Trileptal
oxcarbazepine · Tablet, Film Coated · Oral
Uses
1 INDICATIONS AND USAGE TRILEPTAL is indicated for use as monotherapy or adjunctive therapy in the treatment of partial-onset seizures in adults and as monotherapy in the treatment of partial-onset seizures in pediatric patients aged 4 years and above, and as adjunctive therapy in pediatric patients aged 2 years and above with partial-onset seizures. TRILEPTAL is indicated for: Adults: Monotherapy or adjunctive therapy in the treatment of partial-onset seizures Pediatrics: - Monotherapy in the treatment of partial-onset seizures in children 4-16 years - Adjunctive therapy in the treatment of partial-onset seizures in children 2-16 years ( 1 )
Dosage and administration
Adults: Initiate with a dose of 600 mg/day, given twice a day Adjunctive Therapy: Maximum increment of 600 mg/day at approximately weekly intervals. The recommended daily dose is 1200 mg/day ( 2.1 ) Conversion to Monotherapy: Withdrawal concomitant over 3 to 6 weeks; reach maximum dose of TRILEPTAL in 2 to 4 weeks with increments of 600 mg/day at weekly intervals to a recommended daily dose of 2400 mg/day ( 2.2 ) Initiation of Monotherapy: Increments of 300 mg/day every third day to a dose of 1200 mg/day ( 2.3 ) Initiate at one-half the usual starting dose and increase slowly in patients with a creatinine clearance < 30 mL/min ( 2.7 ) Pediatrics : Initiation with 8 to 10 mg/kg/day, given twice a day. For patients aged 2 to < 4 years and under 20 kg, a starting dose of 16 to 20 mg/kg/day may be considered. Recommended daily dose is dependent upon patient weight. Adjunctive Patients (Aged 2-16 Years): For patients aged 4 to 16 years, target maintenance dose should be achieved over 2 weeks ( 2.4 ). For patients aged 2 to < 4 years, maximum maintenance dose should be achieved over 2 to 4 weeks and should not exceed 60 mg/kg/day ( 2.4 ) Conversion to Monotherapy for Patients (Aged 4-16 Years): Maximum increment of 10 mg/kg/day at weekly intervals, concomitant antiepileptic drugs (AEDs) can be completely withdrawn over 3 to 6 weeks ( 2.5 ) Initiation of Monotherapy for Patients (Aged 4-16 Years): Increments of 5 mg/kg/day every third day ( 2.6 ) 2.1 Adjunctive Therapy for Adults Initiate TRILEPTAL with a dose of 600 mg/day, given twice a day. If clinically indicated, the dose may be increased by a maximum of 600 mg/day at approximately weekly intervals; the maximum recommended daily dose is 1200 mg/day. Daily doses above 1200 mg/day show somewhat greater effectiveness in controlled trials, but most patients were not able to tolerate the 2400 mg/day dose, primarily because of central nervous (CNS) effects. Dosage adjustment is recommended with concomitant use of strong CYP3A4 enzyme inducers or UDP-glucuronosyltransferases (UGT) inducers, which include certain antiepileptic drugs (AEDs) [ see Drug Interactions (7.1, 7.2) ]. 2.2 Conversion to Monotherapy for Adults Patients receiving concomitant AEDs may be converted to monotherapy by initiating treatment with TRILEPTAL at 600 mg/day (given in a twice a day regimen) while simultaneously initiating the reduction of the dose of the concomitant AEDs. The concomitant AEDs should be completely withdrawn over 3 to 6 weeks, while the maximum dose of TRILEPTAL should be reached in about 2 to 4 weeks. TRILEPTAL may be increased as clinically indicated by a maximum increment of 600 mg/day at approximately weekly intervals to achieve the maximum recommended daily dose of 2400 mg/day. A daily dose of 1200 mg/day has been shown in one study to be effective in patients in whom monotherapy has been initiated with TRILEPTAL. Patients should be observed closely during this transition phase. 2.3 Initiation of Monotherapy for Adults Patients not currently being treated with AEDs may have monotherapy initiated with TRILEPTAL. In these patients, initiate TRILEPTAL at a dose of 600 mg/day (given twice a day); the dose should be increased by 300 mg/day every third day to a dose of 1200 mg/day. Controlled trials in these patients examined the effectiveness of a 1200 mg/day dose; a dose of 2400 mg/day has been shown to be effective in patients converted from other AEDs to TRILEPTAL monotherapy (see above). 2.4 Adjunctive Therapy for Pediatric Patients (Aged 2-16 Years) In pediatric patients aged 4-16 years, initiate TRILEPTAL at a daily dose of 8 to 10 mg/kg generally not to exceed 600 mg/day, given twice a day. The target maintenance dose of TRILEPTAL should be achieved over 2 weeks, and is dependent upon patient weight, according to the following chart: 20 to 29 kg-900 mg/day 29.1 to 39 kg-1200 mg/day 39 kg-1800 mg/day In the clinical trial, in which the intention was to reach these target doses, the median daily dose was 31 mg/kg with a range of 6 to 51 mg/kg. In pediatric patients aged 2 to < 4 years, initiate TRILEPTAL at a daily dose of 8 to 10 mg/kg generally not to exceed 600 mg/day, given twice a day. For patients less than 20 kg, a starting dose of 16 to 20 mg/kg may be considered [ see Clinical Pharmacology (12. 