Nelfinavir Mesylate

Class: HIV 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
Brands: Viracept

Introduction

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

Uses for Nelfinavir Mesylate

Treatment of HIV Infection

Treatment of HIV type 1 (HIV-1) infection in conjunction with other antiretrovirals.1

Not recommended in initial regimens used in antiretroviral-naive adults or adolescents;200 less potent antiretroviral activity compared with some other PIs and associated with high incidence of diarrhea.200

Slideshow: Flashback: FDA Drug Approvals 2013

Not a preferred or alternative protease inhibitor for initial regimens in antiretroviral-naive children;201 can be considered in special circumstances in those ≥2 years of age.201

Postexposure Prophylaxis of HIV

Postexposure prophylaxis of HIV infection in health-care workers and others exposed occupationally via percutaneous injury or mucous membrane or nonintact skin contact with blood, tissues, or other body fluids associated with risk for transmission of the virus.199 Used in conjunction with other antiretrovirals.199

Postexposure prophylaxis of HIV infection in individuals who have had nonoccupational exposure to blood, genital secretions, or other potentially infectious body fluids of a person known to be infected with HIV when that exposure represents a substantial risk for HIV transmission.198 Used in conjunction with other antiretrovirals.198

Nelfinavir Mesylate Dosage and Administration

Administration

Oral Administration

Administer orally 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: 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

Postexposure Prophylaxis of HIV
Occupational Exposure
Oral

1.25 g twice daily.199

Initiate postexposure prophylaxis as soon as possible following exposure (within hours rather than days) and continue for 4 weeks, if tolerated.199

Nonoccupational Exposure
Oral

1.25 g twice daily or 750 mg 3 times daily in conjunction with other antiretrovirals.198

Initiate postexposure prophylaxis as soon as possible following exposure (preferably ≤72 hours after exposure) and continue for 28 days.198

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 Mesylate

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

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 jiroveci [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 .1 202

Experts state that use of nelfinavir may be considered in pregnant women in special circumstances when used solely for prevention of perinatal HIV transmission in antiretroviral-naive women when antiretroviral therapy not otherwise indicated and alternatives are not tolerated.202

Pharmacokinetic data indicate plasma concentrations may be lower and more variable during late pregnancy.187 202 (See Special Populations under Pharmacokinetics.)

Lactation

Low concentrations distributed into human milk.168

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

Interactions for Nelfinavir Mesylate

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

Rifapentine: Possible decreased nelfinavir concentrations200

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

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

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 nasal spray/oral inhalation: Possible increased fluticasone concentrations1

Fluticasone nasal spray/oral inhalation: 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 concentrations and AUC of nelfinavir; decreased concentrations and AUC of efavirenz1 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, ergonovine, 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 without low-dose ritonavir214

Fosamprenavir

Studies using amprenavir indicate concomitant use may affect pharmacokinetics of both drugs;205 concomitant use of ritonavir-boosted fosamprenavir with 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 synergistic antiretroviral effects1

Lopinavir/ritonavir

Decreased lopinavir concentrations and increased nelfinavir concentrations207

In vitro evidence of synergistic antiretroviral effects1

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 concentrations1

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

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 concentrations or AUC of either drug221

In vitro evidence of additive to synergistic antiretroviral effects1 221

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 Mesylate 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.202 187

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

  • Pharmacologically related to other PIs (e.g., atazanavir, darunavir, fosamprenavir, indinavir, lopinavir, ritonavir, saquinavir, tipranavir); differs structurally from these drugs and also differs pharmacologically and structurally from other currently available antiretrovirals.1 80

  • 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.

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

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Viracept 250MG Tablets (VIIV HEALTHCARE): 300/$731.06 or 900/$2,154.38

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions January 24, 2013. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† 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; 2012 Apr.

