Butalbital/Acetaminophen/Caffeine/Codeine Capsules Dosage & Rx Info

Butalbital/acetaminophen/caffeine/codeine Capsules Generic Name & Formulations

Legal Class

CIII

General Description

Codeine phosphate 30mg, butalbital 50mg, acetaminophen 325mg, caffeine 40mg; caps.

Pharmacological Class

Opioid + barbiturate + analgesic/antipyretic + methylxanthine.

How Supplied

Contact supplier

Manufacturer

Various generic manufacturers

Mechanism of Action

Butalbital, a barbiturate, is a GABA_A receptor agonist and may inhibit excitatory AMPA receptors. Acetaminophen is a non-opioid, non-salicylate analgesic. The site and mechanism for the analgesic effect of acetaminophen has not been determined but is thought to primarily involve central actions. Caffeine is a methylxanthine and CNS stimulant. The exact mechanism with respect to the indication is not clear; however, the effects of caffeine may be due to antagonism of adenosine receptors. Codeine is an opioid agonist relatively selective for the mu-opioid receptor, but with a much weaker affinity than morphine. The analgesic properties of codeine have been speculated to come from its conversion to morphine, although the exact mechanism of analgesic action remains unknown.

Butalbital/acetaminophen/caffeine/codeine Capsules Indications

Indications

Tension (or muscle contraction) headache.

Limitations of Use

Due to risks of addiction, abuse, and misuse with opioids (can occur at any dosage or duration), reserve for use in patients for whom alternative treatment options (eg, non-opioid, non-barbiturate analgesics) are not tolerated or inadequate to provide analgesia. Should not be used for an extended period of time unless the pain remains severe enough to require an opioid analgesic and for which alternative treatment options continue to be inadequate.

Butalbital/acetaminophen/caffeine/codeine Capsules Dosage and Administration

Adult

Use lowest effective dose for shortest duration. Individualize. 1–2 caps every 4hrs as needed; max 6 caps/day. Also with Codeine: 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

Not established.

Butalbital/acetaminophen/caffeine/codeine Capsules Contraindications

Contraindications

Porphyria. Also with Codeine: children <12yrs. Post-op management in children <18yrs 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.

Butalbital/acetaminophen/caffeine/codeine Capsules Boxed Warnings

Boxed Warning

Serious and life-threatening risks from use of Butalbital/Acetaminophen/Caffeine/Codeine Capsules: Addiction, abuse, and misuse; Life-threatening respiratory depression; Accidental ingestion; Risks from concomitant benzodiazepines or other CNS depressants; Neonatal opioid withdrawal syndrome; Opioid analgesic risk evaluation and mitigation strategy (REMS); Ultra-rapid metabolism of codeine and other risk factors for life-threatening respiratory depression in children; Interactions with drugs affecting CYP450 isoenzymes; Hepatotoxicity.

Butalbital/acetaminophen/caffeine/codeine Capsules Warnings/Precautions

Warnings/Precautions

Risk of hepatotoxicity (acetaminophen >4g/day). Discontinue at 1^st sign of rash or any other hypersensitivity. Also with Codeine: 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). Abuse potential (monitor). Life-threatening respiratory depression esp. during initiation or 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. Risk of life-threatening respiratory depression and death related to ultra-rapid metabolizers of codeine (esp. in children for post-tonsillectomy and/or adenoidectomy pain). 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). COPD, cor pulmonale, decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression; monitor and consider non-opioid analgesics. Opioid-induced hyperalgesia (OIH) and allodynia; consider decreasing dose of current opioid or opioid rotation if OIH is suspected. Monitor for signs of hypotension when initiating or titrating dose. Adrenal insufficiency. Head injury. Increased intracranial pressure, brain tumors; monitor. Seizure disorders. CNS depression. Impaired consciousness, coma, shock; avoid. Biliary tract disease. Acute pancreatitis. Acute abdomen. Reevaluate periodically. Avoid abrupt cessation. Severe renal or hepatic impairment (monitor). Ultra-rapid metabolizers (due to CYP2D6 polymorphism): avoid. Drug abusers. Elderly. Cachectic. Debilitated. Pregnancy; potential neonatal opioid withdrawal syndrome during prolonged use. Labor & delivery, nursing mothers: not recommended.

REMS

YES

Butalbital/acetaminophen/caffeine/codeine Capsules Pharmacokinetics

Absorption

Butalbital, acetaminophen, and codeine are well absorbed from the GI tract.

Distribution

Plasma protein bound: 45% (butalbital); 10–25% (acetaminophen).

Metabolism

Acetaminophen: hepatic via conjugation with glucuronide and sulfate, and oxidation via CYP450. Caffeine: CYP1A2. Codeine: conjugation with glucuronic acid (UGT2B7, UGT2B4) and via O-demethylation (CYP2D6, CYP3A4).

Elimination

Butalbital: renal (59–88%). Acetaminophen: renal (~85%). Caffeine: renal (70%). Codeine: renal (~90%). Half-life: ~35 hours (butalbital); 1.25–3 hours (acetaminophen); ~3 hours (caffeine); ~2.9 hours (codeine).

Butalbital/acetaminophen/caffeine/codeine Capsules Interactions

Interactions

Concomitant other acetaminophen-containing products: not recommended. Also with Codeine: 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. 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. May be affected by CYP2D6 inhibitors (eg, amiodarone, quinidine, fluoxetine, paroxetine, bupropion). Potentiated by CYP3A4 inhibitors (eg, macrolides, azole antifungals, protease inhibitors, grapefruit juice). Antagonized by CYP3A4 inducers (eg, rifampin, carbamazepine, phenytoin). May antagonize diuretics; monitor. Paralytic ileus may occur with anticholinergics. Codeine may increase serum amylase levels. Acetaminophen may cause false (+) urine test for 5-hydroxyindoleacetic acid.

Butalbital/acetaminophen/caffeine/codeine Capsules Adverse Reactions

Adverse Reactions

Drowsiness, lightheadedness, dizziness, sedation, shortness of breath, nausea, vomiting, abdominal pain, intoxicated feeling; hepatotoxicity, serious skin reactions or other hypersensitivity (rare). Also with Codeine: respiratory depression, orthostatic hypotension, syncope, OIH and allodynia.

Butalbital/acetaminophen/caffeine/codeine Capsules Clinical Trials

See Literature

Butalbital/acetaminophen/caffeine/codeine Capsules Note

Not Applicable

Butalbital/acetaminophen/caffeine/codeine Capsules Patient Counseling