3 ) ]. The maximum maintenance dose of TRILEPTAL should be achieved over 2 to 4 weeks and should not exceed 60 mg/kg/day in a twice a day regimen. In the clinical trial in pediatric patients (2 to 4 years of age), in which the intention was to reach the target dose of 60 mg/kg/day, 50% of patients reached a final dose of at least 55 mg/kg/day. Under adjunctive therapy (with and without enzyme-inducing AEDs), when normalized by body weight, apparent clearance (L/hr/kg) decreased when age increased such that children 2 to < 4 years of age may require up to twice the oxcarbazepine dose per body weight compared to adults; and children 4 to ≤ 12 years of age may require a 50% higher oxcarbazepine dose per body weight compared to adults. Dosage adjustment is recommended with concomitant use of strong CYP3A4 enzyme inducers or UGT inducers, which include certain AEDs [ see Drug Interactions (7.1, 7.2) ]. 2.5 Conversion to Monotherapy for Pediatric Patients (Aged 4-16 Years) Patients receiving concomitant AEDs may be converted to monotherapy by initiating treatment with TRILEPTAL at approximately 8 to 10 mg/kg/day given twice a day, while simultaneously initiating the reduction of the dose of the concomitant AEDs. The concomitant AEDs can be completely withdrawn over 3 to 6 weeks, while TRILEPTAL may be increased as clinically indicated by a maximum increment of 10 mg/kg/day at approximately weekly intervals to achieve the recommended daily dose. Patients should be observed closely during this transition phase. The recommended total daily dose of TRILEPTAL is shown in Table 1.
Dosage forms and strengths
Film-coated Tablets: 150 mg: pale grey-green, ovaloid, slightly biconvex, scored on both sides. Imprinted with “T/D” on one side and “C/G” on the other side. 300 mg: yellow, ovaloid, slightly biconvex, scored on both sides. Imprinted with “TE/TE” on one side and “CG/CG” on the other side. 600 mg: light pink, ovaloid, slightly biconvex, scored on both sides. Imprinted with “TF/TF” on one side and “CG/CG” on the other side. Oral Suspension: 300 mg/5 mL (60 mg/mL): off-white to slightly brown or slightly red suspension. Film-coated tablets: 150 mg, 300 mg and 600 mg ( 3 ) Oral suspension: 300 mg/5 mL (60 mg/mL) ( 3 )
Contraindications
4 CONTRAINDICATIONS TRILEPTAL is contraindicated in patients with a known hypersensitivity to oxcarbazepine or to any of its components, or to eslicarbazepine acetate [ see Warnings and Precautions (5.2, 5.3) ]. Known hypersensitivity to oxcarbazepine or to any of its components, or to eslicarbazepine acetate ( 4 , 5.2 )
Warnings and precautions
Hyponatremia: Monitor serum sodium levels ( 5.1 ) Cross Hypersensitivity Reaction to Carbamazepine: Discontinue immediately if hypersensitivity occurs ( 5.3 ) Serious Dermatological Reactions: If occurs, consider discontinuation ( 5.4 ) Suicidal Behavior and Ideation: Monitor for suicidal thoughts/behavior ( 5.5 ) Withdrawal of AEDs: Withdraw TRILEPTAL gradually ( 5.6 ) Cognitive/Neuropsychiatric Adverse Reactions: May cause cognitive dysfunction, somnolence, and coordination abnormalities. Use caution when operating machinery ( 5.7 ) Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multi-Organ Hypersensitivity: Monitor and discontinue if another cause cannot be established ( 5.8 ) Hematologic Events: Consider discontinuing ( 5.9 ) Seizure Control During Pregnancy: Active metabolite may decrease ( 5.10 ) Risk of Seizure Aggravation: Discontinue if occurs ( 5.11 ) 5.1 Hyponatremia Clinically significant hyponatremia (sodium < 125 mmol/L) can develop during TRILEPTAL use. In the 14 controlled epilepsy studies, 2.5% of TRILEPTAL-treated patients (38/1524) had a sodium of less than 125 mmol/L at some point during treatment, compared to no such patients assigned placebo or active control (carbamazepine and phenobarbital for adjunctive and monotherapy substitution studies, and phenytoin and valproate for the monotherapy initiation studies). Clinically significant hyponatremia generally occurred during the first 3 months of treatment with TRILEPTAL, although there were patients who first developed a serum sodium < 125 mmol/L more than 1 year after initiation of therapy. Most patients who developed hyponatremia were asymptomatic, but patients in the clinical trials were frequently monitored and some had their TRILEPTAL dose reduced, discontinued, or had their fluid intake restricted for hyponatremia. Whether or not these maneuvers prevented the occurrence of more severe events is unknown. Cases of symptomatic hyponatremia and syndrome of inappropriate antidiuretic hormone secretion (SIADH) have been reported during postmarketing use. In clinical trials, patients whose treatment with TRILEPTAL was discontinued due to hyponatremia generally experienced normalization of serum sodium within a few days without additional treatment. Measurement of serum sodium levels should be considered for patients during maintenance treatment with TRILEPTAL, particularly if the patient is receiving other medications known to decrease serum sodium levels (e.g., drugs associated with inappropriate ADH secretion), or if symptoms possibly indicating hyponatremia develop (e.g., nausea, malaise, headache, lethargy, confusion, obtundation, or increase in seizure frequency or severity). 