Section 01 · Monograph

Fenfluramine

Reviewed Nov 2026FDA label

FinteplaSerotonergic agent

Black Box Warning

Valvular heart disease (VHD): fenfluramine is associated with the historical fenfluramine/phentermine ('fen-phen') cardiac valvulopathy signal, related to serotonergic (5-HT2B receptor agonist) activity — echocardiogram required before, during (approximately every 6 months), and after (3-6 months post-discontinuation) treatment
Pulmonary arterial hypertension (PAH): also linked to 5-HT2B agonist activity; monitor via echocardiogram on the same schedule as VHD surveillance
Available only through the restricted FINTEPLA REMS program due to these serious cardiovascular risks

Treatment of seizures associated with Dravet syndrome in patients ≥2 years of ageFDA-labeled
Treatment of seizures associated with Lennox-Gastaut syndrome in patients ≥2 years of ageFDA-labeled

Precise anticonvulsant mechanism not fully established
Fenfluramine and its active metabolite norfenfluramine act as serotonin-releasing agents and directly stimulate multiple serotonin (5-HT) receptor subtypes (including 5-HT1D, 5-HT2A, and 5-HT2C)
Also acts as a positive modulator at the sigma-1 receptor
The same serotonergic activity (5-HT2B agonism) implicated in efficacy is mechanistically linked to the valvulopathy/PAH risk in the boxed warning

Dravet syndrome, without concomitant stiripentol: initiate 0.1mg/kg twice daily; titrate weekly based on response/tolerability to a maximum of 0.35mg/kg twice daily, not to exceed 26mg/day
Dravet syndrome, with concomitant stiripentol (plus clobazam/valproate regimens): lower maximum dose of 0.2mg/kg twice daily, not to exceed 17mg/day, due to interaction-related increased fenfluramine exposure
Lennox-Gastaut syndrome: initiate 0.1mg/kg twice daily; titrate weekly to a maximum of 0.2mg/kg twice daily, not to exceed 26mg/day
Oral solution, dosed using the provided calibrated oral dosing syringe; taper gradually when discontinuing

Dose adjustment required for concomitant strong CYP1A2 or CYP2D6 inhibitors (cap doses lower) and for renal/hepatic impairment

Hypersensitivity to fenfluramine or any excipient
Use with or within 14 days of monoamine oxidase inhibitors (MAOIs), due to risk of serotonin syndrome/hypertensive reaction

Stiripentol (a potent CYP1A2/CYP2C19/CYP3A4 inhibitor, typically used with clobazam) meaningfully increases fenfluramine exposure — lower maximum fenfluramine dose required
Strong/moderate CYP1A2 or CYP2D6 inhibitors increase fenfluramine levels — dose capped accordingly
Strong CYP1A2, CYP2B6, or CYP3A4 inducers may decrease fenfluramine exposure
Avoid concomitant MAOIs (contraindicated) and use caution with other serotonergic drugs (SSRIs, SNRIs, triptans) due to serotonin syndrome risk
Caution with other drugs affecting appetite/weight or CNS depressants (additive somnolence)

Common (≥10%): decreased appetite, somnolence/sedation/lethargy, diarrhea, constipation, abnormal echocardiogram findings, fatigue/malaise, ataxia/balance disorder/gait disturbance, blood pressure elevation, drooling/salivary hypersecretion, pyrexia, upper respiratory tract infection
Weight loss/decreased appetite can be clinically significant, particularly in young children
Serotonin syndrome (rare but serious) especially with other serotonergic agents
Increased suicidal ideation/behavior risk consistent with AED class labeling

Echocardiogram at baseline before starting treatment
Echocardiogram approximately every 6 months during treatment
Echocardiogram 3-6 months after discontinuation
Blood pressure monitoring
Weight/growth and appetite, particularly in children
REMS program enrollment and periodic compliance requirements for prescriber, pharmacy, and patient/caregiver

No adequate human pregnancy data; animal studies showed fetal structural abnormalities and developmental toxicity at clinically relevant exposures — use during pregnancy only if potential benefit justifies potential fetal risk
Not recommended during pregnancy given animal reproductive toxicity findings; consider a pregnancy registry if available
Unknown whether fenfluramine/norfenfluramine are present in human milk; effects on breastfed infant and milk production unknown — weigh maternal need for therapy against potential infant risk