Nelfinavir (Monograph)

Brand name: Viracept
Drug class: HIV Protease Inhibitors
- Protease Inhibitors
VA class: AM800
Chemical name: [3S-[2(2S*,3S*),3α,4aβ,8aβ]] -N-(1,1-dimethylethyl)decahydro-2-[2-hydroxy-3-[(3-hydroxy-2 -methylbenzoyl)amino]-4-(phenylthio)butyl]-3-isoquinolinecarboxamide monomethanesulfonate (salt)
Molecular formula: C₃₂H₄₅N₃O₄S•CH₄O₃S
CAS number: 159989-65-8

Medically reviewed by Drugs.com on Jan 30, 2024. Written by ASHP.

Introduction

Antiretroviral; HIV protease inhibitor (PI).¹ ² ³ ⁴ ⁷ ⁸

Treatment of HIV Infection

Treatment of HIV-1 infection in adults, adolescents, and pediatric patients ≥2 years of age; usually used in conjunction with 2 HIV nucleoside reverse transcriptase inhibitors (NRTIs).¹

Experts state nelfinavir not recommended for initial treatment regimens in antiretroviral-naive adults and adolescents because of inferior virologic efficacy and high incidence of diarrhea.²⁰⁰

For initial treatment in antiretroviral-naive pediatric patients, experts state nelfinavir in conjunction with 2 NRTIs can be considered in children ≥2 years of age, but only in special circumstances when preferred or alternative regimens cannot be used.²⁰¹ Safety and efficacy not established in those <2 years of age,¹ and not recommended in this age group because of insufficient data.²⁰¹

Nelfinavir Dosage and Administration

Oral Administration

Administer orally 2 or 3 times daily with a meal.¹

Tablets are film-coated to facilitate swallowing.¹

For individuals unable to swallow tablets, place appropriate dose of 250-mg tablets in small amount of water and allow to disperse.¹ After tablets dissolve, mix the cloudy liquid well and immediately consume.¹ To ensure that entire dose is consumed, rinse glass with water and swallow the rinse.¹

Dosage

Available as nelfinavir mesylate; dosage expressed as nelfinavir.¹

Must be given in conjunction with other antiretrovirals.¹

Pediatric Patients

Treatment of HIV Infection

Oral

Infants <2 years of age^{† [off-label]}: Reliably effective dosage not established;¹ not recommended in this age group.²⁰¹ (See Pediatric Use under Cautions.)

Children 2 to <13 years of age: 45–55 mg/kg twice daily or 25–35 mg/kg 3 times daily.¹ (See Table 1.)

Children ≥13 years of age: 1.25 g (five 250-mg tablets or two 625-mg tablets) twice daily or 750 mg (three 250-mg tablets) 3 times daily.¹

Table 1. Nelfinavir Dosage for Pediatric Patients 2 to <13 Years of Age (Tablets)
Weight (kg)	No. of 250-mg Tablets 2 times daily (45–55 mg/kg 2 times daily)	No. of 250-mg Tablets 3 times daily (25–35 mg/kg 3 times daily)
10–12	2	1
13–18	3	2
19–20	4	2
≥21	4–5	3

Adults

Treatment of HIV Infection

Oral

1.25 g (five 250-mg tablets or two 625-mg tablets) twice daily or 750 mg (three 250-mg tablets) 3 times daily.¹

Prescribing Limits

Pediatric Patients

Treatment of HIV

Oral

Children 2 to <13 years of age (tablets): Maximum 1.25 g (5 tablets) twice daily or 750 mg (3 tablets) 3 times daily.¹ Dosages >2.5 g daily not studied in children.¹

Special Populations

Hepatic Impairment

Treatment of HIV Infection

Oral

Dosage adjustment not needed in patients with mild hepatic impairment (Child-Pugh class A, score 5–6).¹ Do not use in patients with moderate or severe hepatic impairment (Child-Pugh class B or C, score ≥7).¹

