) is an antiretroviral drug
used in the treatment of the human immunodeficiency virus
(HIV). Nelfinavir belongs to the class of drugs known as protease inhibitors
(PIs) and like other PIs is generally used in combination with other antiretroviral drugs. Nelfinavir is presented as the mesilate (mesylate) ester prodrug
Nelfinavir mesylate (Viracept, formally AG1343) is a potent and orally bioavailable human immunodeficiency virus HIV-1 protease inhibitor (Ki=2nM) and is being widely prescribed in combination with HIV reverse transcriptase inhibitors for the treatment of HIV infection. Nelfinavir mesylate contains the Castor oil derivative Cremophor EL.
Nelfinavir was developed by Agouron Pharmaceuticals as part of a joint venture with Japan Tobacco. Agouron Pharmaceuticals was acquired by Warner Lambert in 1999 and is now a subsidiary of Pfizer. It is marketed in Europe by Hoffman-La Roche
The Food and Drug Administration
approved it for therapeutic use on March 14
, making it the twelfth approved antiretroviral. The initial product launched proved to be the largest "biotech launch" in the history of the pharmaceutical industry achieving first full year sales exceeding $335M US.
on the drug will expire in 2014.
On the 6th June 2007 both the Medicines and Healthcare products Regulatory Agency and the European Medicines Agency put out an alert requesting the recall of any of the drug in circulation because of fears that batches of the therapy may have been contaminated with potentially cancer-causing chemicals
Nelfinavir is currently under investigation for potential repositioning as an anti-cancer agent. When applied to cancer cells in culture, both apoptotic and non-apoptotic cell death is observed. However, there is no evidence that Nelfinavir actually targets cancer cells within a native tumor in a person. But newer results where investigators have studied nelfinavir in laboratory mice showed that this drug can suppress the growth of cancer in such animals.
Nelfinavir should be taken with food. The bioavailability of Nelfinavir is increased 2.5 to 5 times when taken with food. Taking the drug with food also decreases the risk of diarrhea
as a side effect.
Mode of action
Nelfinavir is a protease inhibitor
: it inhibits HIV-1
and HIV-2 proteases. This protease is an enzyme which cleaves viral protein molecules into smaller fragments, and it is vital for both the replication of the virus within the cell and also the release of mature viral particles from an infected cell. Though this mode of action is common to all protease inhibitors, the precise mode of binding of nelfinavir to the enzyme may be sufficiently unique to reduce cross-resistance between it and other PIs. Also, not all PIs inhibit both HIV-1 and HIV-2 proteases.
Nelfinavir can produce a range of adverse effects. Common (experienced by more than one in one hundred patients; greater than 1%) are flatulence, diarrhea
or abdominal pain. Infrequent (experienced by one in one thousand to one in one hundred patients; 0.01 - 0.1%) adverse effects are fatigue, urination, rash
, mouth ulcers
. Rarely (less than one in one thousand patients; under 0.01%) nephrolithiasis
reactions may occur.
Nelfinavir's interaction profile is similar to that of other protease inhibitors
. Most interactions occur at the level of the Cytochrome P450
, by which nelfinavir is metabolised.