Version May 2024
Dosage guidance:
Safety: Before use, test for the HLA-B*1502 allele in patients at increased genetic risk (eg, those of Asian ancestry, including South Asian patients) for oxcarbazepine-associated Stevens-Johnson syndrome/toxic epidermal necrolysis. Do not initiate oxcarbazepine in patients who test positive for HLA-B*1502 when other options are available (Ref).
Focal (partial) onset seizures:
Note: Monotherapy and adjunctive therapy in the treatment of patients with focal onset seizures with or without secondary generalized tonic-clonic seizures. Avoid use in myoclonic or generalized nonmotor (absence) seizures due to potential to worsen generalized convulsions (Ref).
Oral:
Immediate release: Initial: 300 to 600 mg/day in 2 divided doses. May increase dose by ≤600 mg/day increments at weekly intervals to a maximum dose of 2.4 g/day in 2 to 3 divided doses (Ref).
Extended release: Initial: 600 mg once daily. May increase dose by 600 mg/day increments at weekly intervals to a maximum dose of 2.4 g/day (Ref).
Trigeminal neuralgia (off-label use): Oral: Immediate release: Initial: 300 to 600 mg/day in 2 divided doses; adjust dose based on response and tolerability in increments of 300 mg/day every ≥3 days up to a maximum dose of 1.8 g/day (Ref).
Discontinuation of therapy: In chronic therapy, withdraw gradually over 1 to 6 months based upon individual circumstance to minimize the potential of increased seizure frequency (in patients with epilepsy) unless safety concerns require more rapid withdrawal (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Mild to moderate impairment: There are no dosage adjustments provided in the manufacturer's labeling.
Severe impairment (CrCl <30 mL/minute): Immediate release, Extended release: Therapy should be initiated at one-half the usual starting dose (300 mg daily) and increased slowly to achieve desired clinical response (eg, 300 to 450 mg daily at weekly intervals).
ESRD (on dialysis): Immediate release formulations should be used instead of extended release formulation.
Mild to moderate impairment: No dosage adjustments necessary.
Severe impairment:
Immediate release: There are no dosage adjustments provided in the manufacturer's labeling; use caution (has not been studied).
Extended release: There are no dosage adjustments provided in the manufacturer's labeling; use is not recommended (has not been studied).
Oral: Immediate release: Refer to adult dosing.
Oral: Extended release: Initial: 300 mg or 450 mg once daily; dosage may be increased by 300 to 450 mg/day increments at weekly intervals to desired clinical response.
(For additional information see "Oxcarbazepine: Pediatric drug information")
Dosage guidance:
Dosage form information: Immediate-release preparations (oral suspension and tablets) are interchangeable on a mg per mg basis; immediate-release and extended-release preparations are not bioequivalent and not interchangeable on a mg per mg basis.
Partial-onset seizures, monotherapy:
Infants and Children <4 years: Limited data available: Oral: Immediate release (Trileptal): Initial: 7.5 to 10 mg/kg/day in 2 divided doses; titrate dose in increments of 7.5 to 10 mg/kg/day every 5 to 7 days as tolerated; maximum daily dose: 60 mg/kg/day. If intolerance develops during titration, decrease dose by 5 mg/kg/day as needed. Dosing based on an open-label study and 2 retrospective chart reviews (Ref). The open-label study enrolled patients 1 month to <4 years weighing ≥3 kg; 24 patients were enrolled, of which 10 received oxcarbazepine as monotherapy; oxcarbazepine was well tolerated (Ref).
Children ≥4 years and Adolescents ≤16 years:
Initiation of monotherapy: Patients not receiving concomitant antiseizure drugs: Immediate release (Trileptal):
Initial: Oral: 8 to 10 mg/kg/day in 2 divided doses; usual initial daily dose in adults is 600 mg/day; increase dose every third day by 5 mg/kg/day to achieve the recommended monotherapy maintenance dose by weight, as follows:
Maintenance dose:
20 to <25 kg: Oral: 600 to 900 mg/day in 2 divided doses.
25 to <35 kg: Oral: 900 to 1,200 mg/day in 2 divided doses.
35 to <45 kg: Oral: 900 to 1,500 mg/day in 2 divided doses.
45 to <50 kg: Oral: 1,200 to 1,500 mg/day in 2 divided doses.
50 to <60 kg: Oral: 1,200 to 1,800 mg/day in 2 divided doses.
60 to <70 kg: Oral: 1,200 to 2,100 mg/day in 2 divided doses.
≥70 kg: Oral: 1,500 to 2,100 mg/day in 2 divided doses.
Conversion to monotherapy: Patients receiving concomitant antiseizure drugs: Oral: Initial: 8 to 10 mg/kg/day in 2 divided doses (usual initial daily dose in adults is 600 mg/day), with a simultaneous initial reduction of the dose of concomitant antiseizure drugs; withdraw concomitant antiseizure drugs completely over 3 to 6 weeks, while increasing oxcarbazepine dose as needed by no more than 10 mg/kg/day at approximately weekly intervals; increase oxcarbazepine dose to achieve the recommended monotherapy maintenance dose.
Adolescents ≥17 years: Immediate release (Trileptal):
Initiation of monotherapy: Patients not receiving prior antiseizure drugs: Oral: Initial: 300 mg twice daily. Increase dose by 300 mg/day every third day to a maintenance dose of 1,200 mg/day in 2 divided doses.
Conversion to monotherapy: Patients receiving concomitant antiseizure drugs: Oral: Initial: 300 mg twice daily while simultaneously reducing the dose of concomitant antiseizure drugs. Withdraw concomitant antiseizure drugs completely over 3 to 6 weeks, while increasing the oxcarbazepine dose in increments of 600 mg/day at weekly intervals up to target maintenance dose of 2,400 mg/day in 2 divided doses in about 2 to 4 weeks.
Partial-onset seizures, adjunctive therapy:
Immediate release (Trileptal):
Infants and Children <2 years: Limited data available: Oral: Initial: 7.5 to 10 mg/kg/day in 2 divided doses; titrate dose in increments of 7.5 to 10 mg/kg/day every 5 to 7 days; maximum daily dose: 60 mg/kg/day. If intolerance develops during titration, decrease dose by 5 mg/kg/day as needed (Ref). Dosing based on a multicenter randomized trial, an open-label study, and 2 retrospective chart reviews; both prospective studies enrolled patients 1 month to <4 years weighing ≥3 kg. The multicenter study randomized 128 patients to either high-dose (60 mg/kg/day) or low-dose (10 mg/kg/day) regimens; patients receiving the high-dose regimen had a significantly greater decrease in seizure frequency per 24 hours compared to the low dose group. Oxcarbazepine was generally well tolerated; however, the high dose group experienced more adverse effects although they were generally mild in severity (Ref).
