Pharmacokinetics
The elimination half-life of fenfluramine has been reported as ranging from 13 to 30 hours. The mean elimination half-lives of its enantiomers have been found to be 19 hours for dexfenfluramine and 25 hours for levfenfluramine. Norfenfluramine, the major active metabolite of fenfluramine, has an elimination half-life that is about 1.5 to 2 times as long as that of fenfluramine, with mean values of 34 hours for dexnorfenfluramine and 50 hours for levnorfenfluramine. Chemistry
Fenfluramine is a substituted amphetamine and is also known as 3-trifluoromethyl-N-ethylamphetamine. It is a racemic mixture of two enantiomers, dexfenfluramine and levofenfluramine. Some analogues of fenfluramine include norfenfluramine, benfluorex, flucetorex, and fludorex. History
Fenfluramine was developed in the early 1960s and was introduced in France in 1963. Approximately 50 million Europeans were treated with fenfluramine for appetite suppression between 1963 and 1996. Fenfluramine was approved in the United States in 1973. The combination of fenfluramine and phentermine was proposed in 1984. Approximately 5 million people in the United States were given fenfluramine or dexfenfluramine with or without phentermine between 1996 and 1998.In the early 1990s, French researchers reported an association of fenfluramine with primary pulmonary hypertension and dyspnea in a small sample of patients. Fenfluramine was withdrawn from the U.S. market in 1997 after reports of heart valve disease and continued findings of pulmonary hypertension, including a condition known as cardiac fibrosis. It was subsequently withdrawn from other markets around the world. It was banned in India in 1998.Fenfluramine was an appetite suppressant which was used to treat obesity.
In a large survey of AERD patients, it was reported that Zyflo (zileuton) was significantly more effective at controlling the symptoms of the disease than Singulair (montelukast).Biologic medications such as dupilumab, mepolizumab, and omalizumab may also be of benefit. In a 2021 survey of biologics, dupilumab was found to be most effective in treating symptoms of AERD.Despite optimal medical management, many patients continue to require oral steroid medications to alleviate asthma and chronic nasal congestion. Surgery
Often surgery is required to remove nasal polyps, although they typically recur, particularly if aspirin desensitization is not undertaken. 90% of patients have been shown to have recurrence of nasal polyps within five years after surgery, with 47% requiring revision surgery in the same time period. A complete endoscopic sinus surgery followed by aspirin desensitization has been shown to reduce the need for revision surgeries. Exact cause of nasal polyp formation is unknown. However, Differential gene expression analysis of AERD nasal polyp epithelial cells versus AERD non polyp nasal mucosa revealed DMRT3 could be potentially involved in nasal polyp development in AERD patients. Furthermore, several genes are downregulated, hinting at the dedifferentiation phenomenon in AERD polyps. Diet
The majority of those with aspirin exacerbated respiratory disease experience respiratory reactions to alcohol. One study found that 83% reported such reactions. Of those who had reactions, 75% had a sinus reaction (runny nose, nasal congestion) and 51% had a lower respiratory reaction (wheezing, shortness of breath).