nelfinavir (Rx)

>10%

Diarrhea (14-20%)

1-10%

Nausea (3-7%)

Flatulence (1-5%)

Abdominal pain (1%)

Anemia (1%)

Allergic reaction (1%)

Impaired concentration (1%)

Lipodystrophy (1%)

Metabolic acidosis (1%)

Rash (1-3%)

Leukopenia (1%)

Thrombocytopenia (1%)

Weakness (1%)

<1%

QTc prolongation

Torsades de pointes

Diabetes mellitus, new onset and exacerbation

Hyperglycemia

Contraindications

Hypersensitivity

Coadministration with major CYP3A4 substrates and/or inducers

Drugs that are contraindicated with nelfinavir include alpha1-adrenoreptor agonists (eg, alfuzosin), antiarrhythmics (amiodarone, bepridil, flecainide, propafenone, quinidine), rifampin, voriconazole, ergot derivatives (dihydroergotamine, ergonovine, ergotamine, methylergonovine), cisapride, St. John’s wort, lovastatin, simvastatin, lurasidone, pimozide, sildenafil (when used for PAH), midazolam, and triazolam

Cautions

Risk to pregnant/ pediatric pts: EMS (ethyl methanesulfonate) impurity shown to be teratogenic, mutagenic & carcinogenic in animal studies

Oral powder contains 11.2 mg of phenylalanine per gram of powder

Risk of immune reconstitution syndrome if used in combination with other antiretroviral drugs

Caution in patients with hemophilia A or B (risk of bleeding); increased bleeding, including spontaneous skin hematomas and hemarthrosis reported with protease inhibitors; in more than half of cases, administration of protease inhibitors was continued or reintroduced

Increased risks of fat redistribution, hemolytic anemia, hyperbilirubinemia if used in combination with other antiretroviral drugs

Increases risk of developing new onset diabetes mellitus; exacerbation of DM & hyperglycemia

Not for use in patients with moderate to- evere hepatic impairment

In pediatrics, drug exposure is highly variable

Pregnancy

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to drug during pregnancy; healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) at 1-800-258-4263

Published reports of hepatic adverse events ranging from elevated liver enzymes to hepatic failure in pregnant patients exposed to drug and as part of combination treatment of HIV-1 infection reported; overall adverse event profile, including hepatic adverse events, and literature reports of decreased exposures in second and third trimesters, consider alternative antiretroviral drugs during pregnancy; if drug is used during pregnancy, clinical monitoring recommended

Therapy may reduce efficacy of estrogen-based oral contraceptives; advise patients to use alternative or additional contraceptive measures when oral contraceptives containing ethinyl estradiol or norethindrone and nelfinavir are coadministered

Lactation

The Centers for Disease Control and Prevention recommend that HIV-1 infected patients in the United States not breastfeed their infants to avoid risking potential transmission of HIV-1 infection

Based on limited published data, drug is present in low levels in human milk, and adverse effects in infants exposed to nelfinavir have been reported; because of potential for HIV-1 transmission (in HIV-negative infants), developing viral resistance (in HIV-positive infants), and the potential for serious adverse reactions in breastfed infants similar to those seen in adults, instruct mothers not to breastfeed if they are receiving therapy

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Protease Inhibitor; inhibits cleavage of Gag-Pol polyprotein precursors, which in turn causes the formation of immature, noninfectious viral particles.

Pharmacokinetics

Absorption: food increases AUC 2-3x

Vd: 2-7 L/kg

Protein Bound: >98%

Metabolism: hepatic via CYP3A4 & CYP2C19; major metabolite has activity comparable to parent drug

Half-life, plasma: 3.5-5 hr

Peak Plasma Time: 2-4 hr

Enzymes Inhibited: CYP3A4

Excretion: Feces: (87%); urine: (1-2%)

Oral Administration

Mix oral powder with small amount of water, milk, formula or dietary supplement and consume entire dose

Do not mix with acidic food or juice

If not consumed immediately, refrigerate no more than 6 hr

May use crushed 250 mg tablets instead of oral powder

Take all doses with high-fat meals