The U.S. Food and Drug Administration (FDA)<unk>  labeling includes a boxed warning stating the drug is associated with valvular heart disease (VHD) and pulmonary arterial hypertension (PAH). Because of the risks of VHD and PAH,<unk>  is available only through a restricted drug distribution program, under a risk evaluation and mitigation strategy (REMS). The<unk>  REMS requires health care professionals who prescribe<unk>  and pharmacies that dispense<unk>  to be specially certified in the<unk>  REMS and that patients be enrolled in the REMS. As part of the REMS requirements, prescribers and patients must adhere to the required cardiac monitoring with echocardiograms to receive<unk> . At higher therapeutic doses, headache, diarrhea, dizziness, dry mouth, erectile dysfunction, anxiety, insomnia, irritability, lethargy, and stimulation have been reported with<unk> . There have been reports associating chronic<unk>  treatment with emotional instability, cognitive deficits, depression, psychosis, exacerbation of pre-existing psychosis (schizophrenia), and sleep disturbances. It has been suggested that some of these effects may be mediated by serotonergic neurotoxicity/depletion of serotonin with chronic administration and/or activation of serotonin 5-HT2A receptors. Heart valve disease The distinctive valvular abnormality seen with<unk>  is a thickening of the leaflet and chordae tendineae. One mechanism used to explain this phenomenon involves heart valve serotonin receptors, which are thought to help regulate growth. Since<unk>  and its active metabolite norfenfluramine stimulate serotonin receptors, this may have led to the valvular abnormalities found in patients using<unk> . In particular norfenfluramine is a potent inhibitor of the re-uptake of 5-HT into nerve terminals.<unk>  and its active metabolite norfenfluramine affect the 5-HT2B receptors, which are plentiful in human cardiac valves. The suggested mechanism by which<unk>  causes damage is through over or inappropriate stimulation of these receptors leading to inappropriate valve cell division. Supporting this idea is the fact that this valve abnormality has also occurred in patients using other drugs that act on 5-HT2B receptors. According to a study of 5,743 former users conducted by a plaintiff's expert cardiologist, damage to the heart valve continued long after stopping the medication. Of the users tested, 20% of women, and 12% of men were affected. For all ex-users, there was a 7-fold increase of chances of needing surgery for faulty heart valves caused by the drug.
Fenfluramine
Benzoctamine
Tesofensine
Bremazocine
Dezocine
Clorotepine
Bethanechol
Ephedrine