EMA: New Aliskiren Restrictions and Decisions on Aprotinin, Orlistat

Reed Miller

February 21, 2012

February 17, 2012 (London, United Kingdom) — New contraindications and warnings for medicines with aliskiren (Rasilez/Tekturna, Novartis) are among the opinions arising from the February 13-16 meeting of the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP).

The ALTITUDE study of aliskiren was stopped early because type 2 diabetes patients with renal impairment randomized to the drug on top of an ACE inhibitor or angiotensin-receptor blocker (ARB) had more adverse events, with no offsetting benefit, than patients taking placebo with ACE inhibitors or ARBs.

Based on the CHMP's review of the ALTITUDE data, the EMA now recommends that aliskiren-containing drugs be contraindicated in patients with diabetes or moderate to severe renal impairment who are taking ACE inhibitors or ARBs. "For all other patients receiving aliskiren-containing medicines in combination with an ACE inhibitor or an ARB, the balance of benefits and risks of continuing treatment should be considered carefully," the EMA recommends.

Aprotinin Gets Green Light

The EMA is now recommending lifting the EU-wide suspension of the marketing authorization for the antifibrinolytic aprotinin (Trasylol, Bayer Healthcare Pharmaceuticals) after the CHMP determined that the results of the BART study were unreliable.

The agency suspended marketing of the drug after results of the BART study, published in 2008, appeared to show that high-risk heart-surgery patients taking aprotinin had a worse 30-day survival than patients taking other medicines. However, the CHMP determined there "were a number of problems with the way the BART study was conducted, which cast doubt on the previous conclusions," including imbalanced application of heparin, inappropriate monitoring, and the questionable exclusion of some patients from the initial analysis. The BART results were not replicated in other studies, and the overall data available showed that aprotinin's benefits are greater than its risks for its intended indication, the CHMP concluded. The CHMP also calls for the establishment of an aprotinin registry.

Orlistat Benefits Worth the Risks

The CHMP finalized its review of the risk of liver injury with orlistat drugs, such as Xenical (Roche) and Alli (GlaxoSmithKline), with the conclusion that the weight-loss drug's benefits outweigh the risks in patients with a body mass index of >28 kg/m2. The committee also recommends that the safety information for all of these drugs be harmonized.

According to the CHMP, safety monitoring data show four cases of severe liver injury with Xenical where the role of orlistat could not be excluded from August 2009 to January 2011. Xenical may have contributed to up to 21 cases of severe liver toxicity from 1997 to January 2011. There were also nine reports of liver failure in people using Alli between May 2007and January 2011.

However, the committee points out that these numbers must be considered in the context of the 20 million Xenical and Alli users in the EU. The CHMP "considered that there was no strong evidence that orlistat increases the risk of severe liver injury and there was no known mechanism by which orlistat was expected to cause liver disorders."