Nelfinavir Mesylate

Pronunciation: nel-FIN-a-vir MES-i-late
Class: Protease inhibitor

Trade Names

Viracept
- Tablets, oral 250 mg
- Tablets, oral 625 mg

Pharmacology

Inhibits HIV protease, the enzyme required to form functional proteins in HIV-infected cells.

Slideshow: Flashback: FDA Drug Approvals 2013

Pharmacokinetics

Absorption

Food increased C max and AUC by 2- to 5-fold. C max was 3 to 4 mg/L. C max at steady state was 4.7 mg/L.

Distribution

Vd is 2 to 7 L/kg and protein binding is greater than 98%.

Metabolism

Nelfinavir is metabolized by multiple CYP-450 isoforms, including CYP3A and CYP2C19. Major oxidative metabolite has activity comparable with parent drug.

Elimination

The half-life is 3.5 to 5 h; 87% is excreted in the feces (78% metabolites, 22% unchanged) and 1% to 2% in the urine (unchanged).

Special Populations

Hepatic Function Impairment

C max and AUC were increased 22% and 62%, respectively, in subjects with moderate hepatic impairment when compared with subjects with normal hepatic function. Patients with severe hepatic impairment were not studied.

Children

Use of nelfinavir in the pediatric population is associated with highly variable drug exposure, possibly due to inconsistent food intake in pediatric patients.

Indications and Usage

Treatment of HIV infection in combination with other antiretroviral agents.

Unlabeled Uses

As part of a 3-drug regimen for occupational HIV postexposure prophylaxis.

Contraindications

Coadministration with the following drugs that are highly dependent on CYP3A for Cl and for which elevated plasma levels are associated with serious and/or life-threatening events: alfuzosin, amiodarone, cisapride, ergot derivatives (dihydroergotamine, ergotamine, methylergonovine), lovastatin, oral midazolam, pimozide, quinidine, rifampin, sildenafil (when used for the treatment of pulmonary hypertension), simvastatin, St. John's wort, and triazolam. These drugs may lead to reduced efficacy of nelfinavir.

Dosage and Administration

Adults and Children (13 y and older)

PO 1,250 mg twice daily or 750 mg 3 times daily in combination with other antiretroviral agents (max, 2,500 mg/day).

Children (2 to 12 y of age)

PO 45 to 55 mg/kg twice daily or 25 to 35 mg/kg 3 times daily in combination with other antiretroviral agents (max, 2,500 mg/day).

General Advice

  • Administer with food.
  • For patients unable to swallow the tablets, the medicine may be dissolved in a small amount of water. Once dissolved, the cloudy liquid should be mixed well and consumed immediately. Rinse the glass with water and swallow the rinse to ensure the entire dose is consumed.

Storage/Stability

Store between 59° and 86°F.

Drug Interactions

Alfuzosin, amiodarone, cisapride, dronedarone, ergot derivatives (eg, dihydroergotamine, ergonovine, ergotamine, methylergonovine), lurasidone, oral midazolam, pimozide, quinidine, ranolazine, triazolam, vasopressin receptor antagonists (eg, conivaptan, tolvaptan)

Nelfinavir may elevate blood levels of these drugs, which may increase the risk of arrhythmias or other potential serious adverse reactions. Coadministration with nelfinavir is contraindicated.

Aripiprazole, brentuximab, dihydropyridine calcium channel blockers (eg, amlodipine, nifedipine), eplerenone, erlotinib, eszopiclone, lamivudine, quetiapine, risperidone, trazodone, tyrosine kinase receptor inhibitors (eg, dasatinib, lapatinib, sorafenib)

Plasma concentrations of these agents may be elevated, increasing the pharmacologic effects and risk of adverse reactions. Close clinical and/or laboratory monitoring is warranted. Adjust the dose of these agents as needed.

Azithromycin

Nelfinavir AUC and C max may be decreased slightly. The AUC and C max of azithromycin may be increased. Dose adjustment is not recommended; closely monitor for liver enzyme abnormalities and hearing impairment.

Azole antifungals (eg, ketoconazole)

The nelfinavir AUC and C max may be increased. Monitor for nelfinavir toxicity and adjust the dose as needed.

Bosentan

Bosentan plasma concentrations may be elevated, increasing the risk of adverse reactions. Bosentan should be started at or adjusted to 62.5 mg once daily or every other day based on tolerability.

Cabazitaxel, crizotinib, docetaxel, erythromycin, mTOR inhibitors (eg, everolimus, temsirolimus), nilotinib, rivaroxaban, romidepsin, salmeterol, ticagrelor, toremifene

Plasma concentrations of these agents may be elevated, increasing the pharmacologic effects and risk of adverse reactions. Avoid coadministration.

