ANEXSIA 7.5/325
Clinical safety rating
cautionComprehensive clinical and safety monograph for ANEXSIA 7.5/325 (ANEXSIA 7.5/325).
Hydrocodone is a mu-opioid receptor agonist, producing analgesia and euphoria. Acetaminophen inhibits cyclooxygenase (COX) enzymes, reducing prostaglandin synthesis and providing analgesic and antipyretic effects.
| Metabolism | Hydrocodone: CYP3A4 and CYP2D6; Acetaminophen: primarily via glucuronidation (UGT1A1, UGT1A6, UGT1A9) and sulfation, with minor oxidation by CYP2E1. |
| Excretion | Renal: ~90-100% as hydrocodone metabolites (conjugated) and unchanged hydrocodone; ~60% as acetaminophen metabolites (glucuronide, sulfate, cysteine); <5% unchanged acetaminophen. Biliary/fecal: <5%. |
| Half-life | Hydrocodone: 3.8-4.5 hours (immediate-release). Acetaminophen: 2-3 hours. Clinical note: Half-life prolonged in hepatic impairment; requires dose adjustment. |
| Protein binding | Hydrocodone: ~20-30% (albumin). Acetaminophen: ~10-25% (albumin). |
| Volume of Distribution | Hydrocodone: 3-4 L/kg (extensive tissue distribution). Acetaminophen: ~1 L/kg (uniformly distributed). |
| Bioavailability | Oral: Hydrocodone ~70% (high first-pass metabolism); Acetaminophen ~85-90% (minimal first-pass). |
| Onset of Action | Oral: 30-60 minutes (hydrocodone analgesia); acetaminophen antipyretic effect begins within 30 minutes. |
| Duration of Action | Hydrocodone: 4-6 hours (analgesic effect). Acetaminophen: 4-6 hours (antipyretic/analgesic). Clinical note: Duration may be shorter in opioid-tolerant patients. |
| Molecular Weight | Hydrocodone: 299.36 Da; Acetaminophen: 151.16 Da |
1 tablet (hydrocodone 7.5 mg / acetaminophen 325 mg) orally every 4 to 6 hours as needed for pain; maximum 6 tablets per day (hydrocodone 45 mg / acetaminophen 1950 mg).
| Dosage form | TABLET |
| Renal impairment | For GFR 30-59 mL/min: administer every 6 hours; maximum 4 tablets per day. For GFR 15-29 mL/min: administer every 8 hours; maximum 3 tablets per day. For GFR <15 mL/min: not recommended due to accumulation of metabolites. |
| Liver impairment | Child-Pugh Class A: no adjustment necessary. Child-Pugh Class B: reduce dose by 25-50% and extend dosing interval to every 6-8 hours; maximum 4 tablets per day. Child-Pugh Class C: contraindicated due to risk of hepatotoxicity. |
| Pediatric use | Not recommended for pediatric patients; safety and efficacy not established for children under 18 years. For adolescents ≥18 years: adult dosing. |
| Geriatric use | Initiate at 1 tablet (hydrocodone 5 mg / acetaminophen 325 mg) every 6 hours as needed; titrate cautiously due to increased sensitivity, decreased renal function, and risk of respiratory depression. Maximum 4 tablets per day. |
| 1st trimester | Avoid use during first trimester; NSAIDs associated with increased risk of miscarriage and congenital malformations. Hydrocodone use may cause neural tube defects. |
| 2nd trimester | Use with caution; NSAIDs may cause oligohydramnios and fetal renal dysfunction. Hydrocodone may cause fetal dependence. |
| 3rd trimester | Contraindicated; NSAIDs risk premature closure of ductus arteriosus and oligohydramnios. Hydrocodone may cause neonatal withdrawal syndrome. |
Clinical note
Comprehensive clinical and safety monograph for ANEXSIA 7.5/325 (ANEXSIA 7.5/325).
| Placental transfer | Both hydrocodone and acetaminophen cross the placenta. Hydrocodone is detected in fetal plasma at maternal levels. Acetaminophen crosses readily. |
| Breastfeeding | Hydrocodone is excreted into breast milk in low levels, but may cause infant sedation or respiratory depression. NSAIDs are excreted in low amounts. Use only if benefit outweighs risk and monitor infant for adverse effects. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | FDA Category C (hydrocodone) and Category D (acetaminophen) in third trimester. First trimester: Acetaminophen associated with rare gastroschisis; hydrocodone risk of neural tube defects. Second trimester: No major malformations except with prolonged opioid use. Third trimester: Acetaminophen safe; hydrocodone risk of neonatal opioid withdrawal syndrome (NOWS). Avoid near term. |
| Fetal Monitoring | Maternal: Liver function tests (LFTs) if chronic acetaminophen use; urine drug screens if abuse history; respiratory status with high doses. Fetal: Ultrasound for growth restriction with chronic opioid use; fetal heart rate monitoring during labor; assess for NOWS at delivery. |
| Fertility Effects | Hydrocodone may cause hyperprolactinemia and hypogonadism with chronic use, potentially impairing ovulation and spermatogenesis. Acetaminophen use in pregnancy not associated with fertility impairment. Short-term use has minimal impact. |
■ 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 due to acetaminophen.
| Serious Effects |
Hypersensitivity to hydrocodone, acetaminophen, or any componentSignificant respiratory depressionAcute or severe bronchial asthma in an unmonitored setting or without resuscitative equipmentKnown or suspected gastrointestinal obstruction, including paralytic ileusConcurrent use of monoamine oxidase inhibitors (MAOIs) or within 14 days of such therapySevere hepatic impairmentThird trimester of pregnancy (prolonged use)
| Precautions | Risk of opioid addiction, abuse, and misuse; life-threatening respiratory depression; accidental ingestion; neonatal opioid withdrawal syndrome; risks from concomitant use of alcohol, benzodiazepines, or other CNS depressants; hepatotoxicity; severe hypotension; adrenal insufficiency; seizures; GI obstruction; impaired mental/physical abilities; use in elderly, cachectic, or debilitated patients; renal impairment; hepatic impairment; pregnancy; labor and delivery; nursing mothers; pediatric use; driving and operating machinery. |
| Food/Dietary | Avoid alcohol consumption due to increased risk of acetaminophen hepatotoxicity and CNS depression. No specific food restrictions, but grapefruit juice may theoretically affect hydrocodone metabolism via CYP3A4 inhibition; however, clinical significance is uncertain. |
| Clinical Pearls | ANEXSIA 7.5/325 (hydrocodone/acetaminophen) carries a boxed warning for acetaminophen hepatotoxicity; maximum acetaminophen dose from all sources should not exceed 4 g/day. Hydrocodone is metabolized by CYP2D6 to hydromorphone; ultrarapid metabolizers may experience toxicity. Avoid concurrent use with other CNS depressants including alcohol. Prescribe with caution in patients with renal impairment (hydrocodone accumulation) or hepatic impairment (acetaminophen toxicity). Monitor for signs of respiratory depression, especially at therapy initiation and dose titration. Use the lowest effective dose for the shortest duration. |
| Patient Advice | Do not exceed 6 tablets per day due to acetaminophen content. · Avoid alcohol while taking this medication. · Do not drive or operate heavy machinery until you know how this medication affects you. · Take exactly as prescribed; do not share with others. · Seek emergency help if you experience difficulty breathing, severe drowsiness, or signs of allergic reaction. · Store securely out of reach of children and dispose of unused medication properly. |
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