Children 2 to <4 years:
Patient weight <20 kg: Oral: Initial: 8 to 10 mg/kg/day in 2 divided doses; may consider initiating at a higher dose of 16 to 20 mg/kg/day due to increased clearance in this age; increase dose slowly over 2 to 4 weeks; maximum daily dose: 60 mg/kg/day.
Patient weight ≥20 kg: Oral: Initial: 8 to 10 mg/kg/day in 2 divided doses (usual maximum initial daily dose: 600 mg/day); increase dose slowly over 2 to 4 weeks; maximum daily dose: 60 mg/kg/day.
Note: In children 2 to 4 years of age, 50% of patients were titrated to a final dose of at least 55 mg/kg/day with target dose of 60 mg/kg/day. Due to a higher drug clearance, children 2 to <4 years of age may require up to twice the dose per body weight compared to adults.
Children ≥4 years and Adolescents ≤16 years:
Initial: Oral: 8 to 10 mg/kg/day in 2 divided doses; usual maximum initial daily dose: 600 mg/day; increase dose slowly over 2 weeks to the target maintenance dose by weight, as follows:
Maintenance dose:
20 to 29 kg: Oral: 900 mg/day in 2 divided doses.
29.1 to 39 kg: Oral: 1,200 mg/day in 2 divided doses.
>39 kg: Oral: 1,800 mg/day in 2 divided doses.
Note: Use of these pediatric target maintenance doses in one clinical trial resulted in doses ranging from 6 to 51 mg/kg/day (median dose: 31 mg/kg/day) in pediatric patients 4 to 16 years of age (Ref). Due to a higher drug clearance, children 4 to ≤12 years of age may require a 50% higher dose per body weight compared to adults.
Adolescents ≥17 years: Oral: Initial: 300 mg twice daily; dose may be increased by ≤600 mg/day increments at weekly intervals up to target maintenance dose of 1,200 mg/day in 2 divided doses. Although doses >1,200 mg/day were somewhat more efficacious, most patients were unable to tolerate 2,400 mg/day (due to CNS effects).
Extended release (Oxtellar XR):
Children and Adolescents 6 to ≤16 years:
Initial: Oral: 8 to 10 mg/kg/day once daily; maximum initial daily dose: 600 mg/day during the first week of therapy. Increase dose at weekly intervals in 8 to 10 mg/kg/day increments over 2 to 3 weeks (maximum dosage incremental increase: 600 mg/dose) to the target maintenance dose based on weight, as follows:
Maintenance dose:
20 to 29 kg: Oral: 900 mg once daily.
29.1 to 39 kg: Oral: 1,200 mg once daily.
>39 kg: Oral: 1,800 mg once daily.
Adolescents ≥17 years: Oral: Initial: 600 mg once daily; dosage may be increased by 600 mg/day increments at weekly intervals. Recommended daily dose is 1,200 to 2,400 mg once daily. Although daily doses >1,200 mg daily were somewhat more efficacious, most patients were unable to tolerate 2,400 mg/day (due to CNS effects).
Conversion from immediate release (Trileptal) to extended release (Oxtellar XR): Children ≥6 years and Adolescents: Higher doses of Oxtellar XR may be necessary; on a mg per mg basis dosage forms are not bioequivalent.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Mild to moderate impairment: There are no dosage adjustments provided in the manufacturer's labeling.
Severe impairment (CrCl <30 mL/minute):
Immediate release (eg, Trileptal): Children ≥2 years and Adolescents: Oral: Therapy should be initiated at lower starting dose (eg, one-half the usual starting dose) and increased slowly to achieve desired clinical response.
Extended release (eg, Oxtellar XR):
Children 6 to ≤16 years: Oral: There are no specific recommendations for this age group in the manufacturer's labeling; in older pediatric patients, initial dosage reductions and a slower titration are recommended.
Adolescents ≥17 years: Oral: Therapy should be initiated at one-half the usual starting dose (300 mg/day) and increased slowly at weekly intervals in 300 to 450 mg/day increments to achieve desired clinical response.
End-stage kidney disease (ESKD) (on dialysis): Immediate-release formulations should be used instead of extended-release formulation.
Children ≥2 years and Adolescents:
Mild to moderate impairment: Immediate release (eg, Trileptal), Extended release (eg, Oxtellar XR): No dosage adjustments are recommended.
Severe impairment:
Immediate release (eg, Trileptal): There are no dosage adjustments in the manufacturer's labeling; has not been studied; use caution particularly if concomitant antiseizure therapy
Extended release (eg, Oxtellar XR): There are no dosage adjustment in the manufacturer's labeling; use is not recommended (has not been studied).
Agranulocytosis, leukopenia (Ref), aplastic anemia, pancytopenia (Ref), and thrombocytopenia (Ref) have been reported with oxcarbazepine. One retrospective study in pediatric patients in Korea reported an oxcarbazepine-induced leukopenia rate of ~5% which led to pancytopenia in two patients (1%) (Ref). Leukopenia often reverses, even with continued treatment; however, some cases may require dose reduction or discontinuation (Ref). The prevalence of thrombocytopenia is reported to be ~2% (Ref).
Mechanism: Unknown; may be due to immune-mediated or toxic mechanisms, similar to carbamazepine due to structural similarity (Ref). Thrombocytopenia may be due to hyper-destruction of platelets (Ref).
Onset: Varied; days or months after initiation of therapy. In one study, onset of leukopenia was observed 11 days to 14 years after initiation (Ref).
Risk factors:
• Leukopenia: Possible male predominance (Ref)
• Thrombocytopenia: Correlation with daily dose but not serum concentration (Ref)
A variety of delayed hypersensitivity reactions, ranging from mild with maculopapular eruption (also known as morbilliform rash) to severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome, toxic epidermal necrolysis (SJS/TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported (Ref).
Mechanism: Non–dose-related; immunologic. Delayed hypersensitivity reactions, including maculopapular eruptions and SCARs are T-cell-mediated (Ref).
Onset: Delayed hypersensitivity reactions: Varied. Maculopapular rash usually occurs within 2 to 4 weeks after initiation (Ref). SCARs usually occur 1 to 8 weeks after initiation (Ref); reexposure may lead to more rapid onset (usually with 1 to 4 days) (Ref).
Risk factors:
• HLA-B*1502 allele increases risk of SJS/TEN especially in South-East Asian populations (Ref); avoidance of oxcarbazepine should be considered in oxcarbazepine-naive patients who test positive for HLA-B*1502 (Ref).
• Viral reactivation, in particular human herpesvirus 6 (HHV-6) reactivation may be associated with a prolonged and more severe course of DRESS (Ref).
• High degree of cross-reactivity exists between aromatic antiseizure medications, including phenytoin, carbamazepine, phenobarbital, primidone, and oxcarbazepine (Ref).
