Hypertension phentermine

Common adverse reactions seen with phentermine use include heart palpitations, tachycardia, elevated blood pressure, stimulation, restlessness, dizziness, insomnia, euphoria, dysphoria, tremor, headache, dry mouth, constipation, and diarrhea. Phentermine should be avoided in patients with unstable cardiac status, hypertension, hyperthyroidism, agitated states, or glaucoma. In combination with fenfluramine or dexfenfluramine, pulmonary hypertension and valvular heart disease have been reported. The risk of developing either serious adverse effect cannot be ruled out with use of phentermine alone. Since phentermine is related to the amphetamines, the... 

Phentermine use should be avoided in patients concomitantly receiving or having received an MAOI within the preceding 14 days. Combination therapy with any stimulant or MAOI has the potential for causing hypertensive crisis. Alcohol is not recommended for patients prescribed phentermine.38... 

After many health problems and deaths, the FDA removed Pondimin and Redux from market. Since then, there have been 200 reported cases of primary pulmonary hypertension relating to fen-phen and dexfen-phen. Of those cases, 40 have resulted in death. The FDA has received more than 100 reports of heart valve damage directly related to fen-phen or fenfluramine therapy there are no reports from individuals taking phentermine alone for weight loss. 

For instance, in September 2004, Bayer settled 2861 product liability cases for 1.09 billion for its cholesterol medicine cerivastatin (Baycol), which was linked to 100 deaths and withdrawn from market in 2001. In July 2004, the company settled 2771 cases for 1.06 billion. Bayer still has 7577 additional cases to settle (see Section 28.4.4.5 for additional information). In another example, a 1 billion jury verdict was upheld against Wyeth for its fenfluramine or dexfenfluramine and phentermine (Fen-Phen) drug combination, which was linked to primary pulmonary hypertension (PPH). Wyeth has set aside 16.6 billion to cover future liability on the drug (see Section 28.4.4.2 for more on this case). ... 

The Chairman of FDA s Advisory Committee commented on the risk of death from developing PPH. "We have had what 1 think appears to be a reasonable estimate of the risk of deaths from pulmonary hypertension. We need to understand clearly that if a million patients take this drug, at least a couple dozen of them will die annually as a result of this complication. That seems the best estimate. This is something that has to be weighed seriously." The appearance of heart valvulopathies in otherwise asymptomatic people in their thirties or forties was unexpected and caught patients and practitioners by surprise. Both fenfluramine and phentermine cause an increase in the amount of serotonin available in the body, which can cause cardiac valvulopathies. 

Havron, M.D., Diet drugs and pulmonary hypertension, /. Pam. Tract., 43, 434-435,1996 Cleare, A.J., Phentermine, psychosis, and family history, /. Clin. PsychopharmacoL, 16,470 71, 1996. 

Fenfluramine has not been systematically studied in the treatment of BN, but dexfenfluramine has been evaluated with disappointingly mixed results. Due to an association with the development of heart valve abnormalities and pulmonary hypertension, particularly when coadministered with phentermine (lonamin) in the so-called Fen-Phen strategy, these medications have recently been removed from the U.S. market. 

Contraindications Advanced arteriosclerosis, agitated states, cardiovascular disease, concurrent use or within 14 days of discontinuation of MAOI therapy, glaucoma, history of drug abuse, hypertension (moderate-to-severe), hyperthyroidism, hypersensitivity to phentermine or sympathomimetic amines... 

Older drugs still available in some countries include phenylpropanolamine, benzphetamine, amphetamine, methamphetamine, phentermine, diethylpropion, mazindol, and phendimetrazine. These drugs are all amphetamine mimics and are central nervous system appetite suppressants they are generally helpful only during the first few weeks of therapy. Their toxicity is significant and includes hypertension (with a risk of cerebral hemorrhage) and addiction liability. 

Anorexiants [P] Hypertensive episodes due to release of stored norepinephrine (benzphetamine, diethylpropion, mazindol, phendimetrazine, phentermine). 

The amphetamines were replaced by amphetamine analogs—substances somewhat less potent than amphetamines. Fen-Phen, the combination of fenfluramine and phentermine, was a popular appetite suppressant in the 1990s, but was associated with severe health problems such as pulmonary hypertension, heart valve dysfunction, and nerve damage. As a result, both drugs were withdrawn from the market. 

Tomita T, Zhao Q. Autopsy findings of heart and lungs in a patient with primary pulmonary hypertension associated with use of fenfluramine and phentermine. Chest 2002 121 649-652. 

Mark EJ, Patalas ED, Chang HT, Evans RJ, Kessler SC. Fatal pulmonary hypertension associated with short-term use of fenfluramine and phentermine. N Engl... 

Strother J, Fedullo P, Yi ES, Masliah E. Complex vascular lesions at autopsy in a patient with phentermine-fenfluramine use and rapidly progressing pulmonary hypertension. Arch Pathol Lab Med 1999 123 539-540. 

Of the other central stimulants, aminorex, doxapram, fenfluramine, and fenfluramine plus phentermine can cause chronic pulmonary hypertension, as can chlorphentermine, phentermine, phenmetrazine, and D-norpseudoephedrine (SED-9, 8). A genetic predisposition may be involved (SED-9,8). Pulmonary hypertension may develop or be diagnosed a long time after the drug has been withdrawn. 

Spontaneous rupture of a retroperitoneal aneurysm occurred in a 70-year-old woman who had been taking phentermine hydrochloride, 30 mg/day, for about 1 month (6). Other long-term medications included fluoxetine and amitriptyline, and she had no history of coronary artery disease, hypertension, diabetes, or complications of pregnancy. Although it is plausible that phentermine could have contributed to the ruptured aneurysm, other possibilities should be considered, particularly rupture of an anomalous retroperitoneal blood vessel. 

The autopsy findings in the heart and lungs of a patient with pulmonary hypertension associated with fenfluramine and phentermine have been described (13). 

Pulmonary hypertension and multivalvular damage after prolonged use of fenfluramine with phentermine have been reported in a 70-year-old Israeh woman (61). 

Fatal pulmonary hypertension occurred in a 32-year-old man who had been taking phentermine in unknown doses for 4 months (62). 

Bruce CJ, Connolly HM. Valvular heart disease, pulmonary hypertension and fenfluramine-phentermine use. Cardiol Rev 1998 15 17-19. 

New pharmacological treatments have been developed for the treatment of obesity. These include the combination of phentermine and fenfluramine (phen-fen) and, alternatively, dexfenfluramine (Redux). Phentermine (Fastin, lonamin) is a stimulant and fenfluramine (Pondimin) is a serotonin agonist. In combination they have persistent appetite suppression and weight loss effects. These medications can cause anxiety and insomnia and must be used with extreme caution if taken with antidepressants, especially SSRIs. Dexfenfluramine works similarly, but avoids the side effect of increased anxiety, and instead tends to cause diarrhea, dry mouth, and somnolence. There have also been reports of pulmonary hypertension, a potentially fatal condition, especially when taken for longer than three months. Some researchers (Ricuarte et al. 1991 McCann et al. 1994) have expressed concern because rats given these medications showed evidence of neuronal toxicity. Thus, they are effective medications, but must be used with caution. 

Weintraub et al. 1984). This combination (later to become known as fen-phen) appeared to be more effective and better tolerated in comparative clinical trials than either drug given alone. The combination of fenfluramine and phentermine soon became extremely popular in the US. By 1996, over 18 million prescriptions for this combination were being issued annually. Unfortunately, the fenfluramine moiety of the combination appeared to cause pulmonary hypertension and/or mitral valve prolapse in some patients. It was withdrawn from the market in 1997. 

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