Nelfinavir Mesylate (Monograph)

Brand name: Viracept
Drug class: HIV Protease Inhibitors

Medically reviewed by Drugs.com on Aug 10, 2024. Written by ASHP.

Introduction

Antiretroviral; HIV protease inhibitor (PI).

Uses for Nelfinavir Mesylate

Treatment of HIV Infection

Treatment of HIV-1 infection in adults and pediatric patients ≥2 years of age; used in conjunction with other antiretroviral agents.

Nelfinavir, a protease inhibitor (PI), was previously a component of a fully suppressive antiretroviral regimen; however, guidelines no longer recommend its use due to inferior virological efficacy and toxicities. Consult guidelines for the most current information on recommended regimens. Selection of an initial antiretroviral regimen should be individualized based on factors such as virologic efficacy, toxicity, pill burden, dosing frequency, drug-drug interaction potential, resistance test results, comorbid conditions, access, and cost.

Nelfinavir Mesylate Dosage and Administration

General

Patient Monitoring

Consider monitoring for hyperglycemia, new-onset diabetes mellitus, or exacerbation of preexisting diabetes mellitus.

Administration

Oral Administration

Administer orally 2 or 3 times daily with a meal.

Commercially available as tablets (an oral powder for solution was discontinued).

For patients 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.

Do not mix nelfinavir tablets with acidic food or juice (e.g., apple juice, applesauce, orange juice) since the mixture may have a bitter taste.

If a dose of nelfinavir is missed, take the dose as soon as it is remembered and the next dose at the regularly scheduled time. If a dose is skipped, do not administer a double dose to make up for the missed dose.

Dosage

Available as nelfinavir mesylate; dosage expressed as nelfinavir.

Pediatric Patients

Treatment of HIV Infection

Oral

Pediatric HIV guidelines no longer recommend the use of nelfinavir in children or adolescents due to its variable pharmacokinetics and inferior efficacy.

Children 2 to <13 years of age: 45–55 mg/kg twice daily or 25–35 mg/kg three times daily using 250-mg tablets.

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) three times daily.

See Full Prescribing Information for additional dosing guidelines for nelfinavir tablets based on age and body weight.

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) three times daily.

Special Populations

Hepatic Impairment

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

Safety and efficacy not established.

Geriatric Patients

No specific dosage recommendations.

Cautions for Nelfinavir Mesylate

Contraindications

Concomitant use with drugs highly dependent on CYP3A for clearance 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).
Concomitant use with drugs that are CYP3A inducers where significantly reduced nelfinavir plasma concentrations may be associated with a potential loss of virologic response, and possible development of resistance or cross-resistance to other antiretrovirals (e.g., rifampin, St. John’s wort [Hypericum perforatum].

Warnings/Precautions

Risk of Serious Adverse Reactions Due to Drug Interactions

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

Hepatic Impairment

Metabolized in the liver. Plasma concentrations of nelfinavir increased in patients with moderate hepatic impairment; do not use in moderate or severe hepatic impairment (Child-Pugh class B or C, score ≥7).

Diabetes Mellitus/Hyperglycemia

Hyperglycemia, new-onset diabetes mellitus, or exacerbation of preexisting diabetes mellitus reported with use of HIV protease inhibitors (PIs); diabetic ketoacidosis has occurred.

Hemophilia

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

Increased hemostatic (e.g., factor VIII) therapy may be needed.

Fat Redistribution

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.

Specific Populations

Pregnancy

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

Hepatic adverse effects, including hepatic enzyme elevations and hepatic failure, reported in pregnant patients exposed to nelfinavir; consider alternative antiretroviral agents during pregnancy.

Lactation

Limited data indicate nelfinavir is present in human breastmilk.

Per HHS perinatal HIV transmission guideline, inform patients that feeding with appropriate formula or pasteurized donor human milk from a milk bank eliminates postnatal HIV transmission risk to the infant. Additionally, achieving and maintaining viral suppression with antiretroviral therapy during pregnancy and postpartum reduces risk of breastfeeding HIV transmission to <1%, but not does not completely eliminate risk. Replacement feeding with formula or banked pasteurized donor milk is recommended when patients with HIV are not on antiretroviral therapy and/or do not have a suppressed viral load during pregnancy (at a minimum throughout the third trimester), as well as at delivery.

