Adult Dosing

Tension headache

• 1-2 caps PO q4 hrs
• Max: 6 capsules/day

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
• Intolerance to aspirin, caffeine, butalbital or codeine
• Von Willebrand disease
• Syndrome of nasal polyps, angioedema and bronchospastic reactivity to aspirin or other nonsteroidal anti-inflammatory drugs
• Peptic ulcer or other serious GI lesions
• Porphyria
• Asthma or urticaria induced by aspirin or other nonsteroidal anti-inflammatory drugs
• Uncontrolled hypertension
• Glucose-6-phosphate dehydrogenase (G6PD) deficiency
• Patients <20 years with influenza, varicella, or febrile viral infections

• 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: Use with caution; dose adjustments not defined

Hepatic Dose Adjustment

• Severe hepatic impairment: Use with caution; 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)
• Anaphylactic shock and other severe allergic reactions have occurred with therapeutic doses of aspirin. Any allergy to aspirin should be certainly clarified, although a specific history of allergy may be lacking
• Patients with peptic ulcer or other GI lesions, and patients with bleeding disorders receiving aspirin therapy may be prone to significant bleeding. Pre-operative administration of aspirin may prolong the bleeding time
• Presence of head injury or other intracranial lesions may significantly enhance the respiratory depressant effects of codeine and other narcotics and also their capacity to elevate the cerebrospinal fluid pressure. CNS depressant effects, such as drowsiness, may be seen with the use of narcotics which may further obscure the clinical course of patients with head injuries
• Codeine or other narcotics may obscure signs for judging the diagnosis or clinical course of patients with acute abdominal conditions
• Butalbital and codeine exhibit habit-forming and abuse potential. Extended use of Fiorinal® with Codeine (butalbital, aspirin, caffeine, and codeine phosphate capsules, USP) is not recommended
• Association between aspirin and Reye syndrome exists
• Patients with nasal polyps and asthma are more susceptible to hypersensitivity reactions to aspirin

Cautions: Use cautiously in:

• Severe renal impairment
• Severe hepatic impairment
• Prostatic hypertrophy
• Urethral stricture
• Elevated intracranial pressure
• Coagulation disorders
• Patients on anticoagulant therapy
• Patients with underlying hemostatic defects
• Persons with known allergies
• Hypothyroidism
• Addison’s disease
• Ultra-rapid metabolizers of codeine
• Teenagers with chicken pox or flu
• Elderly patients
• Debilitated patients
• Surgery or trauma patients
• Gastroesophageal reflux disease
• Gout
• Chronic alcohol use
• Drug abuse

Supplemental Patient Information

• Advise patients to avoid engaging in potentially hazardous tasks such as driving a car or operating a machinery as aspirin/butalbital/caffeine/codeine may impair the mental and/or physical abilities required to perform such activities
• Advise patients to avoid concomitant use of alcohol and other CNS depressants
• Advise patients to strictly follow dosing instructions
• Instruct nursing mothers to observe for signs of morphine toxicity in their infants including increased sleepiness, difficulty in breastfeeding, breathing difficulties or limpness. Instruct nursing mothers to immediately talk to the baby's doctor if they notice these signs; and if they are unable to reach the doctor right away, to take the baby to an emergency room or call local emergency services

Pregnancy Category:C

Breastfeeding: Possibly unsafe; avoid aspirin during breastfeeding, especially with very young infants; although a rare single low dose of aspirin daily is unlikely to cause problems in the infant. The risks with chronic high dose aspirin use are less clear. In this context, monitor infant salicylate serum levels, particularly in neonates. Avoid breastfeeding for 1-2 hrs after an aspirin dose to minimize antiplatelet effects. Caffeine is observed rapidly in breastmilk after maternal ingestion. Fussiness, jitteriness and poor sleep patterns have occurred in the infants of mothers with very high doses of caffeine intake equivalent to about 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 resulting in mild iron deficiency anemia may occur in some breastfed infants whose mothers consume >450 mL of coffee daily. Maximum dosages of oral narcotics in mothers while breastfeeding can cause infant drowsiness. Newborn infants are particularly sensitive to the effects of even small dosages of narcotic analgesics, particularly 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. Mothers with ultrarapid CYP2D6 metabolism may excrete unexpectedly higher amounts of morphine into their milk after use of codeine and increase the risk of adverse effects in infant. Prefer alternative agents while nursing a newborn or preterm infant as there is no published experience with butalbital or combination products containing butalbital during breastfeeding. This information is based upon LactMed database (available at http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT).Based upon data from AAP Policy Guidelines, irritability and poor sleeping pattern may occur as caffeine is excreted slowly; no effects were observed with moderate intake of caffeinated beverages (2-3 cups per day). Codeine is found compatible. Information (available at http://aappolicy.aappublications.org/cgi/content/full/pediatrics;108/3/776 last accessed 20 January 2011). Manufacturer advises to make a decision for discontinuing nursing or to discontinue the drug taking into account the importance of the drug to the mother.