Hyponatremia is a common adverse reaction with oxcarbazepine in adult and pediatric patients. The reported incidence of oxcarbazepine-induced hyponatremia varies greatly in the literature (Ref). In a cohort study of adult patients with epilepsy treated with either carbamazepine or oxcarbazepine, hyponatremia (serum sodium ≤134 mmol/L) occurred in 46% of patients receiving oxcarbazepine; 22% of those cases classified as severe hyponatremia (≤128 mmol/L) (Ref). An earlier study demonstrated an incidence of 30% and 12% for hyponatremia and severe hyponatremia, respectively (Ref). In a study of pediatric patients, hyponatremia without clinical symptoms occurred in 27% of patients receiving oxcarbazepine; 3% of cases were severe (Ref). Hyponatremia associated with oxcarbazepine in the clinical trials was mostly asymptomatic. Study patients were monitored frequently with interventions such as reduction in fluid intake, dose reductions, or discontinuation of oxcarbazepine. Cases of symptomatic hyponatremia have been reported mostly with mild symptoms (eg, dizziness, diplopia, confusion, lethargy, headache), but symptoms can lead to seizures and in very severe cases coma (Ref).
Mechanism: Dose-related; unknown but may be caused by direct activation or enhanced sensitivity of vasopressin V2 receptors (V2R), which play a key role in water reabsorption, as well as a direct effect on the renal collecting tubules. Hyponatremia does not appear to result from increased release of antidiuretic hormone (Ref).
Onset: Varied; clinically significant hyponatremia generally occurs during the first 3 months of treatment; although, there are reports of patients who developed a serum sodium <125 mmol/L more than 1 year after initiation of treatment.
Risk factors:
• High doses/serum drug concentrations (Ref)
• Females (Ref)
• Age >40 years (Ref)
• Concurrent use of other antiseizure medications (Ref)
• Concurrent use of medications known to decrease serum sodium (eg, diuretics)
• The study in pediatric patients did not find dose, serum levels, age, or concurrent use of other antiseizure medications to be predictive for the development of hyponatremia (Ref)
Oxcarbazepine is associated with CNS effects in adult and pediatric patients, including cognitive symptoms (eg, psychomotor slowing, lack of concentration, speech disturbance or language problems), dizziness, drowsiness, fatigue, and coordination abnormalities (eg, ataxia and abnormal gait). A postmarketing surveillance study obtained from dispensed British National Health Service prescriptions reported that the most frequent clinical reason for discontinuation was drowsiness/sedation (~2.5% of cohort) (Ref). According to the manufacturer, psychiatric effects such as manic behavior and psychosis have been reported. However, oxcarbazepine has also been associated with positive mood-stabilizing properties (Ref).
Mechanism: May be dose-related; related to pharmacologic action.
Risk factors:
• May be dose related
• Concurrent administration of other CNS sedating agents
Antiseizure medications have been associated with suicidal ideation and suicidal tendencies. However, the FDA meta-analysis has been criticized due to several important limitations (Ref). The risk of suicide is increased in epilepsy (Ref), but the occurrence of suicidal ideation/tendencies in epilepsy is multifactorial. While some antiseizure medications (but not all) have been associated with treatment-emergent psychiatric effects such as anxiety and depression, other factors such as post-ictal suicidal behavior and pertinent patient history must also be evaluated to provide an accurate assessment of risk for any individual drug (Ref).
Onset: Varied; peak incidence of suicidality across antiseizure medications (not specific to individual agents) has been noted to occur between 1 and 12 weeks of therapy (Ref). A review of clinical trials noted that risk extended from 1 week to 24 weeks of therapy, corresponding to the duration of most trials.
Risk factors:
• History of depression (Ref)
• Use in conditions other than epilepsy or bipolar disorder (Ref)
• In patients with bipolar disorder, risk for repeat suicide attempt was increased in patients with alcohol/substance abuse disorder, rapid cycling, and earlier age at onset of first manic episode (Ref)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Incidence of adverse effects is from monotherapy and adjunctive antiseizure drug studies. Incidence in children was similar. Incidence is reported for immediate release (IR) formulation unless otherwise noted as extended release (ER).
>10%:
Endocrine & metabolic: Hyponatremia (ER, IR: 1% to 46%) (Berghuis 2017, Dong 2005, Holtman 2002) (table 1)
|
Drug (Oxcarbazepine) |
Comparator (Carbamazepine) |
Placebo |
Population |
Dose |
Dosage Form |
Number of Patients (Oxcarbazepine) |
Number of Patients (Carbamazepine [C] or Placebo [P]) |
Comments |
|---|---|---|---|---|---|---|---|---|
|
46% |
26% |
N/A |
N/A |
N/A |
N/A |
289 |
C: 1,132 |
Sodium level ≤134 mEq/L; Berghuis 2017 |
|
30% |
14% |
N/A |
N/A |
N/A |
N/A |
97 |
C: 451 |
Sodium level ≤134 mEq/L; Dong 2005 |
|
27% |
N/A |
N/A |
Children and adolescents |
N/A |
N/A |
75 |
N/A |
Sodium level ≤135 mEq/L; Holtman 2002 |
|
22% |
7% |
N/A |
N/A |
N/A |
N/A |
289 |
C: 1,132 |
Sodium level ≤128 mEq/L; Berghuis 2017 |
|
12% |
3% |
N/A |
N/A |
N/A |
N/A |
97 |
C: 451 |
Sodium level ≤128 mEq/L; Dong 2005 |
|
10% |
N/A |
2% |
N/A |
1,200 mg/day |
Extended-release oral |
N/A |
N/A |
Shift in serum sodium concentrations from normal to low (<135 mEq/L) |
|
7% |
N/A |
2% |
N/A |
2,400 mg/day |
Extended-release oral |
N/A |
N/A |
Shift in serum sodium concentrations from normal to low (<135 mEq/L) |
|
5% |
N/A |
N/A |
Adults |
2,400 mg/day |
Immediate-release oral |
86 |
N/A |
Monotherapy in patients previously treated with other antiseizure medications |
|
3% |
N/A |
0% |
N/A |
N/A |
Immediate-release oral |
1,524 |
N/A |
Sodium of less than 125 mmol/L at some point during treatment |
|
3% |
N/A |
1% |
Adults |
600 mg/day |
Immediate-release oral |
163 |
P: 166 |
Adjunctive Therapy |
