Nelfinavir

  • Abbreviation: NFV
    Antiretroviral Subclass:
    Protease Inhibitors

Background

  • U.S. Manufacturer:
    ViiV Healthcare

    Approval

    Nelfinavir received approval from the U.S. Food and Drug Administration (FDA) in 1997 for the treatment of adults and children with HIV infection. Initial approval was based on studies showing increases in CD4 T-lymphocyte counts and reductions in HIV viral load in individuals receiving nelfinavir either alone or in combination with 1 or 2 nucleoside analogues. These changes were superior to those seen with nucleoside analogues alone.

    Generic Approval

    NA

Formulations and Dosing

  • Nelfinavir is available in tablets for adult and pediatric dosing. The oral powder formulation is no longer available. For adults or children who are unable to swallow pills, the tablets may be crushed or dissolved in water.

    • Nelfinavir must be taken with a meal.
    • No dose adjustment is necessary in renal insufficiency.
    • Please consult product labeling for detailed dosing information.

    Adult Dosing

    Dosage Formulation Notes
    1,250 mg BID or 750 mg TID Tablets  

    Key to abbreviations: BID, twice daily; TID, 3 times daily.

    Pediatric Dosing

    Age Dosage Formulation Weight
    adolescent 1,250 mg BID or 750 mg TID (Adult dosing) Tablets  
    2 to 13 years 45-55 mg/kg BID or 25-35 mg/kg TID Tablets  
    <2 years Not FDA approved; serum drug levels variable.    

    Key to abbreviations: BID, twice daily; TID, 3 times daily.

    In pediatric patients, nelfinavir exposure is highly variable.

Coformulations

Clinical Use

  • Initial vs Subsequent Therapy

    Treatment guidelines of the U.S. Department of Health and Human Services state that nelfinavir is "not recommended" for initial treatment of HIV infection in adults and adolescents, because it is less effective than other agents.

    Failure of a regimen containing nelfinavir may decrease the likelihood that subsequent protease inhibitor-containing regimens will succeed, but there is evidence that changing to a regimen containing ritonavir + another protease inhibitor (eg, saquinavir) may achieve long-term suppression of viral load following failure of an initial nelfinavir-containing regimen.(1)

    Nelfinavir has been studied as a component of subsequent therapies. In patients with nucleoside analogue experience, combinations containing nelfinavir + efavirenz were effective at suppressing viral load.(2) Nelfinavir combined with saquinavir and nucleoside analogues has been studied in patients without prior protease inhibitor use and compares favorably with regimens containing one protease inhibitor.(3) In patients with virologic relapse on indinavir-containing regimens, regimens containing nelfinavir + efavirenz + abacavir + adefovir were effective in the short term, especially if the viral load was <15,000 copies/mL at the time of switching.(4)

    Factors Affecting Adherence

    The most common symptomatic side effect of nelfinavir is diarrhea, which usually can be controlled with nonprescription antidiarrheals or antimotility agents. As with other protease inhibitors, nelfinavir may cause dyslipidemia and abnormalities of body fat distribution.

    It is important to assess patient motivation and discuss possible side effects and strategies for their management before treatment with a protease inhibitor is initiated.

    Nelfinavir has been studied in patients taking the drug during pregnancy; it is classified as an FDA Pregnancy Category B drug. However, the FDA recommends that it not be used for the treatment of pregnant women (see "Special Issues" below).

    Resistance

    Resistance to nelfinavir is associated with the selection of 1 or more of several resistance mutations.

    Implications of nelfinavir resistance for treatment with other antiretrovirals

    Resistance mutations selected by nelfinavir may or may not confer or contribute to resistance against other protease inhibitors. The commonly selected D30N mutation does not appear to be associated with resistance to other drugs, while the L90M mutation, which is less commonly selected by nelfinavir, confers or contributes to resistance to all other protease inhibitors.

    Genotypic or phenotypic testing may be useful in predicting the likelihood of response to other protease inhibitors following failure of regimens containing nelfinavir.

    Implications of resistance to other antiretrovirals for nelfinavir treatment

    The likelihood of sustained response to nelfinavir is diminished in the setting of resistance to other protease inhibitors.

    Genotypic or phenotypic resistance testing may be useful in predicting the likelihood of response to nelfinavir following failure of regimens containing other protease inhibitors.

    Special Uses

    In 2007, nelfinavir manufactured in Europe was recalled from the market because of high levels of ethyl methane mesylate (EMS). Nelfinavir manufactured in United States was found to have lower levels of EMS than the European product. However, the FDA recommended that pregnant women not be treated with nelfinavir and that pediatric patients not be initiated on nelfinavir. By early 2008, nelfinavir manufactured both in Europe and in the United States was determined to meet safety standards, and the FDA and European Medicines Agency had lifted its warnings about safety.(5)

Resources and Links

Assistance Programs: ViiV Connect