TYLOX-325
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TYLOX-325 (TYLOX-325).
Acetaminophen and oxycodone combination. Acetaminophen inhibits cyclooxygenase (COX) enzymes, primarily in the CNS, reducing prostaglandin synthesis. Oxycodone is a mu-opioid receptor agonist, activating descending pain pathways and altering pain perception.
| Metabolism | Acetaminophen is primarily metabolized via conjugation (glucuronidation and sulfation) and via CYP2E1 (minor pathway forming toxic NAPQI). Oxycodone is metabolized via CYP3A4 (to noroxycodone) and CYP2D6 (to oxymorphone). |
| Excretion | Renal: acetaminophen metabolites (60-70% as glucuronide conjugate, 20-30% as sulfate conjugate, 5-10% as cysteine conjugate, 5% unchanged). Oxycodone: renal (primarily metabolites, <10% unchanged); biliary/fecal: minor (oxycodone metabolites). |
| Half-life | Acetaminophen: 2-3 hours (prolonged in hepatic impairment). Oxycodone: 3-5 hours (extended-release preparation); terminal half-life 4.5-5.5 hours. Clinical context: repeated dosing may lead to accumulation; half-life prolongation in elderly, renal or hepatic disease. |
| Protein binding | Acetaminophen: 10-25% (albumin). Oxycodone: 45% (primarily albumin). |
| Volume of Distribution | Acetaminophen: 0.9-1.0 L/kg; extensive distribution. Oxycodone: 2.6-3.6 L/kg; high tissue penetration including CNS. |
| Bioavailability | Acetaminophen: oral 85-90%. Oxycodone: oral 60-87% (variable first-pass metabolism). |
| Onset of Action | Oral: 10-15 minutes for analgesic effect (oxycodone); antipyretic/analgesic for acetaminophen: 30-60 minutes. |
| Duration of Action | Oral: analgesia 4-6 hours (immediate-release); antipyresis 4-6 hours. Clinical notes: concurrent use with other CNS depressants may prolong effects. |
| Molecular Weight | 351.82 |
1-2 capsules (oxycodone 5-10 mg / acetaminophen 325-650 mg) orally every 4-6 hours as needed for pain; maximum 12 capsules per day.
| Dosage form | CAPSULE |
| Renal impairment | eGFR 30-60 mL/min: administer at reduced frequency (e.g., every 8-12 hours); eGFR <30 mL/min: avoid use or use with extreme caution (reduce dose by 50% and monitor); hemodialysis: not recommended due to acetaminophen accumulation. |
| Liver impairment | Child-Pugh A (mild): no adjustment necessary; Child-Pugh B (moderate): reduce oxycodone dose by 50% and limit acetaminophen to ≤2000 mg/day; Child-Pugh C (severe): contraindicated. |
| Pediatric use | Not approved for children <18 years; weight-based dosing: oxycodone 0.05-0.15 mg/kg/dose (max 5 mg) and acetaminophen 10-15 mg/kg/dose (max 650 mg) orally every 4-6 hours as needed; total daily acetaminophen ≤75 mg/kg/day. |
| Geriatric use | Initiate at lowest dose (e.g., 1 capsule every 6 hours); titrate cautiously; avoid in patients with renal impairment or hepatic dysfunction; monitor for opioid-induced constipation, respiratory depression, and acetaminophen hepatotoxicity; consider alternative non-opioid analgesics if feasible. |
| 1st trimester | Oxycodone/APAP: oxycodone crosses placenta; APAP is generally considered safe at therapeutic doses, but high doses may be hepatotoxic. Avoid chronic use due to risk of opioid dependence. Use only if clearly needed. |
| 2nd trimester | Similar to t1; avoid prolonged use due to risk of preterm labor and maternal dependence. |
| 3rd trimester | Chronic use may lead to neonatal opioid withdrawal syndrome (NOWS). APAP at high doses may cause fetal hepatotoxicity. Use during labor may cause respiratory depression in neonate. |
Clinical note
Comprehensive clinical and safety monograph for TYLOX-325 (TYLOX-325).
| Placental transfer | Oxycodone: Crosses placenta readily; fetal plasma levels approximate maternal levels. APAP: Crosses placenta but generally considered safe at therapeutic doses. |
| Breastfeeding | Oxycodone is excreted into breast milk in low amounts; relative infant dose is about 1.7-6.8% of weight-adjusted maternal dose. APAP is also excreted but considered compatible. Monitor infant for sedation, poor feeding, or respiratory depression. American Academy of Pediatrics considers oxycodone usually compatible with breastfeeding but caution with maternal high doses or prolonged use. Avoid in mothers with impaired metabolism (e.g., CYP2D6 ultrarapid metabolizers) due to risk of opioid toxicity in infant. |
■ 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; interaction with alcohol.
| Serious Effects |
Hypersensitivity to oxycodone, acetaminophen, or any componentSignificant respiratory depressionAcute or severe bronchial asthma in an unmonitored setting or without resuscitative equipmentKnown or suspected gastrointestinal obstruction (including paralytic ileus)Severe hepatic impairmentConcurrent use of monoamine oxidase inhibitors (MAOIs) or within 14 days of such therapy
| Precautions | Respiratory depression, opioid-induced hyperalgesia, adrenal insufficiency, severe hypotension, seizures, serotonin syndrome, hepatotoxicity, risk of overdose with acetaminophen, risks of use in patients with head injury or increased intracranial pressure. |
| Food/Dietary | Avoid alcohol. High-fat meals may delay absorption of oxycodone but do not significantly alter overall exposure. No specific food restrictions beyond alcohol. |
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| Lactation Rating | L3 (Moderately Safe) for short-term use; consider L4 if chronic high-dose or maternal CYP2D6 ultrarapid metabolizer. |
| Teratogenic Risk | Pregnancy Category C. Oxycodone crosses placenta. First trimester: risk of neural tube defects not established; avoid unless benefit outweighs risk. Second/third trimester: chronic use may cause neonatal opioid withdrawal syndrome (NOWS). Third trimester: high doses near term may cause neonatal respiratory depression. |
| Fetal Monitoring | Monitor maternal respiratory status, sedation, bowel function. Fetal: fetal heart rate monitoring during labor if used; assess for NOWS in neonates after chronic in utero exposure. Consider umbilical cord drug levels if indicated. |
| Fertility Effects | No known direct effect on fertility. Chronic opioid use may cause menstrual irregularities via hypothalamic-pituitary-gonadal axis suppression, potentially impairing fertility. |
| Clinical Pearls | Tylox-325 contains oxycodone and acetaminophen. Avoid in patients with known hypersensitivity to opioids or acetaminophen. The maximum daily acetaminophen dose is 4 g; monitor for hepatotoxicity. Use with caution in patients with respiratory compromise, head injury, or increased intracranial pressure. Coadministration with CNS depressants (e.g., benzodiazepines) increases risk of respiratory depression. Constipation is common; prescribe stool softeners prophylactically. Discontinue gradually to avoid withdrawal. |
| Patient Advice | Take exactly as prescribed; do not exceed 4 grams of acetaminophen per day from all sources. · Avoid alcohol while taking this medication. · May cause dizziness or drowsiness; do not drive or operate heavy machinery until you know how this medication affects you. · Do not take with other medications containing acetaminophen without consulting your doctor. · Contact your doctor if you experience signs of liver damage (yellow skin/eyes, dark urine, abdominal pain) or respiratory depression (slow/shallow breathing). · Store securely out of reach of others; this medication can be habit-forming and may be a target for misuse. |