Dexfenfluramine
The purified d-enantiomer of fenfluramine, marketed as Redux and approved by the FDA in 1996 for obesity. It was withdrawn alongside fenfluramine in 1997 after the same serotonin-mediated valvular heart disease and pulmonary hypertension emerged.
01 Overview
Dexfenfluramine was developed as a cleaner, more selective serotonergic anorectic than racemic fenfluramine and enjoyed a brief high-profile launch as Redux. Its approval was controversial given existing signals of pulmonary hypertension from the aminorex and fenfluramine experiences.
When echocardiographic studies revealed valvulopathy in fen-phen and Redux users, the FDA requested withdrawal in September 1997. It is a textbook example of a serotonergic weight-loss drug removed for cardiac and pulmonary vascular toxicity.
02 Mechanism
The active d-enantiomer releases serotonin and blocks its reuptake to suppress appetite; 5-HT2B agonism causes the same cardiac valve and pulmonary vascular toxicity as fenfluramine.
03 Dosing
| Tier | Dose | Route | Notes |
|---|---|---|---|
| Former therapeutic dose | 30 mg/day | Oral | 15 mg twice daily; withdrawn 1997. |
04 Effects
| Effect | Magnitude | Evidence | |
|---|---|---|---|
| Appetite suppressionSerotonergic satiety with little stimulation. | modest weight loss | Clinical | |
| Reduced carbohydrate cravingSerotonergic effect on macronutrient selection. | modest | Clinical |
05 Side effects
| Effect | Severity | Frequency | Evidence | Countermeasures |
|---|---|---|---|---|
| Cardiac valvulopathyValvular regurgitation from serotonergic valve remodelling. | Severe | Uncommon but serious | Clinical | |
| Pulmonary hypertensionIncreased risk of primary pulmonary hypertension. | Life-threatening | Rare | Observational |