5.2 Anaphylactic Reactions and Angioedema Rare cases of anaphylaxis and angioedema involving the larynx, glottis, lips and eyelids have been reported in patients after taking the first or subsequent doses of TRILEPTAL. Angioedema associated with laryngeal edema can be fatal. If a patient develops any of these reactions after treatment with TRILEPTAL, the drug should be discontinued and an alternative treatment started. These patients should not be rechallenged with the drug [ see Warnings and Precautions (5.3) ]. 5.3 Cross Hypersensitivity Reaction to Carbamazepine Approximately 25% to 30% of patients who have had hypersensitivity reactions to carbamazepine will experience hypersensitivity reactions with TRILEPTAL. For this reason, patients should be specifically questioned about any prior experience with carbamazepine, and patients with a history of hypersensitivity reactions to carbamazepine should ordinarily be treated with TRILEPTAL only if the potential benefit justifies the potential risk. If signs or symptoms of hypersensitivity develop, TRILEPTAL should be discontinued immediately [ see Warnings and Precautions (5.2, 5.8) ]. 5.4 Serious Dermatological Reactions Serious dermatological reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have been reported in both children and adults in association with TRILEPTAL use. Such serious skin reactions may be life threatening, and some patients have required hospitalization with very rare reports of fatal outcome. The median time of onset for reported cases was 19 days after treatment initiation. Recurrence of the serious skin reactions following rechallenge with TRILEPTAL has also been reported. The reporting rate of TEN and SJS associated with TRILEPTAL use, which is generally accepted to be an underestimate due to underreporting, exceeds the background incidence rate estimates by a factor of 3- to 10-fold. Estimates of the background incidence rate for these serious skin reactions in the general population range between 0.5 to 6 cases per million-person years. Therefore, if a patient develops a skin reaction while taking TRILEPTAL, consideration should be given to discontinuing TRILEPTAL use and prescribing another antiepileptic medication. Association With HLA-B*1502 Patients carrying the HLA-B*1502 allele may be at increased risk for SJS/TEN with TRILEPTAL treatment. Human Leukocyte Antigen (HLA) allele B*1502 increases the risk for developing SJS/TEN in patients treated with carbamazepine. The chemical structure of TRILEPTAL is similar to that of carbamazepine. Available clinical evidence, and data from nonclinical studies showing a direct interaction between TRILEPTAL and HLA-B*1502 protein, suggest that the HLA-B*1502 allele may also increase the risk for SJS/TEN with TRILEPTAL. The frequency of HLA-B*1502 allele ranges from 2% to 12% in Han Chinese populations, is about 8% in Thai populations, and above 15% in the Philippines, and in some Malaysian populations. Allele frequencies up to about 2% and 6% have been reported in Korea and India, respectively.
Side effects
The following serious adverse reactions are described below and elsewhere in the labeling: Hyponatremia [see Warnings and Precautions (5.1)] Anaphylactic Reactions and Angioedema [see Warnings and Precautions (5.2)] Cross Hypersensitivity Reaction to Carbamazepine [see Warnings and Precautions (5.3)] Serious Dermatological Reactions [see Warnings and Precautions (5.4)] Suicidal Behavior and Ideation [see Warnings and Precautions (5. 5 )] Cognitive/Neuropsychiatric Adverse Reactions [see Warnings and Precautions (5. 7 )] Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multi-Organ Hypersensitivity [see Warnings and Precautions (5. 8 )] Hematologic Events [see Warnings and Precautions (5. 