Wiemer-Kruel Adelheid, Stiller Brigitte, Bast Thomas
Clinic for Children and Adolescents, Epilepsy Center Kork, Tuberous Sclerosis Center, Kehl-Kork, Germany.
Department of Congenital Heart Disease and Pediatric Cardiology, University Heart Centre Freiburg Bad Krozingen, University of Freiburg, Germany.
Neuropediatrics. 2019 Dec;50(6):400-403. doi: 10.1055/s-0039-1695786. Epub 2019 Sep 20.
A 6.5-year-old female patient with a TSC2 mutation had been given everolimus (EVE) for 3 years for pharmacoresistant focal epilepsy and for life-threatening, severe ventricular dysrhythmia. EVE had been started with daily dose of 0.15 mg/kg/day and was increased up to 0.6 mg/kg/day. Target blood trough levels of around 9 µg/L had been documented. Although EVE therapy revealed no effect on seizure activity, cardiac rhythm normalized completely. Thus, EVE was reduced to a dose of 0.3 mg/kg/day leading to stable blood trough levels of 4 to 5 µg/L. Due to refractory tonic seizures with a frequency of 1 to 4 per day, we initiated cannabidiol (CBD) treatment, raising it to a daily dose of 200 mg. After 6 weeks, the EVE blood trough levels rose to 12.0 µg/L. Although we halved the EVE dose, her EVE blood trough level continued increasing up to 16.0 µg/L.The CBD dose was increased to 500 mg/day (20.4 g/kg/day), but EEG parameters and seizures failed to respond. Serum concentrations of EVE were unstable under the co-medication with CBD. Depending on the CBD dose, they varied between 1.7 and 12.3 µg/L, while EVE was always administered at the same dose.Although never before reported, CBD and EVE appear to interact, due to the metabolic pathway through CYP 450 3A4. Although we detected no side effects in our patient, we strongly recommend drug monitoring using the combination of CBD with EVE to prevent harmful overdosing.
一名携带TSC2突变的6.5岁女性患者因药物难治性局灶性癫痫和危及生命的严重室性心律失常接受依维莫司（EVE）治疗3年。EVE起始剂量为每日0.15mg/kg/天，随后增至0.6mg/kg/天。记录到的目标血药谷浓度约为9μg/L。尽管EVE治疗对癫痫发作活动无效果，但心律完全恢复正常。因此，EVE剂量减至0.3mg/kg/天，血药谷浓度稳定在4至5μg/L。由于每天发作1至4次的难治性强直发作，我们开始使用大麻二酚（CBD）治疗，并将其剂量增至每日200mg。6周后，EVE血药谷浓度升至12.0μg/L。尽管我们将EVE剂量减半，但其血药谷浓度继续上升至16.0μg/L。CBD剂量增至500mg/天（20.4mg/kg/天），但脑电图参数和癫痫发作仍无反应。在与CBD联合用药时，EVE的血清浓度不稳定。根据CBD剂量不同，其浓度在1.7至12.3μg/L之间波动，而EVE的给药剂量始终相同。尽管此前未见报道，但由于通过细胞色素P450 3A4的代谢途径，CBD和EVE似乎存在相互作用。尽管我们的患者未检测到副作用，但我们强烈建议对CBD与EVE联合用药进行药物监测，以防止有害的过量用药。
