TRILEPTAL

What it is

Trileptal contains oxcarbazepine and is available as film-coated tablets containing 150 mg, 300 mg or 600 mg oxcarbazepine. An oral suspension formulation is also available, containing 60 mg oxcarbazepine per mL. Trileptal can be taken with or without food.

Approved indications

— Treatment of partial seizures and generalised tonic-clonic seizures in adults and children, as monotherapy or adjunctive therapy.

Dosing overview

In adults, Trileptal should be initiated with a dose of 600 mg per day given in two divided doses. Good therapeutic effects are seen at doses between 600 mg per day and 2400 mg per day, with the dose increased by a maximum of 600 mg per day at approximately weekly intervals if clinically indicated. The maximum daily dose is 2400 mg per day. In paediatric patients, Trileptal should be initiated with a dose of 8–10 mg per kilogram per day given in two divided doses. If clinically indicated, the dose may be increased by a maximum of 10 mg per kilogram per day at approximately weekly intervals from the starting dose, to a maximum daily dose of 60 mg per kilogram per day. No special dose recommendations are necessary in elderly patients because therapeutic doses are individually adjusted. In patients with impaired renal function (creatinine clearance less than 30 mL per minute), Trileptal therapy should be initiated at half the usual starting dose of 300 mg per day and increased slowly to achieve the desired clinical response.

Key safety warnings

Class I hypersensitivity reactions including rash, pruritus, urticaria, angioedema and anaphylaxis have been reported, with cases of anaphylaxis and angioedema involving the larynx, glottis, lips and eyelids reported after taking the first or subsequent doses of Trileptal. Multi-organ hypersensitivity reactions have occurred in close temporal association (median time to detection 13 days, range 4–60 days) to the initiation of Trileptal therapy, with many cases resulting in hospitalisation and some considered life-threatening. Serious dermatological reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis and erythema multiforme, have been reported very rarely in association with the use of Trileptal. Retrospective studies in patients of Han Chinese and Thai origin found a strong correlation between Stevens-Johnson syndrome and toxic epidermal necrolysis skin reactions associated with carbamazepine and the presence of the HLA-B*1502 allele; as oxcarbazepine is chemically similar to carbamazepine, there is a possibility that patients carrying this allele also have an increased risk of these skin reactions with oxcarbazepine. Testing for the presence of the HLA-B*1502 allele should be considered in patients with ancestry in genetically at-risk populations prior to initiating treatment with Trileptal, and Trileptal should be avoided in tested patients who are found to be positive for HLA-B*1502 unless the benefits clearly outweigh the risks. Serum sodium levels below 125 mmol per litre, usually asymptomatic and not requiring adjustment of therapy, have been observed in up to 2.7 per cent of Trileptal treated patients. In patients with pre-existing renal conditions associated with low sodium levels, inappropriate antidiuretic hormone secretion, or in patients treated concomitantly with sodium-lowering drugs or non-steroidal anti-inflammatory drugs, serum sodium levels should be measured prior to initiating therapy, after approximately two weeks, and then at monthly intervals for the first three months during therapy. Antiepileptic drugs, including oxcarbazepine, increase the risk of suicidal thoughts or behaviour in patients taking these drugs for any indication, and patients treated with any antiepileptic drug for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behaviour, and any unusual changes in mood or behaviour.

Contraindications

Trileptal is contraindicated in patients with known hypersensitivity to oxcarbazepine or eslicarbazepine or to any of the excipients.

PBS listing

Trileptal tablets 150 mg, 300 mg and 600 mg, and oral suspension 60 mg per mL are listed on the PBS with streamlined restriction. The ex-manufacturer prices are A$40.20 for 150 mg tablets, A$66.34 for 300 mg tablets, A$110.84 for 600 mg tablets, and A$40.20 for oral suspension 250 mL.

Regulatory history

Trileptal 150 mg tablets were first registered on the ARTG on 9 October 2000, with 300 mg and 600 mg tablets registered on 13 October 2000. The oral suspension 60 mg per mL was registered on 17 December 2001.