Dosing and uses of Trileptal, Oxtellar XR (oxcarbazepine)
Adult dosage forms and strengths
tablet
- 150mg
- 300mg
- 600mg
tablet, extended-release
- 150mg
- 300mg
- 600mg
oral suspension
- 300mg/5mL
Partial Seizures
Adjunctive treatment
- Trileptal: 300 mg PO q12hr initially; may increase at weekly intervals by 600 mg/day up to 1200 mg/day
- Oxtellar XR: 600 mg PO qDay initially; may increase at weekly intervals by 600 mg/day increments to target dosage range of 1200-2400 mg qDay
Monotherapy (if converting from other AED)
- Initial: 300 mg PO q12hr; increase by 600 mg/day qWeek up to 2400 mg/day
- Reduce and withdraw concomitant antiepileptic drugs (AEDs) over 3-6 weeks while reaching maximum oxcarbazepine dose in 2-4 weeks
Monotherapy (if AED naive)
- Initial: 300 mg PO q12hr; increase by 300 mg/day q3Day to 1200 mg/day divided q12hr
Bipolar Disorder (Off-label)
300 mg/day PO initially; may titrate to 1800-2400 mg/day maximum
Diabetic Neuropathy (Off-label)
150-300 mg/day PO initially; may increase to 900-1200 mg/day (general recommendation)
Doses up to 1800 mg/day studied, with positive results
Neuralgia/Neuropathy (Off-label)
300 mg PO q8-12hr initially; may adjust dose to 400-2000 mg divided q8-12hr (maximum tolerated or effective dose)
Dosing Considerations
Coadministration with CYP-inducing AEDs (eg, carbamazepine, phenobarbital, phenytoin): Increased oxcarbazepine dose may be required because of decreased exposure to 10-monohydroxy derivative (MHD [active metabolite])
Conversion from immediate release to Oxtellar XR: Higher doses of Oxtellar XR may be required
Dosing Modifications
Renal impairment
- CrCl <30 mL/min: Decrease initial dose by 50%; titrate up slowly
Hepatic impairment
- Mild to moderate: No dose adjustment required
- Severe: Unknown if dosage adjustment necessary
Pediatric dosage forms and strengths
tablet
- 150mg
- 300mg
- 600mg
tablet, extended-release
- 150mg
- 300mg
- 600mg
oral suspension
- 300mg/5mL
Partial Seizures (Adjunctive Treatment)
Trileptal (age 2-4 years)
- Initial: 8-10 mg/kg/day PO divided q12hr; not to exceed 600 mg/day
- <20 kg: May start with16-20 mg/kg/day; may titrate to higher dose over 2-4 weeks; not to exceed 60 mg/kg/day
Trileptal (age 4-16 years)
- Initial: 8-10 mg/kg/day PO divided q12hr; not to exceed 600 mg/day
- Target maintenance dose: May titrate to higher dose over 2 weeks to reach the following dosage ranges
- 20-29 kg: 450 mg PO q12hr
- 29.1-39 kg: 600 mg PO q12hr
- >39 kg: 900 mg PO q12hr
Oxtellar XR (age 6-17 years)
- Initial: 8-10 mg/kg PO qDay; not to exceed 600 mg/day in the first week
- Target maintenance dose: May titrate to higher dose at weekly intervals in 8-10 mg/kg/day increments (not to exceed 600 mg) to reach the following target maintenance dosage ranges over a 2-3 week period
- 20-29 kg: 900 mg PO qDay
- 29.1-39 kg: 1200 mg PO qDay
- >39 kg: 1800 mg PO qDay
Partial Seizures (Monotherapy)
Trileptal (age 4-16 years)
- AED: Initial, 8-10 mg/kg/day PO divided q12hr; may increase qWeek by maximum increment of 10 mg/kg/day
- AED-naive: Initial 8-10 mg/kg/day PO divided q12hr; may increase q3Days by 5 mg/kg/day
- Target maintenance: Weight-based dosing may be as high as 2100 mg/day for >60 kg
- 20-24.99 kg: 600-900 mg/day
- 25-34.99 kg: 900-1200 mg/day
- 35-44.99 kg: 900-1500 mg/day
- 45-49.99 kg: 1200-1500 mg/day
- 50-59.99 kg: 1200-1800 mg/day
- 60-69.99 kg: 1200-2100 mg/day
- 70 kg: 1500-2100 mg/day
Dosing Considerations
Coadministration with CYP-inducing AEDs (eg, carbamazepine, phenobarbital, phenytoin): Increased oxcarbazepine dose may be required because of decreased exposure to MHD (active metabolite)
Conversion from immediate-release to Oxtellar XR: Higher doses of Oxtellar XR may be required
Dosage modifications
Renal impairment
- CrCl <30 mL/min: Decrease initial dose by 50%, titrate up slowly
Hepatic impairment
- Mild to moderate: No dose adjustment required
- Severe: Unknown if dosage adjustment necessary for immediate release dosage form; extended release, not recommended
Geriatric dosage forms and strengths
For extended-release dosage administration consider initial dose of 300-450 mg/day
May increase at weekly intervals to desired effect; not to exceed 2400 mg/day
Trileptal, Oxtellar XR (oxcarbazepine) adverse (side) effects
>10%
Dizziness (30-50%)
Diplopia (30-50%)
Headache (26-30%)
Nausea/vomiting (26-30%)
Nystagmus (26-30%)
Somnolence (26-30%)
Ataxia (10-30%)
