Abstracts

RATIONALE: Rash is a major adverse drug reaction which may lead to discontinuation of an antiepileptic drug (AED). The rate of treatment discontinuation due to rash in clinical practice is unknown for newer AEDs, including oxcarbazepine (OXC), levetiracetam (LEV), zonisamide (ZNS), topiramate (TPM), tiagabine (TGB)and lamotrigine (LTG). The rate of rash with these AEDs in patients who had a history of rash with previous AEDs is similarly unknown.
METHODS: Epilepsy patients placed on OXC, LEV, ZNS, TPM, TGB, and LTG since 1995 were enrolled prospectively from 17 academic centers which comprise the PADS (Postmarketing Antiepileptic Drug/Device Survey) study group. Data on patients who had at least six months of follow-up and who developed rash within the first six months of therapy or reported a history of rash on prior AEDs were evaluated.
RESULTS: The rate of rash leading to AED discontinuation was low in patients on OXC (1/47; 2.1%), LEV (0/61; 0.0%), ZNS (0/25; 0.0%), and TGB (0/178; 0.0%). Patients on TPM (4/535; 0.7%) had a significantly lower rate of drug discontinuation due to rash compared to patients on LTG (27/387; 7.0%) (p[lt]0.001).
None of the patients with a history of rash on up to three previous AEDs developed a rash with OXC (0/2), LEV (0/6), ZNS (0/2), and TGB (0/13). Only one of eight patients on LTG, who reported a rash with two or more prior AEDs, developed a rash which caused discontinuation of treatment. Three of 62 patients who had a history of rash on previous AEDs also developed a rash with TPM, which led to treatment discontinuation in two patients. However, none of the nine patients with a history of rash with multiple (two to three) previous AEDs developed a rash with TPM.
CONCLUSIONS: To date, preliminary postmarketing experience indicates a very low rate of rash leading to drug discontinuation in patients on the newest AEDs with the possible exception of LTG. We found little cross-reactivity to these AEDs in patients with a history of drug sensitivity, even for LTG. This finding may aid clinicians in the selection of AED therapy. Ongoing data collection may further clarify rates of relatively infrequent adverse events, such as rash.
Support: UCB, Ortho-McNeil, Glaxo-Wellcome, Elan Pharmaceuticals, Novartis.
Disclosure: Grant - UCB, Ortho-McNeil, Glaxo-Wellcome, Elan Pharmaceuticals, Novartis. Consulting - UCB, Ortho-McNeil, Glaxo-Wellcome, Elan Pharmaceuticals, Novartis. Honoraria - UCB, Ortho-McNeil, Glaxo-Wellcome, Elan Pharmaceuticals, Novartis.