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).¹

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.¹

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.^{200 201 202} Consult guidelines for the most current information on recommended regimens.^{200 201 202} 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.^{200 201 202}

Nelfinavir Mesylate Dosage and Administration

General

Patient Monitoring

• Consider monitoring for hyperglycemia, new-onset diabetes mellitus, or exacerbation of preexisting diabetes mellitus.¹

Administration

Oral Administration

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

Commercially available as tablets (an oral powder for solution was discontinued).¹

For patients 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

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.¹

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.¹ If a dose is skipped, do not administer a double dose to make up for the missed dose.¹

Dosage

Available as nelfinavir mesylate; dosage expressed as nelfinavir.¹

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.²⁰¹

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.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) three times daily.¹

See Full Prescribing Information for additional dosing guidelines for nelfinavir tablets based on age and body weight.¹

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.¹

Special Populations

Hepatic Impairment

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

Safety and efficacy not established.¹

Geriatric Patients

No specific dosage recommendations.¹

Related/similar drugs

Biktarvy, Descovy, Truvada, tenofovir disoproxil, emtricitabine, abacavir, Atripla

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).¹

• 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].¹

Warnings/Precautions

Risk of Serious Adverse Reactions Due to Drug Interactions

Concomitant use with certain drugs not recommended or requires particular caution.¹

Hepatic Impairment

Metabolized in the liver.¹ 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).¹

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.¹

Hemophilia

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

Increased hemostatic (e.g., factor VIII) therapy may be needed.¹

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.¹ 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

Specific Populations

Pregnancy

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

Hepatic adverse effects, including hepatic enzyme elevations and hepatic failure, reported in pregnant patients exposed to nelfinavir; consider alternative antiretroviral agents during pregnancy.¹

Lactation

Limited data indicate nelfinavir is present in human breastmilk.¹

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.²⁰² 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.²⁰² 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.²⁰²

Females and Males of Reproductive Potential

May reduce efficacy of estrogen-containing oral contraceptives.¹ Advise patients receiving nelfinavir and using oral contraceptives containing ethinyl estradiol or norethindrone to use additional or alternative contraceptives.¹

Pediatric Use

Safety and efficacy not established in pediatric patients <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 pediatric patients.¹

Consider that use of nelfinavir in pediatric patients is associated with highly variable drug exposure.¹

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

Common Adverse Effects

Adverse effects (≥2%) of adult and adolescent patients ≥13 years of age include: diarrhea, nausea, rash, flatulence.¹

Most commonly reported adverse effects in pediatric patients 2 to <13 years of age include: diarrhea, leukopenia/neutropenia, rash, anorexia, abdominal pain.¹

Drug Interactions

Metabolized by CYP3A and CYP2C19.¹

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

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

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).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 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

Special Populations

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

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

Distribution

Extent

Distributed into human milk.¹

Plasma Protein Binding

98%.¹

Elimination

Metabolism

Metabolized by CYP3A and CYP2C19.¹

Elimination Route

Excreted principally in feces as unchanged drug and metabolites.¹

Half-life

3.5–5 hours.¹

Special Populations

Studies have not shown gender-related differences in pharmacokinetics; further research needed to determine if there are race-related differences.¹

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}

• Varying degrees of cross-resistance among PIs.^{1 4 11 13 14}

• 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

• Inform patients of the critical nature of adherence with HIV therapy and importance of remaining under the care of a clinician.¹ Advise patients of the importance of taking as prescribed; do not alter or discontinue antiretroviral regimen without consulting clinician.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

• Advise patients that redistribution/accumulation of body fat may occur, with unknown long-term health effects.¹

• Inform patients that hyperglycemia, new-onset diabetes mellitus, or exacerbation of preexisting diabetes mellitus may occur.¹ Advise patients to inform their healthcare provider if an increase in thirst or urination develops while receiving nelfinavir.¹

• If using oral contraceptives, advise patients to use an alternative or concomitant nonhormonal contraceptive measures.¹

• 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).¹

• Advise women to inform clinicians if they are or plan to become pregnant or plan to breast-feed.¹ Inform patients that an antiretroviral pregnancy registry is available that monitors fetal outcomes of infants exposed to nelfinavir.¹ Providers can register patients by calling the Antiretroviral Pregnancy Registry at 1-800-258-4263.¹

• Inform patients of other important precautionary information.¹

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.

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