Oxcarbazepine dosing

Adjunctive therapy (600 mg/day twice/day) - If clinically indicated, the dose may be increased by a maximum of 600 mg/day at approximately weekly intervals the recommended daily dose is 1200 mg/day. Daily doses more than 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. Observe and monitor closely the plasma levels of the concomitant AEDs during the period of oxcarbazepine titration, especially at oxcarbazepine doses more than 1200 mg/day. 

Hyponatremia Clinically significant hyponatremia generally occurred during the first 3 months of treatment with oxcarbazepine, although there were patients who first developed a serum sodium less than 125 mmol/L greater 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 dose reduced or discontinued or had their fluid intake restricted for hyponatremia. When oxcarbazepine was discontinued, normalization of serum sodium generally occurred within a few days without additional treatment. 

When converting from adjunctive to monotherapy in the treatment of epiiepsy, titrate concomitant drug down over 3- weeks whiie titrating oxcarbazepine up over 2-4 weeks, with an initiai daiiy oxcarbazepine dose of 600 mg divided in 2 doses... 

Information about the concurrent use of oxcarbazepine and other antiepi-lepties is limited, but growing. The overall picture seems to be that, oxcarbazepine is a less potent enzyme inducer than carbamazepine, and therefore it does not markedly affect the serum levels of other antiepilep-ties. If oxearbazepine is substituted for carbamazepine, be aware that drug levels of some other antiepileptics may rise. High oxcarbazepine doses may inerease phenytoin levels, and the manufacturer notes that a decrease in the phenytoin dose may be required. The clinical relevance of the modest reductions in lamotrigine levels is uncertain. For mention of modestly reduced levetiracetam levels, see Levetiracetam + Other antiepileptics , p.543. 

Carbamazepine and valproate appear to lower olanzapine levels. The combination of olanzapine and valproate appears to increase the risk of hepatic injury in children. Olanzapine reduces lamot-rigine levels and lamotiigine may increase olanzapine levels, although these changes are not expected to be clinically significant in the majority of patients. Oxcarbazepine dose not appear to affect the pharmacokinetics of olanzapine. 

Carbamazepine increases the metabolism of risperidone, resulting in reduced risperidone levels. Oxcarbazepine dose not significantly affect the pharmacokinetics of risperidone. 

A kidney transplant patient taking ciclosporin 270 mg daily and valproate, gabapentin, prednisone, doxepin, allopurinol, levothyroxine and pravastatin was also given oxcarbazepine. Fourteen days later, with the dose of oxcarbazepine at 750 mg daily, the ciclosporin trough level fell below 100 nanograms/mL and after a further 2 days was 87 nanograms/mL. The ciclosporin dose was increased to 290 mg daily and the oxcarbazepine dose reduced to 600 mg daily. Ciclosporin levels then remained stable above 100 nanograms/mL and seizure frequency was reduced by 95%. ... 

In a retrospective study of the medical records of 26 children and adolescents with epilepsy who had been rapidly switched from carbamazepine to oxcarbazepine (dose conversion ratios 1.0-1.5), the transition was well tolerated three patients had adverse events (rashes) 21T],... 

Oxcarbazepine Modulate sodium channels Loading dose Not recommended due to excessive adverse effects Maintenance dose 600-1200 mg/day. Start at 300 mg twice daily and titrate upward as indicated by response Half-life Not established Parent drug 2 hours 1 0-monohydroxy metabolite 9 hours Apparent volume of distribution 0.5-0.7 L/kg Protein binding 40% Primary elimination route Hepatic Diplopia, dizziness, somnolence Hyponatremia, 25-30% cross sensitivity in patients with hypersensitivity to carbamazepine... 

Oxcarbazepine Trileptal Tablets 150, 300, 600 mg 300-1200 mg/day in two divided doses May cause fewer adverse... 

In adults, the starting dose of oxcarbazepine as monotherapy is 300 mg once or twice daily. This can be increased by 600 mg/day each week to a maximum dose of 2,400 mg/day. This is titrated to the target dose over 2 weeks. See manufacturer s recommendations for dosing by weight. 

In patients converted from carbamazepine, the typical maintenance doses of oxcarbazepine are 1.5 times the carbamazepine dose. 

