Abstract
Carbamazepine (CBZ) occasionally causes haematological disorders such as thrombocytopenia, and recently a case of oxcarbazepine (OXCBZ)-induced thrombocytopenia has been described. The aim of our study was blood platelet count determination in epileptic patients treated with CBZ and OXCBZ, and its relationship with the dose and serum levels of these drugs and its metabolites. The serum levels of CBZ and its epoxide, and the pharmacologically active monohydroxy derivative of OXCBZ were determined in 137 patients treated with CBZ, and 60 patients treated with OXCBZ. The platelet count, mean platelet volume, and platelet size distribution width were also determined. The difference between the platelet counts of the patient groups treated with CBZ and OXCBZ was not significant. No significant correlations between the platelet count and serum levels of the administered antiepileptic drugs and their metabolites were found. However, significant negative correlations between the platelet count and the daily doses of CBZ and OXCBZ were obtained (p<0.01). In 5 cases (4 treated with CBZ and 1 with OXCBZ) the platelet count was <150 x 10(9)/l. In accordance with the mean platelet volume and platelet distribution width, the thrombocytopenia observed in some of the patients studied was due to a hyper-destruction of peripheral blood platelets. However, the results obtained suggest that the mechanism of CBZ or OXCBZ-induced thrombocytopenia is not due to a direct toxicity of these drugs or their major metabolites on the circulating platelets. Although, the patients treated with OXCBZ shown a lower prevalence for thrombocytopenia (1.7%) than those treated with CBZ (2.9%), the routine platelet count monitoring in patients treated with both drugs may be recommended.
Highlights
Oxcarbazepine (Trileptal®, OXCBZ) is an antiepileptic drug used for the treatment of partial seizures, which has been developed through the structural modification of carbamazepine (Tegretol®, CBZ) with the aim of avoiding metabolites causing side effects
In the case of the 60 patients treated with OXCBZ, for a dose of 1167.27 ± 57.03 mg/day, the serum concentration of MHCBZ was 16.47 ± 0.80 mg/l
The distribution of the platelet count in the patients treated with CBZ and OXCBZ is shown in Fig. 1, without finding any significant differences between the groups of patients for the platelet count (265.34 ± 6.96 x 109/l vs 252.1 ± 9.78 x 109/l), VPM (7.95 ± 0.09 fl vs 7.99 ± 0.12 fl) or platelet size distribution width (PDW) (49.92 ± 0.68 % vs 49.56 ± 1.15 %)
Summary
Oxcarbazepine (Trileptal®, OXCBZ) is an antiepileptic drug used for the treatment of partial seizures, which has been developed through the structural modification of carbamazepine (Tegretol®, CBZ) with the aim of avoiding metabolites causing side effects. CBZ is metabolised to carbamazepine-10,11-epoxide (CBZE), and subsequently transformed into trans-10,11-dihydrocarbamazepine, with the pharmacological activity and proposed action mechanism of CBZE similar to that of the parent drug. A decrease in blood platelets is not considered a major side effect of OXCBZ8; Mahmud et al.[9] recently described a case of thrombocytopenia secondary to OXCBZ administration, and these authors recommend that physicians prescribing this drug should carry out blood-profile monitoring for the patients treated. Carbamazepine (CBZ) occasionally causes haematological disorders such as thrombocytopenia, and recently a case of oxcarbazepine (OXCBZ)-induced thrombocytopenia has been described. The aim of our study was blood platelet count determination in epileptic patients treated with CBZ and OXCBZ, and its relationship with the dose and serum levels of these drugs and its metabolites
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