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. [PubMed 8537887]

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. [PubMed 9397180]

4. Moyle G, Gazzard B. Current knowledge and future prospects for the use of HIV protease inhibitors. Drugs. 1996; 51:701-12. [PubMed 8861542]

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. [PubMed 8834868]

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. [PubMed 8787890]

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. [PubMed 9756769]

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. [PubMed 8627733]

11. Ridky T, Leis J. Development of drug resistance to HIV-1 protease inhibitors. J Biol Chem. 1995; 270:29621-3. [PubMed 8530341]

13. Deeks SG, Smith M, Holodniy M et al. HIV-1 protease inhibitors: a review for clinicians. JAMA. 1997; 277:145-53. [IDIS 378091] [PubMed 8990341]

14. Izzedine H, Diquet B, Launay-Vacher V et al. Pharmacokinetics of nelfinavir in an HIV patient with renal insufficiency. AIDS. 1999; 13:1989. [PubMed 10513666]

16. Moyle GJ. Resistance to antiretroviral compounds: implications for the clinical management of HIV infection. Immunol Infect Dis. 1995; 5:170-82.

17. Pollard RB. Use of proteinase inhibitors in clinical practice. Pharmacotherapy. 1994; 14:21-9S.

30. McCance-Katz EF, Farber S, Selwyn PA et al. Decrease in methadone levels with nelfinavir mesylate. Am J Psychiatry. 2000; 157:481. [IDIS 444066] [PubMed 10698844]

33. Spooner KM, Lane HC, Masur H. Guide to major clinical trials of antiretroviral therapy administered to patients infected with human immunodeficiency virus. Clin Infect Dis. 1996; 23:15-27. [IDIS 369501] [PubMed 8816123]

51. Armbruster C, Vorbach H, Menyawi IE et al. Pharmacokinetics of nelfinavir during haemodialysis in a patient with HIV infection. AIDS. 2000; 14:99-101. [PubMed 10714579]

68. AIDSTRIALS. From: AIDS Clinical Trials Information Service (database). 1997 Oct.

70. Conant M, Markowitz M, Hurley A et al. A preliminary evaluation of nelfinavir mesylate, an inhibitor of human immunodeficiency virus (HIV)-1 protease, to treat HIV infection. J Infect Dis. 1998; 177:1533-40. [IDIS 407146] [PubMed 9607830]

71. Moyle GJ, Youle M, Higgs C et al. Safety, pharmacokinetics, and antiretroviral activity of the potent specific human immunodeficiency virus protease inhibitor nelfinavir: results of a phase I/II trial and extended follow-up in patients infected with human immunodeficiency virus. J Clin Pharmacol. 1998; 38:736-43. [IDIS 412399] [PubMed 9725550]

72. Merck & Co, West Point, PA: Personal communication.

73. Krogstad P, Wiznia A, Luzuriaga K et al. Treatment of human immunodeficiency virus 1-infected infants and children with the protease inhibitor nelfinavir mesylate. Clin Infect Dis. 1999; 28:1109-18. [IDIS 428195] [PubMed 10452644]

74. McDonald CK, Kuritzkes DR. Human immunodeficiency virus type 1 protease inhibitors. Arch Intern Med. 1997; 157:951-9. [IDIS 388175] [PubMed 9140265]

75. Feigal DW Jr. Dear healthcare provider letter: HIV protease inhibitors and patients with hemophilia. Rockville, MD: US Food and Drug Administration; 1996 Jul 17.

76. Elion R, Kaul S, Knupp C et al. The safety profile and antiviral activity of the combination of stavudine, didanosine, and nelfinavir in patients with HIV infection. Clin Ther. 1999; 21:1853-63. [IDIS 440857] [PubMed 10890257]

77. Hélal A. HIV protease inhibitors and increased bleeding in hemophilia? Can Med Assoc J. 1997; 156:90.

80. Agouron Pharmaceuticals, La Jolla, CA: Personal communication.

82. Lumpkin MM. Dear healthcare provider letter: Reports of diabetes and hyperglycemia in patients receiving protease inhibitors for the treatment of human immunodeficiency virus (HIV). Rockville, MD: US Food and Drug Administration; 1997 Jun 11.

83. Lillibridge JH, Liang BH, Kerr BM et al. Characterization of the selectivity and mechanism of human cytochrome P450 inhibition by the human immunodeficiency virus-protease inhibitor nelfinavir mesylate. Drug Metabol Dispos. 1998; 26:609-16.

85. Centers for Disease Control and Prevention. Prevention and treatment of tuberculosis among patients infected with human immunodeficiency virus: principles of therapy and revised recommendations. MMWR Recomm Rep. 1998; 47(No. RR-20):1-58.