Carbamazepine

Concurrent use may decrease nelfinavir plasma concentrations. Nelfinavir may not be effective. In addition, plasma concentrations of carbamazepine may be elevated, increasing the pharmacologic effects and risk of adverse reactions. Close clinical monitoring is warranted if concomitant use cannot be avoided.

Cilostazol

Cilostazol plasma concentrations may be elevated, increasing the pharmacologic effects and risk of adverse reactions. Consider a cilostazol dosage of 50 mg twice daily in patients receiving nelfinavir.

Colchicine

Colchicine and nelfinavir should not be given to patients with hepatic or renal impairment. For treatment of gout flares, coadminister colchicine 0.6 mg followed by 0.3 mg 1 hour later. Dose to be repeated no earlier than 3 days. For prophylaxis of gout flares, if the original colchicine regimen was colchicine 0.6 mg twice daily, adjust the dosage to 0.3 mg once a day; if the original colchicine dosage was 0.6 mg once daily, adjust the regimen to colchicine 0.3 mg every other day. For treatment of familial Mediterranean fever, coadminister colchicine at a maximum daily dosage of 0.3 mg twice a day.

Contraceptives, hormonal

Concentrations of ethinyl estradiol and norethindrone may be reduced. Advise patients to use alternate or additional contraceptive measures during nelfinavir therapy.

Delavirdine, efavirenz

Nelfinavir AUC and C max may be increased. In addition, the AUC and C max of delavirdine and efavirenz may be decreased. Appropriate doses for these combinations with respect to safety and efficacy have not been established. Monitor the clinical response and be prepared to adjust the nelfinavir dose as needed.

Didanosine

Administer nelfinavir with food 1 h after or more than 2 h before didanosine.

Drugs that prolong the QT interval (eg, procainamide, ziprasidone)

The risk of life-threatening cardiac arrhythmias, including torsades de pointes, may be increased. Caution is advised when 2 drugs that are suspected to prolong the QT interval are given concurrently. If coadministration is not contraindicated in the respective product information, monitor patients for QT prolongation, especially when a new drug is added to a stable regimen of another QT-prolonging agent.

Fluticasone (inhaled/nasal)

Concomitant use may increase plasma concentrations of fluticasone, resulting in reduced serum cortisol concentrations. Coadminister with caution. Consider alternatives to fluticasone, particularly for long-term use.

Food

Grapefruit juice may increase the plasma concentrations of nelfinavir; avoid coadministration. Garlic may reduce nelfinavir plasma concentrations; avoid coadministration.

HMG-CoA reductase inhibitors (eg, atorvastatin, lovastatin, rosuvastatin, simvastatin)

Plasma concentrations of these agents may be elevated, increasing the pharmacologic effects and risk of adverse reactions (eg, myopathy including rhabdomyolysis). Coadministration of lovastatin or simvastatin with nelfinavir is contraindicated. Use the lowest possible dose of atorvastatin or rosuvastatin and closely monitor the patient. Consider use of fluvastatin or pravastatin as alternative therapy.

Iloperidone

Iloperidone plasma concentrations may be elevated, increasing the pharmacologic effects and risk of adverse reactions. The iloperidone dose should be reduced by one-half when coadministered with nelfinavir. If therapy with nelfinavir is discontinued, the iloperidone dose should be increased to the original dose.

Immunosuppressants (eg, cyclosporine, sirolimus, tacrolimus)

Immunosuppressant and nelfinavir plasma concentrations may be elevated, which could increase and prolong the therapeutic effects and adverse reactions. Closely monitor renal function and immunosuppressant concentrations when starting, stopping, or changing the nelfinavir dose. Adjust the immunosuppressant and nelfinavir dose as necessary.

Indinavir

Coadministration resulted in an 83% increase in nelfinavir AUC and a 51% increase in indinavir AUC. Appropriate doses for these combinations with respect to safety and efficacy have not been established.

Interleukins

May inhibit nelfinavir metabolism, increasing the risk of toxicity. It may be necessary to adjust the nelfinavir dose.

Ixabepilone

Ixabepilone plasma concentrations may be elevated, increasing the pharmacologic effects and risk of adverse reactions. Avoid coadministration. If coadministration cannot be avoided, consider a reduction in ixabepilone dose.

Maraviroc

Maraviroc plasma concentrations may be elevated, increasing the pharmacologic effects and risk of adverse reactions. A dosage adjustment of maraviroc may be needed if coadministered with nelfinavir, depending on the entire antiretroviral regimen. Coadministration of maraviroc and nelfinavir may be contraindicated in patients with severe renal impairment (CrCl less than 30 mL/min), depending on the entire antiretroviral regimen.

