Butalbital/aspirin/caffeine/codeine Generic Name & Formulations
Tension (or muscle contraction) headache when non-opioid analgesic and alternative treatments are inadequate.
Limitations of Use
Reserve for use in patients for whom alternative treatment options (eg, non-opioid, non-barbiturate analgesics): have not been tolerated, or are not expected to be tolerated; or have not provided adequate analgesia, or are not expected to provide adequate analgesia.
Butalbital/aspirin/caffeine/codeine Dosage and Administration
Use lowest effective dose for shortest duration. Individualize. 1–2 caps every 4hrs, as needed; max 6 caps/day. Concomitant use or discontinuation of CYP2D6 inhibitors, CYP3A4 inhibitors or inducers: monitor closely and consider dose adjustments (see full labeling). Withdraw gradually (esp. if opioid-dependent), taper by ≤10–25% every 2–4 weeks.
Children <12yrs of age. Post-op management in children <18yrs of age following tonsillectomy and/or adenoidectomy. Significant respiratory depression. Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment. Known or suspected GI obstruction, including paralytic ileus. During or within 14 days of MAOIs. Hemophilia. Reye's syndrome. NSAID allergy. Syndrome of asthma, rhinitis, and nasal polyps.
Butalbital/aspirin/caffeine/codeine Boxed Warnings
Abuse, addiction, and misuse. Risk evaluation and mitigation strategy (REMS). Life threatening respiratory depression. Accidental ingestion (may be fatal). Risks from concomitant use of drugs affecting CYP450 isoenzymes, benzodiazepines, or CNS depressants. Neonatal opioid withdrawal syndrome. Ultra-rapid metabolism of codeine to morphine (may be fatal).
Risk of addiction, abuse, and misuse (monitor). Assess the potential need for access to naloxone when initiating and renewing therapy. Consider prescribing naloxone based on risk factors for overdose (eg, history of opioid use disorder, prior opioid overdose, household members or other close contacts at risk for accidental ingestion or overdose). Life-threatening respiratory depression; monitor within first 24–72hrs of initiating therapy and following dose increases. Accidental exposure may cause fatal overdose (esp. in children). Sleep-related breathing disorders (including central sleep apnea (CSA), sleep-related hypoxemia); consider dose reduction if CSA develops. COPD, cor pulmonale, decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression; monitor and consider non-opioid analgesics. Risk of respiratory depression and death related to ultra-rapid metabolizers of codeine (esp. children in post-op tonsillectomy and/or adenoidectomy); avoid. Avoid in adolescents 12–18yrs with conditions associated with hypoventilation (eg, post-op status, obstructive sleep apnea, obesity, severe pulmonary disease, neuromuscular disease, concomitant drugs that cause respiratory depression). Adrenal insufficiency. Head injury. Increased intracranial pressure, brain tumors; monitor. CNS depression. Impaired consciousness, coma, shock; avoid. Biliary tract disease. Peptic ulcer disease; avoid. Monitor for ulceration and bleeding. Acute pancreatitis. Seizure disorders. Coagulation abnormalities. Bleeding disorders. Reevaluate periodically. Avoid abrupt cessation. Renal or hepatic impairment: initiate lower doses; monitor. Severe renal failure (GFR<10mL/min): avoid. Elderly. Cachectic. Debilitated. Pregnancy (avoid during ≥30 weeks gestation): increased risk of premature closure of the fetal ductus arteriosus; (20–30 weeks gestation): may cause fetal renal dysfunction/oligohydramnios; if treatment needed, limit dose and duration of use. Risk of neonatal opioid withdrawal syndrome during prolonged use. Labor & delivery, nursing mothers: not recommended.
Increased risk of hypotension, respiratory depression, sedation with benzodiazepines or other CNS depressants (eg, non-benzodiazepine sedatives/hypnotics, anxiolytics, general anesthetics, phenothiazines, tranquilizers, muscle relaxants, antipsychotics, alcohol, other opioids); reserve concomitant use in those for whom alternative options are inadequate; limit dosages/durations to minimum required; monitor closely; consider prescribing naloxone if concomitant use is warranted. Increased risk of bleeding with chronic, heavy alcohol use (≥3 drinks/day). Risk of serotonin syndrome with serotonergic drugs (eg, SSRIs, SNRIs, TCAs, triptans, 5-HT3 antagonists, mirtazapine, trazodone, tramadol, cyclobenzaprine, metaxalone, MAOIs, linezolid, IV methylene blue); monitor and discontinue if suspected. Avoid concomitant mixed agonist/antagonist opioids (eg, butorphanol, nalbuphine, pentazocine) or partial agonist (eg, buprenorphine); may reduce effects and/or precipitate withdrawal symptoms. Potentiated by CYP3A4 inhibitors (eg, macrolides, azole antifungals, protease inhibitors); if concomitant use is necessary, consider reducing dose of Butalbital/Aspirin/Caffeine/Codeine; monitor for respiratory depression and sedation. Antagonized by CYP3A4 inducers (eg, rifampin, carbamazepine, phenytoin); if concomitant use is necessary, consider increasing dose of Butalbital/Aspirin/Caffeine/Codeine; monitor for respiratory depression and sedation. May be affected by CYP2D6 inhibitors (eg, amiodarone, quinidine, fluoxetine, paroxetine, bupropion); if concomitant use is necessary, consider adjusting dose and monitor closely. May antagonize diuretics; monitor. Paralytic ileus may occur with anticholinergics; monitor. May potentiate effects of anticoagulants (eg, warfarin, heparin, enoxaparin, clopidogrel, prasugrel, rivaroxaban, apixaban); monitor. Avoid concomitant uricosurics (eg, probenecid), corticosteroids. May potentiate carbonic anhydrase inhibitors (eg, acetazolamide, methazolamide); consider reducing dose of these. Concomitant methotrexate: monitor for toxicity esp. in elderly or renal impairment. Monitor renal function closely with concomitant nephrotoxic agents. May antagonize ACEIs, beta-blockers; monitor BP and renal function. May potentiate hypoglycemic agents (eg, insulin, glimepiride, glipizide). Increased risk of bleeding or lead to decreased renal function with concomitant NSAIDs; avoid. Caution with phenytoin, valproic acid. Codeine may increase serum amylase levels. May interfere with lab tests in blood or urine (eg, serum amylase, fasting blood glucose, cholesterol, protein, SGOT, uric acid, prothrombin time, bleeding time, glucose, 5- hydroxyindoleacetic acid, Gerhardt ketone, VMA, uric acid, diacetic acid, and spectrophotometric detection of barbiturates).
Butalbital/aspirin/caffeine/codeine Adverse Reactions
Nausea, abdominal pain, drowsiness, dizziness; hypersensitivity reactions, DRESS (discontinue if occurs), respiratory depression, severe hypotension, syncope.
Butalbital/aspirin/caffeine/codeine Clinical Trials
Formerly known under the brand name Fiorinal with Codeine.
Butalbital/aspirin/caffeine/codeine Patient Counseling