Neurology Division, "Annunziata" Hospital, Cosenza, Italy.
Ann Pharmacother. 2010 Dec;44(12):2031-4. doi: 10.1345/aph.1P335. Epub 2010 Nov 23.
To report on a patient with epilepsy who developed leukopenia and thrombocytopenia during phenobarbital/lamotrigine treatment.
A 45-year-old woman with a 10-year history of complex partial seizures being treated with phenobarbital 100 mg/day presented due to the development of complex partial seizure episodes (8 episodes/month in the last 6 months). Results of laboratory tests on admission showed normal platelets (250 x 10³/μL) and white blood cells (8.2 x 10³/μL). After clinical evaluation, lamotrigine titrated to a final dose of 100 mg twice daily was added to the phenobarbital. About 2 months later no epileptic manifestations were reported, but hematologic tests revealed a decrease in both platelets (36 x 10³/μL) and white blood cells (2.0 x 10³/μL). One day later, phenobarbital was discontinued and the patient developed 2 episodes of complex partial seizure. Levetiracetam titrated to 1500 mg/day was added to lamotrigine, with a normalization of platelets (260 x 10³/μL) and white blood cell (7.9 x 10³/μL) counts about 20 days later. After a few days, levetiracetam was discontinued and phenobarbital rechallenge during lamotrigine treatment induced a new blood dyscrasia in about 2 weeks (platelets 80 x 10³/μL; white blood cells 3.2 x 10³/μL). Phenobarbital was discontinued and levetiracetam was restarted, with a recovery of normal hematopoiesis in 25 days. The patient is presently receiving treatment with both lamotrigine 200 mg/day and levetiracetam 1500 mg/day and shows no seizure symptoms, blood abnormalities, or other adverse effects.
Using the Horn Drug Interaction Probability Scale, we estimated a probable relationship between the drug-drug interaction and blood dyscrasia. The underlying mechanism of this interaction has not been well characterized. Cytochrome P450 enzyme induction by phenobarbital could be responsible for the production of reactive metabolites of lamotrigine that might be causative for the observed hematologic effects. A pharmacodynamic interaction between the 2 drugs is also a possible mechanism of this interaction.
Our patient with epilepsy developed blood dyscrasia during lamotrigine/phenobarbital treatment. Clinicians should carefully monitor hematologic parameters during lamotrigine/phenobarbital treatment.
报告 1 例在苯巴比妥/拉莫三嗪治疗期间发生白细胞减少和血小板减少的癫痫患者。
一位 45 岁女性，患有复杂部分性癫痫 10 年，接受苯巴比妥 100mg/天治疗，因复杂部分性发作（过去 6 个月每月发作 8 次）就诊。入院时实验室检查结果显示血小板（250x10³/μL）和白细胞（8.2x10³/μL）正常。临床评估后，加用拉莫三嗪滴定至最终剂量 100mg，每日 2 次。大约 2 个月后，未报告癫痫发作，但血液检查显示血小板（36x10³/μL）和白细胞（2.0x10³/μL）均减少。1 天后，停用苯巴比妥，患者出现 2 次复杂部分性发作。加用左乙拉西坦滴定至 1500mg/天，约 20 天后血小板（260x10³/μL）和白细胞（7.9x10³/μL）计数恢复正常。几天后，停用左乙拉西坦，拉莫三嗪治疗期间再次使用苯巴比妥，大约 2 周后引起新的血液学异常（血小板 80x10³/μL；白细胞 3.2x10³/μL）。停用苯巴比妥，重新开始使用左乙拉西坦，25 天后恢复正常造血。目前，患者接受拉莫三嗪 200mg/天和左乙拉西坦 1500mg/天治疗，无癫痫发作症状、血液异常或其他不良反应。
根据 Horn 药物相互作用概率量表，我们估计药物-药物相互作用和血液学异常之间存在可能的关系。这种相互作用的潜在机制尚未得到很好的描述。苯巴比妥诱导细胞色素 P450 酶可能导致拉莫三嗪的反应性代谢物产生，这可能是观察到的血液学效应的原因。两种药物之间的药效学相互作用也是这种相互作用的一种可能机制。
我们的癫痫患者在拉莫三嗪/苯巴比妥治疗期间发生血液学异常。临床医生应在拉莫三嗪/苯巴比妥治疗期间仔细监测血液学参数。