Methadone

May decrease methadone concentration. Monitor for withdrawal symptoms and adjust the dose as necessary.

Muscarinic receptor antagonists (eg, darifenacin, fesoterodine, solifenacin, tolterodine)

Muscarinic receptor antagonist plasma concentrations may be elevated, increasing the pharmacologic effects and risk of adverse reactions. When coadministered with nelfinavir, the daily dose of darifenacin should not exceed 7.5 mg; the daily dose of fesoterodine should not exceed 4 mg; the daily dose of solifenacin should not exceed 5 mg; the daily dose of tolterodine should not exceed 2 mg.

Nevirapine

Nelfinavir plasma concentrations may be reduced, decreasing the efficacy. Monitor nelfinavir blood levels and adjust dose as necessary.

Opioid analgesics (eg, buprenorphine, fentanyl, oxycodone)

Concurrent use may increase opioid analgesic plasma concentrations and prolong the half-life, increasing the risk of adverse reactions (eg, respiratory depression). Closely monitor respiratory function during opioid analgesic administration and for a longer period than usual after stopping the opioid analgesic. If the opioid analgesic is administered continuously, reduce the opioid analgesic dose as needed.

Phenobarbital

May decrease nelfinavir plasma concentrations. Use with caution. Closely monitor the clinical response and adjust treatment as needed.

Phenytoin

Nelfinavir may decrease blood levels of phenytoin. Monitor phenytoin plasma levels and adjust dose as necessary.

Phosphodiesterase type 5 inhibitors (eg, sildenafil, tadalafil, vardenafil)

Concurrent use may increase the phosphodiesterase type 5 (PDE5) inhibitor concentration and the risk of adverse reactions (eg, hypotension, priapism, syncope, visual disturbances).

For treatment of erectile dysfunction

Use with caution and increase monitoring for adverse reactions. Do not exceed sildenafil 25 mg every 48 h, tadalafil 10 mg every 72 h, or vardenafil 2.5 mg every 24 h.

For treatment of pulmonary arterial hypertension

Coadministration of sildenafil and nelfinavir is contraindicated. Start tadalafil at or adjust the tadalafil dosage to 20 mg once daily. Increase the dosage to 40 mg once daily based upon individual tolerability.

Proton pump inhibitors (eg, omeprazole), rifampin, St. John's wort

Coadministration may decrease nelfinavir plasma concentrations, which may lead to loss of virologic response to nelfinavir or other coadministered antiretroviral agents. Coadministration with rifampin and St. John's wort is contraindicated.

Rifabutin

May increase rifabutin concentration and decrease nelfinavir concentration. It is recommended that the dose of rifabutin be reduced to one-half the usual dose when administered with nelfinavir; 1,250 mg twice daily is the preferred dose of nelfinavir when coadministered with rifabutin.

Ritonavir

May increase nelfinavir plasma concentrations. Appropriate doses for these combinations, with respect to safety and efficacy, have not been established.

Saquinavir

Both nelfinavir and saquinavir AUC may be increased. Appropriate doses for this combination with respect to safety and efficacy have not been established.

Saxagliptin

Saxagliptin plasma concentrations may be elevated, increasing the pharmacologic effects and risk of adverse reactions. Limit the dosage of saxagliptin to 2.5 mg daily in patients receiving nelfinavir.

Selective 5-HT 1 receptor agonists (eg, eletriptan, sumatriptan)

Selective 5-HT 1 receptor agonist plasma concentrations may be elevated, increasing the pharmacologic effects and risk of adverse reactions. Selective 5-HT 1 receptor agonists should not be used within 72 h of nelfinavir.

Vilazodone

Vilazodone plasma concentrations may be elevated, increasing the pharmacologic effects and risk of adverse reactions. The vilazodone dose should be reduced to 20 mg in patients receiving nelfinavir.

Warfarin

Coadministration may increase or decrease warfarin concentrations. Closely monitor anticoagulant activity, especially when adding nelfinavir therapy.

Zidovudine

Zidovudine AUC and C max may be reduced, decreasing the therapeutic effects. If an interaction is suspected, consider increasing the zidovudine dose.

Adverse Reactions

The following adverse reactions are for nelfinavir in combination with other antiretrovirals.

Cardiovascular

QTc prolongation, torsades de pointes (postmarketing).

CNS

Anxiety, asthenia, depression, dizziness, emotional lability, headache, hyperkinesia, insomnia, malaise, migraine, paresthesia, seizures, sleep disorder, somnolence, suicidal ideation (less than 2%).

Dermatologic

Rash (3%); dermatitis, folliculitis, fungal dermatitis, maculopapular rash, pruritus, sweating, urticaria (less than 2%).