Renal Impairment

Treatment of HIV Infection

Oral

Safety and efficacy not established;¹ some experts state dosage adjustments not necessary.²⁰⁰

Cautions for Nelfinavir

Contraindications

Concomitant use with drugs highly dependent on CYP3A for metabolism and for which elevated plasma concentrations are associated with serious and/or life-threatening events (e.g., alfuzosin, amiodarone, cisapride, ergot alkaloids, oral midazolam, pimozide, quinidine, sildenafil used for treatment of pulmonary arterial hypertension [PAH], triazolam).¹ Concomitant use with drugs that may decrease nelfinavir concentrations (e.g., rifampin, St. John’s wort [Hypericum perforatum].¹ (See Specific Drugs under Interactions.)

Warnings/Precautions

Interactions

Concomitant use with certain drugs not recommended or requires particular caution.¹ (See Specific Drugs under Interactions.)

Hyperglycemic Effects

Hyperglycemia, new-onset diabetes mellitus, or exacerbation of preexisting diabetes mellitus reported with use of HIV PIs; diabetic ketoacidosis has occurred.¹ ⁸² ¹³⁰ ¹³¹ ¹³²

Monitor blood glucose and initiate or adjust dosage of oral hypoglycemic agent or insulin as needed.¹

Hemophilia A and B

Increased bleeding, including spontaneous skin hematomas and hemarthrosis, reported with PIs; causal relationship not established.¹ ⁷⁵ ⁷⁷ ¹²⁴

Caution in patients with a history of hemophilia type A or B.⁷⁵ Increased hemostatic (e.g., antihemophilic factor) therapy may be needed.¹

Adipogenic Effects

Possible redistribution or accumulation of body fat, including central obesity, dorsocervical fat enlargement (“buffalo hump”), peripheral wasting, breast enlargement, and general cushingoid appearance.¹ ¹³⁷ ¹³⁸ ¹³⁹ ¹⁴⁰ ¹⁴¹ ¹⁴² ¹⁴³ ¹⁴⁴ Mechanisms and long-term consequences of fat redistribution unknown; causal relationship not established.¹

Immune Reconstitution Syndrome

During initial treatment, patients who respond to antiretroviral therapy may develop an inflammatory response to indolent or residual opportunistic infections (e.g., Mycobacterium avium complex [MAC], M. tuberculosis, cytomegalovirus [CMV], Pneumocystis jirovecii [formerly P. carinii]); this may necessitate further evaluation and treatment.¹

Autoimmune disorders (e.g., Graves' disease, polymyositis, Guillain-Barré syndrome) reported in the setting of immune reconstitution; time to onset is variable and can occur many months after initiation of antiretroviral therapy.¹

HIV Resistance

Possibility of HIV resistance to nelfinavir and possible cross-resistance to other PIs.¹ Effect of nelfinavir therapy on subsequent therapy with other PIs unclear.¹

Ethyl Methane Sulfonate (EMS)

Nelfinavir preparations manufactured before 2008 may have contained low levels of ethyl methane sulfonate (EMS), an impurity produced by the manufacturing process.¹⁷⁸ ²⁰² EMS has been teratogenic, mutagenic, and carcinogenic in animals; no human data exist and no increase in birth defects has been observed in the antiretroviral pregnancy registry.¹⁷⁸ ²⁰² All nelfinavir preparations manufactured and released since March 31, 2008 meet EMS limits established by FDA for all patient populations, including children and pregnant women.²⁰²

Specific Populations

Pregnancy

Category B.¹

Antiretroviral Pregnancy Registry at 800-258-4263 or [Web].¹ ²⁰²

Experts state that nelfinavir not recommended for initial treatment regimens in antiretroviral-naive pregnant women.²⁰² Clinical trial data in adults indicate lower rate of viral suppression with nelfinavir regimens compared with regimens containing the fixed combination of lopinavir and ritonavir (lopinavir/ritonavir) or efavirenz.²⁰² If nelfinavir used for treatment of HIV-1 in pregnant women, experts recommend a dosage of 1.25 g twice daily.²⁰²

Pharmacokinetic data indicate plasma concentrations may be lower and more variable during late pregnancy.¹⁷⁹ ²⁰² (See Special Populations under Pharmacokinetics.)

