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. |
| Molecular Weight | Oxycodone: 315.36 Da; Topiramate: 339.36 Da |
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 | Avoid use during first trimester due to risk of neural tube defects and congenital anomalies associated with topiramate and opioid exposure. |
| 2nd trimester | Use only if benefit outweighs risk; may cause fetal opioid dependence and withdrawal; topiramate may impair fetal growth. |
| 3rd trimester | Avoid prolonged use; risk of neonatal opioid withdrawal syndrome (NOWS) and respiratory depression; topiramate may cause metabolic acidosis and fetal growth restriction. |
Clinical note
Comprehensive clinical and safety monograph for XARTEMIS XR (XARTEMIS XR).
| Placental transfer | Both oxycodone and topiramate cross the placenta. Oxycodone reaches fetal plasma concentrations similar to maternal; topiramate accumulates in fetal compartment with higher concentration than maternal. |
| Breastfeeding | Both oxycodone and topiramate are excreted into breast milk. Oxycodone can cause infant sedation and respiratory depression, especially in CYP2D6 ultra-rapid metabolizers. Topiramate may cause diarrhea and irritability in nursing infants. Due to limited safety data, breastfeeding is not recommended during therapy; if used, monitor infant for excessive drowsiness and poor feeding. |
■ 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 |
Hypersensitivity to oxycodone, topiramate, or any component of the formulationSignificant respiratory depressionAcute or severe bronchial asthma in an unmonitored setting or in absence of resuscitative equipmentKnown or suspected gastrointestinal obstruction, including paralytic ileusConcurrent use of monoamine oxidase inhibitors (MAOIs) or within 14 days of such therapyGlaucoma (due to topiramate component)
| 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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| Lactation Rating | L4 - Possibly Hazardous |
| 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 | 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. |
| Food/Dietary | Avoid consumption of alcohol while taking XARTEMIS XR; alcohol can increase the risk of respiratory depression and hepatotoxicity. Grapefruit juice may increase oxycodone levels and is not recommended. High-fat meals may delay absorption but do not significantly alter overall exposure; take consistently with regard to meals. |
| Clinical Pearls | XARTEMIS XR (oxycodone/acetaminophen) is an extended-release formulation intended for around-the-clock management of pain. Do not crush or chew tablets, as this can lead to rapid release and potentially fatal overdose. Monitor for respiratory depression, especially in opioid-naive patients. Avoid concurrent use with other CNS depressants including alcohol. Caution in patients with severe hepatic impairment due to acetaminophen component; maximum daily acetaminophen dose should not exceed 4 g from all sources. |
| Patient Advice | Swallow tablet whole; do not crush, chew, or dissolve. · Take exactly as prescribed; do not increase dose or frequency without consulting your doctor. · Avoid alcohol and other sedatives while taking this medication. · Do not drive or operate machinery until you know how this medicine affects you. · Report any signs of respiratory difficulty, severe drowsiness, or allergic reaction immediately. · Do not stop suddenly without tapering to avoid withdrawal symptoms. · Keep out of reach of children; accidental ingestion can be fatal. |