Trileptal-induced TEN, SJS, and Hypersensitivity Reactions Reported to FDA
In April 2005 the FDA and Novartis Pharmaceuticals Corp. issued a MedWatch safety alert about the risk of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) associated with use of Trileptal (oxcarbazepine) in adults and children. Information regarding numerous reports of these serious skin reactions, as well as a limited number of multi-organ hypersensitivity reactions that have been reported to the FDA, was set forth in an April 18, 2005 "Dear Doctor" letter concerning Trileptal.
Trileptal, which comes in tablet form and as an oral suspension, is indicated for use as monotherapy or adjunctive therapy in the treatment of partial seizures in adults and in children aged four to 16 years.
According to the April 2005 FDA MedWatch alert about Trileptal, there have been reports of serious and potentially life-threatening dermatologic reactions, including SJS and TEN, in adult and pediatric patients receiving Trileptal. According to the FDA and Novartis, the median time of onset was 19 days and some patients required hospitalization to treat the most serious of the serious skin reactions.
The incidence of reports about Trileptal-induced Stevens-Johnson syndrome and toxic epidermal necrolysis made through the FDA Adverse Events Reporting System ("AERS") -- which reporting level is generally considered an underestimate due to the widely-held belief that only ten percent of adverse events are ever reported to the FDA -- exceeds the background incidence rate estimate (0.5 - 6.0 cases/million person-years) for SJS and TEN by a factor of 3- to 10-fold. Due to the general "under-reporting" problem, the real factor number is probably significantly higher.
Replacement of Trileptal with another antiepileptic medication should be considered in patients who develop a serious skin reaction during Trileptal treatment.
Multi-organ hypersensitivity reactions have also been reported after initiation of Trileptal therapy in adult and pediatric patients, with a median time to detection of 13 days (range, 4 - 60 days). Although the number of hypersensitivity reaction reports is limited, many of these patients required hospitalization, some for life-threatening conditions.
Signs and symptoms of the Trileptal-induced hypersensitivity reactions were diverse due to the variable nature of disease expression, but patients typically presented with fever and rash associated with other organ system involvement. Manifestations included -- but were not limited to -- lymphadenopathy, hepatitis, liver function test abnormalities, hematologic abnormalities (eosinophilia, thrombocytopenia, neutropenia), pruritis, nephritis, oliguria, hepatorenal syndrome, arthralgia, and asthenia.
Replacement of Trileptal with alternative therapy is recommended if multi-organ hypersensitivity is suspected.
(Posted by: Tom Lamb)