|
3% |
N/A |
N/A |
Children and adolescents |
N/A |
N/A |
75 |
N/A |
Sodium level ≤125 mEq/L; Holtman 2002 |
|
1% |
N/A |
1% |
Adults |
1,200 mg/day |
Immediate-release oral |
171 |
P: 166 |
Adjunctive Therapy |
|
1% |
N/A |
N/A |
N/A |
N/A |
Extended-release oral |
N/A |
N/A |
Clinically significant hyponatremia |
Gastrointestinal: Abdominal pain (5% to 13%), nausea (15% to 25%), vomiting (ER: 15%; IR: 7% to 33%)
Nervous system: Ataxia (ER: 1% to 3%; IR: 2% to 17%) (table 2), dizziness (ER, IR: 20% to 41%) (table 3), drowsiness (ER: 12% to 14%; IR: 19% to 31%) (table 4), fatigue (ER: 3% to 6%; IR: 12% to 21%) (table 5), headache (ER: 8% to 15%; IR 13% to 32%), vertigo (2% to 12%)
|
Drug (Oxcarbazepine) |
Placebo |
Population |
Dose |
Dosage Form |
Number of Patients (Oxcarbazepine) |
Number of Patients (Placebo) |
Comments |
|---|---|---|---|---|---|---|---|
|
13% |
4% |
Children and adolescents |
N/A |
Immediate-release oral |
171 |
139 |
Adjunctive therapy/monotherapy in patients previously treated with other antiseizure medications |
|
17% |
5% |
Adults |
1,200 mg/day |
Immediate-release oral |
171 |
166 |
Adjunctive Therapy |
|
9% |
5% |
Adults |
600 mg/day |
Immediate-release oral |
163 |
166 |
Adjunctive Therapy |
|
7% |
N/A |
Adults |
2,400 mg/day |
Immediate-release oral |
86 |
N/A |
Monotherapy in patients previously treated with other antiseizure medications |
|
5% |
0% |
Adults |
N/A |
Immediate-release oral |
55 |
49 |
Monotherapy in patients not previously treated with other antiseizure medications |
|
4% |
2% |
Adults |
N/A |
Immediate-release oral |
55 |
49 |
Monotherapy in patients not previously treated with other antiseizure medications; defined as "abnormal coordination" |
|
3% |
1% |
Adults |
1,200 mg/day |
Extended-release oral |
122 |
121 |
Patients receiving concomitant antiseizure medications |
|
3% |
1% |
Adults |
1,200 mg/day |
Immediate-release oral |
171 |
166 |
Adjunctive Therapy; defined as "abnormal coordination" |
|
2% |
N/A |
Adults |
2,400 mg/day |
Immediate-release oral |
86 |
N/A |
Monotherapy in patients previously treated with other antiseizure medications; defined as "abnormal coordination" |
|
1% |
1% |
Adults |
600 mg/day |
Immediate-release oral |
163 |
166 |
Adjunctive Therapy; defined as "abnormal coordination" |
|
1% |
1% |
Adults |
2,400 mg/day |
Extended-release oral |
123 |
121 |
Patients receiving concomitant antiseizure medications |
|
Drug (Oxcarbazepine) |
Placebo |
Population |
Dose |
Dosage Form |
Number of Patients (Oxcarbazepine) |
Number of Patients (Placebo) |
Comments |
|---|---|---|---|---|---|---|---|
|
28% |
8% |
Children and adolescents |
N/A |
Immediate-release oral |
171 |
139 |
Adjunctive therapy/monotherapy in patients previously treated with other antiseizure medications |
|
41% |
15% |
Adults |
2,400 mg/day |
Extended-release oral |
123 |
121 |
Patients receiving concomitant antiseizure medications |
|
32% |
13% |
Adults |
1,200 mg/day |
Immediate-release oral |
171 |
166 |
Adjunctive Therapy |
|
28% |
N/A |
Adults |
2,400 mg/day |
Immediate-release oral |
86 |
N/A |
Monotherapy in patients previously treated with other antiseizure medications |
|
26% |
13% |
Adults |
600 mg/day |
Immediate-release oral |
163 |
166 |
Adjunctive Therapy |
|
22% |
6% |
Adults |
N/A |
Immediate-release oral |
55 |
49 |
Monotherapy in patients not previously treated with other antiseizure medications |
|
20% |
15% |
Adults |
1,200 mg/day |
Extended-release oral |
122 |
121 |
Patients receiving concomitant antiseizure medications |
|
Drug (Oxcarbazepine) |
Placebo |
Population |
Dose |
Dosage Form |
Number of Patients (Oxcarbazepine) |
Number of Patients (Placebo) |
Comments |
|---|---|---|---|---|---|---|---|
|
31% |
13% |
Children and adolescents |
N/A |
Immediate-release oral |
171 |
139 |
Adjunctive therapy/monotherapy in patients previously treated with other antiseizure medications |
|
28% |
12% |
Adults |
1,200 mg/day |
Immediate-release oral |
171 |
166 |
Adjunctive Therapy |
|
20% |
12% |
Adults |
600 mg/day |
Immediate-release oral |
163 |
166 |
Adjunctive Therapy |
|
19% |
N/A |
Adults |
2,400 mg/day |
Immediate-release oral |
86 |
N/A |
Monotherapy in patients previously treated with other antiseizure medications |
|
14% |
9% |
Adults |
2,400 mg/day |
Extended-release oral |
123 |
121 |
Patients receiving concomitant antiseizure medications |
|
12% |
9% |
Adults |
1,200 mg/day |
Extended-release oral |
122 |
121 |
Patients receiving concomitant antiseizure medications |
|
Drug (Oxcarbazepine) |
Placebo |
Population |
Dose |
Dosage Form |
Number of Patients (Oxcarbazepine) |
Number of Patients (Placebo) |
Comments |
|---|---|---|---|---|---|---|---|
|
13% |
9% |
Children and adolescents |
N/A |
Immediate-release oral |
171 |
139 |
Adjunctive therapy/monotherapy in patients previously treated with other antiseizure medications |
|
21% |
N/A |
Adults |
2,400 mg/day |
Immediate-release oral |
86 |
N/A |
Monotherapy in patients previously treated with other antiseizure medications |
|
15% |
7% |
Adults |
600 mg/day |
Immediate-release oral |
163 |
166 |
Adjunctive Therapy |
|
12% |
7% |
Adults |
1,200 mg/day |
Immediate-release oral |
171 |
166 |
Adjunctive Therapy |
|
6% |
1% |
Adults |
1,200 mg/day |
Extended-release oral |
122 |
121 |
Patients receiving concomitant antiseizure medications |
|
3% |
1% |
Adults |
2,400 mg/day |
Extended-release oral |
123 |
121 |
Patients receiving concomitant antiseizure medications |
Ophthalmic: Diplopia (ER: 10% to 13%; IR: 12% to 30%), nystagmus disorder (ER: 3%; IR: 2% to 20%), visual disturbance (ER: 1% to 3%; IR: 4% to 14%)
1% to 10%:
Cardiovascular: Chest pain (2%), edema (2%), hypotension (1%), lower extremity edema (2%)
Dermatologic: Acne vulgaris (1% to 2%), diaphoresis (3%), skin rash (4%)
Endocrine & metabolic: Hot flash (2%), increased thirst (2%), weight gain (2%)
Gastrointestinal: Anorexia (5%), constipation (4% to 5%), diarrhea (7%), dysgeusia (5%), dyspepsia (ER, IR: 2% to 6%), gastritis (ER, IR: 2% to 3%), toothache (2%), upper abdominal pain (ER: 3%), xerostomia (3%)
