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Dexfenfluramine Side Effects

Applies to dexfenfluramine: oral capsule.


Several side effects are frequently associated with the use of dexfenfluramine. Headache (16%), asthenia (16%), abdominal pain (7%), chills (3%), accidental injury (3%), infection, flu syndrome, back pain, fever, and allergic reactions have been reported during administration of dexfenfluramine in clinical studies.[Ref]


Early cases of valvular heart disease were primarily reported in patients taking the combination fenfluramine and phentermine ("fen-phen") for an average duration of 10 months (range 1 to 16 months) prior to presentation. All were American women between the ages of 35 to 72 years, with an average of 43.3 years, and none had a history of cardiac problems. The disease was usually multivalvular, involving the mitral, aortic, and/or tricuspid valves. Approximately half of these women also presented with concomitant pulmonary hypertension. Some have required surgery to replace the diseased valves. The histopathology observed during surgery resembled that in carcinoid syndrome or ergotamine toxicity, indicating that a serotonergic mechanism may be involved. Later cases, however, have also included patients taking the combination dexfenfluramine and phentermine ("dexfen-phen"), as well as patients on either fenfluramine or dexfenfluramine alone. Analysis of available data suggests that fenfluramine and dexfenfluramine are the causal agents. Consequently, both drugs were withdrawn from the market on September 15, 1997. It is not known at the present time if the valvulopathies associated with fenfluramine and dexfenfluramine are reversible following drug discontinuation. Symptomatic disease has not been noted to resolve after stopping treatment, although symptoms of heart failure have been controlled with medications in several patients. Deterioration from no detectable murmur to a need for valve replacement has been reported in a couple of patients.

Multiple cases of primary pulmonary hypertension (PPH) associated with the use of dexfenfluramine have been documented. Four particular case reports describe women between the ages of 26 to 46 who had been taking dexfenfluramine for a period of six months or longer prior to the episode of pulmonary hypertension. Dyspnea was the initial complaint described by all four women. A female predominance appears to exist in those who develop PPH (at a ratio of 2:1). The initial symptom of PPH is generally dyspnea followed by angina pectoris, syncope, or lower extremity edema.

A case of fatal pulmonary hypertension has also been reported in a 29-year-old woman 8 months following the use of fenfluramine (of which dexfenfluramine is the dextro isomer) and phentermine for only 23 days. Histopathological findings upon autopsy indicated severe pulmonary hypertension. She did not smoke and had no family history of pulmonary hypertension. No obvious risk factors other than obesity were present, although preexisting disease was not ruled out.[Ref]

The most serious adverse effect associated with dexfenfluramine is the development of valvular heart disease, some (27 per 113 cases as of September 30, 1997) of which have required surgical intervention. Asymptomatic valvulopathy, primarily aortic regurgitation, has also been detected by echocardiograms in approximately one-third of a group of 291 patients on the combination of phentermine with either fenfluramine or dexfenfluramine. In addition, life-threatening pulmonary hypertension has been reported with the use of dexfenfluramine. The risk of developing primary pulmonary hypertension during long-term use (three months or longer) of anorexiants is estimated to be between 23 and 46 cases per 1 million users per year. Other cardiovascular side effects associated with dexfenfluramine use include hypertension, angina pectoris, palpitation, vasodilation and migraine. Less frequently occurring effects include tachycardia, postural hypotension, peripheral vascular disorder, syncope, arrhythmia, extrasystoles, hemorrhage, thrombophlebitis and varicose veins.[Ref]


Gastrointestinal side effects of dexfenfluramine include diarrhea (18%), vomiting (3%), constipation, nausea, dyspepsia, increased appetite, rectal disorder, gastritis, gastroenteritis, and flatulence. Less frequent effects include colitis, eructation, gastrointestinal hemorrhage, enteritis and peptic ulcer.[Ref]


Hepatic side effects are infrequent and include hepatitis and hepatomegaly.[Ref]


Dexfenfluramine has been associated with significant decreases in serum triglycerides, total cholesterol, and significant increases in HDL cholesterol. In addition, significant decreases in fasting serum insulin and increased insulin sensitivity have been reported.[Ref]

Endocrinologic effects include goiter, diabetes mellitus and thyroid disorder. Additionally, changes in cholesterol, triglycerides, and insulin sensitivity have been reported.[Ref]


Hematologic side effects such as anemia and lymphedema are seldom reported. Side effects such as coagulation disorder, lymphadenopathy, polycythemia and thrombocytopenia have been observed rarely during dexfenfluramine use.[Ref]


Metabolic effects such as thirst (3%), gout, edema, hypoglycemia and hypokalemia have been observed infrequently.[Ref]


Arthralgias, myalgias and arthritis are among the most common musculoskeletal effects reported. Less frequently reported effects include leg cramps, joint disorder, bone disorder, tenosynovitis, myasthenia and rheumatoid arthritis.[Ref]

Nervous system

Nervous system effects such as insomnia (20%), dry mouth (13%), somnolence (7%), dizziness (5.5%), depression (5%), vertigo (3%), emotional lability (3%), abnormal dreams (2%), abnormal thinking (2%), nervousness, anxiety, increased libido, hypertonia and paresthesia are common. Less common effects include tremor, amnesia, euphoria, decreased libido, incoordination, neuralgia, speech disorder, ataxia, hyperkinesia, sleep disorder, abnormal gait, agitation, confusion, depersonalization, diplopia, hostility, hypokinesia, and peripheral neuritis. In addition, controversial reports support that neurotoxicity, which has been questionably evident in animal studies, may be relevant to humans.[Ref]


Pharyngitis (6%), cough (4%), bronchitis (3%), rhinitis and sinusitis are among frequently reported respiratory side effects. In addition, a case of recurrent interstitial pneumonitis was observed in a patient given dexfenfluramine.[Ref]


Dermatologic side effects associated with the use of dexfenfluramine include rash (2%), alopecia, sweating, urticaria, and pruritus. Infrequently, cases of skin disorder, fungal dermatitis, hirsutism, eczema and psoriasis have been reported.[Ref]


Abnormal vision, conjunctivitis, eye disorder, glaucoma, dry eyes, and mydriasis have seldom been observed.[Ref]

A 50-year-old female with a history of narrow glaucoma angles had an attack of bilateral acute angle-closure glaucoma thought to be precipitated by dexfenfluramine. The patient had begun taking dexfenfluramine 30 mg per day one month prior to the glaucoma episode. The patient had no previous clinical symptoms in favor of previous episodes of angle closure prior to dexfenfluramine treatment.[Ref]


Taste abnormalities and amblyopia have been frequently reported. Tinnitus and vestibular disorders are less common.[Ref]


Genitourinary side effects include urinary frequency (3%), polyuria (2%), menstrual disorder, urinary tract infection, nocturia and dysmenorrhea. Amenorrhea, dysuria, oliguria, albuminuria, breast pain, kidney calculus and kidney pain are less common.[Ref]


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Further information

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Some side effects may not be reported. You may report them to the FDA.