FDA Wrong to Deny Public Citizen’s Petition for Black Box Warning on Combined Use of Blood Pressure Medications

Combined Use of ACE inhibitors, ARBs and Aliskiren Endangers Patients – With No Added Benefit

Note: On April 3, the U.S. Food and Drug Administration denied Public Citizen’s 2012 petition for a black box warning against the combined use of ACE inhibitors, ARBs and the direct renin inhibitor aliskiren.

WASHINGTION, D.C. – The U.S. Food and Drug Administration’s (FDA) refusal to require a black box warning against the combined use of three widely used classes of blood pressure medications is ill-advised, Public Citizen said today.

In 2012, Public Citizen petitioned the FDA for a black box warning against the combined use of angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs) and direct renin inhibitors (of which aliskiren is the only approved medication). Each of these three medication classes is effective when used individually, but several large studies have shown that combining medications from two or more of the classes increases the risks of dangerously low blood pressure, high blood potassium levels and kidney failure, with no added benefit.

The FDA acknowledged that these risks apply to all medications within the three classes.

However, the agency has recommended, in a labeled “contraindication,” only against the use of the direct renin inhibitor aliskiren with either an ACE inhibitor or ARB in patients with diabetes (though, inexplicably, two ACE inhibitors [captopril and fosinopril] do not carry even this limited contraindication). The agency has not made the same absolute recommendation, in the form of a contraindication, against combining ACE inhibitors and ARBs, instead only advising, elsewhere in the medications’ labels, to avoid such therapy “in general.”

In addition, the FDA claimed that a black box warning was not needed to alert physicians of these dangers because the use of combination therapy has become less common, even though the agency itself estimates that approximately 385,000 U.S. patients were still on such combination therapy as of 2011.

“Public Citizen strongly believes that only a black box warning can adequately alert the remaining physicians prescribing combination therapy to its dangers,” said Dr. Sammy Almashat, researcher with Public Citizen’s Health Research Group. “Burying such a warning deep within the medications’ physician labels, as the FDA is currently doing, guarantees that hundreds of thousands of patients will continue to unknowingly be exposed to these preventable harms.”