Maraviroc

Class: HIV Entry and Fusion Inhibitors
VA Class: AM800
Chemical Name: 4,4 - Difluoro - N - {(1S) - 3 - [exo - 3 - (3 - isopropyl - 5 - methyl - 4H - 1,2,4 - triazol - 4 - yl) - 8 - azabicyclo[3.2.1]oct - 8 - yl] - 1 - phenylpropyl}cyclohexanecarboxamide
Molecular Formula: C29H41F2N5O
CAS Number: 376348-65-1
Brands: Selzentry

Warning(s)

  • Hepatotoxicity reported;1 may be preceded by severe rash or signs of a systemic allergic reaction (e.g., fever, eosinophilia, elevated IgE antibody levels).1 (See Hepatic Effects under Cautions.)

  • Immediately evaluate signs or symptoms of hepatitis or allergic reactions.1

Introduction

Antiretroviral; HIV entry inhibitor;1 6 8 200 CC chemokine receptor 5 (CCR5) antagonist.1 6 8 200

Uses for Maraviroc

Treatment of HIV Infection

Treatment of HIV-1 infection in adults and adolescents ≥16 years of age infected with only CCR5-tropic HIV-1.1

Not recommended in patients with dual/mixed-tropic or CXCR4-tropic HIV-1 infection; viral response was minimal in such patients in phase 2 study.1

Coreceptor tropism testing using a highly sensitive assay is required for appropriate use of maraviroc.1 Consider that low levels of CXCR4-tropic or dual/mixed-tropic HIV-1 not detected at screening are associated with virologic failure.1 (See Coreceptor Tropism Assay under Cautions.)

Slideshow: Flashback: FDA Drug Approvals 2013

In clinical studies in antiretroviral-naive adults, more patients receiving maraviroc experienced virologic failure and developed resistence to lamivudine than individuals receiving efavirenz.1

For initial treatment in antiretroviral-naive adults and adolescents, maraviroc in conjunction with zidovudine and lamivudine (or emtricitabine) is considered an acceptable (not preferred or alternative) regimen; maraviroc in conjunction with tenofovir and emtricitabine (or lamivudine) and maraviroc in conjunction with abacavir and lamivudine (or emtricitabine) may also be acceptable regimens, but additional data needed.200

Safety and efficacy not yet established in pediatric patients <16 years of age.1

Maraviroc Dosage and Administration

Administration

Oral Administration

Administer orally without regard to food.1

Dosage

Dosage depends on whether maraviroc is administered concomitantly with drugs affecting hepatic metabolism or the P-glycoprotein transport system.200 1

Must be given in conjunction with other antiretrovirals.1

Pediatric Patients

Treatment of HIV Infection
Adolescents Receiving a Potent CYP3A Inhibitor (with or without a CYP3A Inducer)
Oral

Adolescents ≥16 years of age receiving concomitant therapy with a potent CYP3A inhibitor (e.g., protease inhibitors [PIs] [except ritonavir-boosted tipranavir], delavirdine, ketoconazole, itraconazole, clarithromycin, other potent CYP3A inhibitors [nefazodone, telithromycin]) with or without a potent CYP3A inducer: 150 mg twice daily.1 200

Adolescents Receiving Drugs that are not CYP3A Inhibitors or Inducers
Oral

Adolescents ≥16 years of age receiving concomitant therapy with ritonavir-boosted tipranavir, nevirapine, nucleoside and nucleotide reverse transcriptase inhibitors (NRTIs), enfuvirtide, raltegravir, or other drugs that are not potent CYP3A inhibitors or inducers: 300 mg twice daily.1 200

Adolescents Receiving a Potent CYP3A Inducer (without a Potent CYP3A Inhibitor)
Oral

Adolescents ≥16 years of age receiving concomitant therapy with a potent CYP3A inducer (e.g., efavirenz, etravirine, rifampin, carbamazepine, phenobarbital, phenytoin) and the regimen does not include a potent CYP3A inhibitor: 600 mg twice daily.1 200