9 )] The most common (≥ 10% more than placebo for adjunctive or low dose for monotherapy) adverse reactions in adults and pediatrics were: dizziness, somnolence, diplopia, fatigue, nausea, vomiting, ataxia, abnormal vision, headache, nystagmus, tremor, and abnormal gait ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Novartis Pharmaceuticals Corporation at 1-888-669-6682 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Most Common Adverse Reactions in All Clinical Studies Adjunctive Therapy/Monotherapy in Adults Previously Treated With Other AEDs The most common (≥ 10% more than placebo for adjunctive or low dose for monotherapy) adverse reactions with TRILEPTAL: dizziness, somnolence, diplopia, fatigue, nausea, vomiting, ataxia, abnormal vision, headache, nystagmus tremor, and abnormal gait. Approximately 23% of these 1537 adult patients discontinued treatment because of an adverse reaction. The adverse reactions most commonly associated with discontinuation were: dizziness (6.4%), diplopia (5.9%), ataxia (5.2%), vomiting (5.1%), nausea (4.9%), somnolence (3.8%), headache (2.9%), fatigue (2.1%), abnormal vision (2.1%), tremor (1.8%), abnormal gait (1.7%), rash (1.4%), and hyponatremia (1.0%). Monotherapy in Adults Not Previously Treated With O ther AEDs The most common (≥ 5%) adverse reactions with TRILEPTAL in these patients were similar to those in previously treated patients. Approximately 9% of these 295 adult patients discontinued treatment because of an adverse reaction. The adverse reactions most commonly associated with discontinuation were: dizziness (1.7%), nausea (1.7%), rash (1.7%), and headache (1.4%). Adjunctive Therapy/Monotherapy in Pediatric Patients 4 Years Old and Above Previously Treated With O ther AEDs The most common (≥ 5%) adverse reactions with TRILEPTAL in these patients were similar to those seen in adults. Approximately 11% of these 456 pediatric patients discontinued treatment because of an adverse reaction. The adverse reactions most commonly associated with discontinuation were: somnolence (2.4%), vomiting (2.0%), ataxia (1.8%), diplopia (1.3%), dizziness (1.3%), fatigue (1.1%), and nystagmus (1.1%). Monotherapy in Pediatric Patients 4 Years Old and Above Not Previously Treated With O ther AEDs The most common (≥ 5%) adverse reactions with TRILEPTAL in these patients were similar to those in adults. Approximately 9.2% of 152 pediatric patients discontinued treatment because of an adverse reaction. The adverse reactions most commonly associated (≥ 1%) with discontinuation were rash (5.3%) and maculopapular rash (1.3%). Adjunctive Therapy/Monotherapy in Pediatric Patients 1 Month to < 4 Years Old Previously Treated or Not Previously Treated with O ther AEDs: The most common (≥ 5%) adverse reactions with TRILEPTAL in these patients were similar to those seen in older children and adults, except for infections and infestations which were more frequently seen in these younger children. Approximately 11% of these 241 pediatric patients discontinued treatment because of an adverse reaction. The adverse reactions most commonly associated with discontinuation were: convulsions (3.7%), status epilepticus (1.2%), and ataxia (1.2%). Controlled Clinical Studies of Adjunctive Therapy/Monotherapy in Adults Previously Treated With O ther AEDs Table 3 lists adverse reactions that occurred in at least 2% of adult patients with epilepsy, treated with TRILEPTAL or placebo as adjunctive treatment and were numerically more common in the patients treated with any dose of TRILEPTAL. Table 4 lists adverse reactions in patients converted from other AEDs to either high-dose TRILEPTAL (2400 mg/day) or low-dose (300 mg/day) TRILEPTAL. Note that in some of these monotherapy studies patients who dropped out during a preliminary tolerability phase are not included in the tables. Table 3: Adverse Reactions in a Controlled Clinical Study of Adjunctive Therapy With TRILEPTAL in Adults Abbreviations: EEG, electroencephalogram; NOS, not otherwise specified.
Drug interactions
Phenytoin: Increased phenytoin levels. Reduced dose of phenytoin may be required ( 7.1 ) Carbamazepine, Phenytoin, and Phenobarbital: Decreased plasma levels of MHD (the active metabolite). Dose adjustments may be necessary ( 7.1 ) Oral Contraceptive: TRILEPTAL may decrease the effectiveness of hormonal contraceptives ( 7.3 ) 7.1 Effect of TRILEPTAL on Other Drugs Phenytoin levels have been shown to increase with concomitant use of TRILEPTAL at doses greater than 1200 mg/day [see Clinical Pharmacology (12.3)] . Therefore, it is recommended that the plasma levels of phenytoin be monitored during the period of TRILEPTAL titration and dosage modification. A decrease in the dose of phenytoin may be required. 7.2 Effect of Other Drugs on TRILEPTAL Strong inducers of cytochrome P450 enzymes and/or inducers of UGT (e.g., rifampin, carbamazepine, phenytoin and phenobarbital) have been shown to decrease the plasma/serum levels of MHD, the active metabolite of TRILEPTAL (25% to 49%) [see Clinical Pharmacology (12.3)] . If TRILEPTAL and strong CYP3A4 inducers, or UGT inducers are administered concurrently, it is recommended that the plasma levels of MHD be monitored during the period of TRILEPTAL titration. Dose adjustment of TRILEPTAL may be required after initiation, dosage modification, or discontinuation of such inducers. 7.3 Hormonal Contraceptives Concurrent use of TRILEPTAL with hormonal contraceptives may render these contraceptives less effective [see Use in Specific Populations (8.3) and Clinical Pharmacology (12.3)] . Studies with other oral or implant contraceptives have not been conducted.
