ANEXSIA 5/325
Clinical safety rating
cautionComprehensive clinical and safety monograph for ANEXSIA 5/325 (ANEXSIA 5/325).
Hydrocodone is a semi-synthetic opioid agonist that binds to mu-opioid receptors in the CNS, inhibiting ascending pain pathways and altering pain perception. Acetaminophen is a para-aminophenol derivative with analgesic and antipyretic effects, primarily through central COX-2 inhibition and activation of descending serotonergic pathways.
| Metabolism | Hydrocodone: primarily hepatic via CYP3A4 and CYP2D6 to active metabolites (hydromorphone). Acetaminophen: hepatic metabolism via conjugation (glucuronidation, sulfation) and CYP2E1-mediated oxidation to toxic NAPQI. |
| Excretion | Oxycodone: renal excretion of metabolites (conjugated and unconjugated) and parent drug; ~10% excreted unchanged. Acetaminophen: renal excretion of metabolites (glucuronide and sulfate conjugates); ~2-4% excreted unchanged. |
| Half-life | Oxycodone: terminal half-life 3.2-4.3 hours (immediate-release); prolonged in hepatic impairment. Acetaminophen: terminal half-life 2-3 hours (therapeutic doses); prolonged in hepatic impairment or overdose. |
| Protein binding | Oxycodone: 38-45% bound to albumin and alpha-1-acid glycoprotein. Acetaminophen: 10-25% bound to albumin at therapeutic concentrations. |
| Volume of Distribution | Oxycodone: Vd 2.0-3.0 L/kg; distributes extensively into tissues. Acetaminophen: Vd 0.8-1.0 L/kg; relatively uniform distribution. |
| Bioavailability | Oxycodone: oral bioavailability 60-87% (immediate-release). Acetaminophen: oral bioavailability 88-98% (therapeutic doses). |
| Onset of Action | Oxycodone: oral immediate-release, 10-15 minutes (analgesic effect). Acetaminophen: oral, 30-60 minutes (antipyretic/analgesic effect). |
| Duration of Action | Oxycodone: immediate-release, 4-6 hours (analgesic effect). Acetaminophen: 4-6 hours (antipyretic/analgesic effect). |
| Molecular Weight | Codeine base: 299.36 Da; Acetaminophen: 151.16 Da |
1-2 tablets orally every 4-6 hours as needed for pain; maximum 8 tablets per day.
| Dosage form | TABLET |
| Renal impairment | GFR 30-50 mL/min: use with caution, increase dosing interval to every 6 hours; GFR <30 mL/min: avoid use due to hydrocodeone accumulation. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50% and monitor; Child-Pugh C: contraindicated. |
| Pediatric use | Not recommended for children under 18 years due to risk of respiratory depression. |
| Geriatric use | Start with lowest dose (1 tablet every 6 hours), monitor renal and hepatic function, and avoid in frail elderly due to increased fall and cognitive impairment risk. |
| 1st trimester | Avoid if possible; associated with neural tube defects and cardiac malformations. |
| 2nd trimester | Avoid due to risk of oligohydramnios and fetal renal impairment. |
| 3rd trimester | Avoid; risk of premature closure of ductus arteriosus and persistent pulmonary hypertension of the newborn. |
Clinical note
Comprehensive clinical and safety monograph for ANEXSIA 5/325 (ANEXSIA 5/325).
| Placental transfer | Both codeine and acetaminophen cross the placenta readily; codeine is metabolized to morphine which accumulates in fetal tissues. |
| Breastfeeding | Limited data; moderate amounts of codeine and acetaminophen appear in breast milk. Use lowest dose for shortest duration. Monitor infant for sedation and respiratory depression. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | First trimester: Associated with increased risk of neural tube defects and cardiovascular malformations; avoid use. Second and third trimesters: Chronic exposure may cause fetal renal toxicity, oligohydramnios, and premature closure of ductus arteriosus. Use only if clearly needed. |
| Fetal Monitoring | Monitor maternal liver function, renal function, and signs of respiratory depression. Monitor fetal growth via ultrasound; assess amniotic fluid index if used chronically. In neonate, observe for withdrawal symptoms (irritability, hypertonia, poor feeding) if used near term. |
| Fertility Effects | Opioids may impair fertility by altering hormone levels (e.g., decreased LH, FSH, testosterone). Paracetamol can affect spermatogenesis at high doses. Limited human data; use with caution in couples planning pregnancy. |
■ FDA Black Box Warning
Risk of addiction, abuse, and misuse; life-threatening respiratory depression; accidental ingestion; neonatal opioid withdrawal syndrome; risks from concomitant use with benzodiazepines or other CNS depressants; and hepatotoxicity from acetaminophen overdose.
| Serious Effects |
Hypersensitivity to codeine or acetaminophenAcute or severe bronchial asthmaRespiratory depressionGastrointestinal obstructionConcurrent use of MAOIsCYP2D6 ultra-rapid metabolizers (for codeine)Children <12 years for post-tonsillectomy/adenoidectomy pain
| Precautions | Risk of opioid 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; adrenal insufficiency; severe hypotension; gastrointestinal obstruction; seizure; and serotonin syndrome. |
| Food/Dietary | Avoid alcohol. Grapefruit juice may enhance side effects; limit intake. Take with food to reduce gastrointestinal discomfort. |
| Clinical Pearls | ANEXSIA 5/325 contains hydrocodone 5 mg and acetaminophen 325 mg. Maximum acetaminophen dose from all sources should not exceed 4 g/day in adults; avoid in severe hepatic impairment. Hydrocodone is a Schedule II controlled substance with abuse potential; monitor for respiratory depression, especially in opioid-naive patients. Use with caution in patients with COPD, sleep apnea, or increased intracranial pressure. Consider naloxone co-prescription for high-risk patients. For acute pain, limit duration to 3-7 days. |
| Patient Advice | Take exactly as prescribed; do not increase dose or frequency without consulting your doctor. · Do not consume alcohol or other sedatives (e.g., benzodiazepines) while taking this medication. · Avoid other products containing acetaminophen (e.g., Tylenol, cold remedies) to prevent liver damage. · This medication may cause drowsiness or dizziness; do not drive or operate machinery until you know how it affects you. · Store securely out of reach of others; dispose of unused medication via drug take-back programs. · Seek emergency help if you have trouble breathing, severe drowsiness, or signs of allergic reaction. |
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