Efficacy and safety of fenfluramine in Dravet syndrome; A monocentric, observational study focused on initial dose, blood concentration, and reduction of concomitant medications.

OBJECTIVE

To evaluate the optimal initial dose, efficacy, and adverse events of fenfluramine (FFA) in the treatment of intractable epilepsy in Dravet syndrome (DS) in Japanese patients.

METHODS

This single-center, observational study included Dravet patients treated with FFA. Information retrospectively collected from medical records included age, sex, concomitant antiseizure medications (including stiripentol [STP]), the initial and maximum dose of FFA, differences in the effects of FFA with and without STP, convulsive seizure frequency, adverse events, and FFA blood concentration.

RESULTS

Of the 27 patients, 13 (48.1%) were male, and the median age was 14.9 years. After the initiation of FFA, 59.3% and 25.9% of patients were 50% and 90% responders, respectively. Of the sixteen 50% responders, 13 (81.3%) had either discontinued a concomitant antiseizure medication or were in the process of reducing the dose. In 88.9% of patients, the initial dose of FFA was less than 0.2 mg/kg/day, and ≥ 50% seizure reduction was achieved in 45.8% at less than 0.2 mg/kg/day. The effectiveness of FFA was not significantly different with or without STP. Among the ≥ 50% responders, cognitive and behavioral function improved in 9 (56.3%). The major adverse events were diarrhea (29.6%). No patients developed valvular heart disease or pulmonary artery hypertension. Among patients whose blood concentrations of FFA were measured, all 50% responders had < 80 ng/mL.

SIGNIFICANCE: FFA effectively reduced convulsive seizures in DS even at low concentrations. we recommend the initiation of low-dose FFA, which may allow dose reduction or discontinuation of concomitant antiseizure medications in FFA responders.