Acetaminophen and codeine

The selected tablets and oral solution are labeled for mild to moderate pain when an opioid is appropriate and alternatives are ineffective, not tolerated, or otherwise inadequate. Addiction, overdose, and death can occur at any dose or duration. Use the lowest effective dose for the shortest appropriate duration; neither codeine’s antitussive pharmacology nor acetaminophen’s fever effect creates a separate labeled indication for this combination.

These product-label regimens require an individualized prescription and a stated maximum number of tablets per day. Opioid-naive initiation, titration, comorbidity, prior opioid exposure, and treatment duration need prescriber assessment. Pediatric effectiveness below age 18 is not established in the selected labels.

The tablet label lists maximum 24-hour totals of codeine phosphate 360 mg and acetaminophen 4,000 mg. Count acetaminophen from prescription, OTC, cold/flu, and other combination products; do not add another APAP product without clinician review. The prescribed regimen may permit substantially less, and liver disease, alcohol exposure, frailty, or adverse effects can require a different plan. Higher-dose codeine and a high APAP total do not become safe merely because they are below these ceilings.

The selected liquid contains acetaminophen 120 mg and codeine phosphate 12 mg per 5 mL, with 7% alcohol. Its labeled adult dose is 15 mL every 4 hours as needed, supplying 360 mg APAP and 36 mg codeine per dose. Prescriptions should state both mg and mL; use a graduated metric oral syringe or medicine cup, never a household spoon. The 5 mL and 12.5 mL unit-dose cups do not automatically equal a prescribed 15 mL dose. Do not substitute concentrations by volume.

Reassess pain, sedation, breathing, and misuse risk before escalation or opioid conversion; no universal equianalgesic ratio is assumed. Discuss access to an appropriately labeled overdose reversal product such as naloxone. Physical dependence requires an individualized gradual taper rather than abrupt discontinuation; the labels describe small reductions with close follow-up, not one schedule suitable for everyone. Consider opioid-induced hyperalgesia if increasing doses worsen pain.

Both labels contraindicate use below age 12; postoperative pain treatment below age 18 after tonsillectomy/adenoidectomy; significant respiratory depression; acute/severe asthma without monitoring or resuscitative equipment; known/suspected GI obstruction including ileus; ingredient hypersensitivity; and concurrent MAOI use or use within the preceding 14 days. Avoid codeine in adolescents 12–18 with hypoventilation risks unless the benefit-risk assessment justifies it; this warning is separate from the absolute age/procedure contraindications.

The boxed warnings cover addiction/abuse/misuse, life-threatening respiratory depression, accidental ingestion, benzodiazepine/CNS-depressant combinations, neonatal withdrawal after prolonged pregnancy exposure, REMS education/counseling, pediatric codeine toxicity, complex CYP interactions, and acetaminophen hepatotoxicity. The oral solution additionally boxes dosing-error risk. These are combined-product warnings, not the single-ingredient APAP OTC warning framework.

Drowsiness, dizziness, nausea/vomiting, constipation, and sweating can occur; serious reactions include respiratory depression, shock, severe skin/allergic reactions, liver injury, and serotonin syndrome with interacting medicines. Suspected overdose needs emergency help even if the patient initially feels well. Opioid toxicity may require ventilation and repeat product-directed reversal with observation; APAP toxicity requires separate assessment and timely N-acetylcysteine when indicated. Early APAP symptoms can be mild while liver injury appears later; do not await symptoms or assume opioid reversal resolves both toxicities.

CYP2D6 inhibitors such as fluoxetine, paroxetine, bupropion, or quinidine can reduce morphine formation, impair analgesia, or trigger withdrawal; stopping them can increase morphine and respiratory toxicity. CYP3A4 inhibitors such as erythromycin, azoles, or ritonavir can increase codeine available for conversion to morphine; stopping them can reduce effect. CYP3A4 inducers can reduce effect, while stopping an inducer can increase toxicity. Clinician-directed dose review and frequent breathing/sedation assessment are required whenever these drugs change.

Benzodiazepines, alcohol, gabapentinoids, muscle relaxants, other opioids, and other CNS depressants add sedation and potentially fatal respiratory depression; reserve combinations for justified situations and discuss reversal access. MAOIs are contraindicated during use and for 14 days after stopping them. Other serotonergic agents require assessment for serotonin syndrome and stopping the combination if suspected. Mixed opioid agonist/antagonists can reduce analgesia or precipitate withdrawal. Anticholinergics increase constipation/retention risk, and opioid effects can reduce diuretic efficacy.

