Currently Enrolling Trials
Fintepla (fenfluramine) is a selective serotonin reuptake inhibitor.
Fintepla is specifically indicated for the treatment of seizures associated with Dravet syndrome in patients 2 years of age and older.
Fintepla is supplied as an oral solution. The initial starting and maintenance dosage is 0.1 mg/kg twice daily, which can be increased weekly based on efficacy and tolerability. Please see the drug label for the recommended titration schedule, if needed.
- Patients not on concomitant stiripentol who are tolerating Fintepla at 0.1 mg/kg twice daily and require further reduction of seizures may benefit from a dosage increase up to a maximum recommended maintenance dosage of 0.35 mg/kg twice daily (maximum daily dosage of 26 mg).
- Patients taking concomitant stiripentol and clobazam who are tolerating Fintepla at 0.1 mg/kg twice daily and require further reduction of seizures may benefit from a dosage increase up to a maximum recommended maintenance dosage of 0.2 mg/kg twice daily (maximum daily dosage of 17 mg).
Mechanism of Action
Fintepla (fenfluramine) is a selective serotonin reuptake inhibitor. The mechanisms by which fenfluramine exerts its therapeutic effects in the treatment of seizures associated with Dravet syndrome are unknown. Fenfluramine and the metabolite, norfenfluramine, increase extracellular levels of serotonin through interaction with serotonin transporter proteins, and exhibit agonist activity at serotonin 5HT-2 receptors.
Adverse effects associated with the use of Fintepla may include, but are not limited to, the following:
- decreased appetite
- abnormal echocardiogram
- balance disorder
- gait disturbance
- blood pressure increased
- salivary hypersecretion
- upper respiratory tract infection
- decreased weight
- status epilepticus
The Fintepla drug label comes with the following Black Box Warning: There is an association between serotonergic drugs with 5-HT2B receptor agonist activity, including fenfluramine (the active ingredient in Fintepla), and valvular heart disease and pulmonary arterial hypertension. Echocardiogram assessments are required before, during, and after treatment with Fintepla. Fintepla is available only through a restricted program called the Fintepla REMS.
Clinical Trial Results
The FDA approval of Fintepla for Dravat Syndrome was based on two randomized, double-blind, placebo controlled trials in patients 2 to 18 years of age. Study 1 (N=117) compared a 0.7 mg/kg/day and a 0.2 mg/kg/day dose of Fintepla with placebo in patients who were not receiving stiripentol. Study 2 (N=85) compared a 0.4 mg/kg/day dose of Fintepla with placebo in patients who were receiving stiripentol and either clobazam, valproate, or both. In both studies, patients had a clinical diagnosis of Dravet syndrome and were inadequately controlled on at least one AED or other antiseizure treatment including vagal nerve stimulation or a ketogenic diet. Both trials had a 6-week baseline period, during which patients were required to have a minimum of 6 convulsive seizures while on stable AED therapy. The baseline period was followed by randomization into a 2-week (Study 1) or 3-week (Study 2) titration period and a subsequent 12-week maintenance period, where the dose of Fintepla remained stable. The primary efficacy endpoint in both studies was the change from baseline in the frequency of convulsive seizures per 28 days during the combined 14-week (Study 1) or 15-week (Study 2) titration and maintenance periods (i.e., treatment period).
In Study 1 and Study 2, the reduction in convulsive seizure frequency per 28 days was statistically significantly greater for all dose groups of Fintepla compared to placebo. A reduction in convulsive seizures was observed within 3 to 4 weeks of starting Fintepla, and the effect remained generally consistent over the 14- or 15-week treatment period.