Abnormal gait (16-20%)
Tremor (16-20%)
Abdominal pain (11-15%)
Fatigue (11-15%)
Vertigo (11-15%)
Vision abnormalities (11-15%)
1-10%
Dyspepsia (5-6%)
Rash (4%)
Insomnia (2-4%)
Abnormal thinking (<4%)
Hyponatremia (1-3%)
Muscle weakness (1-2%)
Hypotension (<2%)
Speech disorder (1%)
Asthenia
Postmarketing Reports
Angioedema
Anaphylaxis
Multiorgan immune hypersensitivity reaction
Hematic and lymphatic systems: Bone marrow depression, agranulocytosis, aplastic anemia, pancytopenia, neutropenia
Digestive system: Pancreatitis and/or lipase and/or amylase increased
Metabolism and nutrition disorders: Folic acid deficiency, hypothyroidism
Skin and appendages: Erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis
Skeletal: Fractures, decreased bone mineral, osteoporosis
Body as a whole: Multiorgan hypersensitivity disorders characterized by features such as rash, fever, lymphadenopathy, abnormal liver function tests, eosinophilia, and arthralgia
Warnings
Contraindications
Hypersensitivity
Cautions
See FDA warning on potential suicidal behavior; monitor patients for notable changes in behavior that might be associated with suicidal thoughts or depression (notify health-care provider immediately if symptoms occur)
Caution performing tasks that require mental alertness
Potentially fatal skin reactions may occur (eg, Stevens-Johnson syndrome)
May render oral contraceptives ineffective because of metabolic enzyme induction
Discontinue if dermatological reactions occur
Significant hyponatremia may develop (monitor especially in patients at risk of hyponatremia)
Pancytopenia, agranulocytosis, and leukopenia reported rarely
May reduce efficacy of oral contraceptives; additional contraceptive measures recommnended
Long term use has been associated with decreased mineral density, osteopenia, osteoporosis, and fractures, CNS-related adverse effects including difficulty with concentration, psychomotor slowing, speech or language problems, somonolence or fatigue, coordination of abnormalities, including ataxia and gait disturbances
Hypothyroidism reported; monitor thyroid function, especially in children; discontinuation of therapy associated with return of normal thyroxine levels
Patients carrying the HLA-B*1502 allele may be at increased risk for Stevens-Johnson syndrome and epidermal necrolysis
Half-life of primary active metabolite is prolonged 3- to 4-fold and AUC is doubled in patients with CrCl <30 mL/min; adjust dose in these patients
Do not discontinue anticonvulsants abruptly
DRESs
- Drug reaction with eosinophilia and systemic symptoms (DRESS), also known as multi-organ hypersensitivity, reported
- Some of these events have been fatal or life-threatening
- DRESS typically, although not exclusively, presents with fever, rash, and/or lymphadenopathy, in association with other organ system involvement (eg, hepatitis, nephritis, hematologic abnormalities, myocarditis, or myositis), sometimes resembling an acute viral infection
Pregnancy and lactation
Pregnancy category: C
Due to physiologic changes during pregnancy, plasma levels of the active metabolite of oxcarbazepine, MHD, may gradually decrease throughout pregnancy
Lactation: Oxcarbazepine and its active metabolite (MHD) are excreted in human milk; milk-to-plasma concentration ratio of 0.5 was found for both
Because of the potential for serious adverse reactions in nursing infants, a decision should be made as to whether a mother should discontinue nursing or whether she should discontinue use of the drug, taking into account the drug's importance to the mother
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Trileptal, Oxtellar XR (oxcarbazepine)
Mechanism of action
MHD stabilizes neuronal membranes by blocking Na+ channels; this may inhibit repetitive firing and may decrease the propagation of synaptic impulses; may also increase potassium conductance and modulate the activity of high-voltage activated calcium channels
Absorption
Bioavailability: Complete
Peak serum time: 4-6 hr
Distribution
Protein bound: 40% (MHD); primarily bound to albumin
Vd: 49 L
Metabolism
Rapidly reduces by cytosolic enzymes in the liver to active metabolite
Metabolites (active): MHd
Enzymes induced: CYP3A4
Enzymes inhibited: CYP2C19
Elimination
Half-life: 2 hr (immediate-release parent drug); 9 hr (immediate-release derivative MHD); 7-11 hr (extended-release parent drug); 9-11 hr (extended-release derivative MHD)
Excretion: Urine (>95%)