Genitourinary: Urinary frequency (2%), urinary tract infection (5%), vaginitis (2%)
Hematologic & oncologic: Bruise (4%), lymphadenopathy (2%), purpuric rash (2%), rectal hemorrhage (2%)
Hypersensitivity: Hypersensitivity reaction (2%)
Infection: Infection (2%), viral infection (7%),
Nervous system: Abnormal gait (ER: ≤3%; IR: 5% to 10%) (table 6), abnormality in thinking (2%), amnesia (4% to 5%), anxiety (7%), balance impairment (ER: 7%), confusion (7%), dysmetria (1% to 2%), emotional lability (3% to 8%), falling (4%), feeling abnormal (1%), hypoesthesia (3%), insomnia (2% to 6%), lack of concentration (2%) (table 7), myasthenia (1% to 2%), nervousness (2% to 7%), seizure (2%; decreased seizure threshold [exacerbation of seizures]: 5%), speech disturbance (1% to 3%) (table 8)
|
Drug (Oxcarbazepine) |
Placebo |
Population |
Dose |
Dosage Form |
Number of Patients (Oxcarbazepine) |
Number of Patients (Placebo) |
Comments |
|---|---|---|---|---|---|---|---|
|
8% |
3% |
Children and adolescents |
N/A |
Immediate-release oral |
171 |
139 |
Adjunctive therapy/monotherapy in patients previously treated with other antiseizure medications |
|
10% |
1% |
Adults |
1,200 mg/day |
Immediate-release oral |
171 |
166 |
Adjunctive Therapy |
|
5% |
1% |
Adults |
600 mg/day |
Immediate-release oral |
163 |
166 |
Adjunctive Therapy |
|
3% |
1% |
Adults |
1,200 mg/day |
Extended-release oral |
122 |
121 |
Patients receiving concomitant antiseizure medications |
|
0% |
1% |
Adults |
2,400 mg/day |
Extended-release oral |
123 |
121 |
Patients receiving concomitant antiseizure medications |
|
Drug (Oxcarbazepine) |
Placebo |
Population |
Dose |
Dosage Form |
Number of Patients (Oxcarbazepine) |
Number of Patients (Placebo) |
Comments |
|---|---|---|---|---|---|---|---|
|
2% |
1% |
Children and adolescents |
N/A |
Immediate-release oral |
171 |
139 |
Adjunctive therapy/monotherapy in patients previously treated with other antiseizure medications |
|
Drug (Oxcarbazepine) |
Placebo |
Population |
Dose |
Dosage Form |
Number of Patients (Oxcarbazepine) |
Number of Patients (Placebo) |
Comments |
|---|---|---|---|---|---|---|---|
|
3% |
1% |
Children and adolescents |
N/A |
Immediate-release oral |
171 |
139 |
Adjunctive therapy/monotherapy in patients previously treated with other antiseizure medications |
|
2% |
N/A |
Adults |
2,400 mg/day |
Immediate-release oral |
86 |
N/A |
Monotherapy in patients previously treated with other antiseizure medications |
|
1% |
0% |
Adults |
1,200 mg/day |
Immediate-release oral |
171 |
166 |
Adjunctive Therapy |
|
1% |
0% |
Adults |
600 mg/day |
Immediate-release oral |
163 |
166 |
Adjunctive Therapy |
Neuromuscular & skeletal: Asthenia (ER, IR: 2% to 7%), back pain (4%), muscle spasm (2%), sprain (2%), tremor (ER, IR: 4% to 8%)
Ophthalmic: Blurred vision (ER: 4%)
Otic: Otalgia (2%), otic infection (2%)
Respiratory: Bronchitis (3%), cough (5%), epistaxis (4%), nasopharyngitis (ER: 3%), pharyngitis (3%), pneumonia (2%), pulmonary infection (4%), rhinitis (10%), sinusitis (ER, IR: 3% to 4%), upper respiratory tract infection (7% to 10%)
Miscellaneous: Fever (3%)
<1%: Nervous system: Suicidal ideation, suicidal tendencies
Frequency not defined:
Cardiovascular: Bradycardia, cardiac failure, flushing, hypertension, orthostatic hypotension, palpitations, syncope, tachycardia
Dermatologic: Alopecia, contact dermatitis, eczema, erythematosus rash, facial rash, folliculitis, genital pruritus, maculopapular rash, miliaria, psoriasis, skin photosensitivity, vitiligo
Endocrine & metabolic: Change in libido, decreased T4, heavy menstrual bleeding, hyperglycemia, hypocalcemia, hypoglycemia, hypokalemia, increased gamma-glutamyl transferase, intermenstrual bleeding, weight loss
Gastrointestinal: Aphthous stomatitis, biliary colic, blood in stool, cholelithiasis, colitis, duodenal ulcer, dysphagia, enteritis, eructation, esophagitis, flatulence, gastric ulcer, gingival hemorrhage, gingival hyperplasia, hematemesis, hemorrhoids, hiccups, increased appetite, retching, sialadenitis, stomatitis
Genitourinary: Dysuria, hematuria, leukorrhea
Hepatic: Increased liver enzymes
Nervous system: Aggressive behavior, apathy, aphasia, aura, cerebral hemorrhage, delirium, delusion, dystonia, euphoria, extrapyramidal reaction, hemiplegia, hyperreflexia, hypertonia, hyporeflexia, hypotonia, hysteria, impaired consciousness, intoxicated feeling, malaise, manic behavior, migraine, neuralgia, nightmares, panic disorder, paralysis, personality disorder, precordial pain, psychomotor retardation, psychosis, rigors, stupor, voice disorder
Neuromuscular & skeletal: Hyperkinetic muscle activity, hypokinesia, right hypochondrium pain, systemic lupus erythematosus, tetany
Ophthalmic: Accommodation disturbance, blepharoptosis, cataract, conjunctival hemorrhage, hemianopia, mydriasis, ocular edema, photophobia, scotoma, xerophthalmia
Otic: Otitis externa
Renal: Nephrolithiasis, polyuria, renal pain
Respiratory: Asthma, dyspnea, laryngismus, pleurisy
Postmarketing:
Cardiovascular: Atrioventricular block
Dermatologic: Acute generalized exanthematous pustulosis, erythema multiforme, Stevens-Johnson syndrome (Chung 2021), toxic epidermal necrolysis (Chung 2021), urticaria (Kim 2020)
Endocrine & metabolic: Hypothyroidism, SIADH
Gastrointestinal: Increased serum amylase, increased serum lipase, pancreatitis
Genitourinary: Priapism (Negin 2005)
Hematologic & oncologic: Agranulocytosis, aplastic anemia, leukopenia (Jung 2019, Milia 2008), pancytopenia (Calamaras 2007, Jung 2019), thrombocytopenia (Tutor-Crespo 2007)
Hepatic: Hepatitis (Hsu 2010)
Hypersensitivity: Anaphylaxis, angioedema (Knudsen 2007)
Immunologic: Drug reaction with eosinophilia and systemic symptoms (Chung 2021)
Nervous system: Dysarthria
Neuromuscular & skeletal: Bone fracture (long-term therapy) (Cheng 2019, Vestergaard 2004), decreased bone mineral density (long-term therapy), osteoporosis (long-term therapy)
Ophthalmic: Oculogyric crisis (Gatzonis 1999)
Otic: Tinnitus (Hamed 2017)
Hypersensitivity to oxcarbazepine, eslicarbazepine acetate, or any component of the formulation.
