codeine/acetaminophen/butalbital/caffeine (Fioricet with Codeine): Dosing and Uses

Dosing and uses of Fioricet with Codeine (codeine/acetaminophen/butalbital/caffeine)

• Adult
• Pediatric

Adult dosage forms and strengths

codeine/acetaminophen/butalbital/caffeine

FDA is asking manufacturers to limit acetaminophen in prescription products to 325 mg/dosage unit; manufacturers have until January 14, 2014 to comply

capsule: Schedule III

• 30mg/325mg/50mg/40mg

Tension Headache

1-2 tab/cap PO q4hr; not to exceed 6 tab/cap per day

Pediatric dosage forms and strengths

codeine/acetaminophen/butalbital/caffeine

FDA is asking manufacturers to limit acetaminophen in prescription products to 325 mg/dosage unit; manufacturers have until January 14, 2014 to comply

capsule: Schedule III

• 30mg/325mg/50mg/40mg

Tension Headache

<12 years: Safety and efficacy not established

≥12 years: 1-2 tab/cap PO q4hr; not to exceed 6 tab/cap per day (not to exceed acetaminophen 4 g/day)

Fioricet with Codeine (codeine/acetaminophen/butalbital/caffeine) adverse (side) effects

>10%

Codeine

• Drowsiness
• Constipation

1-10%

Codeine

• Bradycardia, hypotension, tachycardia
• Confusion, dizziness, false feeling of well being, headache, lightheadedness, malaise, paradoxical CNS stimulation, restlessness, weakness
• Rash, urticaria
• Anorexia, nausea, vomiting, xerostomia
• LFT's increased
• Ureteral spasm, urination decreased
• Dyspnea
• Burning at injection site, blurred vision, histamine release

Frequency not defined

Acetaminophen

• Angioedema, laryngeal edema
• Pruritic maculopapular rash, urticaria
• Agranulocytosis, leukopenia, neutropenia, pancytopenia, thrombocytopenia, thrombocytopenic purpura
• Hepatotoxicity
• Anaphylactoid reaction

ButalbitaL

• Drowsiness, dizziness, intoxicated feeling, lightheadedness, sedation
• Abdominal pain, nausea, vomiting
• Shortness of breath

Caffeine

• Tachycardia, palpitations (dose dependent)
• Insomnia, irritability restlessness, nervousness, tremor, tinnitus
• Diarrhea, nausea, vomiting
• Diuresis

Warnings

Black box warnings

Contains acetaminophen

Hepatotoxicity may occur with acetaminophen doses that exceed 4 grams/day (ie, 4,000 mg/day)

Acetaminophen associated with cases of acute liver failure, at times resulting in liver transplant and death

Most cases of liver injury are associated with the use of acetaminophen at doses that exceed 4 grams/day, and often involve more than 1 acetaminophen-containing product

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 a day (12 dosage units) and still not exceed the maximum daily dose of acetaminophen (ie, 4000 mg/day)

Postoperative pain in children

• Deaths have occurred in children with obstructive sleep apnea who receive codeine for postoperative pain following tonsillectomy and/or adenoidectomy
• Codeine is converted to morphine by the liver; these children had evidence of being ultra-rapid metabolizers (via CYP2D6) of codeine, which is an inherited (genetic) ability that causes codeine to be converted rapidly into life-threatening or fatal amounts of morphine (see Pharmacology)

Contraindications

Hypersensitivity

Hepatitis or severe hepatic/renal impairment

Repeated administration in patients with anemia, cardiovascular, pulmonary, or renal disease

Porphyria

Postoperative use in children following tonsillectomy and/or adenoidectomy (see Black box warnings)

Cautions

Acetaminophen associated with cases of acute liver failure, at times resulting in liver transplant and 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 may cause rare serious skin reactions (eg, acute generalized exanthematous pustulosis, Stevens-Johnson Syndrome, toxic epidermal necrolysis), which can be fatal; discontinued at the first appearance of skin rash

G6PD deficiency

Avoid driving car or operating machinery

May increase respiratory depressant effects; caution with head injury, COPD, or other conditions with decreased respiratory drive

Codeine may cause tolerance/dependency

Pregnancy and lactation

Pregnancy category: C; may prolong delivery and cause respiratory depression/withdrawal symptoms in newborn

Lactation: excreted in breast milk; caution advised

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 with Codeine (codeine/acetaminophen/butalbital/caffeine)

Mechanism of action

Codeine: Opioid agonist; analgesia

Acetaminophen: Acts on hypothalamus to produce analgesia and antipyresis

Butalbital: Barbiturate; elicits generalized CNS depressant effects

Caffeine: Vasoconstrictive properties of cerebral blood vessels may be helpful when treating headaches

Pharmacogenomics

10% of codeine is metabolized to morphine by CYP2D6; the active morphine metabolite has a higher affinity for opioid receptors

CYP2D6 poor metabolizers may not achieve adequate analgesia

Ultra-rapid metabolizers (up to 7% of Caucasians and up to 30% of Asian and African populations) may have increased toxicity due to rapid conversion