86. Kravcik S, Sahai J, Kerr B et al. Nelfinavir mesylate (NFV) increases saquinavir-soft gel capsule (SQV-SGC) exposure in HIV+ patients. In: Program and abstracts of the Fourth Conference on Retroviruses and Opportunistic Infections–1997, Washington, DC, 1997 Jan 22–26. Abstract No. 389.

90. Spatzenegger M, Jaeger W. Clinical importance of hepatic cytochrome P450 in drug metabolism. Drug Metabol Rev. 1995; 27:397-417.

91. Agouron Pharmaceuticals. Viracept– an HIV Protease Inhibitor: Agouron Pharmaceuticals; Viracept Expanded Access Program. Protocol No. AG1343-515. La Jolla, CA: 1996 Sep.

92. Gehlhaar DK, Verkhivker GM, Rejto PA et al. Molecular recognition of the inhibitor AG-1343 by HIV-1 protease: conformationally flexible docking by evolutionary programming. Chem Biol. 1995; 2:317-24. [PubMed 9383433]

102. Perelson AS, Essunger P, Cao Y et al. Decay characteristics of HIV-1-infected compartments during combination therapy. Nature. 1997; 387:188-91. [PubMed 9144290]

118. Perry C, Benfield P. Nelfinavir. Drugs. 1997; 54:81-7. [PubMed 9211082]

120. FDA summary basis of approval on nelfinavir. Rockville, MD; 1997.

121. Saag MS, Tebas P, Sension M et al. Randomized, double-blind comparison of two nelfinavir doses plus nucleosides in HIV-infected patients (Agouron study 511). AIDS. 2001; 15:1971-8. [PubMed 11600825]

124. Reviewers’ comments (personal observations).

125. Patick AK, Boritzki TJ, Bloom LA. Activities of the human immunodeficiency virus type 1 (HIV-1) protease inhibitor nelfinavir mesylate in combination with reverse transcriptase and protease inhibitors against acute HIV-1 infection in vitro. Antimicrob Agents Chemother. 1997; 41:2159-64. [PubMed 9333041]

126. Aboulker JP, Babiker A, Chaix ML et al. Highly active antiretroviral therapy started in infants under 3 months of age: 72-week follow-up for CD4 cell count, viral load and drug resistance outcome. AIDS. 2004; 18:237-45. [PubMed 15075541]

127. Krogstad P, Wiznia A, Luzuriaga K et al. Treatment of human immunodeficiency virus 1-infected infants and children with the protease inhibitor nelfinavir mesylate. Clin Infect Dis. 1999; 28:1109-18. [IDIS 428195] [PubMed 10452644]

130. Dube MP, Johnson DL, Currier JS et al. Protease inhibitor-associated hyperglycaemia. Lancet. 1997; 350:713-4. [IDIS 390850] [PubMed 9291911]

131. Visnegarwala F, Krause KL, Musher DM. Severe diabetes associated with protease inhibitor therapy. Ann Intern Med. 1997; 127:947. [IDIS 395210] [PubMed 9382374]

132. Eastone JA, Decker CF. New-onset diabetes mellitus associated with use of protease inhibitor. Ann Intern Med. 1997; 127:948. [IDIS 395211] [PubMed 9382376]

133. Pharmacia & Upjohn, Kalamazoo, MI: Personal communication.

134. Reviewers’ comments (personal observations) on delavirdine 8:18.08.

137. Lo JC, Mulligan K, Tai VW et al. “Buffalo hump” in men with HIV-1 infection. Lancet. 1998; 351:867-70. [PubMed 9525364]

138. Miller KD, Jones E, Yanovski JA et al. Visceral abdominal-fat accumulation associated with use of indinavir. Lancet. 1998; 351:871-5. [IDIS 403462] [PubMed 9525365]

139. Wurtz R. Abnormal fat distribution and use of protease inhibitors. Lancet. 1998; 351:1735-6. [IDIS 415049] [PubMed 9734915]

140. Carr A, Samaras K, Chisholm DJ et al. Abnormal fat distribution and use of protease inhibitors. Lancet. 1998; 351:1736. [IDIS 415050] [PubMed 9734916]

141. Ho TTY, Chan KCW, Wong KH et al. Abnormal fat distribution and use of protease inhibitors. Lancet. 1998; 351:1736-7. [IDIS 415051] [PubMed 9734917]