Available data suggest nelfinavir does not increase overall birth defect rate.²⁰²

Lactation

Low concentrations distributed into human milk.¹⁶⁸ ²⁰²

Instruct HIV-infected women not to breast-feed because of risk of HIV transmission and risk of adverse effects in the infant.¹ ²⁰²

Pediatric Use

Safety and efficacy not established in infants and children <2 years of age.¹ Some data collected in this age group, but reliably effective dosage not established.¹ Some evidence that those <2 years of age have a lower response rate than older children.¹

Consider that use of nelfinavir in children is associated with highly variable drug exposure.¹ (See Pharmacokinetics.)

Use of nelfinavir in children 2–13 years of age supported by evidence from adequate and well-controlled studies in adults and pharmacokinetic and clinical studies supporting activity in pediatric patients.¹ ⁸⁰ ¹²⁴ ¹²⁶ ¹²⁷ ¹⁵² ¹⁵³ ¹⁶¹ ²⁰¹ ²¹³ Diarrhea reported less frequently in children than in adults.⁸⁰ ¹²⁴

Geriatric Use

Insufficient experience in those ≥65 years of age to determine whether they respond differently than younger adults.¹

Hepatic Impairment

Do not use in patients with moderate or severe hepatic impairment (Child-Pugh B or C, score ≥7).¹

Renal Impairment

Safety and efficacy not established in patients with renal impairment;¹ only limited pharmacokinetic information available.¹⁴ ⁵¹ ¹⁶⁰

Common Adverse Effects

Diarrhea,¹ nausea,¹ flatulence,¹ rash.¹

Drug Interactions

Metabolized by CYP3A and CYP2C19.¹ ⁸⁰ ⁸³

Inhibits CYP3A; does not inhibit CYP2D6, CYP2C9, CYP2C19, CYP2C8, CYP1A2, or CYP2E1.¹ ⁸⁰ ⁸³

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Pharmacokinetic interactions likely with drugs that are inhibitors, inducers, or substrates of CYP3A or CYP2C19 with possible alteration in metabolism of nelfinavir and/or other drug.¹

