oxcarbazepine

RECENT MAJOR CHANGES Dosage and Administration ( 2.8 ) 9/2025

1 INDICATIONS AND USAGE Oxcarbazepine 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 to 16 years -Adjunctive therapy in the treatment of partial-onset seizures in children 2 to 16 years ( 1 ) Oxcarbazepine tablets are 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.

2 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 oxcarbazepine tablets 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 twiceaday. 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Years): Maximum increment of 10 mg/kg/day at weekly intervals, concomitant antiepileptic drugs (AEDs) can be completely withdrawn over 3 to 6 weeks ( 2.5 ) Initiation of Monotherapy for Patients (Aged 4-16 Years) Increments of 5 mg/kg/day every third day ( 2.6 ) 2.1 Adjunctive Therapy for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 Oxcarbazepine tablets USP 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-glucouronosyltransferase (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 oxcarbazepine tablets 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 oxcarbazepine tablets should be reached in about 2 to 4 weeks. Oxcarbazepine tablets 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 oxcarbazepine tablets. 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 oxcarbazepine tablets. In these patients, initiate oxcarbazepine tablets at a dose of 600 mg/day (given a 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 oxcarbazepine tablets monotherapy (see above). 2.4 Adjunctive Therapy for Pediatric Patients (Aged 2-16 Years) In pediatric patients aged 4-16 years, initiate oxcarbazepine tablets 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 oxcarbazepine tablets should be achieved over 2 weeks, and is dependent upon patient weight, according to the followin …

3 DOSAGE FORMS AND STRENGTHS Film-coated tablets: 150 mg, 300 mg and 600 mg ( 3 ) Film-coated Tablets: 150 mg: yellow colored, oval shaped, biconvex, film coated tablets scored on both sides and debossed with "6" and "91" separating with scoring on one side and plain on other side. 300 mg: yellow colored, oval shaped, biconvex, film coated tablets scored on both sides and debossed with "6" and "92" separating with scoring on one side and plain on other side. 600 mg: yellow colored, oval shaped, biconvex, film coated tablets scored on both sides and debossed with "6" and "93" separating with scoring on one side and plain on other side.

4 CONTRAINDICATIONS Known hypersensitivity to oxcarbazepine or to any of its components, or to eslicarbazepine acetate ( 4 , 5.2 ) Oxcarbazepine tablets are 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 )] .

6 ADVERSE REACTIONS 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 Zydus Pharmaceuticals USA Inc. at 1-877-993-8779 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 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) ] 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 oxcarbazepine: dizziness, somnolence, diplopia, fatigue, nausea, vomiting, ataxia, abnormal vision, headache, nystagmus tremor, and abnormal gait. Approximately 23% of these 1,537 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%). Monotherapy in Adults Not Previously Treated with Other AEDs The most common (≥5%) adverse reactions with oxcarbazepine 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 Other AEDs The most common (≥5%) adverse reactions with oxcarbazepine 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 %), 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 Other AEDs The most common (≥5%) adverse reactions with oxcarbazepine 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 Other AEDs: The most common (≥5%) adverse reactions with oxcarbazepine 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 chil …

7 DRUG INTERACTIONS Phenytoin: Increased phenytoin levels. Reduced dose of phenytoin may be required. ( 7.1 ) Carbamazepine, Phenytoin, Phenobarbital: Decreased plasma levels of MHD (the active metabolite). Dose adjustments may be necessary. ( 7.1 ) Oral Contraceptive: Oxcarbazepine tablets may decrease the effectiveness of hormonal contraceptives. ( 7.3 ) 7.1 Effect of Oxcarbazepine Tablets on Other Drugs Phenytoin levels have been shown to increase with concomitant use of Oxcarbazepine Tablets 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 Oxcarbazepine Tablets titration and dosage modification. A decrease in the dose of phenytoin may be required. 7.2 Effect of Other Drugs on Oxcarbazepine Tablets 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 Oxcarbazepine (25% to 49%) [see Clinical Pharmacology (12.3) ]. If Oxcarbazepine 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 Oxcarbazepine titration. Dose adjustment of Oxcarbazepine Tablets may be required after initiation, dosage modification, or discontinuation of such inducers. 7.3 Hormonal Contraceptives Concurrent use of Oxcarbazepine Tablets 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.

