Oxcarbazepine in the Real World

Carbamazepine has long been a mainstay of epilepsy pharmacotherapy. However, this agent is not without problems, such as significant rashes and strong hepatic enzyme induction.

Carbamazepine has long been a mainstay of epilepsy pharmacotherapy. However, this agent is not without problems, such as significant rashes and strong hepatic enzyme induction. The epilepsy community eagerly awaited the release of oxcarbazepine (OXC) to the US market in the late 90s, only to find that in epilepsy practice the reality somewhat lagged the promise. Adverse effects were still prominent, and rash was as much, if not more of a problem compared with carbamazepine. It seemed that oxcarbazepine was not what we might have hoped.

Use of this agent in epilepsy practice is different than by non-neurology prescribers. In particular, perceived adverse effects seemed to be less in primary care and other such settings. To what degree was not so clear, however, until now. Buggy et all looked at post-marketing surveillance data in the UK, based on GP prescription database data from 2000 to 2003. Surveys were sent to GPs after six or more months of OXC therapy. The surveys gathered use (e.g. monotherapy v. adjunctive therapy) and outcomes data. 4,434 forms were sent and about 44% were ultimately analyzed.

2,243 patients were included in the study. The mean age in the cohort was 40.4 years old, and virtually all prescriptions were to adults. 58.8% of prescriptions were for epilepsy or convulsions. Off-label uses included trigeminal neuralgia (4.6%) and otherwise largely a variety of pain-related indications. OXC was used as adjunctive therapy in 68.3% of patients, most commonly with lamotrigine, valproate and phenytoin. At six months, 73.2% of patients were still taking OXC. When GPs were questioned in general about efficacy (unrelated to any specific patient), only 68.0% categorized OXC as effective in general.

Discontinuation reasons were analyzed when data were available. The most common reason for stopping OXC was "not effective." Some adverse effects were much more common in the first month of therapy: Drowsiness/sedation, nausea/vomiting, malaise/lassitude, dizziness and rash were the most commonly cited. Interestingly, patients reporting dizziness were prescribed a lower average dose of OXC compared to those without this adverse effect.

Patients over 65 years old (n=193) were also separately analyzed. A higher percentage were treated with monotherapy (64.3%) compared to the cohort as a whole. And dosing was, appropriately, much lower: 61.7% of patients in this group were prescribed 600 mg./day or less. In decreasing order of incidence, the most common adverse effects which resulted in discontinuing therapy were hyponatremia, dizziness, drowsiness, diarrhea, and rash.

A few other points are also worthy of mention. Most patients with hyponatremia reported that this had occured in the past with carbamazepine therapy. No cardiac dysrhythmias or serious blood dyscrasias were reported. There were five pregnancies, all of which resulted in live births without major structural abnormalities. The usual limitations related to survey and retrospective studies obtain.

Some conclusions can be drawn from this study. OXC was, in general, used successfully by GPs, with an adverse effect profile not hugely different from that in specialty practice. No new adverse effects were noted in this real world setting. Off-label use was common. Thus, It seems that this agent has about the same overall profile in the trenches as it does in the ivory tower.