Roche recalls nelfinavir (Viracept) due to chemical impurity
10 July 2007. Related: Treatment alerts.
Patients are requested to contact their doctors as soon as possible to start alternative therapies.
On 6th June 2007, Roche, in agreement and cooperation with Health Authorities (EMEA, Swissmedic and MHRA), recalled in Europe and some other world regions all batches of nelfinavir (Viracept) powder and tablets. [1] The US, Canada and Japan were not affected by this recall, as nelfinavir is manufactured by Pfizer in those countries.
The recall was triggered by the presence of a contaminant called methane sulfonic acid ethyl ester in the active substance, after market reports related to a bad smell of the tablets, and of nausea and vomiting.
Patients are requested to contact their doctors as soon as possible to start alternative therapies.
Methane sulfonic ethylester is a normal byproduct of the manufacturing process but is only present in very small amounts. The normal tolerated levels are 3 parts per million (ppm). Due to human error in the maintenance of the production line it would appear levels of this compound increased. This molecule is classed as a carcinogen.
This problem does not affect any other Roche products.
Information from Roche has suggested that in the worst-case scenario, some batches seem to have contained 2,300 ppm.
The effects of methane sulfonic acid ethyl ester in humans have not been studied. Animal studies show that the class of chemicals called alkyl mesylates which includes methane sulfonic acid ethyl ester are genotoxic carcinogens. The potential long-term consequences to patients are currently unknown. Roche in association with Health Authorities is looking into the measures to be taken in order to monitor patients.
Studies in which rats were given water containing methane sulfonic ethylester for 3 months at a dose of 10mg/kg/day developed tumours.
If a patient has taken contaminated nelfinavir with the worst case scenario 2300ppm, then their dose would have been 0.1mg/kg/day. This is 100-fold less exposure than that known to cause tumours in rats. There is insufficient data to estimate the level of risk at the exposed dose in humans.
There are references below with regards to data we have on methane sulfonic ethylester. [2, 3, 4]
References:
- EMEA announces recall of Viracept (6 June 2007):
http://www.emea.europa.eu/pdfs/general/direct/pr/25128307en.pdf - Sega GA. A review of the genetic effects of ethyl methanesulfonate. Mutation Res. 1984 134: 113-42.
- Op het Veld CV et a. Effect of nucleotide excision repair on hprt gene mutations in rodent cells exposed to DNA ethylating agents. Mutagenesis 1997 Nov;12(6);417-24.
- IARC monographs on the evaluation of carcinogenic risks to humans. Overall Evaluations of Carcinogenicity: An updating of IARC monographs volume 1 to 42. supplement 7, 1987.