nelfinavir (Viracept)

Indications

• treatment of HIV infection, for use in connection with nucleoside analog

* potential to be repurposed as COVID-19 therapy

Contraindications

• phenylketonuria (powder contains phenylalanine)
• concurrent administration of terfenadine, astemizole, cisapride, triazolam or midazolam

pregnancy category = b

safety in lactation = -

Dosage

• 750 mg PO TID
• administer with meals

Powder: (oral) 50 mg/g (each gram of powder contains 11.2 mg of phenylalanine (144 g)

Tablet: 250 mg

Storage

• store in orginal container (reason unclear)

Pharmacokinetics

• absorption after oral administration is 2-3 fold higher when taken with food vs. fasting
• 1/2life is 3.5-5 hours
• metabolized in the liver by cyt P450 3A4
• the majority of drug is eliminated in the feces

elimination via liver

1/2life = 3.5-5 hours

Adverse effects

• common (> 10%)
  • diarrhea (may be treated with loperamide)
• less common (1-10%)
  • decreased concentration, rash, nausea, flatulence, abdominal pain, weakness
• uncommon (< 1%)
  • anxiety, depression, dizziness, emotional lability, hyperkinesia, insomnia, migraine, seizures, sleep disorder, somnolence, suicidal ideation, fever, headache, malaise, dermatitis, pruritus, urticaria, increased liver function tests, hyperlipidemia, hyperuricemia, hypoglycemia, anorexia, dyspepsia, epigastric pain, mouth ulceration, GI bleeding, pancreatitis, vomiting, renal calculus, sexual dysfunction, anemia, leukopenia, thrombocytopenia, hepatitis, arthralgia, arthritis, cramps, myalgia, myasthenia, myopathy, paresthesia, back pain, dyspepsia, pharyngitis, rhinitis, sinusitis, diaphoresis, allergy
• other
  • lipodystrophy syndrome
  • elevated amylase
  • hyperglycemia
  • probably not associated with birth defects in infants born to women taking nelfinavir during pregnancy

• drug adverse effects of antiretroviral protease inhibitors
• drug adverse effects of antiretroviral agents

Drug interactions

• nelfinavir inhibits cyt P450 3A4
• nelfinavir plasma levels are reduced by rifampin & rifabutin
• not recommended in combination with:
  • rifampin
  • triazolam
  • midazolam
  • ergot alkaloids
  • terfenadine
  • astemizole
  • cisapride
• nelfinavir may decrease plasma levels of ethinyl estradiol
• nelfinavir may increase plasma levels of rifabutin, saquinavir, indinavir
• effectiveness of oral contraceptives is diminished
• phenytoin, phenobarbital & carbamazepine may diminish effectiveness of nelfinavir
• any drug that inhibits cyt P450 3A4 may increase levels of nelfinavir
• any drug that induces cyt P450 3A4 may diminish levels of nelfinavir
• nelfinavir inhibits cyt P450 3A4, thus inhibits its own metabolism & metabolism of other cyt P450 3A4 substrates

• drug interaction(s) of fluticasone with HIV1 protease inhibitors
• drug interaction(s) of antiretroviral protease inhibitor in combination with ritonavir
• drug interaction(s) of statins with antiviral protease inhibitors
• drug interaction(s) of antibiotics with warfarin
• drug interaction(s) of eplerenone with nelfinavir

Mechanism of action

• inhibits HIV-1 protease
• HIV protease inhibition prevents cleavage of viral proteins resulting in formation of immature non-infectious particles
• nelfinavir also inhibits cyt P450 3A4

More general terms

• antiretroviral protease inhibitor

Additional terms

• cytochrome P450 3A4 (cytochrome P450 C3, nifedipine oxidase, P450-PCN1, NF-25, CYP3A4)

Database

• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=64143
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=64142
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=4451