Table 1 Clinical use of fenfluramine and its pharmacological properties
Drug name | Fenfluramine |
|---|---|
Chemical structure |
|
Indication | Add-on treatment in Dravet and Lennox-Gastaut syndrom from 2 years of age |
Mode of action | Modulates serotonergic neurotransmission Acts directly on some specific serotonin receptors (HTR) including 5-HT1D, 5-HT2A, and 5-HT2C receptors Positively modulates the sigma-1 receptor |
Route of administration | Oral solution |
Pharmacokinetics | Fat-soluble, high bioavailability not influenced by nutrition Steady state usually reached after 4 days Plasma-elimination half-life of 20 h Primarily renal elimination |
Dose regimen | Start at 0.1 mg/kg twice daily (0.2 mg/kg/body weight (bw)/day), increase to 0.2 mg/kg twice daily (0.4 mg/kg bw/day) after 7 days, and to a maximum of 2 × 0.35 mg/kg daily (0.7 mg/kg bw/day) after a further 7 days Slower uptitration in an outpatient setting of 0.1 mg/kg bw or 1 ml per week improves tolerability, faster uptitration in emergency situations is possible. The maximum total daily dose of 26 mg FFA or 0.7 mg/kg bw must not be exceeded (17 mg FFA or 0.4 mg/kg bw if stiripentol is coadministered). |
Typical adverse events | Decreased appetite, loss of weight, fatigue, somnolence |
Precautions | Prior to FFA, patients must undergo an echocardiogram to exclude valvular heart disease or pulmonary hypertension. Echocardiogram monitoring should be conducted every 6 months for the first 2 years and annually thereafter. |
Pivotal trials | Lagae et 2020; Nabbout et al. 2020; Knupp et al. 2022; Sullivan et al. 2023 [11,12,13,14] |