Use in specific populations
Pregnancy: May cause fetal harm ( 8.1) 8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to AEDs, such as TRILEPTAL, during pregnancy. Encourage women who are taking TRILEPTAL during pregnancy to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry by calling 1-888-233-2334 or visiting http://www.aedpregnancyregistry.org/. Risk Summary Although TRILEPTAL is closely related structurally to carbamazepine, which is considered to be teratogenic in humans, available human data from published literature and ongoing pregnancy registry studies on use of oxcarbazepine during pregnancy have not demonstrated an increased prevalence of major congenital malformations with first trimester exposure. However, all published studies reviewed have important methodological limitations, including unmeasured confounding and a small number of exposed cases ( see Data ). There are risks to the mother and fetus associated with partial onset seizures ( see Clinical Considerations ). There are no data on the risks associated with the use of TRILEPTAL and miscarriage or other adverse maternal outcomes. Increased incidences of fetal structural abnormalities and other manifestations of developmental toxicity (embryolethality, growth retardation) were observed in the offspring of animals treated with either oxcarbazepine or its active 10-hydroxy metabolite (MHD) during pregnancy at doses similar to the maximum recommended human dose (MRHD). In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. Clinical Considerations Disease-associated Maternal and/or Embryofetal Risk Epilepsy, with or without exposure to antiepileptic drugs, has been associated with several adverse outcomes during pregnancy, including preeclampsia, preterm labor, antepartum and postpartum hemorrhage, placental abruption, poor fetal growth, prematurity, fetal death, and maternal mortality. The risk of maternal or fetal injury may be greatest for patients with untreated or poorly controlled convulsive seizures. Women with epilepsy who become pregnant should not abruptly discontinue antiepileptic drugs, including TRILEPTAL, due to the risk of status epilepticus or severe seizures, which may be life-threatening [see Warnings and Precautions (5.6)] . Maternal Adverse Reactions An increase in seizure frequency may occur during pregnancy because of altered levels of the active metabolite of oxcarbazepine. Monitor patients carefully during pregnancy and through the postpartum period [see Warnings and Precautions (5.10)] . Data Human Data Data from a published retrospective cohort study and ongoing pregnancy registry studies on the use of oxcarbazepine during pregnancy have not demonstrated an increased prevalence of major congenital malformations with first trimester exposure. A retrospective cohort study conducted in Nordic countries (Denmark, Finland, Iceland, Norway, and Sweden) from 1996-2020 found that there was no increased prevalence of major congenital malformations when pregnancies exposed to oxcarbazepine during the first trimester were compared to pregnancies exposed to lamotrigine (adjusted risk ratio =1.09; 95% CI 0.83 to 1.44; n pregnancies exposed to oxcarbazepine= 1,313, n exposed cases = 58). In an ongoing pregnancy registry that included data from over 40 countries from 1999 to 2022 and 443 pregnancies exposed to oxcarbazepine, oxcarbazepine exposure during the first trimester was not associated with major congenital malformations (adjusted odds ratio =1.09; 95% CI 0.56 to 2.13, n exposed cases = 10). However, there are important methodological limitations of these studies including unmeasured confounding factors and a small number of exposed cases in the registry. Animal Data When pregnant rats were given oxcarbazepine (0, 30, 300, or 1000 mg/kg/day) orally throughout the period of organogenesis, increased incidences of fetal malformations (craniofacial, cardiovascular, and skeletal) and variations were observed at the intermediate and high doses (approximately 1.2 and 4 times, respectively, the MRHD on a mg/m 2 basis). Increased embryofetal death and decreased fetal body weights were seen at the high dose. Doses ≥ 300 mg/kg/day were also maternally toxic (decreased body weight gain, clinical signs), but there is no evidence to suggest that teratogenicity was secondary to the maternal effects. In a study in which pregnant rabbits were orally administered MHD (0, 20, 100, or 200 mg/kg/day) during organogenesis, embryofetal mortality was increased at the highest dose (1.5 times the MRHD on a mg/m 2 basis). This dose produced only minimal maternal toxicity. In a study in which female rats were dosed orally with oxcarbazepine (0, 25, 50, or 150 mg/kg/day) during the latter part of gestation and throughout the lactation period, a persistent reduction in body weights and altered behavior (decreased activity) were observed in offspring exposed to the highest dose (less than the MRHD on a mg/m 2 basis). Oral administration of MHD (0, 25, 75, or 250 mg/kg/day) to rats during gestation and lactation resulted in a persistent reduction in offspring weights at the highest dose (equivalent to the MRHD on a mg/m 2 basis). 8.2 Lactation Risk Summary Oxcarbazepine and its active metabolite (MHD) are present in human milk after TRILEPTAL administration. The effects of oxcarbazepine and its active metabolite (MHD) on the breastfed infant or on milk production are unknown. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for TRILEPTAL and any potential adverse effects on the breastfed infant from TRILEPTAL or from the underlying maternal condition.
