Adult Dosing

Tension headache

• 1-2 caps PO q4 hrs; Max: 6 caps/day

Note:

• Because of the potential for physical dependence, avoid extended and repeated use of this product

Pediatric Dosing

• Safety and effectiveness in pediatric patients have not been established

[Outline]

• Adult Dosing
• Pediatric Dosing

• Relief of the symptom complex of tension (or muscle contraction) headache

• Hypersensitivity to any of the ingredients of the product
• Porphyria

• Incidences of acute liver failure, at times resulting in liver transplant and death, have been reported with acetaminophen component of this combination drug. These events are mostly associated with acetaminophen doses >4000 mg/day and often involve more than one acetaminophen-containing product
• Respiratory depression and death have been reported in children receiving codeine after tonsillectomy and/or adenoidectomy. These patients had an evidence of being ultra-rapid metabolizers of codeine resulting from a CYP2D6 polymorphism

Renal Dose Adjustment

• Severe renal impairment: Caution advised; dose adjustments not defined

Hepatic Dose Adjustment

• Severe hepatic impairment: Caution advised; dose adjustments not defined

See Supplemental Patient Information

• Respiratory depression and death have been reported in children receiving codeine after tonsillectomy and/or adenoidectomy. These patients had an evidence of being ultra-rapid metabolizers of codeine resulting from a CYP2D6 polymorphism (US Black Box warning)
• Cases of acute liver failure, occasionally resulting in liver transplant and death, have been reported with acetaminophen therapy. These events are mostly associated with acetaminophen doses >4000 mg/day and often involve more than one acetaminophen-containing product. Patients with underlying liver disease and those who ingest alcohol during therapy are at a greater risk for developing acute liver failure [US Black Box Warning]
• Extended use of this drug is not recommended as butalbital and codeine are both habit-forming and potentially abusable
• There have been post-marketing reports of hypersensitivity and anaphylaxis associated with acetaminophen use
• Codeine and other narcotics may cause respiratory depression and elevate cerebrospinal fluid pressure; these effects of codeine are exaggerated in the presence of head injury or other intracranial lesions. CNS depressant effects, such as drowsiness, may be seen with the use of narcotics and may further obscure the clinical course of the patients with head injuries
• Codeine or other narcotics may obscure the diagnosis or clinical course of patients with acute abdominal conditions
• Therapy may impair mental and/or physical abilities required for the performance of hazardous activities such as driving a car or operating machinery

Cautions: Use cautiously in:

• Severe renal impairment
• Severe hepatic impairment
• Head injury
• Elevated intracranial pressure
• Alcohol use
• History of drug abuse
• Acute abdominal conditions
• Impaired respiratory drive
• Ultra-rapid CYP2D6 metabolizers
• Hypothyroidism
• Prostatic hypertrophy
• Urethral stricture
• Addison’s disease
• Elderly patients
• Debilitated patients

Supplemental Patient Information

• Advise patients receiving therapy to refrain from any hazardous activity such as driving a motor vehicle or operating machinery until it is confirmed that they are not adversely affected
• Instruct patients to avoid concomitant use of this drug with alcohol and other CNS depressants
• Instruct patients not to take acetaminophen >4000 mg/day or use more than one product that contains acetaminophen
• Advise patients to discontinue therapy and promptly consult their physician if they develop signs or symptoms of allergy including rash, hives, pruritus, urticaria, swelling of the face/mouth/throat, vomiting, or difficulty breathing
• Advise patients to strictly follow dosing instructions
• Instruct nursing mothers to observe for signs of morphine toxicity in their infants including increased sleepiness, difficulty breastfeeding, breathing difficulties or limpness. Instruct nursing mothers to immediately talk to the baby's doctor if they notice these signs; if they are unable to reach the doctor right away, instruct them to take the baby to an emergency room or call local emergency services

Pregnancy Category:C

Breastfeeding: Acetaminophen is a good choice for analgesia and fever reduction in nursing mothers. Amounts excreted in milk are much less than doses usually given to infants. Adverse effects in breastfed infants appear to be rare. . Maternal medication is usually compatible with breastfeeding; no observable change was seen in the nursing infant while the mother was ingesting the compound. As no published experience is available with butalbital or combination products containing butalbital during breastfeeding, other agents may be preferred, especially while nursing a newborn or preterm infant. Caffeine appears in breastmilk rapidly after maternal ingestion. Adverse events like fussiness, jitteriness, and poor sleep patterns have been reported in the infants of mothers with very high caffeine intakes equivalent to 10 or more cups of coffee daily. No stimulatory effects on infants 3 wks were observed in mothers taking 5 cups of coffee daily. Preterm and younger newborn infants metabolize caffeine very slowly and may have serum levels of caffeine and other active caffeine metabolites similar to their mothers. Decreased breastmilk iron concentrations causing mild iron deficiency anemia in some breastfed infants may occur on intake of >450 mL of coffee. Irritability, poor sleeping pattern may occur as caffeine is excreted slowly; no effect were observed with moderate intake of caffeinated beverages (2-3 cups/day).Maternal use of oral narcotics, including codeine, while breastfeeding can cause drowsiness in infants, particularly newborn infants in the first week of life. Newborn's dosage is limited by the small volumes of colostrum in the first 2-3 days postpartum. Once the mother's milk comes in, it is best to use a non-narcotic analgesic and limit the maternal dosage and duration of treatment with codeine and combinations to 4 days. This information is based upon LactMed & AAP database (available at http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT and http://aappolicy.aappublications.org/cgi/content/full/pediatrics;108/3/776 last accessed 1 June 2011). As per manufacturer's data, because of the potential for serious adverse reactions in nursing infants from acetaminophen, butalbital, caffeine, and codeine, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

