Earlier Zelnorm Recall Was Due To Potential Cardiovascular Safety Signal, With Suicidal Ideation And Behavior Being Another Issue
(Posted by Tom Lamb at DrugInjuryWatch.com)
On October 17, 2018 the FDA's Gastrointestinal Drugs Advisory Committee of the US Food and Drug Administration (FDA) voted to recommend that Zelnorm (tegaserod maleate) be approved for the treatment of irritable bowel syndrome with constipation (IBS-C) in women.
To put into context the issue whether the FDA should allow Zelnorm back on the market -- as will be seen, there was a "Zelnorm recall" in 2007 -- and whether this would be a good idea as regards the matter of drug safety, we provide some background information.
- The FDA initially approved Zelnorm in 2002 for the short-term treatment of women with IBS-C.
- Next, in 2004 the FDA approved Zelnorm for the treatment of all patients, i.e., men as well as women, less than 65 years of age with chronic idiopathic constipation.
- Then, in 2007 the FDA issued a letter recommending the addition of a warning about the potential risk of suicidal ideation and behavior (SI/B) event in Zelnorm drug label (technically called "Prescribing Information" document). However this never happened because the following month Novartis Pharmaceuticals Corp. removed Zelnorm from the US market for cardiovascular (CV) safety concerns.
- In more detail, on March 30, 2007 Novartis withdrew Zelnorm from the US market in compliance with an FDA "recall" request after data in the FDA's adverse events databases showed a higher incidence of myocardial infarction, stroke, and unstable angina among patients who took Zelnorm when compared with those who took placebo.
Now we return to the FDA Advisory Committee October 2018 meeting which resulted in the recommendation that Zelnorm be allowed back on the US market.
First, the application to bring back Zelnorm was made by Sloan Pharma, which acquired the rights to Zelnorm from Novartis.
Second, this time around, the FDA Advisory Committee said that Zelnorm should only be approved for use by women without a history of cardiovascular (CV) ischemic disease and who have no more than one risk factor for CV disease.
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For more on this aspect, we turn to an October 17, 2018 Medscape news report, "FDA Panel OKs Tegaserod for IBS With Constipation in Women With Low CV Risk":
Women without CV disease include those without myocardial infarction, stroke, transient ischemic attack, or angina, and risk factors for CV disease include hypertension, tobacco use, diabetes, hypercholesterolemia, age ≥ 55 years, or obesity.
The [FDA Advisory Committee] panel voted unanimously that "the therapeutic gain (treatment difference between [Zelnorm] and placebo) is generally similar in magnitude between the severely symptomatic and originally approved population."
Regarding which patient populations would be most likely to experience greater benefits compared with risks for treatment with [Zelnorm], seven panel members said females with IBS-C and low CV risk, three voted for severely symptomatic females with IBS-C and low CV risk, and one each voted for females with IBS-C and severely symptomatic females with IBS-C.
But, despite this possible benefit to a limited patient population, is allowing Zelnorm back on the market really warranted in view of the serious and still-lingering drug safety concerns?
For where things seemed to stand at the conclusion of the October 17, 2018 FDA Advisory Committee meeting about Zelnorm, we return to the Medscape news report:
"Given the potential for reintroduction of [Zelnorm] in various subpopulations of interest, elucidating the benefits and risks in the presence of a potential [cardiovascular (CV) as well as suicidal ideation and behavior (SI/B)] safety signal is of particular clinical importance, as patients with IBS-C may have need for additional treatment options but may also be at risk of [adverse events (AEs)," the FDA explains in its briefing document.
"I do think that the CV signal is real, but I think the magnitude of the signal is small," said temporary voting committee member John Teerlink, MD, professor of medicine, University of California San Francisco; director, Heart Failure, and director, Echocardiography, Section of Cardiology, San Francisco Veterans Affairs Medical Center, California.
We point out that the FDA is not obliged to follow recommendations of its advisory committees but it usually does.
While we wait to see whether Zelnorm is allowed back on the US market 11 years after the FDA mandated a recall of Zelnorm, we welcome your Comments (submit below) on this developing drug safety issue.
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