Pregnancy
8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to AEDs, such as TRILEPTAL, during pregnancy. Encourage women who are taking TRILEPTAL during pregnancy to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry by calling 1-888-233-2334 or visiting http://www.aedpregnancyregistry.org/. Risk Summary Although TRILEPTAL is closely related structurally to carbamazepine, which is considered to be teratogenic in humans, available human data from published literature and ongoing pregnancy registry studies on use of oxcarbazepine during pregnancy have not demonstrated an increased prevalence of major congenital malformations with first trimester exposure. However, all published studies reviewed have important methodological limitations, including unmeasured confounding and a small number of exposed cases ( see Data ). There are risks to the mother and fetus associated with partial onset seizures ( see Clinical Considerations ). There are no data on the risks associated with the use of TRILEPTAL and miscarriage or other adverse maternal outcomes. Increased incidences of fetal structural abnormalities and other manifestations of developmental toxicity (embryolethality, growth retardation) were observed in the offspring of animals treated with either oxcarbazepine or its active 10-hydroxy metabolite (MHD) during pregnancy at doses similar to the maximum recommended human dose (MRHD). In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. Clinical Considerations Disease-associated Maternal and/or Embryofetal Risk Epilepsy, with or without exposure to antiepileptic drugs, has been associated with several adverse outcomes during pregnancy, including preeclampsia, preterm labor, antepartum and postpartum hemorrhage, placental abruption, poor fetal growth, prematurity, fetal death, and maternal mortality. The risk of maternal or fetal injury may be greatest for patients with untreated or poorly controlled convulsive seizures. Women with epilepsy who become pregnant should not abruptly discontinue antiepileptic drugs, including TRILEPTAL, due to the risk of status epilepticus or severe seizures, which may be life-threatening [see Warnings and Precautions (5.6)] . Maternal Adverse Reactions An increase in seizure frequency may occur during pregnancy because of altered levels of the active metabolite of oxcarbazepine. Monitor patients carefully during pregnancy and through the postpartum period [see Warnings and Precautions (5.10)] . Data Human Data Data from a published retrospective cohort study and ongoing pregnancy registry studies on the use of oxcarbazepine during pregnancy have not demonstrated an increased prevalence of major congenital malformations with first trimester exposure. A retrospective cohort study conducted in Nordic countries (Denmark, Finland, Iceland, Norway, and Sweden) from 1996-2020 found that there was no increased prevalence of major congenital malformations when pregnancies exposed to oxcarbazepine during the first trimester were compared to pregnancies exposed to lamotrigine (adjusted risk ratio =1.09; 95% CI 0.83 to 1.44; n pregnancies exposed to oxcarbazepine= 1,313, n exposed cases = 58). In an ongoing pregnancy registry that included data from over 40 countries from 1999 to 2022 and 443 pregnancies exposed to oxcarbazepine, oxcarbazepine exposure during the first trimester was not associated with major congenital malformations (adjusted odds ratio =1.09; 95% CI 0.56 to 2.13, n exposed cases = 10). However, there are important methodological limitations of these studies including unmeasured confounding factors and a small number of exposed cases in the registry. Animal Data When pregnant rats were given oxcarbazepine (0, 30, 300, or 1000 mg/kg/day) orally throughout the period of organogenesis, increased incidences of fetal malformations (craniofacial, cardiovascular, and skeletal) and variations were observed at the intermediate and high doses (approximately 1.2 and 4 times, respectively, the MRHD on a mg/m 2 basis). Increased embryofetal death and decreased fetal body weights were seen at the high dose. Doses ≥ 300 mg/kg/day were also maternally toxic (decreased body weight gain, clinical signs), but there is no evidence to suggest that teratogenicity was secondary to the maternal effects. In a study in which pregnant rabbits were orally administered MHD (0, 20, 100, or 200 mg/kg/day) during organogenesis, embryofetal mortality was increased at the highest dose (1.5 times the MRHD on a mg/m 2 basis). This dose produced only minimal maternal toxicity. In a study in which female rats were dosed orally with oxcarbazepine (0, 25, 50, or 150 mg/kg/day) during the latter part of gestation and throughout the lactation period, a persistent reduction in body weights and altered behavior (decreased activity) were observed in offspring exposed to the highest dose (less than the MRHD on a mg/m 2 basis). Oral administration of MHD (0, 25, 75, or 250 mg/kg/day) to rats during gestation and lactation resulted in a persistent reduction in offspring weights at the highest dose (equivalent to the MRHD on a mg/m 2 basis).
Pediatric use
8.4 Pediatric Use TRILEPTAL is indicated for use as adjunctive therapy for partial-onset seizures in patients aged 2 to 16 years. The safety and effectiveness for use as adjunctive therapy for partial-onset seizures in pediatric patients below the age of 2 have not been established. TRILEPTAL is also indicated as monotherapy for partial-onset seizures in patients aged 4 to 16 years. The safety and effectiveness for use as monotherapy for partial-onset seizures in pediatric patients below the age of 4 have not been established. TRILEPTAL has been given to 898 patients between the ages of 1 month to 17 years in controlled clinical trials (332 treated as monotherapy) and about 677 patients between the ages of 1 month to 17 years in other trials [ s ee Warnings and Precautions (5.11), Adverse Reactions (6.1) , Clinical Pharmacology (12.3), and Clinical Studies (14 ) ].
Geriatric use
8.5 Geriatric Use There were 52 patients over age 65 in controlled clinical trials and 565 patients over the age of 65 in other trials. Following administration of single (300 mg) and multiple (600 mg/day) doses of TRILEPTAL in elderly volunteers (60 to 82 years of age), the maximum plasma concentrations and area under the curve (AUC) values of MHD were 30% to 60% higher than in younger volunteers (18 to 32 years of age). Comparisons of creatinine clearance in young and elderly volunteers indicate that the difference was due to age-related reductions in creatinine clearance. Close monitoring of sodium levels is required in elderly patients at risk for hyponatremia [ see Warnings and Precautions (5.1) ].