• CNS: Drowsiness, lightheadedness, dizziness, sedation, abuse
• GI: Nausea, vomiting, abdominal pain, hepatotoxicity, constipation
• RESP: Dyspnea, shortness of breath, respiratory depression
• HEMA: Agranulocytosis, thrombocytopenia
• DERM: Erythema multiforme, toxic epidermal necrolysis, rash
• HYPERSENSITIVITY: Stevens-Johnson syndrome, hypersensitivity reactions, anaphylaxis, photosensitivity, allergic reactions
• MISC: Intoxicated feeling

Acetaminophen

• Analgesic, antipyretic; acts primarily in the CNS, increasing the pain threshold by inhibiting both isoforms of cyclooxygenase, COX-1 and COX-2, enzymes involved in prostaglandin (PG) synthesis; reduces fever through direct action on hypothalamic heat-regulating center
• Rapid and almost complete absorption
• Metabolized by liver; CYP450: CYP2E1, CYP1A2
• Excreted in urine 85%
• Half-life: 1.25-3 hrs

Butalbital

• Barbiturate; acts as nonselective depressants of the central nervous system (CNS), by binding at a distinct binding site associated with a Cl^-ionopore at the GABAA receptor, increasing the duration of time for which the Cl^- ionopore is open
• Well absorbed from the gastrointestinal tract
• Metabolized by liver
• Renally excreted 59-88% (3.6% unchanged)
• Half-life: 35 hrs

Caffeine

• Analeptic; precise mechanism of action unknown; probably produces cerebral vasoconstriction and antagonizes adenosine A1 and A2 receptors
• Rapidly absorbed
• Metabolized by liver; CYP450: CYP1A2
• Excretion: Urine 70% (3% unchanged)
• Half-life: 3 hrs

Codeine

• Narcotic analgesic; produces analgesia and sedation by binding to multiple opioid receptors
• Readily absorbed from GI tract
• Metabolized by liver; CYP450: CYP2D6
• Excreted in urine and feces
• Half-life: 2.9 hrs

US Trade Name(s)

• Fioricet w/ Codeine

US Availability

acetaminophen/butalbital/caffeine/codeine (generic)

• CAPS: 325 mg/50 mg/40 mg/30 mg
• CAPS: 300 mg/50 mg/40 mg/30 mg

Fioricet w/ Codeine (acetaminophen/butalbital/caffeine/codeine)

• CAPS: 325 mg/50 mg/40 mg/30 mg

Phrenilin with Caffeine and Codeine (acetaminophen/butalbital/caffeine/codeine) (generic)

• CAPS: 325 mg/50 mg/40 mg/30 mg

Canadian Trade Name(s)

• N/A

Canadian Availability

• N/A

UK Trade Name(s)

• N/A

UK Availability

• N/A

Australian Trade Name(s)

• N/A

Australian Availability

• N/A

[Outline]

Analgesics

Analgesics; Combinations

• APAP 325 MG / butalbital 50 MG / caffeine 40 MG / codeine phosphate 30 MG Oral Capsule (Breckenridge Pharmaceutical, Inc.)
• APAP 325 MG / butalbital 50 MG / caffeine 40 MG / codeine phosphate 30 MG Oral Capsule (Physicians Total Care, Inc.)
• APAP 325 MG / butalbital 50 MG / caffeine 40 MG / codeine phosphate 30 MG Oral Capsule (Qualitest Pharmaceuticals)
• APAP 325 MG / butalbital 50 MG / caffeine 40 MG / codeine phosphate 30 MG Oral Capsule (Watson Laboratories, Inc.)
• APAP 325 MG / butalbital 50 MG / caffeine 40 MG / codeine phosphate 30 MG Oral Capsule (West-ward Pharmaceutical Corp)
• Fioricet with Codeine (acetaminophen 325 MG / butalbital 50 MG / caffeine 40 MG / codeine phosphate 30 MG) Oral Capsule (Watson Pharmaceuticals, Inc.)
• Phrenilin with Caffeine and Codeine (acetaminophen 325 MG / butalbital 50 MG / caffeine 40 MG / codeine phosphate 30 MG) Oral Capsule (Valeant Pharmaceuticals North America)