Viracept

Viracept - General Information

A potent HIV protease inhibitor. It is used in combination with other antiviral drugs in the treatment of HIV in both adults and children. [PubChem]

Pharmacology of Viracept

Viracept 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. Viracept 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.

Viracept for patients

Patients should be informed that VIRACEPT is not a cure for HIV infection and that they may
continue to acquire illnesses associated with advanced HIV infection, including opportunistic
infections.

Patients should be told that the long-term effects of VIRACEPT are unknown at this time. They
should be told that there is currently no data demonstrating that VIRACEPT therapy can reduce
the risk of transmitting HIV to others through sexual contact or blood contamination.

Patients should be advised to take VIRACEPT every day as prescribed. Patients should not alter
the dose or discontinue therapy without consulting with their doctor. If a dose is missed, patients
should take the dose as soon as possible and then return to their normal schedule. However, if a dose
is skipped, the patient should not double the next dose.

The most frequent adverse event associated with VIRACEPT is diarrhea, which can usually be controlled
with non-prescription drugs, such as loperamide, which slow gastrointestinal motility.

VIRACEPT may interact with some drugs, therefore, patients should be advised to report to their doctor
the use of any other prescription or non-prescription medication.

Patients receiving oral contraceptives should be instructed that alternate or additional contraceptive
measures should be used during therapy with VIRACEPT.

Viracept 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

Viracept 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.

Additional information about Viracept

Viracept Indication: Used in combination with other antiviral drugs in the treatment of HIV in both adults and children.
Mechanism Of Action: Viracept inhibits the HIV viral proteinase enzyme which prevents cleavage of the gag-pol polyprotein, resulting in noninfectious, immature viral particles.
Drug Interactions: Alprazolam The protease inhibitor increases the effect of the benzodiazepine
Chlordiazepoxide The protease inhibitor increases the effect of the benzodiazepine
Clonazepam The protease inhibitor increases the effect of the benzodiazepine
Clorazepate The protease inhibitor increases the effect of the benzodiazepine
Cyclosporine The protease inhibitor increases the effect of cyclosporine
Diazepam The protease inhibitor increases the effect of the benzodiazepine
Eletriptan The protease inhibitor increases the effect and toxicity of eletriptan
Eplerenone The protease inhibitor increases the effect and toxicity of eplerenone
Estazolam The protease inhibitor increases the effect of the benzodiazepine
Fentanyl The protease inhibitor increases the effect and toxicity of fentanyl
Flurazepam The protease inhibitor increases the effect of the benzodiazepine
Fusidic Acid The protease inhibitor increases the effect and toxicity of fusidic acid
Halazepam The protease inhibitor increases the effect of the benzodiazepine
Midazolam The protease inhibitor increases the effect of the benzodiazepine
Prazepam The protease inhibitor increases the effect of the benzodiazepine
Quazepam The protease inhibitor increases the effect of the benzodiazepine
Sildenafil The protease inhibitor increases the effect and toxicity of sildenafil
Tacrolimus The protease inhibitor increases the effect and toxicity of tacrolimus
Triazolam The protease inhibitor increases the effect of the benzodiazepine
Vardenafil The protease inhibitor increases the effect and toxicity of vardenafil
Warfarin The protease inhibitor increases the anticoagulant effect
Acenocoumarol The protease inhibitor increases the anticoagulant effect
Dicumarol The protease inhibitor increases the anticoagulant effect
Anisindione The protease inhibitor increases the anticoagulant effect
Amiodarone Viracept increases the effect and toxicity of amiodarone
Atorvastatin Viracept increases the effect and toxicity of the statin
Dihydroergotamine Viracept increases the effect and toxicity of ergot derivative
Dihydroquinidine barbiturate Viracept increases the effect and toxicity of quindine
Ergotamine Viracept increases the effect and toxicity of ergot derivative
Felodipine Viracept increases the effect and toxicity of felodipine
Lovastatin Viracept increases the effect and toxicity of the statin
Methadone Viracept decreases the effect of methadone
Nevirapine Nevirapine decreases the effect of nelfinavir
Pimozide Viracept increases the effect and toxicity of pimozide
Quinidine Viracept increases the effect and toxicity of quinidine
Quinidine barbiturate Viracept increases the effect and toxicity of quinidine
Ranolazine Increased levels of ranolazine - risk of toxicity
Rifampin Rifampin decreases the effect of nelfinavir
Simvastatin Viracept increases the effect and toxicity of the statin
St. John's Wort St. John's Wort decreases the effect of indinavir
Solifenacin This potent CYP3A4 inhibitor slows darifenacin / solifenacin metabolism
Darifenacin This potent CYP3A4 inhibitor slows darifenacin / solifenacin metabolism
Sunitinib Possible increase in sunitinib levels
Terfenadine Increased risk of cardiotoxicity and arrhythmias
Astemizole Increased risk of cardiotoxicity and arrhythmias
Cisapride Increased risk of cardiotoxicity and arrhythmias
Aprepitant This CYP3A4 inhibitor increases the effect and toxicity of aprepitant
Ciclesonide Increased effects/toxicity of ciclesonide
Erlotinib This CYP3A4 inhibitor increases levels/toxicity of erlotinib
Ethinyl Estradiol Ritonavir could decrease the contraceptive efficacy
Mestranol Ritonavir could decrease the contraceptive efficacy
Food Interactions: Take with food.
Generic Name: Nelfinavir
Synonyms: 1UN; Nelfinavir mesylate; NFV; NLF
Drug Category: Anti-HIV Agents; HIV Protease Inhibitors
Drug Type: Small Molecule; Approved

Other Brand Names containing Nelfinavir: Viracept;
Absorption: Well absorbed following oral administration.
Toxicity (Overdose): Oral LD₅₀ is over 5g/kg in rats. Side effects include thirst and hunger, unexplained weight loss, increased urination, fatigue, and dry, itchy skin.
Protein Binding: >98%
Biotransformation: 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.
Half Life: 3.5 - 5 hours
Dosage Forms of Viracept: Tablet Oral
Powder Oral
Chemical IUPAC Name: (3S,4aS,8aS)-N-tert-butyl-2-[(2R,3R)-2-hydroxy-3-[(3-hydroxy-2-methylbenzoyl)amino]-4-phenylsulfanylbutyl]-3,4,4a,5,6,7,8,8a-octahydro-1H-isoquinoline-3-carboxamide
Chemical Formula: C32H45N3O4S
Nelfinavir on Wikipedia: https://en.wikipedia.org/wiki/Nelfinavir
Organisms Affected: Human Immunodeficiency Virus