen/caffeine
- (50mg/325mg/40mg)15mL (Alagesic LQ)
Tension Headache
<12 years: Safety and efficacy not established
≥12 years
- 50 mg/300-325 mg/40 mg: 2 tablets or capsules PO q4hr; not to exceed 6 tablets or capsules/day
- 50 mg/500 mg/40 mg: 1 tablet/capsule PO q4hr; not to exceed 6 tablets or capsules/day
- 50 mg/750 mg/40 mg: 1 tablet/capsule PO q4hr; not to exceed 5 tablets or capsules/day
- 15-30 mL solution PO q4hr; not to exceed 90 mL solution/day
- Not to exceed 4 g/day of acetaminophen for any dosage form or regimen
Dosing Modifications
Renal impairment: Not studied; use caution and reduce dosing if necessary in severe renal impairment
Hepatic impairment: Not studied; use caution and reduce dosing if necessary in severe hepatic impairment
Fioricet, Orbivan (butalbital/acetaminophen/caffeine) adverse (side) effects
Frequency not defined
ButalbitaL
- Dizziness, drowsiness, feeling of intoxication, lightheadedness, sedation
- Abdominal pain, nausea, vomiting
- Shortness of breath
Acetaminophen
- Angioedema, laryngeal edema
- Pruritic maculopapular rash, urticaria
- Agranulocytosis, leukopenia, neutropenia, pancytopenia, thrombocytopenia, thrombocytopenic purpura
- Hepatotoxicity
- Anaphylactoid reaction
Caffeine
- Tachycardia, palpitations (dose dependent)
- Insomnia, irritability, nervousness, restlessness, tinnitus, tremor
- Diarrhea, nausea, vomiting
- Diuresis
Warnings
Black box warnings
Contains acetaminophen
Hepatotoxicity may occur with acetaminophen doses that exceed 4 g/day; take into account all acetaminophen-containing products the patient is taking, including PRN doses and OTC products
Acetaminophen has been associated with cases of acute liver failure, at times resulting in liver transplantation or death
New dosage limit allows no more than 325 mg/dosage unit for prescription medications that contain acetaminophen
Healthcare professionals can direct patients to take 1 or 2 tablets, capsules, or other dosage units of a prescription product containing 325 mg of acetaminophen up to 6 times daily (12 dosage units) and still not exceed the maximum daily dose of acetaminophen (ie, 4 g/day)
Contraindications
Hypersensitivity
Cautions
Use caution in hepatitis or severe hepatic/renal impairment
Use caution in repeated administration to patients with anemia, or with cardiovascular, pulmonary, or renal disease porphyria
Acetaminophen has been associated with cases of acute liver failure, at times resulting in liver transplantation or death; risk increases in individuals with underlying liver disease, alcohol ingestion, and/or use of more than 1 acetaminophen-containing product (see Black box warnings)
Acetaminophen: Risk for rare, but serious skin reactions that can be fatal; these reactions include Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP); symptoms may include skin redness, blisters and rash
Patients with G6PD deficiency
Butalbital may cause sedation; avoid driving a car, operating machinery, or administering with other CNS depressants (eg, alcohol)
Caution with special-risk patients (eg, elderly or debilitated or those with severe renal or hepatic dysfunction or with acute abdominal conditions)
Butalbital may be habit-forming; for short-term use only
Pregnancy and lactation
Pregnancy category: C; case reports of withdrawal seizures in newborns whose mothers had taken butalbital-containing drug during pregnancy
Lactation: Excreted in breast milk in small amounts; not recommended
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Fioricet, Orbivan (butalbital/acetaminophen/caffeine)
Mechanism of action
Butalbital: Barbiturate; elicits generalized CNS depressant effects; depresses sensory cortex; decreases motor activity
Acetaminophen: Nonopioid, nonsalicylate analgesic; acts on hypothalamus to produce analgesia and antipyresis
Caffeine: Vasoconstrictive properties of cerebral blood vessels may be helpful when treating headaches; improves skeletal muscle contraction and medullary respiratory center sensitivity; stimulates central inspiratory drive
Absorption
Butalbital and caffeine: Well absorbed
Bioavailability: 100% acetaminophen
Distribution
Protein bound: Butalbital (45%); acetaminophen (20-50%)
Metabolism
ButalbitaL
- Metabolized in liver by CYP450 enzyme system
- Induces hepatic enzymes, but to lesser degree than phenobarbital
Acetaminophen
- Metabolized in liver by microsomal enzyme systems
- 80-85% conjugated principally with glucuronic acid and to a lesser extent with sulfuric acid and cysteine
- 4% metabolized by CYP450 to toxic metabolite (N acetyl-p-benzoquinoneimine, N-acetylimidoquinone [NAPQI]), which is detoxified by conjugation with glutathione; high doses may deplete fixed amount of glutathione in body, causing NAPQI accumulation
Caffeine
- Metabolized in liver via CYP1A2 to paraxanthine, theobromine, and theophylline
Elimination
Half-life: 35 hr butalbital; 2-4 hr acetaminophen; 3-7 hr caffeine
Excretion: Butalbital (59-88% in urine); acetaminophen (90-100% in urine, principally as acetaminophen glucuronide with acetaminophen sulfate/mercaptate); caffeine (principally in urine)