Specific Drugs

Drug	Interaction	Comments
Abacavir	In vitro evidence of synergistic antiretroviral effects¹
Alfuzosin	Possible increased alfuzosin concentrations; may result in hypotension¹	Concomitant use contraindicated¹
Antiarrhythmic agents (amiodarone, quinidine)	Possible increased antiarrhythmic agent concentrations; potential for serious or life-threatening effects (e.g., cardiac arrhythmias)¹	Concomitant use with amiodarone or quinidine contraindicated¹
Anticonvulsants (carbamazepine, phenobarbital, phenytoin)	Decreased phenytoin concentrations and AUC; no change in nelfinavir concentrations¹ Possible decreased nelfinavir concentrations with carbamazepine or phenobarbital¹ ⁹⁰	Monitor phenytoin concentrations; adjustment of phenytoin dosage may be needed ¹
Antifungals, azoles (ketoconazole)	Ketoconazole: Increased nelfinavir concentrations and AUC¹
Antimycobacterials (rifabutin, rifampin, rifapentine)	Rifabutin: Increased rifabutin concentrations; decreased nelfinavir concentrations¹ Rifampin: Decreased nelfinavir concentrations;¹ possible decreased antiretroviral activity and development of resistance¹	Rifabutin: Reduce rifabutin dosage by 50%;¹ nelfinavir 1.25 g twice daily is preferred regimen when concomitant therapy is necessary¹ Rifampin: Concomitant use contraindicated¹ Rifapentine: Concomitant use not recommended²⁰⁰
Atazanavir	No in vitro evidence of antagonistic antiretroviral effects²⁰³
Avanafil	Possible increased avanafil concentrations and AUC	Do not use concomitantly¹⁸⁸
Benzodiazepines (e.g., midazolam, triazolam)	Pharmacokinetic interaction with midazolam or triazolam; potential for prolonged or increased sedation or respiratory depression¹	Concomitant use with oral midazolam or triazolam contraindicated¹
Bosentan	Possible increased bosentan concentrations¹	If bosentan and nelfinavir used concomitantly, initiate or adjust bosentan dosage to 62.5 mg once daily or every other day based on individual tolerability¹
Buprenorphine	No clinically important pharmacokinetic interaction²⁰⁰	Dosage adjustments not necessary²⁰⁰
Cisapride	Pharmacokinetic interaction; potential for serious or life-threatening reactions (e.g., cardiac arrhythmias)¹	Concomitant use contraindicated¹
Colchicine	Possible increased colchicine concentrations¹	Patients with renal or hepatic impairment: Avoid concomitant use of colchicine and nelfinavir¹ Colchicine for treatment of gout flares: In those receiving nelfinavir, use initial colchicine dose of 0.6 mg followed by 0.3 mg 1 hour later; repeat dose no earlier than 3 days later¹ Colchicine for prophylaxis of gout flares: In those receiving nelfinavir, decrease colchicine dosage to 0.3 mg once daily in those originally receiving 0.6 mg twice daily or decrease dosage to 0.3 mg once every other day in those originally receiving 0.6 once daily¹ Colchicine for treatment of familial Mediterranean fever (FMF): In those receiving nelfinavir, use maximum colchicine dosage of 0.6 mg daily (may be given as 0.3 mg twice daily)¹
Corticosteroids (fluticasone)	Fluticasone (orally inhaled, intranasal): Possible increased fluticasone concentrations¹	Fluticasone (orally inhaled, intranasal): Consider alternatives in patients receiving nelfinavir, especially when long-term use of the corticosteroid is anticipated¹
Co-trimoxazole	Interaction unlikely¹
Dapsone	Interaction unlikely¹
Darunavir	No in vitro evidence of antagonistic antiretroviral effects²⁰⁴
Delavirdine	Decreased delavirdine concentrations and AUC; increased nelfinavir concentrations and AUC¹ In vitro evidence of synergistic antiretroviral effects¹	Appropriate dosages for concomitant use with respect to safety and efficacy not established ¹
Didanosine	No change in nelfinavir concentrations when didanosine administered 1 hour before nelfinavir¹ ⁸⁰ In vitro evidence of additive antiretroviral effects¹	Administer didanosine (without food) 1 hour before or 2 hours after nelfinavir (with food)¹
