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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).

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).

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.

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. Safety and efficacy not established in those <2 years of age, and not recommended in this age group because of insufficient data.

Nelfinavir Dosage and Administration

Oral Administration

Administer orally 2 or 3 times daily with a meal.

Tablets are film-coated to facilitate swallowing.

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

Dosage

Available as nelfinavir mesylate; dosage expressed as nelfinavir.

Must be given in conjunction with other antiretrovirals.

Pediatric Patients

Treatment of HIV Infection
Oral

Infants <2 years of age [off-label]: Reliably effective dosage not established; not recommended in this age group. (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. (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.

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.

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. Dosages >2.5 g daily not studied in children.

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

Renal Impairment

Treatment of HIV Infection
Oral

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

Cautions for Nelfinavir

Contraindications

Warnings/Precautions

Interactions

Concomitant use with certain drugs not recommended or requires particular caution. (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.

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

Hemophilia A and B

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

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

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. Mechanisms and long-term consequences of fat redistribution unknown; causal relationship not established.

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.

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.

HIV Resistance

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

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. 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. 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.

Specific Populations

Pregnancy

Category B.

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

Experts state that nelfinavir not recommended for initial treatment regimens in antiretroviral-naive pregnant women. 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. If nelfinavir used for treatment of HIV-1 in pregnant women, experts recommend a dosage of 1.25 g twice daily.

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

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

Lactation

Low concentrations distributed into human milk.

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

Pediatric Use

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

Consider that use of nelfinavir in children is associated with highly variable drug exposure. (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. Diarrhea reported less frequently in children than in adults.

Geriatric Use

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

Hepatic Impairment

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

Renal Impairment

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

Common Adverse Effects

Diarrhea, nausea, flatulence, rash.

Drug Interactions

Metabolized by CYP3A and CYP2C19.

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

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.

Specific Drugs

Drug

Interaction

Comments

Abacavir

In vitro evidence of synergistic antiretroviral effects

Alfuzosin

Possible increased alfuzosin concentrations; may result in hypotension

Concomitant use contraindicated

Antiarrhythmic agents (amiodarone, quinidine)

Possible increased antiarrhythmic agent concentrations; potential for serious or life-threatening effects (e.g., cardiac arrhythmias)

Concomitant use with amiodarone or quinidine contraindicated

Anticonvulsants (carbamazepine, phenobarbital, phenytoin)

Decreased phenytoin concentrations and AUC; no change in nelfinavir concentrations

Possible decreased nelfinavir concentrations with carbamazepine or phenobarbital

Monitor phenytoin concentrations; adjustment of phenytoin dosage may be needed

Antifungals, azoles (ketoconazole)

Ketoconazole: Increased nelfinavir concentrations and AUC

Antimycobacterials (rifabutin, rifampin, rifapentine)

Rifabutin: Increased rifabutin concentrations; decreased nelfinavir concentrations

Rifampin: Decreased nelfinavir concentrations; possible decreased antiretroviral activity and development of resistance

Rifabutin: Reduce rifabutin dosage by 50%; nelfinavir 1.25 g twice daily is preferred regimen when concomitant therapy is necessary

Rifampin: Concomitant use contraindicated

Rifapentine: Concomitant use not recommended

Atazanavir

No in vitro evidence of antagonistic antiretroviral effects

Avanafil

Possible increased avanafil concentrations and AUC

Do not use concomitantly

Benzodiazepines (e.g., midazolam, triazolam)

Pharmacokinetic interaction with midazolam or triazolam; potential for prolonged or increased sedation or respiratory depression

Concomitant use with oral midazolam or triazolam contraindicated

Bosentan

Possible increased bosentan concentrations

If bosentan and nelfinavir used concomitantly, initiate or adjust bosentan dosage to 62.5 mg once daily or every other day based on individual tolerability

Buprenorphine

No clinically important pharmacokinetic interaction

Dosage adjustments not necessary

Cisapride

Pharmacokinetic interaction; potential for serious or life-threatening reactions (e.g., cardiac arrhythmias)

