European regulator says aliskiren-containing drugs not recommended with ACE inhibitors, ARBs

The European Medicines Agency on Friday recommended against the use of aliskiren-containing drugs in combination with angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs). The agency also said that following a review by the Committee for Medicinal Products for Human Use (CHMP), the medicines should be contraindicated in patients with diabetes or moderate to severe renal impairment who take ACE inhibitors or ARBs.

Novartis, which markets aliskiren as Rasilez in Europe, noted that the product’s information, along with those for combination medicines, will be updated. The drugmaker added that it will also write to doctors in the EU informing them of the changes to the product information. “This decision comes after extensive interactions between Novartis and the CHMP,” remarked David Epstein, head of the company’s drug division.

A review of aliskiren-containing drugs was initiated by the EMA in December after Novartis halted the ALTITUDE study. The trial, which involved patients with type 2 diabetes and renal impairment, was designed to evaluate the benefits of Rasilez in addition to ACE inhibitors or ARBs with respect to reducing the risk of cardiovascular and renal events. However, Novartis’ drug was associated with higher rates of non-fatal stroke, renal complications and other adverse effects.

The regulator indicated that a review of the trial results, as well as data from other studies, suggested a risk of adverse outcomes, including hypotension, stroke and changes in renal function, when aliskiren is combined with ACE inhibitors or ARBs. The EMA said the risk was higher “especially in diabetic patients and those with impaired renal function.” According to the agency, “although less evidence is available for other patient groups, adverse outcomes cannot be excluded and therefore the CHMP no longer recommends the use of this combination.”

In January, Novartis said that it would record a charge of approximately $900 million in the fourth quarter of 2011 related to lower sales expectations for Rasilez. The company indicated that 2012 sales of the drug, which is marketed as Tekturna in the US, will be less than half of last year’s $557 million. The drugmaker added Friday that it “continues discussions” with other health authorities, including the FDA, regarding aliskiren-containing drugs.