Oxcarbazepine: uses, appearance and warnings

Oxcarbazepine tablets 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. Oxcarbazepine tablets 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 )

Film-coated Tablets: 150 mg: pale yellow to brownish light green, oval shaped, film coated tablets, scored (functionally scored) on both sides and debossed with “OX 150ʼʼ on one side. 300 mg: light yellow to yellow, oval shaped, film coated tablets, scored (functionally scored) on both sides and debossed with ʽʽOX 300ʼʼ on one side. 600 mg: light Pink to Pink, oval shaped, film coated tablets, scored (functionally scored) on both sides and debossed with ʽʽOX 600ʼʼ on one side. Film-coated tablets: 150 mg, 300 mg and 600 mg ( 3 )

Tablets 150 mg Film-Coated Tablets: Pale yellow to brownish light green, oval shaped, film coated tablets, scored (functionally scored) on both sides and debossed with ʽʽOX 150ʼʼ on one side. Bottle of 100…………………………………………………………………………………………………………………………………NDC-90096-171-01 300 mg Film-Coated Tablets: Light yellow to yellow, oval shaped, film coated tablets, scored (functionally scored) on both sides and debossed with ʽʽOX 300ʼʼ on one side. Bottle of 100…………………………………………………………………………………………………………………………………NDC-90096-172-01 600 mg Film-Coated Tablets: Light Pink to Pink, oval shaped, film coated tablets, scored (functionally scored) on both sides and debossed with ʽʽOX 600ʼʼ on one side. Bottle of 100…………………………………………………………………………………………………………………………………NDC-90096-173-01 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).

Oxcarbazepine tablets 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 )

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 oxcarbazepine tablets 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 oxcarbazepine tablets use. In the 14 controlled epilepsy studies, 2.5% of oxcarbazepine tablets-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 oxcarbazepine tablets, 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 oxcarbazepine tablets 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 oxcarbazepine tablets 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 oxcarbazepine tablets, 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 oxcarbazepine tablets. Angioedema associated with laryngeal edema can be fatal. If a patient develops any of these reactions after treatment with oxcarbazepine tablets, 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 oxcarbazepine tablets. 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 oxcarbazepine tablets only if the potential benefit justifies the potential risk. If signs or symptoms of hypersensitivity develop, oxcarbazepine tablets 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 oxcarbazepine tablets 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 oxcarbazepine tablets has also been reported. The reporting rate of TEN and SJS associated with oxcarbazepine tablets 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 oxcarbazepine tablets, consideration should be given to discontinuing oxcarbazepine tablets 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 oxcarbazepine tablets treatment. Human Leukocyte Antigen (HLA) allele B * 1502 increases the risk for developing SJS/TEN in patients treated with carbamazepine. The chemical structure of oxcarbazepine tablets is similar to that of carbamazepine. Available clinical evidence, and data from nonclinical studies showing a direct interaction between oxcarbazepine tablets and HLA- B * 1502 protein, suggest that the HLA-B*1502 allele may also increase the risk for SJS/TEN with oxcarbazepine tablets. 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. …

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, vo …

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: 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. …