Nelfinavir

• Treatment of HIV-1 Infection:
  Nelfinavir is indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in combination with other antiretroviral agents in both adults and children aged 2 years and older.
• Off-label Uses:
  Occasionally used in salvage therapy for multidrug-resistant HIV infections.

• Adults:
• 1250 mg orally twice daily (two 625 mg tablets twice daily) with food to improve absorption.
• Alternatively, 750 mg orally three times daily with food.
• Pediatrics (≥2 years):
  Dosage based on body surface area or weight, generally 45 to 50 mg/kg/day divided into two or three doses with meals. Maximum daily dose should not exceed adult dose.
• Elderly:
  No specific dosage adjustment; monitor renal and hepatic function.
• Renal Impairment:
  No dose adjustment required for mild to moderate impairment. Use cautiously in severe impairment.
• Hepatic Impairment:
  Use with caution; monitor liver function closely.
• Administration:
  Oral tablets or powder, always taken with meals to enhance bioavailability.
• Duration:
  Long-term use as part of antiretroviral therapy.

Nelfinavir is an HIV-1 protease inhibitor that selectively binds to and inhibits the viral protease enzyme responsible for cleaving viral polyproteins into functional proteins necessary for viral maturation. This inhibition results in the production of immature, noninfectious viral particles, thereby decreasing viral replication and load.

• Absorption: Rapidly absorbed; peak plasma concentration occurs 2 to 4 hours post-dose.
• Bioavailability: Enhanced by food intake; approximately 20–40%.
• Distribution: Highly protein bound (~98%), widely distributed.
• Metabolism: Extensively metabolized in the liver by CYP3A4 and CYP2C19 enzymes into active metabolites.
• Elimination: Primarily excreted via feces (~87%) and minimally via urine (<1%).
• Half-life: Approximately 3.5 to 5 hours.

• Pregnancy:
  FDA Category B. Animal studies show no evidence of harm, but human data are limited; use only if clearly indicated.
• Lactation:
  Unknown if excreted in human milk; caution is advised. Breastfeeding is generally discouraged in HIV-infected mothers.

• Primary Class: Antiretroviral agent
• Subclass: HIV-1 Protease inhibitor

• Hypersensitivity to nelfinavir or any component of the formulation.
• Concurrent use with drugs highly dependent on CYP3A for clearance with serious adverse effect risk (e.g., cisapride, pimozide, ergot derivatives).
• Severe hepatic impairment.

• Monitor liver function regularly due to risk of hepatotoxicity.
• Cases of new-onset diabetes mellitus and exacerbation of pre-existing diabetes have been reported.
• Lipodystrophy syndrome may occur with long-term use.
• Immune reconstitution syndrome can manifest in some patients after starting therapy.
• Caution in patients with bleeding disorders; episodes reported in hemophiliacs.
• Monitor for PR interval prolongation in patients with cardiac conduction abnormalities.
• Extensive drug interaction potential due to CYP3A4 metabolism.

• Common: Diarrhea, flatulence, nausea, vomiting, abdominal pain, rash.
• Less Common: Fatigue, headache, elevated liver enzymes, lipid abnormalities.
• Serious: Hepatotoxicity, Stevens-Johnson syndrome, pancreatitis, diabetes mellitus, arrhythmias.

• Strong inhibitor and substrate of CYP3A4; interactions common.
• Avoid with CYP3A4 substrates with narrow therapeutic index that may cause serious adverse effects.
• Inducers like rifampin reduce nelfinavir plasma concentrations.
• Use with other antiretrovirals requires careful monitoring and dose adjustments.
• Food increases absorption; take with meals.

• Recommended primarily in specific treatment regimens or salvage therapy.
• Reinforced warnings on metabolic effects and hepatotoxicity.
• No major dosing changes recently.

• Store between 20°C and 25°C (68°F to 77°F).
• Protect from moisture and light.
• Keep container tightly closed.
• Do not freeze.
• Keep out of reach of children.