Fenfluramine (former brand names Pondimin, Ponderax and Adifax), also known as 3-trifluoromethyl-N-ethylamphetamine, is an anorectic that is no longer marketed. In combination with phentermine, it was part of the anti-obesity medication Fen-phen. Fenfluramine was introduced on the U.S. market in 1973 and withdrawn in 1997. It is the racemic mixture of two enantiomers, dexfenfluramine, and levofenfluramine. The drug increases the level of serotonin, a neurotransmitter that regulates mood, appetite and other functions. Fenfluramine causes the release of serotonin by disrupting vesicular storage of the neurotransmitter and reversing serotonin transporter function. The drug was withdrawn from the U.S. market in 1997 after reports of heart valve disease and pulmonary hypertension, including a condition known as cardiac fibrosis. It was subsequently withdrawn from other markets around the world. In this small exploratory and retrospective study, remarkably good results were reported on the use of fenfluramine as an add-on medication for controlling seizures in patients with the Dravet syndrome. The side effects were rare and nonserious and did not result in termination of the treatment. It is possible that this drug may have anticonvulsive effects for other severe epilepsy syndromes, especially in those characterized by photosensitive or induced seizures.

Fenfluramine:
https://drugs.ncats.io/drug/3KC089243P

Fenfluramine is part of a classification of weight loss medications that are used specifically to control your appetite. This particular drug is popular because it makes you feel full which will help you not to eat when you shouldn't.

One of the common reasons that people opt for this product is to combat their cravings when they need it most, such as late at night, which is when most people screw up their diets. All this is possible because Fenfluramine increases the levels of the neurotransmitter Serotonin, a chemical that helps to regulate both your mood and your appetite.

Fenfluramine was first introduced into the US market back in 1973 and with it was brought a number of dangers including heart valve disease and pulmonary hypertension. Contrary to popular belief though, the damage that this drug poses on the heart valve continues long after you stop taking the medication. As a matter of fact, your chances of needing heart surgery for faulty heart valves after taking the drug are increased sevenfold.

Combining Fenfluramine with Phentermine was thought to give the perfect combination of a powerful appetite suppressant and hyper stimulant, all in one. Unfortunately Fen-Phen proved to be a serious disaster, causing heart valve damage and a fatal lung disease called primary pulmonary hypertension. In 1999, a class action lawsuit was filed against Wyeth, the makers of Fen-Phen and since then the damages filed are in the billions.

Fen-Phen, Fenfluramine and Phentermine are three of the most potent and effective prescription diet pills for fast weight loss. Although these are probably some of the most talked about weight loss prescription drugs online, there are still a lot of people out there that aren't aware of the serious dangers and risks of taking these products. Not only can they pose serious potential health complications, their use may even result in fatal consequences. To help people in their ever-present weight loss struggle quickly, and to combat the potential health problems that accompany obesity, anti-obesity medication such as Fen-Phen, Fenfluramine and Phentermine are prescribed for a quick weight loss solution.

Fen-Phen, Fenfluramine and Phentermine all have amazing capabilities of suppressing your appetite and increasing your metabolism fast that are above and beyond what a non-prescription pill can do. But although these three diet drugs may be effective at helping you burning off the extra pounds, the side effects may even be more detrimental to your health than the fat burning effect that they are capable of producing.

Excerpt from geoleaders.com:
https://www.geoleaders.com/fen-phen-fenfluramine-and-phentermine-dangers/

Fen Phen Background:

• In the early 1990s, America was as it is now: coming to terms with its increasing waistline.
• A 1992 National Institutes of Health panel concluded that about a third of the population was considered "overweight" (a BMI greater than 27.8 for men and 27.3 for women). The 1992 panel linked obesity to a number of health risks, among them cardiovascular disease, hypertension, diabetes, high cholesterol, sleep deprivation, and cancer.
• However, the NIH panel also noted that the psychological burden on an obese individual was potentially more detrimental than the medical consequences. Despite the nearly constant stream of body-perfect imagery and information, Americans were doing less and less to improve their weight.
• In 1990s America, women, in particular, were looking for a solution, and the food industry was quick to oblige with new low-fat varieties of consumer products, from potato chips to tomato soup. By 1994, Snackwells reduced-calorie chocolate creme sandwich cookies had replaced Oreos as the nation's most popular cookie.
• Into this fat-conscious milieu came the release of an Institute of Medicine study which stated that obesity should be perceived as not merely a problem of will power but as a chronic condition like hypertension and suggested that the condition be treated as doctors treat other genetic and biological diseases - with extended drug therapy or surgery.
• Diet drugs had not been high on the public's radar, perhaps due to the lingering stigma of the habit-forming, amphetamine-based weight-loss drugs of the 1960s.
• However, by 1994, Isomeride, a non-addictive drug containing a derivative of fenfluramine, was already on the market in Europe.
• Fenfluramine works by releasing into the body extra amounts of serotonin, a chemical linked to a number of brain functions, including a feeling of satiety. An older version of fenfluramine, Pondimin, had been on the U.S. market since 1973, but had not been very successful because its moderate results were overshadowed by uncomfortable side effects, including drowsiness and altered moods.
• In 1983, a University of Rochester pharmacologist named Michael Weintraub postulated that fenfluramine could be combined with the diet drug phentermine, a stimulant which would counter-balance Pondimin's negative effects.
• That same year, doctors began prescribing the fenflurmine-phentermine cocktail, or "Fen Phen," as an "off-label" combination (meaning it was not approved by the FDA).
• "It goes mainstream in February 1995 with an article in Allure, a woman's magazine. Then it's reprinted in Reader's Digest. Pondimin (and phentermine) come back from the dead." By 1995, Fen Phen had the attention of a mass American audience.
• Given the risks associated with the drugs, some doctors cautioned that only those categorized as moderately to severely obese should take Fen Phen, but their recommendations were scarcely heard in the frenzy that followed Redux's approval and its ensuing $52 million marketing campaign.
• The drug was not only easy to obtain by prescription, but also accessible in weight-loss clinics and over the Internet.
• In August 1997, an article in The New England Journal of Medicine by Dr. Heidi Connelly of the Mayo Clinic, revealed her experience treating women with pulmonary hypertension and heart-valve abnormalities. Her patients had been taking the drugs for as little as one month and for as long as 28, but each presented symptoms in various stages that Connelly attributed to the excess of serotonin in their systems.
• As a result of these findings at the Mayo Clinic, and another 75 cases of heart-valve disease reported to the FDA in 1997, both Pondimin and Redux were withdrawn from the market on Sept. 15, 1997.
• The heart-valve problems caused by Fen Phen can require risky heart surgery, and primary pulmonary hypertension is a devastating disease for which there is no cure.

Excerpt from PBS Frontline (2003):
https://www.pbs.org/wgbh/pages/frontline/shows/prescription/hazard/fenphen.html

The decision to withdraw the obesity treatment fen-phen from the market in 1997 caused panic among many dieters. Many people were tempted to risk their health for the sake of losing their weight. However, the health risks associated with fen-phen are too serious to ignore, the Food and Drug Administration decided. Do not be tempted to purchase fen-phen illegally or over the Internet - the consequences could be fatal. fen-phen was to be prescribed for short-term use. It was effective for 60 percent of patients who lost 10 percent of their body weight, and 85,000 people were prescribed the drug each week at the height of its popularity.

Fen-phen combined two drugs that were approved for use individually, but had not been approved by the FDA in combination. Phentermine, an amphetamine that stimulates the central nervous system, was approved in 1959 and is still used today. Phentermine might be useful to start off your weight loss, but you are likely to put the weight back on when you cease taking the tablet. The other ingredient, either fenfluramine or dexfenfluramine, worked to inhibit hunger pangs. Both fenfluramine and dexfenfluramine were removed from the market in 1997.

Excerpt from Livestrong:
https://www.livestrong.com/article/295640-fen-phen-weight-loss/

Although the combination has not been approved by the FDA, in 1996 the total number of prescriptions in the United States for fenfluramine and phentermine exceeded 18 million.