Efavirenz	Increased nelfinavir concentrations and AUC; decreased efavirenz concentrations and AUC¹ ²¹³ In vitro evidence of additive to synergistic antiretroviral effects¹	Dosage adjustment not needed²¹³
Emtricitabine	In vitro evidence of additive to synergistic antiretroviral effects²¹⁸
Enfuvirtide	In vitro evidence of additive to synergistic antiretroviral effects²²³
Ergot alkaloids (dihydroergotamine, ergotamine, methylergonovine)	Possibility of pharmacokinetic interaction; potential for serious or life-threatening reactions (e.g., acute ergot toxicity)¹	Concomitant use contraindicated¹ If treatment of uterine atony and excessive postpartum bleeding is indicated in a woman receiving nelfinavir, use methylergonovine maleate (Methergine) only if alternative treatments cannot be used and if potential benefits outweigh risks; use methylergonovine at lowest dosage and shortest duration possible²⁰²
Estrogens/Progestins	Hormonal contraceptives: Decreased concentrations of ethinyl estradiol and norethindrone¹	Use alternative or concomitant nonhormonal contraceptive measures¹
Etravirine	Possible increased nelfinavir concentrations²¹⁴ No in vitro evidence of antagonistic antiretroviral effects²¹⁴	Do not use concomitantly with etravirine without low-dose ritonavir²¹⁴
Fosamprenavir	Studies using amprenavir indicate concomitant use may affect pharmacokinetics of both drugs;²⁰⁵ concomitant use of ritonavir-boosted fosamprenavir and nelfinavir not evaluated²⁰⁵ In vitro evidence of additive antiretroviral effects²⁰⁵	Appropriate dosages for concomitant use with respect to safety and efficacy not established²⁰⁵
HMG-CoA reductase inhibitors (statins)	Atorvastatin, lovastatin, rosuvastatin, simvastatin: Increased concentrations of the statin, increased risk of statin-associated adverse effects, including myopathy and rhabdomyolysis¹	Atorvastatin: Do not exceed atorvastatin dosage of 40 mg daily;¹ carefully titrate atorvastatin dosage and use lowest necessary dosage¹ Lovastatin: Concomitant use with nelfinavir contraindicated¹ Simvastatin: Concomitant use contraindicated¹
Immunosuppressive agents	Cyclosporine, sirolimus, tacrolimus: Possible increased concentrations of nelfinavir and the immunosuppressive agents¹
Indinavir	Increased AUCs of both drugs¹ ⁸⁰ In vitro evidence of antagonistic antiretroviral effects¹	Appropriate dosages for concomitant use with respect to safety and efficacy not established ¹
Lamivudine	Increased lamivudine peak concentrations and AUC¹ In vitro evidence of additive or synergistic antiretroviral effects¹
Lopinavir/ritonavir	Decreased lopinavir concentrations and increased nelfinavir concentrations²⁰⁷ In vitro evidence of additive to antagonistic antiretroviral effects²⁰⁷	Once-daily lopinavir/ritonavir regimen not recommended with nelfinavir²⁰⁷ If used with nelfinavir in adults, recommended dosage of lopinavir/ritonavir tablets is lopinavir 500 mg/ritonavir 125 mg twice daily;²⁰⁷ alternatively, recommended dosage of lopinavir/ritonavir oral solution is lopinavir 553 mg/ritonavir 133 mg (6.5 mL) twice daily²⁰⁷
Macrolides (azithromycin)	Increased azithromycin peak concentrations and AUC; no clinically important changes in nelfinavir pharmacokinetics¹	Dosage adjustment not needed; monitor for azithromycin adverse effects (e.g., hepatic enzyme abnormalities, hearing impairment)¹
Maraviroc	No in vitro evidence of antagonistic antiretroviral effects²²⁴	Recommended dosage of maraviroc is 150 mg twice daily²²⁴
Methadone	Decreased methadone concentrations and AUC¹ ²⁰⁰	Monitor and titrate methadone dose if needed; consider need to increase methadone dosage¹ ³⁰ ²⁰⁰
Nevirapine	No effect on nelfinavir peak concentrations or AUC;²¹⁵ decreased nelfinavir trough concentrations and substantially decreased concentrations and AUC of major nelfinavir metabolite (M8)²¹⁵ In vitro evidence of synergistic antiretroviral effects¹	Appropriate dosages for concomitant use with respect to safety and efficacy not established¹ ²¹⁵
