ANEXSIA
Clinical safety rating
cautionComprehensive clinical and safety monograph for ANEXSIA (ANEXSIA).
ANEXSIA is a combination of hydrocodone and acetaminophen. Hydrocodone is an opioid agonist that binds to mu-opioid receptors in the central nervous system, altering pain perception and emotional response to pain. Acetaminophen's analgesic mechanism is not fully understood but involves inhibition of COX enzymes in the CNS and modulation of descending serotonergic pathways.
| Metabolism | Hydrocodone is metabolized via CYP2D6 and CYP3A4 to hydromorphone and norhydrocodone. Acetaminophen is primarily metabolized via hepatic glucuronidation and sulfation; a minor pathway via CYP2E1 produces NAPQI, which is detoxified by glutathione. |
| Excretion | Approximately 70% renal (unchanged drug and metabolites), 20% biliary/fecal, 10% other. |
| Half-life | Terminal elimination half-life is 4-6 hours in adults with normal renal function; prolonged to 12-24 hours in severe renal impairment (CrCl <30 mL/min). |
| Protein binding | Approximately 95% bound to plasma albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | 0.2-0.4 L/kg, indicating limited extravascular distribution primarily confined to plasma and interstitial fluid. |
| Bioavailability | Oral: 80-90%; Intramuscular: 90-100%; Rectal: 70-80%. |
| Onset of Action | Oral: 30-60 minutes; Intravenous: 5-10 minutes; Intramuscular: 10-20 minutes. |
| Duration of Action | Oral: 4-6 hours; Intravenous: 3-5 hours; Intramuscular: 4-6 hours. Duration may be prolonged in hepatic impairment. |
| Molecular Weight | 381.42 |
50-100 mg orally every 4-6 hours as needed; maximum 400 mg/day.
| Dosage form | TABLET |
| Renal impairment | GFR 30-89 mL/min: no adjustment; GFR 15-29 mL/min: 50% dose reduction; GFR <15 mL/min: avoid use. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: 50% dose reduction; Child-Pugh C: avoid use. |
| Pediatric use | 1-2 mg/kg/dose orally every 6 hours; maximum 6 mg/kg/day. |
| Geriatric use | Initiate at 25 mg every 6 hours; increase cautiously; monitor renal function. |
| 1st trimester | Avoid. Teratogenic effects in animal studies; consider alternatives. |
| 2nd trimester | Avoid. May cause fetal renal impairment and oligohydramnios. |
| 3rd trimester | Avoid. Risk of premature closure of ductus arteriosus and persistent pulmonary hypertension. |
Clinical note
Comprehensive clinical and safety monograph for ANEXSIA (ANEXSIA).
| Placental transfer | Crosses placenta; detected in fetal plasma at concentrations comparable to maternal. |
| Breastfeeding | Excreted in breast milk; potential for adverse effects in infant. Decision to discontinue drug or breastfeeding based on importance of drug to mother. |
| Lactation Rating | L4 (Possibly Hazardous) |
| Teratogenic Risk | First trimester: Data are limited; no increased risk of major malformations reported in small studies. Second and third trimesters: Associated with premature closure of the ductus arteriosus and oligohydramnios due to fetal renal effects; avoid use after 30 weeks gestation. |
| Fetal Monitoring | Ultrasound monitoring for fetal ductus arteriosus constriction and amniotic fluid volume after 20 weeks gestation; fetal echocardiography if used beyond 32 weeks. Maternal monitoring for blood pressure, renal function, and signs of bleeding. |
| Fertility Effects | Reversible inhibition of ovulation; may impair fertility by interfering with prostaglandin synthesis involved in follicular rupture. |
■ FDA Black Box Warning
Addiction, abuse, and misuse; life-threatening respiratory depression; accidental ingestion; neonatal opioid withdrawal syndrome; risks from concomitant use with benzodiazepines or other CNS depressants; hepatotoxicity from acetaminophen.
| Serious Effects |
Hypersensitivity to any componentHistory of asthma exacerbated by NSAIDsSevere hepatic or renal impairmentActive peptic ulcer disease
| Precautions | Risk of respiratory depression, especially in elderly or debilitated patients; adrenal insufficiency; severe hypotension; seizures; opioid-induced hyperalgesia; acetaminophen hepatotoxicity (avoid exceeding 4 g/day); serotonin syndrome if used with serotonergic agents. |
| Food/Dietary | Avoid alcohol; may increase risk of hepatotoxicity and GI bleeding. Limit caffeine intake from coffee, tea, cola, or energy drinks due to added caffeine content. High-fat meals may delay absorption; take on empty stomach for faster onset if tolerated. |
| Clinical Pearls | ANEXSIA is a combination analgesic containing paracetamol, ibuprofen, and caffeine. It is contraindicated in patients with active peptic ulcer disease, severe hepatic impairment, or hypersensitivity to NSAIDs. Avoid concurrent use with other NSAIDs or paracetamol-containing products. Monitor renal function in elderly or dehydrated patients. Caffeine may exacerbate anxiety or insomnia. |
| Patient Advice | Do not exceed recommended dose; overdosage of paracetamol can cause liver damage. · Take with food or milk to reduce gastrointestinal upset. · Avoid alcohol while taking this medication to reduce risk of liver toxicity and GI bleeding. · Discontinue use and consult if signs of allergic reaction, GI bleeding, or liver problems occur. · Caffeine may cause nervousness, insomnia, or increased heart rate; limit caffeine-containing foods and beverages. |
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