142. Carr A, Samaras K, Chisholm DJ et al. Pathogenesis of HIV-1-protease inhibitor- associated peripheral lipodystrophy, hyperlipidaemia, and insulin resistance. Lancet. 1998; 351:1881-3. [IDIS 415414] [PubMed 9652687]

143. Henry K, Melroe H, Huebesch J et al. Atorvastatin and gemfibrozil for protease- inhibitor-related lipid abnormalities. Lancet. 1998; 352:1031-2. [IDIS 413457] [PubMed 9759748]

144. Gagnon AM, Angel JB, Sorisky A. Protease inhibitors and adipocyte differentiation in cell culture. Lancet. 1998; 352:1032. [PubMed 9759749]

145. Centers for Disease Control and Prevention. Notice to readers: updated guidelines for the use of rifabutin or rifampin for the treatment and prevention of tuberculosis among HIV-infected patients taking protease inhibitors or nonnucleoside reverse transcriptase inhibitors. MMWR Recomm Rep. 2000; 49:185-9.

149. Damle B, Hewlett D, Hsyu PH et al. Pharmacokinetics of nelfinavir in subjects with hepatic impairment. J Clin Pharmacol. 2006; 46:1241-9. [PubMed 17050789]

150. Aweeka F, Jayewardene A, Staprans S et al. Failure to detect nelfinavir in the cerebrospinal fluid of HIV-1-infected patients with and without AIDS dementia complex. J Acquir Immune Defic Syndr. 1999; 20:39-43.

151. Di Martino V, Ezenfis J, Benhamou Y et al. Severe acute pancreatitis related to the use of nelfinavir in HIV infection: report of a case with positive rechallenge. AIDS. 1999; 13:1421-3. [PubMed 10449303]

152. Funk MB, Linde R, Wintergerst U et al. Preliminary experiences with triple therapy including nelfinavir and two reverse transcriptase inhibitors in previously untreated HIV-infected children. AIDS. 1999; 13:1653-8. [PubMed 10509566]

153. Starr SE, Fletcher CV, Spector SA et al for the Pediatric AIDS Clinical Trials Group 382 Team. N Engl J Med. 1999; 341:1874-81.

156. Wiznia A, Stanley K, Korgstad P et al. Combination nucleoside analog reverse trancriptase inhibitor(s) plus nevirapine, nelfinavir, or ritonavir in stable antiretroviral therapy-experienced HIV-infected children: week 24 results of a randomized controlled trial—PACTG 377. AIDS Res Hum Retroviruses. 2000; 16:1113-21. [PubMed 10954886]

160. Taylor S, Little J, Halifax K et al. Pharmacokinetics of nelfinavir and nevirapine in a patient with end-stage renal failure on continuous ambulatory peritoneal dialysis. J Antimicrob Chemother. 2000; 45:716-7. [IDIS 447296] [PubMed 10797104]

161. Fortuny C, Asuncion Vicente M, Medina MM et al. Rash as a side-effect of nelfinavir in children. AIDS. 2000; 14:335-6. [PubMed 10716518]

164. Lumpkin MM, Alpert A. Risk of drug interactions with St. John’s wort and indinavir and other drugs. FDA Public Health Advisory. 2000 Feb 10. From FDA website.

165. Piscitelli SC, Burstein AH, Chaitt D et al. Indinavir concentrations and St. John’s wort. Lancet. 2000; 355:547-8. [IDIS 440260] [PubMed 10683007]

166. Johne A, Brockmoller J, Bauer S et al. Pharmacokinetic interaction of digoxin with an herbal extract from St. John’s wort (Hypericum perforatum). Clin Pharmacol Ther. 1999; 66:338-45. [IDIS 435511] [PubMed 10546917]

167. Ruschitzka F, Meier PJ, Turina M et al. Acute heart transplant rejection due to Saint John’s wort. Lancet. 2000; 355:548-9. [IDIS 440261] [PubMed 10683008]

168. Weidle PJ, Zeh C, Martin A et al. Nelfinavir and its active metabolite, hydroxy-t-butylamidenelfinavir (M8), are transferred in small quantities to breast milk and do not reach biologically significant concentrations in breast-feeding infants whose mothers are taking nelfinavir. Antimicrob Agents Chemother. 2011; 55:5168-71. [PubMed 21876052]

172. American Thoracic Society (ATS) and Centers for Disease Control and Prevention (CDC). Targeted tuberculin testing and treatment of latent tuberculosis infections. Am J Respir Crit Care Med. 2000; 161:S221-47.

