Epilepsia, 45(7):877–878, 2004 Blackwell Publishing, Inc. C 2004 International League Against Epilepsy
Original Letters
Levetiracetam-induced Thrombocytopenia ∗ †Elin Kimland, ‡Bo H¨ojeberg, and ∗ †‡Mia von Euler ∗ Drug Information Center, Division of Clinical Pharmacology, †Stockholm Regional Pharmacovigilance Center, and ‡Division of Neurology, NEUROTEC, Karolinska University Hospital-Huddinge, Karolinska Institutet, Stockholm, Sweden
The patient was a 49-year old man with an anaplastic oligoastrocytoma. The oligoastrocytoma was diagnosed in 1983 and surgically treated in 1983, 1988, and 2001. The patient had received radiation therapy in 1988, N-(2chloroethyl)-N -cyclohexyl-N-nitrosourea (CCNU) treatment from 1998 to 2002, and temozolomid treatment, 200 mg/m2 for 5 days every 4 weeks, since 2002. The treatment with temozolomid was well tolerated, and no signs of bone marrow depression were noted. Epilepsy developed and became refractory to treatment with both phenytoin (PHT; 300 mg/day) and phenobarbital (PB; 30 mg/day). Subsequently levetiracetam (LEV), 250 mg twice daily, was added to reduce seizures, and the daily dose of PHT and PB were increased to 350 mg and 50 mg, respectively. The patient had an infection that was treated with cefuroxim. Because of a concomitant depression, treatment with sertraline, a selective serotonin uptake inhibitor, was started at a dose of 50 mg daily. The patient also was, as he had been for a long time, taking betamethasone (6– 8 mg daily), diazepam (DZP; rarely), oxazepam (5 mg, less than once weekly), vitamin B supplement, and zolpidem (7.5 mg daily) on a regular basis. Twenty days after LEV was introduced, hematuria developed. The platelet count was 7 × 109 /L (reference value, 150–400 × 109 /L); leukocyte count was 9.2 × 109 /L (reference value, 4–10 × 109 /L), and hemoglobin count was 118 g/L (reference value, 130–165 g/L). The day after LEV treatment was started, the thrombocyte count had been 314 × 109 /L. A bone marrow aspiration showed unremarkable morphology with normal megakaryocytes. Steroid treatment with prednisone, 100 mg daily, was started. Platelet infusion (2 units) and intravenous immunoglobulin treatments (30 g daily for 5 days) were given without any significant effect on the platelet count. The patient had received 15 cycles of temozolomid treatment, the last one 5 months before the decrease in platelet levels. Effect on platelets
is rarely seen at this stage of temozolomid treatment, and the reaction was thus considered an adverse effect to either one of the new drugs, LEV or sertraline, or less likely, the combination of them. Both drugs were discontinued the day after the decrease in platelets was observed. A blood sample was analysed with the MAIPA technique (monoclonal antibody immobilization of platelet antigen) and screened for irregular antibodies in the presence of LEV or sertraline. Irregular antibodies for platelets were observed in the presence of LEV but not in the presence of sertraline. This supports the idea that thrombocytopenia was LEV induced. Five weeks after discontinuation of LEV, the patient’s thrombocyte count was 94 × 109 /L. LEV is a new antiepileptic drug (AED) that was released to the Swedish market in 2000 (1). Previously one case report concerning a possible LEV-associated thrombocytopenia has been published (2). That report concerns a 16-year-old girl that first developed a chronic immunemediated thrombocytopenia during treatment with valproate (VPA), oxcarbazepine (OXC), and PHT. All drugs were discontinued, and her thrombocyte count increased. However, after the initiation of LEV monotherapy, her thrombocyte count decreased again, and bleeding developed (2). One report was made to the Swedish Adverse Drug Reactions Advisory Committee (SADRAC) concerning a patient with thrombocytopenia, which improved after discontinuation of LEV. However, in that case, several other factors, such as polypharmacy, infection, and previous thrombocytopenia, might also have contributed to or caused the reaction. The World Health Organization (WHO) adverse drug reaction–monitoring center has received 14 reports concerning thrombocytopenia as an adverse reaction associated with LEV treatment (3). However, not all of these reports are evaluated as to causality because of differences among reporting countries. The company has received sporadic reports of low platelet counts in patients treated with LEV, although causality has not been absolutely clear (personal communication with UCB, 2003). The present case has been reported to SADRAC and INTDIS.
Accepted February 26, 2004. Address correspondence and reprint requests to Dr M. von Euler at Division of Neurology, R52, Karolinska University Hospital-Huddinge, S-141 86 Stockholm, Sweden. E-mail:
[email protected]
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E. KIMLAND ET AL.
LEV can be useful in treatment of therapy-resistant epilepsy. The present case indicates that LEV treatment may have thrombocytopenia as a rare adverse reaction. Acknowledgment: We are grateful to Professor Folke Sj¨oqvist, Dr. Agneta Wickman, Dr. Ulla Lindbom, and Ingela Jersenius, RN, for discussion and helpful suggestions.
Epilepsia, Vol. 45, No. 7, 2004
REFERENCES 1. Swedis (The Swedish Drug Information System) (cited 2003:06–18). 2. Hartmann H, Schumacher U, Seeck M. Verschlechterung einer Immunthrombopenie unter Monotherapie mit Levetiracetam. Aktuel Neurol 2002;29:467–8. 3. Vigibase: WHO’s adverse drug reactions database (cited 2003;06– 18).