Overdosage
10.1 Human Overdose Experience Isolated cases of overdose with TRILEPTAL have been reported. The maximum dose taken was approximately 48,000 mg. All patients recovered with symptomatic treatment. Nausea, vomiting, somnolence, aggression, agitation, hypotension, and tremor each occurred in more than one patient. Coma, confusional state, convulsion, dyscoordination, depressed level of consciousness, diplopia, dizziness, dyskinesia, dyspnea, QT prolongation, headache, miosis, nystagmus, overdose, decreased urine output, and blurred vision also occurred. 10.2 Treatment and Management There is no specific antidote. Symptomatic and supportive treatment should be administered as appropriate. Removal of the drug by gastric lavage and/or inactivation by administering activated charcoal should be considered.
Description
11 DESCRIPTION TRILEPTAL is an AED available as 150 mg, 300 mg, and 600 mg film-coated tablets for oral administration. TRILEPTAL is also available as a 300 mg/5 mL (60 mg/mL) oral suspension. Oxcarbazepine is 10,11-Dihydro-10-oxo-5 H -dibenz[b, f ]azepine-5-carboxamide, and its structural formula is: Oxcarbazepine is a white to faintly orange crystalline powder. It is slightly soluble in chloroform, dichloromethane, acetone, and methanol and practically insoluble in ethanol, ether and water. Its molecular weight is 252.27 g/mol. TRILEPTAL film-coated tablets contain the following inactive ingredients: colloidal silicon dioxide, crospovidone, hydroxypropyl methylcellulose, iron oxide, magnesium stearate, microcrystalline cellulose, polyethylene glycol, talc, and titanium dioxide. TRILEPTAL oral suspension contains the following inactive ingredients: ascorbic acid; dispersible cellulose; ethanol; macrogol stearate; methyl parahydroxybenzoate; propylene glycol; propyl parahydroxybenzoate; purified water; sodium saccharin; sorbic acid; sorbitol; yellow-plum-lemon aroma. Oxcarbazepine structural formula.
Mechanism of action
12.1 Mechanism of Action The pharmacological activity of TRILEPTAL is primarily exerted through the 10-monohydroxy metabolite (MHD) of oxcarbazepine [ see Clinical Pharmacology (12.3) ]. The precise mechanism by which oxcarbazepine and MHD exert their anti-seizure effect is unknown; however, in vitro electrophysiological studies indicate that they produce blockade of voltage-sensitive sodium channels, resulting in stabilization of hyperexcited neural membranes, inhibition of repetitive neuronal firing, and diminution of propagation of synaptic impulses. These actions are thought to be important in the prevention of seizure spread in the intact brain. In addition, increased potassium conductance and modulation of high-voltage activated calcium channels may contribute to the anticonvulsant effects of the drug. No significant interactions of oxcarbazepine or MHD with brain neurotransmitter or modulator receptor sites have been demonstrated.
How supplied
Tablets 150 mg Film-Coated Tablets: pale grey-green, ovaloid, slightly biconvex, scored on both sides. Imprinted with “T/D” on one side and “C/G” on the other side. Bottle of 100……………………………………………………………………………………………...NDC 0078-0456-05 Unit Dose (blister pack) Box of 100 (strips of 10)………………………………………………………………………………....NDC 0078-0456-35 300 mg Film-Coated Tablets: yellow, ovaloid, slightly biconvex, scored on both sides. Imprinted with “TE/TE” on one side and “CG/CG” on the other side. Bottle of 100……………………………………………………………………………………………...NDC 0078-0337-05 Unit Dose (blister pack) Box of 100 (strips of 10)…………………………………………………………………………………NDC 0078-0337-06 600 mg Film-Coated Tablets: light pink, ovaloid, slightly biconvex, scored on both sides. Imprinted with “TF/TF” on one side and “CG/CG” on the other side. Bottle of 100……………………………………………………………………………………………...NDC 0078-0457-05 Unit Dose (blister pack) Box of 100 (strips of 10)…………………………………………………………………………………NDC 0078-0457-35 Store at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C and 30°C (59°F and 86°F) [see USP Controlled Room Temperature]. Dispense in tight container (USP). Suspension 300 mg/5 mL (60 mg/mL) Oral Suspension: off-white to slightly brown or slightly red suspension. Available in amber glass bottles containing 250 mL of oral suspension. Supplied with a 10 mL dosing syringe and press-in bottle adapter. Bottle containing 250 mL of oral suspension……………………………………………………………NDC 0078-0357-52 Store TRILEPTAL oral suspension in the original container. Shake well before using. Use within 7 weeks of first opening the bottle. Store at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C and 30°C (59°F and 86°F) [see USP Controlled Room Temperature].