These cases arouse concern that fenfluramine - phentermine therapy may be associated with valvular heart disease. Candidates for fenfluramine - phentermine therapy should be informed about serious potential adverse effects, including pulmonary hypertension and valvular heart disease:

The New England Journal of Medicine paper on if Valvular Heart Disease is Associated:
https://www.nejm.org/doi/full/10.1056/NEJM199708283370901

What should I avoid while taking Fenfluramine?
Avoid driving or hazardous activity until you know how fenfluramine will affect you. Your reactions could be impaired.

Avoid taking an herbal supplement containing St. John's wort.

Interactions:

Drug Interactions (301) Alcohol/Food Interactions (1) Disease Interactions (3)

What other drugs will affect Fenfluramine?
Other drugs may affect fenfluramine, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell your doctor about all your current medicines and any medicine you start or stop using.

A total of 301 drugs are known to interact with Fenfluramine.

• 83 major drug interactions
• 214 moderate drug interactions
• 4 minor drug interactions

Fenfluramine Drug Information:
https://www.drugs.com/mtm/fenfluramine.html

Pediatric:
Appropriate studies have not been performed on the relationship of age to the effects of fenfluramine in children younger than 2 years of age.

Safety and efficacy have not been established.

Geriatric:
Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of fenfluramine in the elderly. However, elderly patients are more likely to have age-related liver, kidney, or heart problems, which may require caution and an adjustment in the dose for patients receiving this medicine.

Other Medical Problems:
Make sure you tell your doctor if you have any other medical problems, especially:

• Depression
• Eye or vision problems
• Heart disease
• Hypertension (high blood pressure)
• Lung or breathing problems - Use with caution. May make these conditions worse

• Kidney disease, moderate or severe
• Liver disease - Use is not recommended in patients with these conditions

Fenfluramine (Oral Route):
https://www.mayoclinic.org/drugs-supplements/fenfluramine-oral-route/description/drg-20490822

Erowid Experience Vault:
https://erowid.org/experiences/subs/exp_Pharms_Fenfluramine.shtml

Erowid Rhodium Archive (S)-fenfluramine:
https://www.erowid.org/archive/rhodium/chemistry/fenfluramine.html

Pondimin = Tablets
Ponderex = Capsules

2019
Fenfluramine for Treating of Epilepsy
According to Zogenix, fenfluramine is specifically being studied for treating Dravet syndrome, a condition that frequently causes refractory seizures, which are seizures that cannot be controlled with standard medical management. Fenfluramine also has been studied in Lennox Gastaut syndrome (LGS), another epilepsy syndrome characterized by refractory seizures. The FDA has granted Zoginex Breakthrough Therapy Designation for ZX008, which is the low-dose fenfluramine being studied as an investigational product. It's hard to predict whether fenfluramine will be approved for the treatment of refractory epilepsy in Dravet syndrome or LGS. Fenfluramine has already been used on a limited basis for the treatment of epilepsy in Belgium, and the outcomes have been closely followed. Several of the published studies have been conducted in Belgium.

Excerpt from verywellmind.com:
https://www.verywellhealth.com/fenfluramine-for-epilepsy-4176501

Fenfluramine is an amphetamine derivative and a sympathomimetic stimulant with appetite-suppressant property. It decreases caloric intake by increasing serotonin levels in the brain's synapses. Fenfluramine acts as a serotonin reuptake inhibitor. It also causes release of serotonin from the synaptosomes. This in turn increases serotonin transmission in the feeding centre of the brain which suppresses appetite.

Unlike various other amphetamine derivatives, fenfluramine is reported to be unpleasantly lethargic and non-addictive at therapeutic doses. However, high doses have been described as producing euphoria, amphetamine-like effects, sedation, and hallucinogenic effects - along with anxiety, nausea, diarrhea, and sometimes panic attacks - as well as depressive symptoms once the drug had worn off. At very high doses fenfluramine induces a psychedelic state resembling that produced by LSD.