Elevated ethyl methanesulfonate (EMS) in nelfinavir mesylate (Viracept？, Roche) overview.docVIP

AIDS Research and Therapy BioMedCentral Short report Open Access Elevated ethyl methanesulfonate (EMS) in nelfinavir mesylate (Viracept?, Roche): overview Anton Pozniak1, Lutz Müller2, Miklos Salgo2, Judith K Jones3, Peter Larson*4 and David Tweats5 Address: 1Department of HIV and Genitourinary Medicine, Chelsea and Westminster Hospital, London, UK, 2Pharmaceuticals Division, F. Hoffmann-La Roche, Basel, Switzerland, 3The Degge Group, Arlington, VA, USA, 4Pharmaceuticals Division, F. Hoffmann-La Roche, Nutley, NJ, USA and 5Medical School, University of Wales, Swansea, UK Email: Anton Pozniak - anton.pozniak@chelwest.nhs.uk; Lutz Müller - Lutz.Mueller@; Miklos Salgo - miklos.salgo@; Judith K Jones - jkjones@; Peter Larson* - peter_j.larson@; David Tweats - david@tweats.fslife.co.uk * Corresponding author Published: 6 August 2009 Received: 22 June 2009 Accepted: 6 August 2009 AIDS Research and Therapy 2009, 6:18 doi:10.1186/1742-6405-6-18 This article is available from: /content/6/1/18 ? 2009 Pozniak et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Roches protease inhibitor nelfinavir mesylate (Viracept?) produced between March 2007-June 2007 was found to contain elevated levels of ethyl methanesulfonate (EMS), a known mutagen (alkylator) – leading to a global recall of the drug. EMS levels in a daily dose (2,500 mg Viracept/day) were predicted not to exceed a dose of ~2.75 mg/day (~0.055 mg/kg/day based on 50 kg patient). As existing toxicology data on EMS did not permit an adequate patient risk assessment, a comprehensive animal toxicology evaluation of EMS was conducted. General toxicity of EMS was investigated in rats over 28 days. Two studies for DNA damage wer