Disease-related concerns:
• Cardiovascular disease: Clinical trials excluded patients with significant cardiovascular disease or ECG abnormalities. Monitor body weight/fluid retention in patients with HF; evaluate serum sodium with worsening cardiac function or fluid retention.
• Renal impairment: Single-dose studies show that half-life of the primary active metabolite is prolonged 3- to 4-fold and AUC is doubled in patients with CrCl <30 mL/minute; dose adjustment required in these patients.
• Seizure disorder: Exacerbation of or new onset primary generalized seizures has been reported, particularly in children. In case of seizure aggravation, discontinue oxcarbazepine.
Other warnings/precautions:
• Withdrawal: Antiseizure medications should not be discontinued abruptly because of the possibility of increasing seizure frequency; therapy should be withdrawn gradually to minimize the potential of increased seizure frequency, unless safety concerns require a more rapid withdrawal.
Trileptal and Oxtellar XR are not bioequivalent and not interchangeable on a mg-per-mg basis; systemic absorption and resulting serum concentrations are lower with once-daily Oxtellar XR compared to twice-daily Trileptal when administered at the same total daily dose; higher doses of Oxtellar XR may be necessary.
Some dosage forms may contain propylene glycol; in neonates, large amounts of propylene glycol delivered orally, intravenously (eg, >3,000 mg/day), or topically have been associated with potentially fatal toxicities which can include metabolic acidosis, seizures, renal failure, and CNS depression; toxicities have also been reported in children and adults including hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Shehab 2009).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Suspension, Oral:
Trileptal: 300 mg/5 mL (250 mL) [contains alcohol, usp, methyl hydroxybenzoate, propyl hydroxybenzoate, propylene glycol, saccharin sodium; lemon flavor]
Generic: 300 mg/5 mL (250 mL)
Tablet, Oral:
Trileptal: 150 mg, 300 mg, 600 mg [scored]
Generic: 150 mg, 300 mg, 600 mg
Tablet Extended Release 24 Hour, Oral:
Oxtellar XR: 150 mg, 300 mg, 600 mg
May be product dependent
Suspension (OXcarbazepine Oral)
300 mg/5 mL (per mL): $1.09 - $1.14
Suspension (Trileptal Oral)
300 mg/5 mL (per mL): $2.29
Tablet, 24-hour (Oxtellar XR Oral)
150 mg (per each): $10.84
300 mg (per each): $15.05
600 mg (per each): $27.56
Tablets (OXcarbazepine Oral)
150 mg (per each): $0.68 - $1.45
300 mg (per each): $1.01 - $2.64
600 mg (per each): $2.01 - $4.85
Tablets (Trileptal Oral)
150 mg (per each): $5.21
300 mg (per each): $9.52
600 mg (per each): $17.50
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Suspension, Oral:
Trileptal: 60 mg/mL (250 mL) [contains alcohol, usp, methylparaben, polyethylene glycol (macrogol), propylene glycol, propylparaben, saccharin sodium]
Tablet, Oral:
Trileptal: 300 mg, 600 mg
Generic: 150 mg, 300 mg, 600 mg
Oral:
Immediate release: Administer twice daily without regard to meals.
Suspension: Prior to using for the first time, firmly insert the plastic adapter provided with the bottle. Cover adapter with child-resistant cap when not in use. Shake bottle for at least 10 seconds, remove child-resistant cap, and insert the oral dosing syringe provided to withdraw appropriate dose. Dose may be taken directly from oral syringe or may be mixed in a small glass of water immediately prior to swallowing. Rinse syringe with warm water after use and allow to dry thoroughly. Discard any unused portion after 7 weeks of first opening bottle.
Extended release: Administer once daily on an empty stomach at least 1 hour before or 2 hours after food. Swallow whole; do not cut, crush, or chew the tablets.
Bariatric surgery: Some institutions may have specific protocols that conflict with these recommendations; refer to institutional protocols as appropriate. IR and oral suspension formulations are available. If safety and efficacy can be effectively monitored, no change in formulation or administration is required after bariatric surgery; however, conversion to an IR or suspension formulation is advised for high-risk labeled and off-label indications.
Oral:
Immediate release: May be taken without regard to meals
Suspension: Prior to using for the first time, firmly insert the manufacturer supplied plastic adapter into the neck of the bottle; cover the adapter with child-resistant cap when not in use; shake suspension well (for at least 10 seconds) before use; use manufacturer supplied oral syringe to withdraw appropriate dose; dose may be administered directly from syringe or mixed in a small amount of water immediately prior to use; after use, rinse oral syringe with warm water and allow to dry thoroughly; discard any unused portion 7 weeks after first opening bottle
Extended release: Administer on an empty stomach at least 1 hour before or 2 hours after food. Swallow whole; do not cut, crush, or chew the tablets.
Hazardous agent (NIOSH 2016 [group 2]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).
Note: Facilities may perform risk assessment of some hazardous drugs to determine if appropriate for alternative handling and containment strategies (USP-NF 2020). Refer to institution-specific handling policies/procedures.
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Trileptal: http://www.fda.gov/downloads/Drugs/DrugSafety/UCM246799.pdf
Oxtellar XR: http://www.fda.gov/downloads/Drugs/DrugSafety/UCM326087.pdf
Focal (partial) onset seizures:
Immediate release: Monotherapy or adjunctive therapy in the treatment of focal (partial) onset seizures in adults, as monotherapy in the treatment of focal (partial) onset seizures in children ≥4 years of age with epilepsy, and as adjunctive therapy in children ≥2 years of age with focal (partial) onset seizures.
Extended release: Treatment of focal (partial) onset seizures in adults and in children ≥6 years of age.
Trigeminal neuralgia
OXcarbazepine may be confused with carBAMazepine, oxaprozin, oxazepam
Trileptal may be confused with TriLipix
Beers Criteria: Oxcarbazepine is identified in the Beers Criteria as a potentially inappropriate medication to be used with caution in patients 65 years and older due to the potential to cause or exacerbate syndrome of inappropriate antidiuretic hormone secretion (SIADH) or hyponatremia; monitor sodium concentration closely when initiating or adjusting the dose in older adults (Beers Criteria [AGS 2023]).
