Roche is recalling all nelfinavir (Viracept) manufactured at its Swiss plant with immediate effect. Patients who are currently taking nelfinavir are advised to contact their HIV clinic immediately, if they have not already done so, in order to switch to another appropriate antiretroviral drug.
How did nelfinavir become contaminated?
The contaminant, ethyl mesylate (also known as methane sulfonic acid ethylester) that was found in some batches of nelfavinavir is, says Dr Dilruwan Chaminda Herath, Roche UK’s Associate Head of Medical Affairs, “a by-product of manufacture”, which is usually present in extremely low quantities (less than three parts per million). “We assume it was human error during standard maintenance of the production line at the end of 2006 that the contamination occurred,” he told aidsmap.com.
How recently did Roche know about the contamination?
Dr Herath tells us that two weeks ago Roche received six reports – from Spain and France – that a “foul odour” was emanating from some patients’ supplies of nelfinavir, and they “began their normal investigation procedure.” The investigation found variations in the levels of contaminant in different batches, which in the “worse case reached 2,300 parts per million.”
What is the risk to patients?
In terms of assessing the risk to patients, Roche has calculated that someone who ingested nelfinavir containing the highest amount of contaminant would have been exposed to 0.1mg per kilogram per day. Although there have been no human studies regarding the cancer risk of ethyl mesylate ingestion, studies have been done in the test tube and in rats. These found that approximately 100 times greater amounts of the genotoxin were required to be ingested over three months (10mg per kilogram per day) for cancer to develop in rats. “In a worse case scenario,” notes Dr Herath, “the amount ingested by someone on Viracept would be 100 fold less than was found to cause tumours in rats.”
What should patients do?
They should go to their nearest HIV clinic as soon as possible, bringing with them all of the nelfinavir supplies. They will be immediately switched to another anti-HIV drug that is appropriate to them based on prior treatment experience, previous resistance tests and other issues, such as side-effect and tolerability profile. Roche suggests that patients note batch number of their supply for future reference. If they have any concerns about their risk from possible ingestion of the contaminant they should first of all discuss it with their HIV clinician. “Any unusual symptoms or side-effects should be reported via the MHRA Yellow Card scheme,” says Dr Herath.
Who in the UK is affected?
Roche is unable to say exactly how many UK patients are currently taking nelfinavir. It is no longer recommended as a first-line regimen by the British HIV Association (BHIVA), although a 2006 BHIVA audit of first-line regimens reported at the recent BHIVA/BIS Spring Conference found that a small percentage of patients did receive nelfinavir as a first-line therapy. Roche believes many of the estimated 550 patients affected will have taken it for only 30 days as part of Post-exposure Prophylaxis (PEP).
How long before patients can obtain nelfinavir again?
“We evisage that it will take several months to replenish stocks,” says Dr Herath. Although stocks of nelfinavir in the United States, Canada and Japan (where it is manufactured by Pfizer in the US utilising a separate manufacturing process and manufacturing plants) are not affected, Roche is unable to import unaffected drug from these regions because they do not have EMEA marketing approval. “Although the US version of Viracept has the same active ingredient, it is available in a different formulation (625mg as opposed to 250mg tablets) and with a different exipient,” notes Dr Herath.