Concomitant use contraindicated

Colchicine

Possible increased colchicine concentrations

Patients with renal or hepatic impairment: Avoid concomitant use of colchicine and nelfinavir

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 later

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 daily

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)

Corticosteroids (fluticasone)

Fluticasone (orally inhaled, intranasal): Possible increased fluticasone concentrations

Fluticasone (orally inhaled, intranasal): Consider alternatives in patients receiving nelfinavir, especially when long-term use of the corticosteroid is anticipated

Co-trimoxazole

Interaction unlikely

Dapsone

Interaction unlikely

Darunavir

No in vitro evidence of antagonistic antiretroviral effects

Delavirdine

Decreased delavirdine concentrations and AUC; increased nelfinavir concentrations and AUC

In vitro evidence of synergistic antiretroviral effects

Appropriate dosages for concomitant use with respect to safety and efficacy not established

Didanosine

No change in nelfinavir concentrations when didanosine administered 1 hour before nelfinavir

In vitro evidence of additive antiretroviral effects

Administer didanosine (without food) 1 hour before or 2 hours after nelfinavir (with food)

Efavirenz

Increased nelfinavir concentrations and AUC; decreased efavirenz concentrations and AUC

In vitro evidence of additive to synergistic antiretroviral effects

Dosage adjustment not needed

Emtricitabine

In vitro evidence of additive to synergistic antiretroviral effects

Enfuvirtide

In vitro evidence of additive to synergistic antiretroviral effects

Ergot alkaloids (dihydroergotamine, ergotamine, methylergonovine)

Possibility of pharmacokinetic interaction; potential for serious or life-threatening reactions (e.g., acute ergot toxicity)

Concomitant use contraindicated

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 possible

Estrogens/Progestins

Hormonal contraceptives: Decreased concentrations of ethinyl estradiol and norethindrone

Use alternative or concomitant nonhormonal contraceptive measures

Etravirine

Possible increased nelfinavir concentrations

No in vitro evidence of antagonistic antiretroviral effects

Do not use concomitantly with etravirine without low-dose ritonavir

Fosamprenavir

Studies using amprenavir indicate concomitant use may affect pharmacokinetics of both drugs; concomitant use of ritonavir-boosted fosamprenavir and nelfinavir not evaluated

In vitro evidence of additive antiretroviral effects

Appropriate dosages for concomitant use with respect to safety and efficacy not established

HMG-CoA reductase inhibitors (statins)

Atorvastatin, lovastatin, rosuvastatin, simvastatin: Increased concentrations of the statin, increased risk of statin-associated adverse effects, including myopathy and rhabdomyolysis

Atorvastatin: Do not exceed atorvastatin dosage of 40 mg daily; carefully titrate atorvastatin dosage and use lowest necessary dosage

Lovastatin: Concomitant use with nelfinavir contraindicated

Simvastatin: Concomitant use contraindicated

Immunosuppressive agents

Cyclosporine, sirolimus, tacrolimus: Possible increased concentrations of nelfinavir and the immunosuppressive agents

Indinavir

Increased AUCs of both drugs

In vitro evidence of antagonistic antiretroviral effects

Appropriate dosages for concomitant use with respect to safety and efficacy not established

Lamivudine

Increased lamivudine peak concentrations and AUC

In vitro evidence of additive or synergistic antiretroviral effects

Lopinavir/ritonavir

Decreased lopinavir concentrations and increased nelfinavir concentrations

In vitro evidence of additive to antagonistic antiretroviral effects

Once-daily lopinavir/ritonavir regimen not recommended with nelfinavir

If used with nelfinavir in adults, recommended dosage of lopinavir/ritonavir tablets is lopinavir 500 mg/ritonavir 125 mg twice daily; alternatively, recommended dosage of lopinavir/ritonavir oral solution is lopinavir 553 mg/ritonavir 133 mg (6.5 mL) twice daily

Macrolides (azithromycin)

Increased azithromycin peak concentrations and AUC; no clinically important changes in nelfinavir pharmacokinetics

Dosage adjustment not needed; monitor for azithromycin adverse effects (e.g., hepatic enzyme abnormalities, hearing impairment)

