As part of the REMS requirements, prescribers and patients must adhere to the required cardiac monitoring with echocardiograms to receive fenfluramine.At higher therapeutic doses, headache, diarrhea, dizziness, dry mouth, erectile dysfunction, anxiety, insomnia, irritability, lethargy, and CNS stimulation have been reported with fenfluramine.There have been reports associating chronic fenfluramine 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 fenfluramine 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 fenfluramine and its active metabolite norfenfluramine stimulate serotonin receptors, this may have led to the valvular abnormalities found in patients using fenfluramine. In particular norfenfluramine is a potent inhibitor of the re-uptake of 5-HT into nerve terminals. Fenfluramine and its active metabolite norfenfluramine affect the 5-HT2B receptors, which are plentiful in human cardiac valves. The suggested mechanism by which fenfluramine 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 plaintiffs expert cardiologist, damage to the heart valve continued long after stopping the medication.
Promising techniques to reduce the rate of failure include an orthopedic anchoring system, a gluteus maximus muscle flap, an acellular human dermis graft, and an acellular pig collagen graft. In dogs and cats

In dogs, perineal hernia usually is found on the right side. Most cases are in older intact (not neutered) male dogs (93 percent in one study). Breeds that may be at risk include Welsh Corgis, Boxers, Australian Kelpies, Boston Terriers, Collies, Dachshunds, Old English Sheepdogs, and Pekingese. Perineal hernias are rare in female dogs and uncommon in cats. Dogs with benign prostatic hyperplasia have been found to have increased relaxin levels and suspected subsequent weakening of the pelvic diaphragm. In cats, perineal hernias are seen most commonly following perineal urethrostomy surgery or secondary to megacolon. Medical treatment consists of treatment of the underlying disease, enemas, and stool softeners. Because only about 20 percent of cases treated medically are free of symptoms, surgery is often necessary. Recurrence is common with or without surgery. Several surgeries have been described for perineal hernias in dogs. The current standard involves transposition of the internal obturator muscle. This technique has a lower recurrence and complication rate than traditional hernia repair. A new technique uses porcine small intestinal submucosa as a biomaterial to help repair the defect. This is can also be done in combination with internal obturator muscle transposition, especially when that muscle is weak. == References ==