Patient information
Advise the patient to read the FDA-approved patient labeling (Medication Guide and Instructions for Use). Administration Information Counsel patients that TRILEPTAL may be taken with or without food. For TRILEPTAL oral suspension, advise patients to shake the bottle well and prepare the dose immediately afterwards using the oral dosing syringe supplied. Inform patients that TRILEPTAL oral suspension can be mixed in a small glass of water just prior to administration or, alternatively, may be swallowed directly from the syringe. Instruct patients to discard any unused TRILEPTAL oral suspension after 7 weeks of first opening the bottle [ se e Dosage and Administration (2.8 ) and How Supplied/Storage and Handling (16) ] . Hyponatremia Advise patients that TRILEPTAL may reduce the serum sodium concentrations especially if they are taking other medications that can lower sodium. Instruct patients to report symptoms of low sodium like nausea, tiredness, lack of energy, confusion, and more frequent or more severe seizures [ see Warnings and Precautions (5.1) ]. Anaphylactic Reactions and Angioedema Anaphylactic reactions and angioedema may occur during treatment with TRILEPTAL. Advise patients to report immediately signs and symptoms suggesting angioedema (swelling of the face, eyes, lips, tongue, or difficulty in swallowing or breathing) and to stop taking the drug until they have consulted with their physician [ see Warnings and Precautions (5.2) ]. Cross Hypersensitivity Reaction to Carbamazepine Inform patients who have exhibited hypersensitivity reactions to carbamazepine that approximately 25% to 30% of these patients may experience hypersensitivity reactions with TRILEPTAL. Patients should be advised that if they experience a hypersensitivity reaction while taking TRILEPTAL they should consult with their physician immediately [ see Warnings and Precautions (5.3) ]. Serious Dermatological Reactions Advise patients that serious skin reactions have been reported in association with TRILEPTAL. In the event a skin reaction should occur while taking TRILEPTAL, patients should consult with their physician immediately [ see Warnings and Precautions (5.4) ]. Suicidal Behavior and Ideation Patients, their caregivers, and families should be counseled that AEDs, including TRILEPTAL, may increase the risk of suicidal thoughts and behavior and should be advised of the need to be alert for the emergence or worsening of symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm. Behaviors of concern should be reported immediately to healthcare providers [see Warnings and Precautions (5.5)] . Driving and Operating Machinery Advise patients that TRILEPTAL may cause adverse reactions, such as dizziness, somnolence, ataxia, visual disturbances, and depressed level of consciousness. Accordingly, advise patients not to drive or operate machinery until they have gained sufficient experience on TRILEPTAL to gauge whether it adversely affects their ability to drive or operate machinery [see Warnings and Precautions (5.7) and Adverse Reactions (6)] . Multi-Organ Hypersensitivity Instruct patients that a fever associated with other organ system involvement (e.g., rash, lymphadenopathy, hepatic dysfunction) may be drug-related and should be reported to their healthcare provider immediately [ see Warnings and Precautions (5.8) ]. Hematologic Events Advise patients that there have been rare reports of blood disorders reported in patients treated with TRILEPTAL. Instruct patients to immediately consult with their physician if they experience symptoms suggestive of blood disorders [ see Warnings and Precautions (5.9) ]. Drug Interactions Caution female patients of reproductive potential that the concurrent use of TRILEPTAL with hormonal contraceptives may render this method of contraception less effective [see Drug Interactions (7.2) and Use in Specific Populations (8.1)] . Additional non-hormonal forms of contraception are recommended when using TRILEPTAL. Caution should be exercised if alcohol is taken in combination with TRILEPTAL, due to a possible additive sedative effect. Pregnancy Registry Encourage patients to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry if they become pregnant. This registry is collecting information about the safety of AEDs during pregnancy [ see Use i n Specific Populations (8.1) ]. T2025-61
Label text from the FDA structured product label by Novartis Pharmaceuticals Corporation (revised Dec 16, 2025). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Oxcarbazepine in 4 products
Trileptal NDC products (4)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 0078-0337 | Oxcarbazepine 300 mg/1 Tablet, Film Coated | Novartis Pharmaceuticals Corporation | NDA |
| 0078-0357 | Oxcarbazepine 60 mg/mL Suspension | Novartis Pharmaceuticals Corporation | NDA |
| 0078-0456 | Oxcarbazepine 150 mg/1 Tablet, Film Coated | Novartis Pharmaceuticals Corporation | NDA |
| 0078-0457 | Oxcarbazepine 600 mg/1 Tablet, Film Coated | Novartis Pharmaceuticals Corporation | NDA |
Frequently asked questions
What is Trileptal used for?
1 INDICATIONS AND USAGE TRILEPTAL is indicated for use as monotherapy or adjunctive therapy in the treatment of partial-onset seizures in adults and as monotherapy in the treatment of partial-onset seizures in pediatric patients aged 4 years and above, and as adjunctive therapy in pediatric patients aged 2 years and above with partial-onset seizures. TRILEPTAL is indicated for: Adults:…
What are the side effects of Trileptal?
The following serious adverse reactions are described below and elsewhere in the labeling: Hyponatremia [see Warnings and Precautions (5.1)] Anaphylactic Reactions and Angioedema [see Warnings and Precautions (5.2)] Cross Hypersensitivity Reaction to Carbamazepine [see Warnings and Precautions (5.3)] Serious Dermatological Reactions [see Warnings and Precautions (5.4)] Suicidal Behavior and… See the full label for the complete list.
Who makes Trileptal?
Trileptal is listed by 1 labeler in the FDA NDC directory, including Novartis Pharmaceuticals Corporation.