European Medicines Agency starts review of orlistat-containing medicines

Press release 22/09/2011

Evidence relating to very rare cases of liver injury to be considered in depth

The European Medicines Agency has started a review of orlistat-containing anti-obesity medicines, to determine whether the very rare cases of hepatic injury have an impact on their benefit-risk profile and conditions of use.

The review includes the centrally authorised prescription-only medicine Xenical (orlistat 120 mg) and the centrally authorised over-the-counter-medicine Alli (orlistat 60 mg), as well as a number of medicines containing orlistat that have either already or are in the process of being authorised at national level.

The risk of liver reactions with orlistat is well known and had been kept under close review by the Agency's Committee for Medicinal Products for Human Use (CHMP) since the initial marketing authorisation of these medicines. The risks of liver reactions is reflected in the product information for centrally authorised orlistat-containing medicines and addressed in the risk management plan. The CHMP is currently harmonising the product information for both centrally authorised medicines. The vast majority of reports of liver injury are not serious, and severe liver injury has been reported only very rarely. The new review focuses on the strength of evidence relating to severe liver injury.

The most recently submitted analysis, which covers of cases of hepatic events reported with orlistat 120 mg between 8 August 2009 and 31 January 2011, identified a total of 21 suspected cases of which 4 were cases of severe liver toxicity (one fatal case of hepatic failure, one case of hepatic failure leading to liver transplantation, one case of exacerbation of hepatitis and one case of hepatitis). Overall, between 1997 until January 2011 there were 21 cases of suspected serious liver toxicity for which a causal link to orlistat cannot be excluded, although these cases do not provide strong evidence of a link to orlistat as alternative explanations for liver injury are present in many of the cases. Furthermore, the number of cases needs to be considered in the context of cumulative usage of these medicines in 38 million patients.

During the period between May 2007 and January 2011 there were a total of 9 reports of suspected severe liver injury with orlistat 60 mg, although in some cases other possible explanations for liver injury were present and some cases provided insufficient information to allow assessment. These 9 cases need to be considered in the context of cumulative usage in 11 million patients.

The Committee is now reviewing all relevant data on the risk of hepatotoxicity of orlistat-containing medicines and will issue an opinion on whether or not the marketing authorisations for these medicines should be revoked, suspended or changed.


  • The European review of the centrally authorised orlistat-containing medicines (Xenical and Alli) is being conducted in the context of a formal review, initiated at the request of the European Commission under Article 20 of Regulation (EC) No 726/2004 on 5 August 2011.
  • The European review of the nationally authorised orlistat-containing medicines is being conducted in the context of a formal review, initiated at the request of the European Commission under Article 31 of Directive 2001/83/EC, as amended, on 16 September 2011.
  • All other opinions and documents adopted by the CHMP at their September 2011 plenary meeting will be published on Friday, 23 September 2011 at 12.00 noon UK time on a dedicated web page.

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