ANEXSIA 7.5/650
Clinical safety rating
cautionComprehensive clinical and safety monograph for ANEXSIA 7.5/650 (ANEXSIA 7.5/650).
Hydrocodone is a mu-opioid receptor agonist that inhibits ascending pain pathways and alters pain perception; acetaminophen inhibits cyclooxygenase (COX) enzymes, primarily in the CNS, reducing prostaglandin synthesis and fever.
| Metabolism | Hydrocodone: CYP3A4 and CYP2D6; acetaminophen: primarily liver glucuronidation (UGT1A1, UGT1A6, UGT1A9) and sulfation (SULT1A1, SULT1A3), with minor CYP2E1 oxidation. |
| Excretion | Hydrocodone: Renal elimination of metabolites (hydromorphone, norhydrocodone) and unchanged drug accounts for ~60-90% of clearance. Acetaminophen: ~85% of dose is excreted in urine as glucuronide and sulfate conjugates; 5-10% unchanged; 2-5% as mercapturate. |
| Half-life | Hydrocodone: Terminal half-life 3.8-7.2 hours (mean 5.6 h). Acetaminophen: 1.5-2.5 hours (therapeutic) but prolonged to >4 hours in overdose with hepatotoxicity risk. |
| Protein binding | Hydrocodone: ~36% bound to serum proteins. Acetaminophen: 10-25% bound (minimal binding). |
| Volume of Distribution | Hydrocodone: Vd ~3-5 L/kg (wide distribution). Acetaminophen: Vd ~0.9-1.0 L/kg (primarily body water). |
| Bioavailability | Oral: Hydrocodone ~70-80% (variable first-pass). Acetaminophen ~63-89% (mean 75-80%). |
| Onset of Action | Oral: Hydrocodone onset 15-30 minutes; peak effect 1-2 hours. Acetaminophen onset 30-60 minutes; peak effect 1-2 hours. |
| Duration of Action | Hydrocodone: Analgesic duration 4-6 hours (immediate-release). Acetaminophen: 4-6 hours. Combined product dosed every 4-6 hours. |
| Molecular Weight | 299.4 |
1 tablet orally every 4 to 6 hours as needed; maximum 6 tablets per day.
| Dosage form | TABLET |
| Renal impairment | CrCl <30 mL/min: contraindicated; CrCl 30-60 mL/min: maximum 3 tablets per day; given the hydrocodone component, avoid in severe renal impairment. |
| Liver impairment | Child-Pugh Class A: no adjustment; Child-Pugh Class B: reduce dose by 50% and monitor; Child-Pugh Class C: contraindicated due to hydrocodone. |
| Pediatric use | Not recommended in pediatric patients due to risk of respiratory depression; for ages <18, contraindicated. |
| Geriatric use | Initiate with lowest effective dose, monitor for respiratory depression and constipation; maximum 4 tablets per day in patients >65 years. |
| 1st trimester | Avoid. Hydrocodone is teratogenic in animal studies; acetaminophen is generally considered safe but use only if clearly needed. Risk of neural tube defects with first-trimester opioid exposure. |
| 2nd trimester | Use with caution. Acetaminophen is safe; hydrocodone may cause fetal dependence with prolonged use. Monitor for neonatal abstinence syndrome. |
| 3rd trimester | Avoid prolonged use. Acetaminophen is safe; hydrocodone can cause neonatal withdrawal and respiratory depression. Use only if benefits outweigh risks. |
Clinical note
Comprehensive clinical and safety monograph for ANEXSIA 7.5/650 (ANEXSIA 7.5/650).
| Placental transfer | Both hydrocodone and acetaminophen cross the placenta. Hydrocodone has moderate transfer; acetaminophen has extensive transfer. |
| Breastfeeding | Hydrocodone and acetaminophen are excreted into breast milk. Hydrocodone may cause infant sedation, respiratory depression, and withdrawal. Acetaminophen is considered compatible. Avoid or limit use; monitor infant for drowsiness and feeding difficulties. |
| Lactation Rating | L3 - Moderately Safe (hydrocodone) / L1 - Safest (acetaminophen). Overall, caution advised. |
| Teratogenic Risk | FDA Category C. First trimester: Possible increased risk of cardiac defects with oxycodone. Second/third trimester: Chronic use may lead to neonatal opioid withdrawal syndrome; no clear teratogenicity. Acetaminophen is generally safe, but high doses may be hepatotoxic. |
| Fetal Monitoring | Monitor for neonatal withdrawal (NOWS) if chronic use; fetal growth assessment; nonstress test in third trimester; maternal liver function with high acetaminophen doses. |
| Fertility Effects | Possible ovulatory dysfunction with opioid use; acetaminophen not associated with impaired fertility. |
■ FDA Black Box Warning
Risk of addiction, abuse, and misuse; life-threatening respiratory depression; accidental ingestion (especially in children) can be fatal; neonatal opioid withdrawal syndrome; cytochrome P450 3A4 interaction (concomitant use with CYP3A4 inhibitors may increase hydrocodone levels); risk of medication errors (confusion between different strengths).
| Serious Effects |
Severe respiratory depressionAcute or severe bronchial asthmaKnown hypersensitivity to hydrocodone or acetaminophenParalytic ileusConcurrent use of MAOIs or within 14 daysSevere hepatic impairment
| Precautions | Addiction, abuse, and misuse; respiratory depression; neonatal opioid withdrawal syndrome; interactions with CNS depressants; risk of serotonin syndrome with serotonergic drugs; adrenal insufficiency; hypotension; seizures; gastrointestinal obstruction; severe cutaneous reactions (acetaminophen); hepatotoxicity (acetaminophen overdose); acute abdominal conditions; impaired mental/physical abilities; elderly/debilitated patients; renal/hepatic impairment. |
| Food/Dietary | Avoid alcohol due to increased risk of acetaminophen hepatotoxicity and additive CNS depression. Grapefruit juice may increase hydrocodone absorption; consider avoiding. No other significant food interactions. |
| Clinical Pearls | Fixed-dose combination of hydrocodone bitartrate (7.5 mg) and acetaminophen (650 mg). Hydrocodone is a schedule II controlled substance with high abuse potential. Acetaminophen hepatotoxicity risk increases above 3 g/day; prescribe no more than 4 doses per day. Monitor for respiratory depression, especially in opioid-naïve patients. Avoid in severe hepatic impairment. Use with caution in patients with COPD, sleep apnea, or concurrent CNS depressants. Consider naloxone co-prescription if high opioid dose or concurrent benzodiazepine use. |
| Patient Advice | Take exactly as prescribed; do not increase dose or frequency. · Do not take with alcohol or other medications containing acetaminophen. · May cause drowsiness or dizziness; avoid driving or operating machinery until effects are known. · Store securely out of reach of children and others; dispose of unused tablets properly. · Seek emergency care for difficulty breathing, severe sedation, or signs of allergic reaction. · Do not abruptly stop after prolonged use; withdrawal symptoms may occur. |
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