Human pregnancy data are inadequate to establish safety; prolonged opioid exposure can cause neonatal withdrawal requiring a prepared neonatal team. Opioids can cause neonatal respiratory depression around delivery; the labels advise against use during/immediately before labor when other analgesia is more appropriate. Breastfeeding is not recommended during treatment because codeine and morphine enter milk and serious infant sedation, respiratory depression, or death can occur. The combination’s assessment differs from acetaminophen alone.

Below-age-18 safety/effectiveness is not established by these labels. Absolute contraindications are under 12 and under 18 postoperative tonsil/adenoid pain; sleep apnea, obesity, severe pulmonary or neuromuscular disease, postoperative status, and other respiratory depressants heighten adolescent risk. Older, cachectic, or debilitated patients need low initial selection, slow titration, and frequent CNS/respiratory evaluation.

Codeine/metabolites rely substantially on renal elimination, so impairment can increase toxicity; choose doses cautiously and assess renal function, particularly in older adults. Liver disease increases APAP injury risk and can change drug handling. The selected labels provide no validated universal CrCl or hepatic-stage dosing table; do not assume the general adult maximum is suitable for organ disease.

Codeine is a relatively weak mu-opioid agonist; conversion to morphine contributes to analgesia, although the precise analgesic mechanism is not fully established. Acetaminophen provides nonopioid analgesia through incompletely defined central actions. Opioid effects reduce respiratory drive and GI motility and can affect endocrine function; APAP does not prevent those codeine effects.

Codeine is rapidly absorbed, undergoes glucuronidation and CYP2D6 conversion to morphine/CYP3A4 conversion to norcodeine, and is eliminated mainly through the kidneys. Label plasma half-life is about 2.9 hours; peak analgesia occurs within roughly 2 hours and lasts about 4–6 hours. Acetaminophen is rapidly absorbed and mainly hepatically conjugated; a smaller oxidized pathway generates a reactive metabolite detoxified by glutathione. APAP half-life is about 1.25–3 hours and can increase with liver damage/overdose.

Reassess indication, pain/function, sedation, respiratory rate/quality, blood pressure symptoms, constipation, adherence, and misuse risk at initiation, dose changes, and interacting-drug changes. Track daily APAP totals and renal/hepatic risk; evaluate unexplained fatigue/hypotension for adrenal insufficiency or worsening dose-associated pain for hyperalgesia. Taper follow-up includes withdrawal, mood, and substance-use assessment. The labels do not supply one universal monitoring interval for every patient.

Avoid alcohol and unapproved sedatives/APAP products; do not drive or operate machinery until the effects are known. Never share, keep locked away from children, and follow take-back/disposal instructions. Teach caregivers to recognize inability to awaken, slow breathing, or unusual snoring and to call emergency services and give the prescribed/labeled reversal product as directed. Reversal can wear off, so emergency assessment remains necessary. Use metric liquid devices, report rash or allergic symptoms immediately, and seek help for suspected excess APAP even without symptoms.

Selected Eywa/WES tablets are round, flat-faced, beveled: 300/15 mg pink marked W241; 300/30 mg white W242; 300/60 mg blue W243. Bottles of 100 have NDCs 71930-054-12,71930-055-12,71930-056-12. PAI solution is orange-yellow/cherry flavored, supplied as 5 mL unit-dose cups NDC 0121-0504-05 or 12.5 mL cups NDC 0121-1008-12, with separate case NDCs. Other manufacturer imprints/packages differ.

Covered oral tablets contain 300 mg APAP with 15, 30, or 60 mg codeine phosphate; the liquid contains 120 mg APAP/12 mg codeine per 5 mL and 7% alcohol. Both are Schedule III controlled substances. Butalbital/caffeine/codeine combinations, codeine-only products, and other liquid concentrations are outside this reference.

Store both selected products at 20–25°C (68–77°F), in a tight light-resistant container; the solution requires a child-resistant closure. Securely store and properly dispose of unused opioid medicine. Keep the metric dosing device with the correct liquid and do not assume one unit-dose cup equals the prescribed dose.