OXTELLAR XR
Clinical safety rating: caution
Comprehensive clinical and safety monograph for OXTELLAR XR (OXTELLAR XR).
Oxtellar XR (oxcarbazepine) is a prodrug that is converted to its active metabolite, MHD (10,11-dihydro-10-hydroxy-carbazepine). The exact mechanism of action is unknown, but it is thought to stabilize neuronal membranes by blocking voltage-gated sodium channels, thereby inhibiting repetitive neuronal firing and reducing the propagation of synaptic impulses.
| Metabolism | Oxcarbazepine is extensively metabolized by cytosolic enzymes to the active metabolite MHD (10,11-dihydro-10-hydroxy-carbazepine). MHD undergoes further glucuronidation and is excreted renally. Minor metabolism via CYP450 enzymes (CYP3A4/5) accounts for a small fraction. |
| Excretion | Primarily renal (70-80% as unchanged drug and metabolites) and fecal (20-30% via biliary excretion). |
| Half-life | Terminal half-life approximately 20-30 hours in adults; after multiple doses, effective half-life is about 24 hours, allowing once-daily dosing. Steady state reached in 4-5 days. |
| Protein binding | Approximately 40% bound to serum proteins, mainly albumin. |
| Volume of Distribution | 0.7-0.8 L/kg, indicating distribution into total body water and some tissue binding. |
| Bioavailability | Extended-release: 80-90% relative to immediate-release. No significant food effect. |
| Onset of Action | Extended-release formulation: Onset of clinical effect (reduction in seizure frequency) typically observed within 2-3 weeks after starting therapy. Peak plasma concentrations occur 4-12 hours post-dose. |
| Duration of Action | 24 hours for extended-release formulation, supporting once-daily dosing. Immediate-release formulation duration is 6-8 hours (not applicable to OXTELLAR XR). |
Oxcarbazepine extended-release (OXTELLAR XR) adult dosing: 600 mg orally twice daily; initial dose 300 mg twice daily, titrate by 300 mg/day increments weekly; maximum 2400 mg/day.
| Dosage form | TABLET, EXTENDED RELEASE |
| Renal impairment | For creatinine clearance <30 mL/min: start at 150 mg twice daily (300 mg/day) and titrate slowly; patients with ESRD on dialysis: not recommended due to lack of data. |
| Liver impairment | Mild to moderate hepatic impairment (Child-Pugh A or B): no dose adjustment required. Severe hepatic impairment (Child-Pugh C): not studied; use with caution. |
| Pediatric use | For patients 6 years and older: oxcarbazepine XR (OXTELLAR XR) is not approved; use immediate-release oxcarbazepine based on weight: 8-10 mg/kg/day initially, titrated over 2 weeks to target 300-600 mg/day for 20-29 kg, 600-900 mg/day for 29.1-39 kg, 900-1200 mg/day for >39 kg. Not recommended under 6 years. |
| Geriatric use | Elderly patients may have reduced clearance; start at 150 mg twice daily (300 mg/day) and titrate slowly. Monitor for hyponatremia, especially in those on diuretics or with low baseline sodium. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for OXTELLAR XR (OXTELLAR XR).
| Breastfeeding | Oxcarbazepine and its active metabolite (MHD) are excreted into breast milk. The infant's plasma MHD concentration is approximately 10-30% of the maternal level, with M/P ratio for MHD estimated at 0.5-1.0. While generally considered compatible with breastfeeding, monitor the infant for drowsiness, poor feeding, and rash. |
| Teratogenic Risk | Oxcarbazepine, the active moiety in Oxtellar XR, is associated with an increased risk of major congenital malformations, particularly neural tube defects, craniofacial defects, and cardiovascular anomalies, when used during the first trimester. In the second and third trimesters, use may be associated with adverse neurodevelopmental outcomes. The risk is dose-dependent and may be potentiated by concomitant antiepileptic drugs. |
■ FDA Black Box Warning
None
| Serious Effects |
["Known hypersensitivity to oxcarbazepine or any component of the formulation","Concurrent use with monoamine oxidase inhibitors (MAOIs) due to risk of hypertensive crisis"]
| Precautions | ["Hyponatremia (sodium <125 mmol/L) can occur, especially in elderly or patients on other hyponatremic drugs; monitor sodium levels","Serious dermatological reactions (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis) - discontinue if rash develops","Suicidal behavior and ideation: monitor for worsening depression or suicidal thoughts","Dizziness, somnolence, ataxia: caution with activities requiring alertness","Multi-organ hypersensitivity reactions: discontinue if suspected","Withdrawal seizures: do not discontinue abruptly","Hematologic effects: rare agranulocytosis, aplastic anemia; monitor CBC if symptoms occur"] |
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| Fetal Monitoring | Monitor maternal serum trough concentrations of MHD periodically, especially during dose adjustments. Perform fetal ultrasound to assess for neural tube defects and major anomalies. Monitor for signs of maternal toxicity such as hyponatremia, dizziness, and ataxia. Monitor infant for withdrawal or adverse effects postpartum. |
| Fertility Effects | Oxcarbazepine may cause hormonal contraceptive failure due to induction of CYP3A4, potentially impairing fertility control. In animal studies, no significant adverse effects on fertility were observed. Clinical data on direct effects on human fertility are limited. |