An independent analysis of adverse event reports submitted to federal drug regulators suggests that the hypertension medication Entresto, which was just introduced two years ago, may actually be causing dangerously low levels of blood pressure for many users.
In the latest QuarterWatch report (PDF) issued by the Institute for Safe Medication Practices, the potential side effects of Entresto are highlighted, after the group identified at least 6.770 adverse event reports submitted to the FDA during a one-year period.
While the majority of cases involving problems with Entresto (61%) did not have medically serious consequences, the group indicates that the adverse event reports include at least 681 deaths and 1,684 reports of hypotension (low blood pressure) related events.
Entresto is a combination of the drugs sacubitril and valsartan, which is the active ingredient in Diovan. It was introduced by Novartis after it was approved by the FDA in July 2015, based on the evidence of only a single clinical trial, which involving 8,442 patients.
“As a drug combination product, FDA reviewers noted, the single clinical trial did not provide the required evidence that sacubitril in fact added any benefit to the already-proven valsartan,” the ISMP notes. “This requirement was waived.”
ISMP researchers found that, over the 12 month period ending in March 2017, Entresto was linked to more cases of hypotension than any other heart drug on the market during that time. In addition to the 1,684 hypotension reports, the FDA’s adverse event reporting system (FAERS) also received 317 reports of kidney failure and impairment, 152 reports of angioedema, and 87 reports of hyperkalemia.
The independent report notes that FDA reviewers raised concerns about the drug before it was approved, warning that the clinical trial results involved carefully selected patients that led to an underestimation of the risk of hypotension in what would likely be normal use. The ISMP warns that its likely that one out of every four patients who take the drug will experience a hypotension-related event.
The clinical study on which the drug’s approval was based indicated that 14% of treated patients would experience symptomatic hypotension. However, the study’s data indicated that 17.6% would experience some kind of hypotension-related event. Once FDA reviewers looked at all the symptoms the clinical trial participants experienced that were related to hypotension, they raised the estimate to 24.4%. The ISMP’s own look at the data increased that to nearly 30%.
“Hypotension-or low blood pressure-means these patients are getting too much of what otherwise might be a good thing,” the ISMP researchers stated. “How frequently this occurred provided a textbook example of how adverse effects of drugs can be understated with narrow event definitions that do not capture all the likely cases.”