• CNS: Drowsiness, dizziness, lightheadedness
• CV: Angioedema
• RESP: Bronchospasm
• GI: Constipation, flatulence, dyspepsia, hepatotoxicity, GI bleeding, GI ulceration, GI perforation, nausea, abdominal pain, vomiting
• HEMA: Thrombocytopenias, hypoprothrombinemia, myelosuppression, disseminated intravascular coagulation, bleeding, pancytopenia, agranulocytosis, aplastic anemia
• EENT: Tinnitus
• GU: Hyperuricemia, nephrotoxicity
• DERM: Photosensitivity, rash, ecchymosis, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis
• MISC: Salicylism, Reye syndrome

Aspirin

• Salicylates; precise mechanism of action unknown; inhibits prostaglandin synthesis, exhibits analgesia, anti-inflammatory and antipyretic activity and inhibits platelet aggregation by irreversible inhibition of platelet cyclooxygenase and thus inhibits the generation of thromboxane A2
• Hydrolyzed in gut and plasma (aspirin) and metabolized by liver (salicylic acid); CYP450: Unknown
• Excreted in urine
• Half life: 12 mins (aspirin), 3 hrs (salicylic acid)

Butalbital

• Barbiturates; produces sedation
• 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; produces constriction of cerebral blood vessels, antagonizes adenosine A1 and A2 receptors
• Rapidly absorbed
• Metabolized by liver; CYP450: CYP1A2
• Excreted in urine (1% 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)

• Fiorinal w/codeine

US Availability

aspirin/butalbital/caffeine/codeine (generic)

• CAPS: 325 mg/50 mg/40 mg/30 mg

Fiorinal w/codeine (aspirin/butalbital/caffeine/codeine)

• CAPS: 325 mg/50 mg/40 mg/30 mg

Canadian Trade Name(s)

• Fiorinal C1/2
• Pronal-C1/2
• Ratio-tecnal C1/2
• Trianal C1/2
• Fiorinal C1/4 cap
• Pronal-C1/4
• Ratio-tecnal C1/4
• Trianal C1/4

Canadian Availability

Fiorinal C1/2, Pronal-C1/2, Ratio-tecnal C1/2, Trianal C1/2 (aspirin/butalbital/caffeine/codeine)

• CAPS: 330 mg/50 mg/40 mg/30 mg

Fiorinal C1/4 cap, Pronal-C1/4 capsules, Ratio-tecnal C1/4, Trianal C1/4 (aspirin/butalbital/caffeine/codeine)

• CAPS: 330 mg/50 mg/40 mg/15 mg

UK Trade Name(s)

• N/A

UK Availability

• N/A

Australian Trade Name(s)

• N/A

Australian Availability

• N/A

[Outline]

Analgesics

Analgesics; Combinations

• Ascomp with Codeine (aspirin 325 MG / butalbital 50 MG / caffeine 40 MG / codeine phosphate 30 MG) Oral Capsule (Breckenridge Pharmaceutical, Inc.)
• Ascomp with Codeine (aspirin 325 MG / butalbital 50 MG / caffeine 40 MG / codeine phosphate 30 MG) Oral Capsule (Nexgen Pharma, Inc.)
• Aspirin 325 MG / butalbital 50 MG / Caffeine 40 MG / Codeine 30 MG Oral Capsule (Jerome Stevens Pharmaceuticals)
• Aspirin 325 MG / butalbital 50 MG / Caffeine 40 MG / Codeine 30 MG Oral Capsule (Watson Laboratories, Inc.)
• Fiorinal with Codeine (aspirin 325 MG / butalbital 50 MG / caffeine 40 MG / codeine phosphate 30 MG) Oral Capsule (Watson Pharma, Inc.)