EENT

Acute iritis, eye disorder (less than 2%).

GI

Diarrhea (47%); nausea (7%); flatulence (5%); abdominal pain, anorexia, dyspepsia, epigastric pain, GI bleeding, hepatitis, mouth ulceration, pancreatitis, vomiting (less than 2%).

Genitourinary

Kidney calculus, sexual dysfunction, urine abnormality (less than 2%).

Hematologic

Anemia, leukopenia, thrombocytopenia (less than 2%).

Hepatic

Abnormal LFTs (less than 2%); bilirubinemia, jaundice (postmarketing).

Hypersensitivity

Allergic reaction (less than 2%); hypersensitivity reactions, including bronchospasm, edema, fever, and moderate to severe rash (postmarketing).

Lab Tests

Abnormal lymphocytes (6%); abnormal neutrophils (5%); abnormal Hgb (3%); abnormal CPK increase (2%); increases in alkaline phosphatase, ALT, amylase, AST, creatine kinase, GGT, and lactic dehydrogenase (2% or less).

Metabolic

Dehydration, hyperglycemia, hyperlipidemia, hyperuricemia, hypoglycemia (less than 2%); metabolic acidosis (postmarketing).

Musculoskeletal

Arthralgia, arthritis, back pain, cramps, myalgia, myasthenia, myopathy (less than 2%).

Respiratory

Dyspnea, pharyngitis, rhinitis, sinusitis (less than 2%).

Miscellaneous

Accidental injury, fever, pain, redistribution/accumulation of body fat (less than 2%).

Precautions

Pregnancy

Category B . If indicated, do not withhold protease inhibitors, including nelfinavir, during pregnancy because the expected benefit to the HIV-positive mother outweighs the unknown risk to the fetus.

Lactation

Undetermined. HIV-infected mothers should not breast-feed their infants.

Children

Safety and efficacy not established for children younger than 2 y.

Hepatic Function

Should not be used in patients with moderate or severe hepatic impairment.

Diabetes/Hyperglycemia

New-onset diabetes, exacerbation of preexisting diabetes mellitus, and hyperglycemia have been reported in postmarking surveillance.

Fat redistribution

Redistribution/accumulation of body fat, including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, breast enlargement, and cushingoid appearance, have been observed in patients receiving antiretroviral therapy.

Hemophilia

There have been reports of increased bleeding, including skin hematomas and hemarthrosis, in patients with hemophilia type A and B treated with protease inhibitors. A causal relationship has not been established.

Immune reconstitution syndrome

Patients whose immune system responds during initial therapy may experience an inflammatory response to indolent or residual opportunistic infections (such as Mycobacterium avium infection, cytomegalovirus, Pneumocystis jiroveci pneumonia, or tuberculosis). Autoimmune disorders (such as Graves disease, polymyositis, and Guillain-Barré syndrome) have been reported to occur in the setting of immune reconstitution with variable time to onset.

Resistance

HIV cross-resistance between protease inhibitors has been observed.

Overdosage

Symptoms

No data are available.

Patient Information

  • Advise patients to take medication exactly as prescribed, including taking each dose with food to increase absorption.
  • Warn patients not to alter the dose or discontinue the medication without consulting their health care provider.
  • Advise patients that if a dose is missed, to take it as soon as possible and then return to the normal dose. However, if a dose is skipped, the patient should not double the next dose.
  • Instruct patients not to take any other medications, including OTC medications, without checking with their health care provider. This medication interacts with a wide range of all types of medications. Inform patients of the medications that should not be taken with nelfinavir.
  • Inform patients that this medication is not a cure for HIV infection and that the patient may continue to acquire secondary illnesses associated with the disease.
  • Emphasize to patients, families, and significant others that this medication does not reduce the risk of transmitting HIV to others through sexual contact or blood contamination.
  • Inform patients that diarrhea is the most common adverse reaction and that it can usually be controlled by OTC antidiarrheals, such as loperamide.
  • Inform patients to report serious or bothersome adverse reactions to their health care provider.
  • Inform patients that redistribution or accumulation of body fat may occur in patients receiving antiretroviral therapy, including protease inhibitors.
  • Explain that the long-term effects of this medication are not known at this time.
  • Inform patients that nelfinavir reduces concentrations of hormonal contraceptives that contain ethinyl estradiol and norethindrone, and alternate or additional contraceptive measures should be used during therapy with nelfinavir.
  • Advise patients taking sildenafil or other PDE5 inhibitors and nelfinavir that they may be at increased risk of PDE5 inhibitor–associated adverse reactions, including hypotension, visual changes, and prolonged penile erection, and to promptly report these to their health care provider.

Copyright © 2009 Wolters Kluwer Health.

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