Substrate of CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Induces CYP3A4 (weak)
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Alcohol (Ethyl): May enhance the CNS depressant effect of OXcarbazepine. Risk C: Monitor therapy
Atazanavir: OXcarbazepine may decrease the serum concentration of Atazanavir. Risk C: Monitor therapy
Atogepant: CYP3A4 Inducers (Weak) may decrease the serum concentration of Atogepant. Management: For treatment of episodic migraine, the recommended dose of atogepant is 30 mg once daily or 60 mg once daily when combined with CYP3A4 inducers. When used for treatment of chronic migraine, use of atogepant with CYP3A4 inducers should be avoided. Risk D: Consider therapy modification
Bictegravir: OXcarbazepine may decrease the serum concentration of Bictegravir. Management: When possible consider using an alternative antiseizure drug with concurrent bictegravir, emtricitabine, and tenofovir alafenamide. If the combination must be used, monitor closely for evidence of reduced antiviral effectiveness. Risk D: Consider therapy modification
Cabotegravir: OXcarbazepine may decrease the serum concentration of Cabotegravir. Risk X: Avoid combination
CarBAMazepine: CYP3A4 Inducers (Weak) may decrease the serum concentration of CarBAMazepine. Risk C: Monitor therapy
CloZAPine: CYP3A4 Inducers (Weak) may decrease the serum concentration of CloZAPine. Risk C: Monitor therapy
Cobicistat: OXcarbazepine may decrease the serum concentration of Cobicistat. Management: Consider an alternative antiseizure medication when possible. Risk D: Consider therapy modification
CYP3A4 Inducers (Strong): May decrease the serum concentration of OXcarbazepine. Specifically, the concentrations of the 10-monohydroxy active metabolite of oxcarbazepine may be decreased. Risk C: Monitor therapy
Desmopressin: Hyponatremia-Associated Agents may enhance the hyponatremic effect of Desmopressin. Risk C: Monitor therapy
Dolutegravir: OXcarbazepine may decrease the serum concentration of Dolutegravir. Risk X: Avoid combination
Doravirine: OXcarbazepine may decrease the serum concentration of Doravirine. Risk X: Avoid combination
Elvitegravir: OXcarbazepine may decrease the serum concentration of Elvitegravir. Management: For elvitegravir plus a ritonavir-boosted protease inhibitor, use of oxcarbazepine is not recommended; for elvitegravir/cobicistat/emtricitabine/tenofovir combination products, consider using an alternative antiseizure agent when possible. Risk X: Avoid combination
Eslicarbazepine: May enhance the adverse/toxic effect of OXcarbazepine. Risk X: Avoid combination
Fosphenytoin-Phenytoin: May decrease serum concentrations of the active metabolite(s) of OXcarbazepine. Specifically, concentrations of the major active 10-monohydroxy metabolite may be reduced. OXcarbazepine may increase the serum concentration of Fosphenytoin-Phenytoin. Risk C: Monitor therapy
Hormonal Contraceptives: OXcarbazepine may decrease the serum concentration of Hormonal Contraceptives. Management: Advise patients to use an alternative method of contraception or a back-up method during coadministration, and to continue back-up contraception for 28 days after discontinuing oxcarbazepine to ensure contraceptive reliability. Risk D: Consider therapy modification
Lacosamide: Antiseizure Agents (Sodium Channel Blockers) may enhance the adverse/toxic effect of Lacosamide. Specifically the risk for bradycardia, ventricular tachyarrhythmias, or a prolonged PR interval may be increased. Risk C: Monitor therapy
LamoTRIgine: Antiseizure Agents (Sodium Channel Blockers) may enhance the arrhythmogenic effect of LamoTRIgine. Management: Consider the risk of serious arrhythmias or death versus any expected benefit of lamotrigine in patients receiving concomitant sodium channel blockers. Risk D: Consider therapy modification
Ledipasvir: OXcarbazepine may decrease the serum concentration of Ledipasvir. Risk X: Avoid combination
Lenacapavir: OXcarbazepine may decrease the serum concentration of Lenacapavir. Risk X: Avoid combination
LevETIRAcetam: OXcarbazepine may decrease the serum concentration of LevETIRAcetam. Risk C: Monitor therapy
Mefloquine: May diminish the therapeutic effect of Antiseizure Agents. Mefloquine may decrease the serum concentration of Antiseizure Agents. Management: Mefloquine is contraindicated for malaria prophylaxis in persons with a history of seizures. If antiseizure drugs are being used for another indication, monitor antiseizure drug concentrations and treatment response closely with concurrent use. Risk D: Consider therapy modification
MetyraPONE: Antiseizure Agents may diminish the diagnostic effect of MetyraPONE. Management: Consider alternatives to the use of the metyrapone test in patients taking antiseizure agents. Risk D: Consider therapy modification
Mianserin: May diminish the therapeutic effect of Antiseizure Agents. Risk C: Monitor therapy
NiMODipine: CYP3A4 Inducers (Weak) may decrease the serum concentration of NiMODipine. Risk C: Monitor therapy
Orlistat: May decrease the serum concentration of Antiseizure Agents. Risk C: Monitor therapy
Perampanel: May increase the serum concentration of OXcarbazepine. OXcarbazepine may decrease the serum concentration of Perampanel. Management: Increase the perampanel starting dose to 4 mg/day when perampanel is used with oxcarbazepine. Patients receiving this combination should be followed closely for response to perampanel and oxcarbazepine toxicities. Risk D: Consider therapy modification
Rilpivirine: OXcarbazepine may decrease the serum concentration of Rilpivirine. Risk X: Avoid combination
Rivaroxaban: OXcarbazepine may decrease the serum concentration of Rivaroxaban. Risk C: Monitor therapy
Selpercatinib: CYP3A4 Inducers (Weak) may decrease the serum concentration of Selpercatinib. Risk C: Monitor therapy
Simeprevir: OXcarbazepine may decrease the serum concentration of Simeprevir. Risk X: Avoid combination
Sirolimus (Conventional): CYP3A4 Inducers (Weak) may decrease the serum concentration of Sirolimus (Conventional). Risk C: Monitor therapy
Sirolimus (Protein Bound): CYP3A4 Inducers (Weak) may decrease the serum concentration of Sirolimus (Protein Bound). Risk C: Monitor therapy
Sofosbuvir: OXcarbazepine may decrease the serum concentration of Sofosbuvir. Risk X: Avoid combination
Tacrolimus (Systemic): CYP3A4 Inducers (Weak) may decrease the serum concentration of Tacrolimus (Systemic). Risk C: Monitor therapy
Tenofovir Alafenamide: OXcarbazepine may decrease the serum concentration of Tenofovir Alafenamide. Risk X: Avoid combination
Ubrogepant: CYP3A4 Inducers (Weak) may decrease the serum concentration of Ubrogepant. Management: Use an initial ubrogepant dose of 100 mg and second dose (if needed) of 100 mg when used with a weak CYP3A4 inducer. Risk D: Consider therapy modification
Ulipristal: OXcarbazepine may decrease the serum concentration of Ulipristal. Risk X: Avoid combination
Valproate Products: May decrease the serum concentration of OXcarbazepine. Risk C: Monitor therapy
Oxcarbazepine may decrease plasma concentrations of hormonal contraceptives. Use of an additional, nonhormonal contraceptive or alternative nonhormonal birth control is recommended.
