Oxcarbazepine

OXCARBAZEPINE- oxcarbazepine suspension
Hikma Pharmaceuticals USA Inc.

1 INDICATIONS AND USAGE

Oxcarbazepine oral suspension 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.

2 DOSAGE AND ADMINISTRATION

2.1 Adjunctive Therapy for Adults

Initiate oxcarbazepine 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 CNS effects.

Dosage adjustment is recommended with concomitant use of strong CYP3A4 enzyme inducers or 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 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 The concomitant AEDs should be completely withdrawn over 3 to 6 weeks, while the maximum dose of oxcarbazepine should be reached in about 2 to 4 weeks. Oxcarbazepine 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. 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. In these patients, initiate oxcarbazepine 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 oxcarbazepine monotherapy (see above).

2.4 Adjunctive Therapy for Pediatric Patients (Aged 2 to 16 Years)

In pediatric patients aged 4 to 16 years, initiate oxcarbazepine 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 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 oxcarbazepine 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 oxcarbazepine 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 antiepileptic drugs (AEDs) [see Drug Interactions (7.1, 7.2)].

2.5 Conversion to Monotherapy for Pediatric Patients (Aged 4 to 16 Years)

Patients receiving concomitant antiepileptic drugs may be converted to monotherapy by initiating treatment with oxcarbazepine at approximately 8 to 10 mg/kg/day given twice-a-day, while simultaneously initiating the reduction of the dose of the concomitant antiepileptic drugs. The concomitant antiepileptic drugs can be completely withdrawn over 3 to 6 weeks while oxcarbazepine 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 oxcarbazepine is shown in Table 1.

2.6 Initiation of Monotherapy for Pediatric Patients (Aged 4 to 16 Years)

Patients not currently being treated with antiepileptic drugs may have monotherapy initiated with oxcarbazepine. In these patients, initiate oxcarbazepine at a dose of 8 to 10 mg/kg/day given twice-a-day. The dose should be increased by 5 mg/kg/day every third day to the recommended daily dose shown in the table below.

Table 1: Range of Maintenance Doses of Oxcarbazepine for Pediatrics by Weight During Monotherapy

	From	To
Weight in kg	Dose (mg/day)	Dose (mg/day)
20	600	900
25	900	1200
30	900	1200
35	900	1500
40	900	1500
45	1200	1500
50	1200	1800
55	1200	1800
60	1200	2100
65	1200	2100
70	1500	2100