1. Aschenbrenner, Diane S. MS, APRN, BC

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In March, the U.S. Food and Drug Administration (FDA) asked Novartis, the manufacturer of tegaserod maleate (Zelnorm), to withdraw it from the U.S. market because it may increase the risk of myocardial infarction, stroke, and unstable angina. Tegaserod is used for short-term treatment of irritable bowel syndrome with constipation in women and for treatment of chronic idiopathic constipation in patients younger than age 65. Prior to tegaserod's approval in 2002, clinical trials had revealed a slight and not statistically significant increase in the incidence of angina in patients taking it. However, in February, Novartis submitted to the FDA a metaanalysis of 29 clinical trials that showed a slightly but statistically significant higher risk, in comparison with placebo, of cardiovascular effects associated with its use. Thirteen patients (0.1% of those receiving tegaserod) experienced serious and life-threatening events: four had a heart attack (one fatal), six had severe angina, and three had a stroke. In the placebo group, only one patient had symptoms indicative of a stroke, but they resolved spontaneously.


Novartis noted in its official statement that the 13 patients who experienced cardiovascular events had existing cardiovascular disease or risk factors and that the incidence of cardiovascular events associated with tegaserod "corresponds approximately" with the incidence in the general population. The FDA plans to meet to review tegaserod's risks and benefits and also has offered to work with Novartis to create a program that will allow patients who have no other treatment options to continue using the drug if it is determined that the benefits would be greater than the risks. However, any plan for a limited reintroduction of tegaserod to the market would first be discussed at a "public advisory committee meeting." Nurses caring for patients who take tegaserod should be aware that the drug is being withdrawn from the market and should help patients transition to another therapy.


The FDA also requested that manufacturers of pergolide (Permax), a dopamine agonist used along with levodopa and carbidopa to manage Parkinson disease, withdraw it from the U.S. market. Permax is made by Valeant Pharmaceuticals, and Par and Teva manufacture generic versions. The FDA's request came after new studies associated pergolide with a higher risk of regurgitation at the mitral, tricuspid, and aortic valves of the heart, the symptoms of which include shortness of breath, fatigue, and heart palpitations. In 2006 a black box warning was added to the product labeling for pergolide to alert clinicians and patients to the mounting evidence of valve damage with its use, and recently published studies confirm the association.


Pergolide therapy should not be discontinued abruptly. Instead, the dosage should be tapered. Patients who still require treatment with a dopamine agonist should be switched-using a published transition regimen-to one of the several others available that do not damage valves. The FDA, working with the manufacturers, may institute a program to allow patients who have not been able to successfully change to another drug therapy to continue taking pergolide.


U.S. Food and Drug Administration. FDA public health advisory: tegaserod maleate (marketed as Zelnorm). 2007 Mar 30.;


Novartis. Media release: Novartis suspends US marketing and sales of Zelnorm in response to request from FDA. 2007 Mar 30.;


U.S. Food and Drug Administration. FDA news: FDA announces voluntary withdrawal of pergolide products. 2007 Mar 29.;


U.S. Food and Drug Administration. FDA public health advisory: pergolide (marketed as Permax). 2007 Mar 29.