Active ingredient: Nelfinavir - Brands, Medical Use, Clinical Data

Brands, Medical Use, Clinical Data

Drug Category

• Anti-HIV Agents
• HIV Protease Inhibitors

Dosage Forms

• Tablet (oral - 250 mg, 625 mg)
• Powder (oral)

Brands / Synonyms

1UN; Nelfinavir mesylate; Nelfinavir mesylate AG1343; NFV; NLF; Viracept; Viracept

Indications

Used in combination with other antiviral drugs in the treatment of HIV in both adults and children.

Pharmacology

Nelfinavir is a protease inhibitor with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Protease inhibitors block the part of HIV called protease. HIV-1 protease is an enzyme required for the proteolytic cleavage of the viral polyprotein precursors into the individual functional proteins found in infectious HIV-1. Nelfinavir binds to the protease active site and inhibits the activity of the enzyme. This inhibition prevents cleavage of the viral polyproteins resulting in the formation of immature non-infectious viral particles. Protease inhibitors are almost always used in combination with at least two other anti-HIV drugs.

Mechanism of Action

Nelfinavir inhibits the HIV viral proteinase enzyme which prevents cleavage of the gag-pol polyprotein, resulting in noninfectious, immature viral particles.

Absorption

Well absorbed following oral administration.

Toxicity

Oral LD₅₀ is over 5g/kg in rats. Side effects include thirst and hunger, unexplained weight loss, increased urination, fatigue, and dry, itchy skin.

Biotrnasformation / Drug Metabolism

Primarily hepatic via cytochrome P450 (CYP450) enzymes. CYP3A and CYP2C19 appear to be the predominant enzymes that metabolize nelfinavir in humans. One major and several minor metabolites are found in plasma; the major oxidative metabolite has in vitro antiviral activity comparable to that of the parent drug.

Contraindications

VIRACEPT is contraindicated in patients with clinically significant hypersensitivity to any of its components.

Coadministration of VIRACEPT is contraindicated with drugs that are highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events. These drugs are listed in Table 8.

Drug Interactions

DRUG INTERACTIONS

Nelfinavir is an inhibitor of CYP3A (cytochrome P450 3A). Coadministration of VIRACEPT and
drugs primarily metabolized by CYP3A (e.g., dihydropyridine calcium channel blockers) may
result in increased plasma concentrations of the other drug that could increase or prolong
both its therapeutic and adverse effects. Nelfinavir is metabolized in proof by C.P.A.
Coadministration of VIRACEPT and drugs that induce CYP3A may decrease nelfinavir plasma
concentrations and reduce its therapeutic effect. Coadministration of VIRACEPT and drugs that
inhibit CYP3A may increase nelfinavir plasma concentrations.

Based on known metabolic profiles, clinically significant drug interactions are not expected
between VIRACEPT and dapsone, trimethoprim/sulfamethoxazole, clarithromycin, erythromycin,
itraconazole or fluconazole.

Drugs That Should Not Be Coadministered With VIRACEPT
Antiarrhythmics: amiodarone, quinidine
Antihistamines: astemizole, terfenadine
Antimigraine: ergot derivatives
Antimycobacterial agents: rifampin
Benzodiazepines midazolam, triazolam
GI motility agents: cisapride

Drugs Which Require a Dose Reduction When Coadminstered With VIRACEPT
Antimycobacterial agents: rifabutin

Other Potentially Clinically Significant Drug Interactions With VIRACEPT*
Anticonvulsants: carbamazepine, phenobarbital, phenytoin May decrease nelfinavir plasma concentrations**
Anti-HIV protease inhibitors: indinavir, ritonavir May increase nelfinavir plasma concentrations
Oral contraceptives: ethinyl estradiol, norethindrone Plasma concentrations may be decreased by VIRACEPT

* This table is not all inclusive
** VIRACEPT may not be effective due to decreased nelfinavir plasma concentrations in patients
taking these agents concomitantly

Antihistamines

Terfenadine: Administration of terfenadine with VIRACEPT resulted in the appearance of unchanged
terfenadine in plasma; therefore, VIRACEPT should not be administered concurrently with terfenadine
because of the potential for serious and/or life-threatening cardiac arrhythmias. Because a similar
interaction is likely, VIRACEPT should also not be administered concurrently with astemizole.

Anti-HIV Protease Inhibitors

Indinavir: Coadministration of indinavir with VIRACEPT resulted in an 83% increase in nelfinavir
plasma AUC and a 51% increase in indinavir plasma A.C. Currently, there are no safety and efficacy
data available from the use of this combination.

Ritonavir: Coadministration of ritonavir with VIRACEPT resulted in a 152% increase in nelfinavir
plasma AUC and very little change in ritonavir plasma A.C. Currently, there are no safety and efficacy
data available from the use of this combination.

Saquinavir: Coadministration of saquinavir (using an experimental soft-gelatin capsule formulation of
saquinavir 1200mg) with VIRACEPT resulted in an 18% increase in nelfinavir plasma AUC and a 4-fold
increase in saquinavir plasma A.C. If used in combination with saquinavir hard gelatin capsules at the
recommended dose of 600 mg tid, no dose adjustments are needed. Currently, there are no safety and efficacy
data available from the use of this combination.

Antifungal Agents

Ketoconazole: Coadministration of ketoconazole with VIRACEPT resulted in a 35% increase in nelfinavir
plasma A.C. This change was not considered clinically significant and no dose adjustment is needed when
ketoconazole and VIRACEPT are coadministered.

Anti-HIV Reverse Transcriptase Inhibitors

Didanosine: It is recommended that didanosine be administered on an empty stomach; therefore, nelfinavir
should be administered (with food) one hour after or more than two hours before didanosine.

Zidovudine: Coadministration of zidovudine and lamivudine with VIRACEPT resulted in a 35% decrease in
zidovudine plasma A.C. A dose adjustment is not needed when zidovudine is administered with VIRACEPT.

Little or no change in the pharmacokinetics of either drug was observed when VIRACEPT was coadministered
with lamivudine or stavudine.

Antimycobacterial Agents

Rifabutin: Coadministration of rifabutin and VIRACEPT resulted in a 32% decrease in nelfinavir plasma AUC
and a 207% increase in rifabutin plasma A.C. It is recommended that the dose of rifabutin be reduced to
one-half the usual dose when administered with VIRACEPT.

Rifampin: Coadministration of rifampin and VIRACEPT resulted in an 82% decrease in nelfinavir plasma A.C.
VIRACEPT and rifampin should not be coadministered.

Oral Contraceptives

Ethinyl Estradiol and Norethindrone: Coadministration of VIRACEPT with OVCON-35 resulted in a 47% decrease
in ethinyl estradiol and an 18% decrease in norethindrone plasma concentrations. Alternate or additional
contraceptive measures should be used during therapy with VIRACEPT