XARTEMIS XR
Clinical safety rating: caution
Comprehensive clinical and safety monograph for XARTEMIS XR (XARTEMIS XR).
XARTEMIS XR is a combination of oxycodone (a full mu-opioid receptor agonist) and acetaminophen (a centrally acting analgesic with antipyretic properties via cyclooxygenase inhibition).
| Metabolism | Oxycodone is metabolized primarily via CYP3A4 and CYP2D6; acetaminophen is metabolized primarily via conjugation (glucuronidation, sulfation) and CYP2E1 (minor). |
| Excretion | Renal: oxycodone and metabolites ~8.8% free oxycodone, ~8.8% noroxycodone, ~33% conjugated metabolites; naloxone: extensive hepatic metabolism, <1% excreted unchanged in urine. Fecal: naloxone metabolites ~17%. |
| Half-life | Oxycodone: 5.3-6.6 hours (immediate-release), extended-release formulation shows prolonged absorption with apparent half-life ~7.2-9.6 hours; naloxone: 2-3 hours. |
| Protein binding | Oxycodone: 44-55%; naloxone: 45% (weakly bound to albumin and other plasma proteins). |
| Volume of Distribution | Oxycodone: 1.6-2.6 L/kg; naloxone: 2.0-3.0 L/kg. |
| Bioavailability | Oral: oxycodone 60-87% (extended-release), naloxone <2% due to extensive first-pass metabolism. |
| Onset of Action | Oral: analgesia onset 30-60 minutes; peak effect 1-2 hours. |
| Duration of Action | Oral: 12 hours due to extended-release formulation; for chronic pain, dosing q12h. |
1 tablet (oxycodone 7.5 mg / acetaminophen 325 mg) orally every 12 hours; maximum 2 tablets per day.
| Dosage form | TABLET, EXTENDED RELEASE |
| Renal impairment | GFR 30-89 mL/min: no adjustment; GFR 15-29 mL/min: reduce dose by 50% or extend interval to 24 hours; GFR <15 mL/min: avoid use. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50% or extend interval to 24 hours; Child-Pugh C: avoid use. |
| Pediatric use | Not recommended for pediatric patients under 18 years due to risk of respiratory depression and lack of safety data. |
| Geriatric use | Initiate with 1 tablet every 12 hours; monitor renal and hepatic function; adjust dose based on creatinine clearance and tolerability. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for XARTEMIS XR (XARTEMIS XR).
| Breastfeeding | Excreted in breast milk; M/P ratio not established. Monitor infant for respiratory depression, sedation, and withdrawal. Use only if benefit outweighs risk; consider formula feeding. |
| Teratogenic Risk | Pregnancy Category C. First trimester: Limited data; animal studies show fetal harm (cleft palate, skeletal anomalies) at maternal toxic doses. Second/third trimester: Risk of neonatal opioid withdrawal syndrome (NOWS) and respiratory depression if used near term. Avoid prolonged use. |
| Fetal Monitoring |
■ FDA Black Box Warning
Addiction, abuse, and misuse; life-threatening respiratory depression; accidental ingestion; neonatal opioid withdrawal syndrome; cytochrome P450 3A4 interaction; risks from concomitant use with benzodiazepines or other CNS depressants; hepatotoxicity (acetaminophen component).
| Serious Effects |
Significant respiratory depression; acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment; known or suspected gastrointestinal obstruction (including paralytic ileus); hypersensitivity to oxycodone, acetaminophen, or any component of the product.
| Precautions | 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; risks of overdose; severe hypotension; gastrointestinal obstruction; seizures; severe hypersensitivity reactions; adrenal insufficiency; androgen deficiency; use in elderly, cachectic, or debilitated patients; use in patients with chronic pulmonary disease; use in patients with hepatic or renal impairment; use in pregnancy; use in breastfeeding; risk of serotonin syndrome; risk of severe hypotension; risk of drug dependence. |
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| Monitor maternal respiratory rate, sedation, and bowel function; fetal heart rate monitoring if used during labor; assess neonate for NOWS (e.g., tremors, irritability) post-delivery. |
| Fertility Effects | No human data; animal studies show reduced fertility and implantation delay at high doses. Possible reversible menstrual cycle disruption in chronic opioid users. |