butalbital/acetaminophen/caffeine (Rx)

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

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

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.

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)