Pimozide	Pharmacokinetic interaction; potential for serious or life-threatening reactions (e.g., cardiac arrhythmias)¹	Concomitant use contraindicated¹
Proton-pump inhibitors	Omeprazole: Decreased nelfinavir concentrations and AUC¹ Proton-pump inhibitors: Possible loss of virologic response and development of resistance¹
Rilpivirine	Possible increased rilpivirine concentrations; not expected to affect nelfinavir concentrations²²⁶ No in vitro evidence of antagonistic antiretroviral effects ²²⁶
Ritonavir	Increased nelfinavir concentrations;¹ ⁸⁰ no change in ritonavir concentrations In vitro evidence of additive antiretroviral effects¹	Appropriate dosages for concomitant use with respect to safety and efficacy not established ¹
Salmeterol	Increased salmeterol concentrations and increased risk of QT prolongation, palpitations, or sinus tachycardia¹	Concomitant use not recommended¹
Saquinavir	Increased saquinavir concentrations and AUC and increased nelfinavir AUC¹ ⁸⁰ In vitro evidence of additive antiretroviral effects¹	Appropriate dosages for concomitant use with respect to safety and efficacy not established¹
St. John’s wort (Hypericum perforatum)	Decreased nelfinavir concentrations; possible loss of virologic response and increased risk of resistance to nelfinavir or other antiretrovirals¹⁶⁴ ¹⁶⁵	Concomitant use contraindicated¹
Sildenafil	Increased sildenafil concentrations and increased risk of sildenafil-associated adverse effects (e.g., hypotension, visual disturbances, prolonged erection, syncope)¹	Sildenafil (Revatio) for treatment of pulmonary arterial hypertension (PAH): Concomitant use with nelfinavir contraindicated¹ Sildenafil for treatment of erectile dysfunction: Do not exceed sildenafil dosage of 25 mg once every 48 hours; use caution and closely monitor for sildenafil-associated adverse effects (e.g., hypotension, syncope, visual disturbances, prolonged erection, syncope)¹
Simeprevir	Possible altered (increased or decreased) simeprevir concentrations¹⁸⁷	Concomitant use not recommended¹⁸⁷
Stavudine	No effect on concentrations or AUC of either drug²²⁰ In vitro evidence of additive or synergistic antiretroviral effects¹
Tadalafil	Increased tadalafil concentrations and increased risk of tadalafil-associated adverse effects (e.g., hypotension, visual disturbances, prolonged erection, syncope)¹	Tadalafil for treatment of PAH: Initiate or adjust tadalafil dosage to 20 mg once daily; based on individual tolerability, may increase tadalafil dosage to 40 mg once daily¹ Tadalafil for treatment of erectile dysfunction: Do not exceed tadalafil dosage of 10 mg once every 72 hours; use caution and closely monitor for tadalafil-associated adverse effects (e.g., hypotension, syncope, visual disturbances, prolonged erection, syncope)¹ Tadalafil for treatment of benign prostatic hyperplasia: Do not exceed tadalafil dosage of 2.5 mg once daily²⁰⁰
Tenofovir	No effect on pharmacokinetics of either drug²²¹ No in vitro evidence of antagonistic antiretroviral effects²²¹
Tipranavir	In vitro evidence of additive to antagonistic antiretroviral effects²¹¹
Trazodone	Possible increased trazodone concentrations¹	Use with caution; consider using decreased trazodone dosage¹
Vardenafil	Increased vardenafil concentrations and increased risk of vardenafil-associated adverse effects (e.g., hypotension, visual disturbances, prolonged erection, syncope)¹	Vardenafil for treatment of erectile dysfunction: Do not exceed vardenafil dosage of 2.5 mg once every 24 hours; use caution and closely monitor for vardenafil-associated adverse effects (e.g., hypotension, syncope, visual disturbances, prolonged erection, syncope)¹
Warfarin	Possible altered warfarin concentrations¹	Carefully monitor INR¹
Zidovudine	Decreased zidovudine peak concentrations and AUC;¹ ²²² no effect on nelfinavir concentrations²²² In vitro evidence of synergistic antiretroviral effects¹	Routine zidovudine dosage adjustments not warranted²²²

