The terms phentermine and “Phen-Fen” are often used interchangeably, causing confusion. Phentermine is a single prescription medication for weight management. Phen-Fen, however, was a combination of two drugs: fenfluramine and phentermine. While they share a component, their histories and safety profiles are different, explaining why one is still prescribed while the other was removed from the market.
The History of Phen-Phen
In the 1990s, the combination of fenfluramine and phentermine, known as Phen-Phen, grew in popularity as a weight-loss treatment. Though the two drugs were approved separately by the Food and Drug Administration (FDA), their use in combination was never officially approved. By 1996, millions of prescriptions were being written for this combination, fueled by media attention and reports of weight loss.
This enthusiasm was short-lived. In 1997, researchers from the Mayo Clinic published findings in The New England Journal of Medicine detailing heart problems in a group of women who had taken Phen-Phen. The study highlighted cases of valvular heart disease, a condition where heart valves are damaged, and primary pulmonary hypertension (PPH), a type of high blood pressure affecting the lungs. The findings indicated that a percentage of people taking the combination had abnormal echocardiograms, even without symptoms.
Faced with mounting evidence of cardiovascular and pulmonary damage, the FDA took action. In September 1997, the agency requested that the manufacturers of fenfluramine and a related drug, dexfenfluramine, voluntarily withdraw them from the market. The manufacturers complied, ending the use of the Phen-Phen combination.
Understanding the Drug Components
Fenfluramine and Dexfenfluramine
The health issues associated with Phen-Phen were primarily linked to one of its components, fenfluramine, and its derivative, dexfenfluramine. These drugs worked by increasing the levels of serotonin, a neurotransmitter in the brain, which helps to create a feeling of fullness and suppress appetite. This mechanism of action, however, was found to be responsible for the damage to heart valves and the development of pulmonary hypertension.
The excess serotonin was found to activate a specific receptor subtype, 5-HT2B, which is linked to the development of valvular disease and pulmonary hypertension. The damage caused the heart valves to thicken and leak, forcing the heart to work harder to pump blood. This could lead to potentially fatal conditions, which ultimately led to the withdrawal of fenfluramine and dexfenfluramine from the market.
Phentermine
Phentermine, the other half of the Phen-Phen combination, works through a different mechanism. It is a stimulant-like drug that primarily increases the levels of norepinephrine, another neurotransmitter. This signals the body to reduce hunger and increase feelings of fullness.
Phentermine was not the component linked to the heart valve and lung damage that led to the ban of Phen-Fen. It has its own set of potential side effects, which are related to its stimulant properties. These can include increased heart rate, high blood pressure, trouble sleeping, and restlessness. Because it was not associated with the cardiovascular issues caused by fenfluramine, phentermine remains available for prescription use.
Phentermine as a Standalone Treatment
Today, phentermine is still an FDA-approved medication, but it is prescribed as a standalone treatment for short-term weight management. It is recommended for individuals with a body mass index (BMI) over 30, or a BMI over 27 with at least one weight-related health condition. The medication is intended to be used as part of a comprehensive weight loss plan that includes a reduced-calorie diet and increased physical activity.
When used alone, the most common side effects of phentermine include dry mouth, insomnia, dizziness, and constipation. While side effects like heart valve problems and pulmonary hypertension are considered rare with phentermine alone, they cannot be entirely ruled out. Due to its stimulant properties and potential for abuse, phentermine is classified as a controlled substance.
Key Differences Summarized
The primary distinction between Phen-Phen and phentermine lies in their composition and safety. Phen-Phen was a combination of fenfluramine and phentermine taken off the market due to its link to heart valve damage and pulmonary hypertension. In contrast, phentermine is a single-drug therapy that remains available by prescription because its mechanism was not linked to these dangerous side effects.