4CPS-175 Safe use of levetiracetam at doses higher than the maximum recommended

BackgroundLevetiracetam (LEV) is a second-generation antiepileptic drug used as a unique or adjunctive therapy for treating partial or generalised epilepsy. Its maximum dose according to the summary product is 3000 mg/day. In patients with resistant epilepsy sometimes it is used at doses higher than recommended. A recent report suggests that high doses may still be possible without toxicity.1 PurposeTo describe the importance of therapeutic drug monitoring (TDM) of LEV for minimising toxicity when it is used at doses higher than recommended.Material and methodsCase report of 57-years-old male diagnosed with symptomatic focal epilepsy and human immunodeficiency virus (HIV). Antiepileptic treatment consists of LEV 4000 mg/day, topiramate 300 mg/day and clonazepam 4 mg/day since 2010 plus lacosamide 200 mg/day added in 2015. In September 2016 he had a new neurological crisis and dosage was increased to 4500 mg/day. Antiretroviral medication (AM) was changed in 2013 from tenofovir/efavirenz/emtricitabine to abacavir/lamivudine plus efavirenz. In January 2017 AM medication was simplified to dolutegravir/abacavir/lamivudine.ResultsLEV trough plasma levels (LEVTPL) were 35.9 µg/mL (therapeutic range is 10–40 µg/mL) at the beginning of 2016, 6 years after treatment with LVT 4000 mg/day, glomerular filtration (GFR) calculated by CKD-EPI was >60 ml/min/1.73 m2 and the patient did not have clinical signs of toxicity. Three months after increasing LEV dose to 4500 mg/day the patient presented symptoms of intoxication, felt tired and sleepy. TDM confirmed supratherapeutic LEVTPL of 67.1 µg/mL accompanied by a slight deterioration of renal function (GFR: 50 ml/min/1.73 m2). Concomitant medication seemed not to interact with LEV. LEV dose was reduced to 3500 mg/day. Three months’ later, LEVTPL values returned to normal (36.3 µg/mL) and clinical signs of toxicity disappeared.ConclusionLEV at doses higher than recommended could be used safely if there is a close TDM programme to ensure treatment effectiveness and minimise adverse effects.References and/or Acknowledgements1. Stepanova D, Beran R. Measurement of levetiracetam drug levels to assit with seizure control and monitoring of drug interactions with other Anti-Epileptic Medication (AEMs). Seizure2014;23:371–376.No conflict of interest