Nelfinavir Pharmacokinetics

Absorption

Bioavailability

Well absorbed from GI tract; peak plasma concentrations attained within 2–4 hours when administered with food.⁴ ⁸ ⁸⁰

Nelfinavir 625-mg tablets are not bioequivalent to the 250-mg tablets; AUC 24% higher with the 625-mg tablets (given with food) compared with the 250-mg tablets (given with food).¹

Food

Presence of food in the GI tract substantially increases extent of absorption and decreases pharmacokinetic variability of the drug relative to the fasting state.¹ ⁸⁰ Peak plasma concentration and AUC reportedly are 2–5 times greater when administered with a meal (125–1000 kcal with 20–50% fat) rather than under fasting conditions.¹ ⁸⁰

Special Populations

Highly variable plasma concentrations reported in children;¹ may be related to inconsistent food intake.¹

Plasma concentrations attained in pregnant women are more variable during late pregnancy than those reported in nonpregnant adults; concentrations may be lower during second or third trimester than during postpartum period or in nonpregnant women.¹⁷⁹ ²⁰²

Plasma concentrations and AUC in individuals with mild hepatic impairment (Child-Pugh class A) are similar to those in individuals with normal hepatic function.¹ ¹⁴⁹ In those with moderate hepatic impairment (Child-Pugh class B), peak plasma concentrations and AUC are increased 22 and 62%, respectively.¹ ¹⁴⁹ Pharmacokinetics not investigated in individuals with severe hepatic impairment.¹

Distribution

Extent

Not fully characterized.¹

Not detected in CSF in adults.¹⁵⁰

Only minimal or low concentrations cross the human placenta and are distributed into cord blood.²⁰²

Low concentrations of nelfinavir and its active metabolite (M8) are distributed into human milk.¹⁶⁸

Plasma Protein Binding

98%.¹

Elimination

Metabolism

Metabolized by CYP3A and CYP2C19.¹ ⁸⁰

The major metabolite (M8) has in vitro antiviral activity similar to that of nelfinavir.¹

Elimination Route

Excreted principally in feces as unchanged drug and metabolites.¹

Removed by hemodialysis;⁵¹ does not appear to be removed by peritoneal dialysis.¹⁶⁰

Half-life

3.5–5 hours.¹ ⁸⁰

Special Populations

Children 2–13 years of age: Clearance is 2–3 times greater than in adults (weight-adjusted basis).⁸⁰ ¹²⁴

Hepatic impairment: Mean elimination half-life 5.6 hours (range 2.3–13.7 hours) in mild impairment (Child-Pugh class B) and 10.3 hours (range 6.3–16.9 hours) in moderate impairment (Child-Pugh class C).¹⁴⁹

Stability

Storage

Oral

Tablets

15–30°C.¹

Actions and Spectrum

Active against HIV-1 and HIV-2.¹ ⁷ ⁸ The major metabolite (M8) has antiviral activity similar to that of nelfinavir.¹
Inhibits replication of HIV-1 and HIV-2 by interfering with HIV protease.¹ ² ³ ⁴ ⁷ ⁹² ¹²⁰
HIV-1 with reduced susceptibility to nelfinavir have been selected in vitro and have emerged during therapy with the drug.¹ ⁷ ⁹ ⁸⁰
Varying degrees of cross-resistance among PIs.¹ ⁴ ¹¹ ¹³ ¹⁴ ²⁰⁹
Cross-resistance between nelfinavir and nucleoside reverse transcriptase inhibitors (NRTIs) or nonnucleoside reverse transcriptase inhibitors (NNRTIs) unlikely since the drugs have different target enzymes and mechanisms of action.¹

