A drug pulled from the U.S. market in 1997 over heart damage is now prescribed to children with severe epilepsy. Fenfluramine came back in 2020, in both the United States and the European Union, sold as Fintepla for seizures linked to Dravet syndrome and Lennox-Gastaut syndrome in patients aged two and older.
The heart risk did not go away. The FDA label carries a boxed warning for valvular heart disease and pulmonary arterial hypertension, the same two conditions behind the withdrawal. Because of them, the drug is available only through a restricted program, a risk evaluation and mitigation strategy (REMS). Prescribers and pharmacies must be certified, patients must be enrolled, and everyone has to stick to scheduled echocardiograms.
How it fell
Fenfluramine was developed in the early 1960s and launched in France in 1963 as an appetite suppressant. The United States approved it in 1973 under the name Pondimin. It sold modestly on its own. Then came the 1990s, when it was paired with phentermine and marketed hard as fen-phen.
The trouble surfaced fast. French researchers had reported pulmonary hypertension in a small group of patients in the early 1990s. In August 1997, Mayo Clinic doctors described heart valve problems in 24 people who had taken fen-phen. The FDA asked for withdrawal that September, citing echocardiograms that showed abnormal results in roughly 30 percent of people who had taken the combination for up to 24 months, even without symptoms.
The bill came later. Fen-phen litigation produced more than 50,000 product liability lawsuits, and Wyeth set aside $21.1 billion to cover the costs.
A second life
Doctors had noticed in the 1990s that fenfluramine seemed to reduce certain seizures in children. Decades and several clinical trials later, regulators approved it for Dravet syndrome, a life-threatening form of epilepsy marked by severe seizures that often continue despite treatment.
Why it works is not known. The label does not say. The drug releases serotonin and norepinephrine, activates serotonin 5-HT2 receptors and modulates the sigma-1 receptor, and its seizure effect may involve serotonin receptors and that sigma receptor.
Fenfluramine was once a Schedule IV controlled substance in the U.S. A rule issued on December 23, 2022 ended federal control of it.
Common side effects in people treated for seizures include decreased appetite, drowsiness, diarrhea, constipation, fatigue, fever, vomiting, weight loss, falls and abnormal echocardiograms. Some patients also develop status epilepticus.
Researchers are now looking at the drug for Sunflower syndrome, a rare epilepsy in which people wave a hand in front of the face and tend to stare toward the sun. Families weighing the drug should talk to their child’s neurologist and cardiologist.
Sources
- Fenfluramine – Wikipedia
- Fen-Phen Again? Why Ozempic and New Weight-Loss Drugs Are Different
- Fenfluramine/phentermine – Wikipedia
