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 Category: B (Antiretroviral Pregnancy Registry established, register pts by calling (800) 258-4263)

Lactation: HIV+ women are advised not to breastfeed

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