Oxcarbazepine, the active metabolite MHD and the inactive metabolite DHD, crosses the placenta and can be detected in the newborn (Myllynen 2001).
According to the manufacturer, limited data collected from pregnancy registries suggest congenital malformations may be associated with oxcarbazepine monotherapy, including craniofacial defects (such as oral clefts) and cardiac malformations (such as ventricular septal defects). However, use of oxcarbazepine in pregnancy is limited in comparison to other antiseizure drugs and additional information may be needed to evaluate specific birth defects and other pregnancy outcomes (de Jong 2016; Martinez Ferri 2018; Tomson 2019; Weston 2016). In general, the risk of teratogenic effects is higher with antiseizure drug polytherapy than monotherapy (Harden 2009). In case reports, symptoms similar to neonatal abstinence syndrome have been observed in newborns following in utero oxcarbazepine exposure (Chen 2017; Rolnitsky 2013).
Due to pregnancy-induced physiologic changes, plasma concentrations of the active metabolite, MHD, gradually decrease during pregnancy; patients should be monitored during pregnancy and postpartum.
Data collection to monitor pregnancy and infant outcomes following exposure to oxcarbazepine is ongoing. Patients exposed to oxcarbazepine during pregnancy are encouraged to enroll themselves into the NAAED Pregnancy Registry by calling 1-888-233-2334. Additional information is available at www.aedpregnancyregistry.org.
Oxcarbazepine and the active 10-hydroxy metabolite (MHD) are present in breast milk.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.
Seizure frequency; serum sodium as deemed necessary (particularly during first 3 months of therapy); mental alertness and symptoms of CNS depression (dizziness, headache, somnolence); signs/symptoms of skin reactions; hypersensitivity reactions, including DRESS (eg, disparate manifestations associated with lymphatic, hepatic, renal, cardiovascular, and/or hematologic organ systems). Additional serum sodium monitoring recommended during maintenance treatment in patients receiving other medications known to decrease sodium levels, in patients with signs/symptoms of hyponatremia (eg, nausea, malaise, headache, lethargy, confusion, impaired consciousness, seizures), older adult patients, and in patients with an increase in seizure frequency or severity. Periodic thyroid function tests (particularly pediatric patients) and CBC. Monitor for suicidality (eg, suicidal thoughts, depression, behavioral changes). Serum levels of concomitant antiseizure drugs during titration as necessary.
Consider screening patients of Asian descent for the variant human leukocyte antigen (HLA) allele B*1502 prior to initiating therapy. Screening is not recommended in low-risk populations or in current oxcarbazepine patients (risk usually during first few months of therapy).
The metabolite of oxcarbazepine, 10-monohydroxy metabolite (MHD), is considered the active entity primarily responsible for the therapeutic effects. A number of studies have suggested optimal MHD concentrations for efficacy may range from 2 to 55 mcg/mL and some experts suggest a target range of 8 to 35 mcg/mL based on clinical experience; however, a clear correlation between plasma concentrations and therapeutic response has not been demonstrated. Therapeutic drug monitoring of MHD is not routinely warranted; however, it may be beneficial in optimizing seizure control in the following situations: Extremes of age, during pregnancy, to investigate the correlation between drug concentrations and toxicity especially with concurrent disease states such as renal impairment, to identify potential drug interactions, to assess reasons for therapeutic failure, or to rule out noncompliance (Bring 2008; May 2003).
Pharmacological activity results from both oxcarbazepine and its monohydroxy metabolite (MHD). Precise mechanism of antiseizure effect has not been defined. Oxcarbazepine and MHD block voltage-sensitive sodium channels, stabilizing hyperexcited neuronal membranes, inhibiting repetitive firing, and decreasing the propagation of synaptic impulses. These actions are believed to prevent the spread of seizures. Oxcarbazepine and MHD also increase potassium conductance and modulate the activity of high-voltage activated calcium channels.
Absorption: Complete
Distribution: MHD: Vd: 49 L
Protein binding: Oxcarbazepine: 67%; MHD: 40%, primarily to albumin; parent drug and metabolite do not bind to alpha-1 acid glycoprotein
Metabolism: Oxcarbazepine is extensively metabolized in the liver to its active 10-monohydroxy metabolite (MHD); MHD undergoes further metabolism via glucuronide conjugation; 4% of dose is oxidized to the 10,11-dihydroxy metabolite (DHD) (inactive); 70% of serum concentration appears as MHD, 2% as unchanged oxcarbazepine, and the rest as minor metabolites; Note: Unlike carbamazepine, autoinduction of metabolism has not been observed and biotransformation of oxcarbazepine does not result in an epoxide metabolite
Bioavailability: Immediate release tablets and suspension have similar bioavailability (based on MDH serum concentrations). Extended release tablets and immediate release products are not bioequivalent. Immediate release: Decreased in children <8 years; increased in elderly >60 years
Half-life elimination:
Children (Rey 2004): 2 to 5 years: MHD: Single dose: Mean range: 4.8 to 6.7 hours; 6 to 12 years: MHD: Single dose: Mean range: 7.2 to 9.3 hours
Adults: Immediate release: Parent drug: 2 hours; MHD: 9 hours; renal impairment (CrCl 30 mL/minute): MHD: 19 hours; Extended release: Parent drug: 7 to 11 hours; MHD: 9 to 11 hours
Time to peak, serum:
Children 2 to 12 years: Immediate release: Oxcarbazepine: 1 hour; MHD: 3 to 4 hours (Rey 2004)
Adults: Immediate release: MHD: Tablets: Median: 4.5 hours (range: 3 to 13 hours); Suspension: Median 6 hours; Extended release: MHD: 7 hours
Excretion: Urine (95%, <1% as unchanged oxcarbazepine, 27% as unchanged MHD, 49% as MHD glucuronides, 3% as DHD (inactive), and 13% as conjugate of oxcarbazepine and MHD); feces (<4%)
Clearance (per body weight):
Children 2 to <4 years: Increased by ∼80% compared to adults
Children 4 to 12 years: Increased by ∼40% compared to adults
Children ≥13 years: Values approach adult clearance
Altered kidney function: If CrCl <30 mL/minute, elimination half-life of MHD is prolonged to 19 hours and there is a 2-fold increase in AUC.
Older adult: Max plasma concentration and AUC values of MHD were 30% to 60% higher.
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