178. Berelowitz M. Dear healthcare professional letter regarding important information for prescribers of Viracept. New York, NY: Pfizer. 2007 Sep 10. From FDA website.

187. Villani P, Floridia M, Pirillo MF et al. Pharmacokinetics of nelfinavir in HIV-1-infected pregnant and nonpregnant women. Br J Clin Pharmacol. 2006; 62:309-15. [PubMed 16934047]

188. Vivus. Stendra (avanafil) tablets prescribing information. Mountain View, CA; 2012 Apr.

198. Center for Disease Control and Prevention. Antiretroviral postexposure prophylaxis after sexual, injection-drug use, or other nonoccupational exposure to HIV in the United States: Recommendations from the U.S. Department of Health and Human Services. MMWR Morb Mortal Wkly Rep. 2005; 54(No. RR-2):1-19. [PubMed 15647722]

199. Center for Disease Control and Prevention. Updated U.S. public health service guidelines for the management of occupational exposures to HIV and recommendations for postexposure prophylaxis. MMWR Morb Mortal Wkly Rep. 2005; 54(No. RR-9):1-17. [PubMed 15647722]

200. Panel on Antiretroviral Guidelines for Adults and Adolescents, US Department of Health and Human Services (HHS). Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents (April 18, 2012). Updates may be available at HHS AIDS Information (AIDSinfo) website.

201. Panel on Antiretroviral Therapy and Medical Management of HIV-infected Children, US Department of Health and Human Services (HHS). Guidelines for the use of antiretroviral agents in pediatric HIV infection (August 11, 2011). Updates may be available at HHS AIDS Information (AIDSinfo) website.

202. Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission, US Department of Health and Human Services (HHS). Recommendations for use of antiretroviral drugs in pregnant HIV-1-infected women for maternal health and interventions to reduce perinatal HIV transmission in the United States (July 31, 2012). Updates may be available at HHS AIDS Information (AIDSinfo) website.

204. Janssen. Prezista (darunavir) prescribing information. Titusville, NJ; 2012 Jun.

205. ViiV Healthcare. Lexiva (fosamprenavir calcium) tablets and oral suspension prescribing information. Research Triangle Park, NC; 2012 Feb.

206. Merck Sharp & Dohme. Crixivan (indinavir sulfate) capsules prescribing information. Whitehouse Station, NJ; 2012 Apr.

207. Abbott Laboratories. Kaletra (lopinavir/ritonavir) tablets and oral solution prescribing information. North Chicago, IL; 2012 Feb.

209. Abbott Laboratories. Norvir (ritonavir) tablets and oral solution prescribing information. North Chicago, IL; 2012 Feb.

211. Boehringer Ingelheim. Aptivus (tipranavir) capsules and oral solution prescribing information. Ridgefield, CT; 2012 Apr.

213. Bristol-Myers Squibb. Sustiva (efavirenz) capsules and tablets prescribing information. Princeton, NJ; 2012 Jun.

214. Janssen. Intelence (etravirine) tablets prescribing information. Raritan, NJ; 2012 Aug.

215. Boehringer Ingelheim. Viramune (nevirapine) tablets and oral suspension prescribing information. Ridgefield, CT; 2011 Nov.

218. Gilead Sciences. Emtriva (emtricitabine) capsules and oral solution prescribing information. Foster City, CA; 2012 Jul.

220. Bristol-Myers Squibb. Zerit (stavudine) capsules and oral solution prescribing information. Princeton, NJ; 2012 Jan.

221. Gilead Sciences. Viread (tenofovir disoproxil fumarate) tablets prescribing information. Foster City, CA; 2012 Jan.

222. ViiV Healthcare. Retrovir (zidovudine) tablets, capsules, and syrup prescribing information. Research Triangle Park, NC; 2012 May.

223. Genentech USA. Fuzeon (enfuvirtide) for injection prescribing information. South San Francisco, CA; 2012 Aug.

224. ViiV Healthcare. Selzentry (maraviroc) tablets prescribing information. Research Triangle Park, NC; 2012 Aug

226. Tibotec Therapeutics. Edurant (rilpivirine) tablets prescribing information. Raritan, NJ; 2012 Aug.

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