Advice to Patients

Critical nature of compliance with HIV therapy and importance of remaining under the care of a clinician.¹ Importance of taking as prescribed; do not alter or discontinue antiretroviral regimen without consulting clinician.¹
Importance of using in conjunction with other antiretrovirals—not for monotherapy.¹
Antiretroviral therapy is not a cure for HIV infection; opportunistic infections and other complications associated with HIV disease may still occur.¹ Sustained decreases in plasma HIV RNA have been associated with reduced risk of progression to AIDS and death.¹
Advise patients that effective antiretroviral regimens can decrease HIV concentrations in blood and genital secretions and strict adherence to such regimens in conjunction with risk-reduction measures may decrease, but cannot absolutely eliminate, the risk of secondary transmission of HIV to others.²⁰⁰ Importance of continuing to practice safer sex (e.g., using latex or polyurethane condoms to minimize sexual contact with body fluids), never sharing personal items that can have blood or body fluids on them (e.g., toothbrushes, razor blades), and never reusing or sharing needles.¹ ²⁰⁰
Importance of reading patient information provided by the manufacturer.¹
Importance of taking with food.¹
If a dose is missed, it should be taken as soon as it is remembered and the next dose taken at the regularly scheduled time.¹ If a dose is skipped, do not administer a double dose to make up for the missed dose.¹
Redistribution/accumulation of body fat may occur, with as yet unknown long-term health effects.¹
Advise patients that diarrhea is the most frequent adverse effect and can usually be controlled with OTC drugs such as loperamide.¹
Advise patients receiving selective phosphodiesterase type 5 (PDE5) inhibitors (e.g., avanafil, sildenafil, tadalafil, vardenafil) that they may be at increased risk of PDE5 inhibitor-associated adverse effects (e.g., hypotension, visual changes, priapism) and that any symptoms should be promptly reported to clinician.¹ ¹⁸⁸ Should not be used in patients receiving avanafil for treatment of erectile dysfunction¹⁸⁸ or sildenafil for treatment of PAH.¹
If using oral contraceptives, need for alternative or concomitant nonhormonal contraceptive measures.¹
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal products.¹
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹ Advise HIV-infected women not to breast-feed.¹
Importance of advising patients of other important precautionary information.¹ (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Nelfinavir Mesylate
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets, film-coated	250 mg (of nelfinavir)	Viracept	ViiV
		625 mg (of nelfinavir)	Viracept	ViiV

† Off-label: Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. ViiV Healthcare. Viracept (nelfinavir mesylate) tablets and oral powder prescribing information. Research Triangle Park, NC; 2013 May.

2. Longer M, Shetty B, Zamansky I et al. Preformulation studies of a novel HIV protease inhibitor, AG1343. J Pharm Sci. 1995; 84:1090-3. http://www.ncbi.nlm.nih.gov/pubmed/8537887?dopt=AbstractPlus

3. Kaldor SW, Kalish VJ, davies JF et al. Viracept (nelfinavir mesylate, AG13430: a potent orally bioavailable inhibitor of HIV-1 protease. J Med Chem. 1997; 40:3979-85. http://www.ncbi.nlm.nih.gov/pubmed/9397180?dopt=AbstractPlus

4. Moyle G, Gazzard B. Current knowledge and future prospects for the use of HIV protease inhibitors. Drugs. 1996; 51:701-12. http://www.ncbi.nlm.nih.gov/pubmed/8861542?dopt=AbstractPlus

5. Vella S. Rationale and experience with reverse transcriptase inhibitors and protease inhibitors. J Acquir Immune Defic Syndr Hum Retrovirol. 1995; 10(Suppl 1):S58-61.

7. Patick AK, Mo H, Markowitz M et al. Antiviral and resistance studies of AG1343, an orally bioavailable inhibitor of human immunodeficiency virus protease. Antimicrob Agents Chemother. 1996; 40:292-7. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=163104&blobtype=pdf http://www.ncbi.nlm.nih.gov/pubmed/8834868?dopt=AbstractPlus

8. Shetty BV, Kosa MB, Khalil DA et al. Preclinical pharmacokinetics and distribution to tissue of AG1343, an inhibitor of human immunodeficiency virus type 1 protease. Antimicrob Agents Chemother. 1996; 40:110-4. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=163067&blobtype=pdf http://www.ncbi.nlm.nih.gov/pubmed/8787890?dopt=AbstractPlus

9. Patick AK, Duran M, Cao Y et al. Genotypic and phenotypic characterization of human immunodeficiency virus type 1 variants isolated from patients treated with the protease inhibitor nelfinavir. Antimicrob Agents Chemother. 1998; 42:2637-44. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=105911&blobtype=pdf http://www.ncbi.nlm.nih.gov/pubmed/9756769?dopt=AbstractPlus

10. Lech WJ, Wang G, Yang YL et al. In vivo sequence diversity of the protease of human immunodeficiency virus type 1: presence of protease inhibitor-resistant variants in untreated subjects. J Virol. 1996; 70:2038-43. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=190036&blobtype=pdf http://www.ncbi.nlm.nih.gov/pubmed/8627733?dopt=AbstractPlus

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