7.1 Effect of Oxcarbazepine Tablets on Other Drugs Phenytoin levels have been shown to increase with concomitant use of Oxcarbazepine Tablets 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 Oxcarbazepine Tablets titration and dosage modification. A decrease in the dose of phenytoin may be required.

7.2 Effect of Other Drugs on Oxcarbazepine Tablets 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 Oxcarbazepine (25% to 49%) [see Clinical Pharmacology (12.3) ]. If Oxcarbazepine 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 Oxcarbazepine titration. Dose adjustment of Oxcarbazepine Tablets may be required after initiation, dosage modification, or discontinuation of such inducers.

7.3 Hormonal Contraceptives Concurrent use of Oxcarbazepine Tablets 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.

8 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 Oxcarbazepine tablets, during pregnancy. Encourage women who are taking Oxcarbazepine tablets 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 oxcarbazepine tablets 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 oxcarbazepine 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 oxcarbazepine, 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 confoun …

12.1 Mechanism of Action The pharmacological activity of oxcarbazepine 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.

11 DESCRIPTION Oxcarbazepine Tablets USP are an antiepileptic drug available as 150 mg, 300 mg and 600 mg film-coated tablets for oral administration. Oxcarbazepine USP is 10,11-Dihydro-10-oxo-5 H- dibenz[b, f ]azepine-5-carboxamide, and its structural formula is Oxcarbazepine USP is a light orange to creamish white or off-white powder. It is sparingly soluble in chloroform. Its molecular weight is 252.27 g/mol. Oxcarbazepine Tablets, USP contains the following inactive ingredients: colloidal silicon dioxide, crospovidone, polyethylene glycol, hypromellose, iron oxide yellow, iron oxide red, microcrystalline cellulose, magnesium stearate, titanium dioxide and talc. FDA approved organic impurities acceptance criteria differs from USP test. structure

10 OVERDOSAGE 10.1 Human Overdose Experience Isolated cases of overdose with oxcarbazepine tablets 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.

10.1 Human Overdose Experience Isolated cases of overdose with oxcarbazepine tablets 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.

16 HOW SUPPLIED/STORAGE AND HANDLING Oxcarbazepine Tablets USP, 150 mg are yellow colored, oval shaped, biconvex, film coated tablets scored on both sides and debossed with "6" and "91" separating with scoring on one side and plain on other side and are supplied as follows: NDC 70771-1842-1 in bottles of 100 tablets NDC 70771-1842-5 in bottles of 500 tablets NDC 70771-1842-4 in unit-dose blister cartons of 100 Tablets (10 x 10 Unit-dose) Oxcarbazepine Tablets USP, 300 mg are yellow colored, oval shaped, biconvex, film coated tablets scored on both sides and debossed with "6" and "92" separating with scoring on one side and plain on other side and are supplied as follows: NDC 70771-1843-1 in bottles of 100 tablets NDC 70771-1843-5 in bottles of 500 tablets NDC 70771-1843-0 in bottles of 1,000 tablets NDC 70771-1843-4 in unit-dose blister cartons of 100 Tablets (10 x 10 Unit-dose) Oxcarbazepine Tablets USP, 600 mg are yellow colored, oval shaped, biconvex, film coated tablets scored on both sides and debossed with "6" and "93" separating with scoring on one side and plain on other side and are supplied as follows: NDC 70771-1844-1 in bottles of 100 tablets NDC 70771-1844-5 in bottles of 500 tablets NDC 70771-1844-4 in unit-dose blister cartons of 100 Tablets (10 x 10 Unit-dose) Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature]. Dispense in tight container (USP).