Nelfinavir is an HIV protease inhibitor.
Nelfinavir has activity against HIV-1 and HIV-2.
Cleavage of polyproteins by the protease enzyme is an essential step in the HIV life cycle. After cleavage, the immature virus proteins are assembled into particles which bud from the cell as mature, infectious virons. Protease inhibitors compete for the active cleavage site on the protease enzyme, blocking the cleavage of the polyproteins and thus the maturation of new viral particles.
Higher levels of protease inhibitor resistance result from the accumulation of multiple protease inhibitor-resistance mutations. There are many mechanisms of resistance. These include reduced binding affinity between the inhibitor and the protease enzyme, alterations in enzyme catalysis, effects on dimer stability, alterations in inhibitor binding kinetics, and re-shaping of the active site.
The fold change for IC50 in the presence of 50% human serum for nelfinavir was 21.9. The predicted fold change in 100% human serum is 90.6.
Administration with high fat meals results in a 2 – 3 fold higher Cmax and AUC. Nelfinavir is metabolized to an active metabolite M8 and is extensively bound to serum proteins at >98%. Multiple isoenzymes contribute to metabolism of nelfinavir, including CYP450 2C19 and 3A4. Eighty-seven percent is recovered in feces.
The most common adverse effect is diarrhea. It is usually mild to moderate in intensity and can often be managed with an antidiarrheal agent such as loperamide and adequate hydration to prevent dehydration.
Tablet 250mg, 625mg
Oral Suspension 50mg/g
Unboosted: 1250 mg twice daily or 750 mg three times daily with food
Boosted: Nelfinavir 500-750 mg twice daily plus ritonavir 400 mg twice daily
: 20 – 30 mg/kg (up to a maximum of 750 mg per dose) three times daily
Disease state based dosing:
Renal Impairment: no specified dose adjustment
Hepatic Impairment: no specified dose adjustment. Use with caution in patients with moderate to severe hepatic insufficiency
Nelfinavir is contraindicated in patients taking amiodarone, quinidine, dihydroergotamine, ergonovine, ergotamine, methylergonovine, pimozide, midazolam, and triazolam.
Viracept® Oral Powder contains 11.2 mg phenylalanine per gram of powder. Therefore patients with phenylketonuria should use caution.
Nelfinavir is an inhibitor of CYP3A. Therefore co-administration with drugs primarily metabolized by CYP3A may result in increased plasma concentrations of the other drug. Nelfinavir is metabolized by CYP2C19 and CYP3A. Therefore, concomitant use with inducers or inhibitors or CYP3A and CYP2C19 will affect concentrations of nelfinavir.
Category B: No evidence of risk in humans but studies inadequate.
Blood glucose, LFTs, serum lipid profile
Viracept®/Agouron-Pfizer Pharmaceuticals Inc