Females and Males of Reproductive Potential

May reduce efficacy of estrogen-containing oral contraceptives. Advise patients receiving nelfinavir and using oral contraceptives containing ethinyl estradiol or norethindrone to use additional or alternative contraceptives.

Pediatric Use

Safety and efficacy not established in pediatric patients <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 pediatric patients.

Consider that use of nelfinavir in pediatric patients is associated with highly variable drug exposure.

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.

Common Adverse Effects

Adverse effects (≥2%) of adult and adolescent patients ≥13 years of age include: diarrhea, nausea, rash, flatulence.

Most commonly reported adverse effects in pediatric patients 2 to <13 years of age include: diarrhea, leukopenia/neutropenia, rash, anorexia, abdominal pain.

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)	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
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
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
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
Ergot alkaloids (dihydroergotamine, ergotamine, methylergonovine)	Possibility of pharmacokinetic interaction; potential for serious or life-threatening reactions (e.g., acute ergot toxicity)	Concomitant use contraindicated
Estrogens/Progestins	Hormonal contraceptives: Decreased concentrations of ethinyl estradiol and norethindrone	Use alternative or concomitant nonhormonal contraceptive measures
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
Lamivudine	Increased lamivudine peak concentrations and AUC In vitro evidence of additive or synergistic antiretroviral effects
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)
Methadone	Decreased methadone concentrations and AUC	Consider need to increase methadone dosage
Nevirapine	No effect on nelfinavir peak concentrations or AUC 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
Quetiapine	Increased plasma concentrations of quetiapine	Consider alternative antiretroviral therapy in patients already receiving quetiapine If concomitant use cannot be avoided, reduce quetiapine dose to 1/6th of current dose and monitor for quetiapine adverse effects. Refer to quetiapine prescribing information in patients already receiving nelfinavir being initiated on quetiapine for initial dosing and titration
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
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)
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)
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

Nelfinavir Mesylate Pharmacokinetics

Absorption

Bioavailability

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 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

Distributed into human milk.

Plasma Protein Binding

98%.

Elimination

Metabolism

Metabolized by CYP3A and CYP2C19.

Elimination Route

Excreted principally in feces as unchanged drug and metabolites.

Half-life

3.5–5 hours.

Special Populations

Studies have not shown gender-related differences in pharmacokinetics; further research needed to determine if there are race-related differences.

Stability

Storage

Oral

Tablets

15–30°C.

Actions and Spectrum

Active against HIV-1 and HIV-2. The major metabolite (M8) has antiviral activity similar to that of nelfinavir.
Inhibits replication of HIV-1 and HIV-2 by interfering with HIV protease.
HIV-1 with reduced susceptibility to nelfinavir have been selected in vitro and have emerged during therapy with the drug.
Varying degrees of cross-resistance among PIs.
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.

Advice to Patients

Inform patients of the critical nature of adherence with HIV therapy and importance of remaining under the care of a clinician. Advise patients of the importance of taking as prescribed; do not alter or discontinue antiretroviral regimen without consulting clinician.
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. If a dose is skipped, do not administer a double dose to make up for the missed dose.
Advise patients that redistribution/accumulation of body fat may occur, with unknown long-term health effects.
Inform patients that hyperglycemia, new-onset diabetes mellitus, or exacerbation of preexisting diabetes mellitus may occur. Advise patients to inform their healthcare provider if an increase in thirst or urination develops while receiving nelfinavir.
If using oral contraceptives, advise patients to use an alternative or concomitant nonhormonal contraceptive measures.
Stress importance of informing clinicians of existing or contemplated concomitant therapy, including prescription (e.g., PDE5 inhibitors) and OTC drugs and dietary or herbal products (e.g., St. John's Wort).
Advise women to inform clinicians if they are or plan to become pregnant or plan to breast-feed. Inform patients that an antiretroviral pregnancy registry is available that monitors fetal outcomes of infants exposed to nelfinavir. Providers can register patients by calling the Antiretroviral Pregnancy Registry at 1-800-258-4263.
Inform patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

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.