Oxcarbazepine Trileptal Tablet 150, 300,600 mg Suspension 300 mg/5 mL 300-1,200 mj day in two divided doses. Dosage should be slowly adjusted up and down according to response and adverse effects (e.g, 150-300 mg twice daily and increase by 300-600 mg/day at weekly intervals). Dose can be increased rapidly for inpatients. 

Initiation of monotherapy (600 mg/day twice/day) - Increase 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. 

Adjunctive therapy - 8 to 10 mg/kg not to exceed 600 mg/day twice/day. Achieve the target maintenance dose of oxcarbazepine over 2 weeks,... 

Oxcarbazepine Target Maintenance Doses for Pediatric Patients ... 

Conversion to monotherapy Patients receiving concomitant AEDs may be converted to monotherapy by initiating treatment at approximately 8 to 10 mg/kg/day given in a twice-daily regimen, 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 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. 

Maintenance Doses of Oxcarbazepine for Children During Monotherapy ... 

Hepatic function impairment The pharmacokinetics of oxcarbazepine and MHD have not been evaluated in severe hepatic impairment. Adjust dose in renally impaired patients. 

Carcinogenesis In mice, a dose-related increase in the incidence of hepatocellular adenomas was observed with oxcarbazepine. 

Elderly Following administration of single (300 mg) and multiple (600 mg/day) doses of oxcarbazepine to elderly volunteers (60 to 82 years of age), the maximum plasma concentrations and AUC values of MHD were 30% to 60% higher than in younger volunteers (18 to 32 years of age). 

Children After a single-dose administration of 5 to 15 mg/kg of oxcarbazepine, the dose-adjusted AUC values of MHD were 30% to 40% lower in children younger than 8 years of age than in children older than 8 years of age. The clearance in children older than 8 years of age approaches that of adults. 

Cimetidine, erythromycin, and dextropropoxyphene had no effect on the pharmacokinetics of MHD. Results with warfarin show no evidence of interaction with either single or repeated doses of oxcarbazepine. 

With the exception of topiramate (which also requires a high-dose oestroprogestogen), second generation AEDs are not considered to interfere with oestroprogestogen metabolism. The enzyme induction capacity of oxcarbazepine is much weaker than that of carbamazepine. 

Ethosuximide should be discontinued immediately. It is probably appropriate to discontinue the valproic acid over the next week or so. At that time, the dose of oxcarbazepine should be decreased by 50% if there is no increased incidence of seizures following termination of valproic acid. Since the woman has had a relatively long duration of seizure episodes, it is probably not reasonable to discontinue all medication. She should keep a log of her seizure incidence and contact you immediately if the incidence appears to be increasing. 

Geriatric Considerations - Summary Well-tolerated in older adults. Adjust dose based on creatinine clearance. Autoinduction of metabolism does not occur as seen with carbamazepine, but drug interactions are still an issue. Many of the CNS effects occur early in treatment and are transitory. One-third of patients with hypersensitivity reactions to carbamazepine will experience cross-sensitivity to oxcarbazepine. 

Emrich HM, Dose M, Von Zerssen D The use of sodium valproate, carbamazepine and oxcarbazepine in patients with affective disorders. J Affect Disord 8 243-250, 1985... 

Oxcarbazepine is less potent than carbamazepine, both in animal models of epilepsy and in epileptic patients clinical doses of oxcarbazepine may need to be 50% higher than those of carbamazepine to obtain equivalent seizure control. Some studies report fewer hypersensitivity reactions to oxcarbazepine, and cross-reactivity with carbamazepine does not always occur. Furthermore, the drug appears to induce hepatic enzymes to a lesser extent than carbamazepine, minimizing drug interactions. Although hyponatremia may occur more commonly with oxcarbazepine than with carbamazepine, most adverse effects that occur with oxcarbazepine are similar in character to reactions reported with carbamazepine. 

A 10-year-old child had status epilepticus controlled with a combination of valproate, oxcarbazepine, and 48 hours of propofol infusion in a dose of 5.5 mg/kg/ hour. After weaning from propofol, a classic ketogenic diet was instituted in an attempt to provide long-term control of the seizures. A day later status epilepticus recurred and propofol was restarted at a rate of 6-9 mg/ kg/hour to suppress seizure activity (the diet, valproate, and oxcarbazepine were also continued). Shortly thereafter, he developed the classical constellation of malignant ventricular arrhythmias, hyperlipidemia, rhabdomyolysis, lactic acidosis, and biventricular cardiac failure. He did not survive. 

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