Maraviroc

No in vitro evidence of antagonistic antiretroviral effects

Recommended dosage of maraviroc is 150 mg twice daily

Methadone

Decreased methadone concentrations and AUC

Monitor and titrate methadone dose if needed; consider need to increase methadone dosage

Nevirapine

No effect on nelfinavir peak concentrations or AUC; decreased nelfinavir trough concentrations and substantially decreased concentrations and AUC of major nelfinavir metabolite (M8)

In vitro evidence of synergistic antiretroviral effects

Appropriate dosages for concomitant use with respect to safety and efficacy not established

Pimozide

Pharmacokinetic interaction; potential for serious or life-threatening reactions (e.g., cardiac arrhythmias)

Concomitant use contraindicated

Proton-pump inhibitors

Omeprazole: Decreased nelfinavir concentrations and AUC

Proton-pump inhibitors: Possible loss of virologic response and development of resistance

Rilpivirine

Possible increased rilpivirine concentrations; not expected to affect nelfinavir concentrations

No in vitro evidence of antagonistic antiretroviral effects

Ritonavir

Increased nelfinavir concentrations; no change in ritonavir concentrations

In vitro evidence of additive antiretroviral effects

Appropriate dosages for concomitant use with respect to safety and efficacy not established

Salmeterol

Increased salmeterol concentrations and increased risk of QT prolongation, palpitations, or sinus tachycardia

Concomitant use not recommended

Saquinavir

Increased saquinavir concentrations and AUC and increased nelfinavir AUC

In vitro evidence of additive antiretroviral effects

Appropriate dosages for concomitant use with respect to safety and efficacy not established

St. John’s wort (Hypericum perforatum)

Decreased nelfinavir concentrations; possible loss of virologic response and increased risk of resistance to nelfinavir or other antiretrovirals

Concomitant use contraindicated

Sildenafil

Increased sildenafil concentrations and increased risk of sildenafil-associated adverse effects (e.g., hypotension, visual disturbances, prolonged erection, syncope)

Sildenafil (Revatio) for treatment of pulmonary arterial hypertension (PAH): Concomitant use with nelfinavir contraindicated

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)

Simeprevir

Possible altered (increased or decreased) simeprevir concentrations

Concomitant use not recommended

Stavudine

No effect on concentrations or AUC of either drug

In vitro evidence of additive or synergistic antiretroviral effects

Tadalafil

Increased tadalafil concentrations and increased risk of tadalafil-associated adverse effects (e.g., hypotension, visual disturbances, prolonged erection, syncope)

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 daily

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)

Tadalafil for treatment of benign prostatic hyperplasia: Do not exceed tadalafil dosage of 2.5 mg once daily

Tenofovir

No effect on pharmacokinetics of either drug

No in vitro evidence of antagonistic antiretroviral effects

Tipranavir

In vitro evidence of additive to antagonistic antiretroviral effects

Trazodone

Possible increased trazodone concentrations

Use with caution; consider using decreased trazodone dosage

Vardenafil

Increased vardenafil concentrations and increased risk of vardenafil-associated adverse effects (e.g., hypotension, visual disturbances, prolonged erection, syncope)

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)

Warfarin

Possible altered warfarin concentrations

Carefully monitor INR

Zidovudine

Decreased zidovudine peak concentrations and AUC; no effect on nelfinavir concentrations

In vitro evidence of synergistic antiretroviral effects

Routine zidovudine dosage adjustments not warranted

Nelfinavir Pharmacokinetics

Absorption

Bioavailability

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

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).

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. 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.

Special Populations

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

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.

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

Distribution

Extent

Not fully characterized.

Not detected in CSF in adults.

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

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

Plasma Protein Binding

98%.

Elimination

Metabolism

Metabolized by CYP3A and CYP2C19.

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

Elimination Route

Excreted principally in feces as unchanged drug and metabolites.

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

Half-life

3.5–5 hours.

Special Populations

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

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).

Stability

Storage

Oral

Tablets

15–30°C.

Actions and Spectrum

Advice to Patients

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

AHFS DI Essentials™. © Copyright 2024, Selected Revisions February 9, 2015. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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

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