Adults

Treatment of HIV Infection
Adults Receiving a Potent CYP3A Inhibitor (with or without a CYP3A Inducer)
Oral

Patients receiving concomitant therapy with a potent CYP3A inhibitor (e.g., PIs [except ritonavir-boosted tipranavir], delavirdine, ketoconazole, itraconazole, clarithromycin, other potent CYP3A inhibitors [nefazodone, telithromycin]) with or without a potent CYP3A inducer: 150 mg twice daily.1 200

Adults Receiving Drugs that are not CYP3A Inhibitors or Inducers
Oral

Patients receiving concomitant therapy with ritonavir-boosted tipranavir, nevirapine, NRTIs, enfuvirtide, raltegravir, or other drugs that are not potent CYP3A inhibitors or inducers: 300 mg twice daily.1 200

Adults Receiving a Potent CYP3A Inducer (without a Potent CYP3A Inhibitor)
Oral

Patients receiving concomitant therapy with a potent CYP3A inducer (e.g., efavirenz, etravirine, rifampin, carbamazepine, phenobarbital, phenytoin) and the regimen does not include a potent CYP3A inhibitor: 600 mg twice daily.1 200

Special Populations

Hepatic Impairment

Dosage recommendations not available.200 Plasma concentrations may be increased;1 200 use with caution.1 (See Hepatic Impairment under Cautions.)

Renal Impairment

Mild or moderate renal impairment (Clcr≥30 mL/minute): Dosage adjustments not necessary.1

Severe renal impairment (Clcr<30 mL/minute) or end-stage renal disease (ESRD) on regular hemodialysis receiving concomitant therapy with ritonavir-boosted tipranavir, nevirapine, NRTIs, enfuvirtide, and/or raltegravir and not receiving a potent CYP3A inhibitor or inducer: 300 mg twice daily.1 Decrease dosage to 150 mg twice daily if any symptoms of postural hypotension occur.1 (See Renal Impairment under Cautions.)

Severe renal impairment receiving concomitant therapy with a potent CYP3A inhibitor, such as a PI (except ritonavir-boosted tipranavir), delavirdine, ketoconazole, itraconazole, clarithromycin, or other potent CYP3A inhibitor (e.g., nefazodone, telithromycin): Do not use maraviroc.1

Severe renal impairment receiving concomitant therapy with potent CYP3A inducer, such as efavirenz, etravirine, rifampin, carbamazepine, phenobarbital, or phenytoin: Do not use maraviroc.1

Cautions for Maraviroc

Contraindications

  • Severe renal impairment (Clcr <30 mL/minute) or ESRD receiving concomitant therapy with potent CYP3A inhibitor or inducer.1

Warnings/Precautions

Hepatic Effects

Hepatotoxicity with allergic features, including life-threatening events, reported.1 May be preceded by severe rash or signs of systemic allergic reaction (e.g., fever, eosinophilia, elevated IgE antibody levels).1 (See Boxed Warning.)

Hepatitis has occurred without allergic features and in patients without preexisting hepatic disease.1

Use with caution in patients with preexisting liver dysfunction and in those coinfected with HBV or HCV.1 (See Hepatic Impairment under Cautions.)

Perform appropriate laboratory testing (e.g., ALT, AST, bilirubin) prior to and as clinically indicated during maraviroc therapy.1 Assess hepatic function in any patient who develops rash or signs or symptoms of hepatitis or allergic reaction.1

Consider discontinuing maraviroc in any patient with signs or symptoms of hepatitis or with increased liver transaminases with rash or other systemic symptoms.1

Cardiovascular Effects

Cardiovascular events (i.e., myocardial ischemia and/or MI) reported.1 Events generally occurred in individuals with cardiac disease or risk factors for cardiac disease.1 Use with caution in patients at increased risk for cardiovascular events.1

Symptomatic postural hypotension reported in healthy individuals receiving higher than recommended dosages of maraviroc.1

Use with caution in patients with a history of postural hypotension and those receiving a drug that lowers BP.1

Consider that severe renal insufficiency or ESRD may increase risk of postural hypotension because of increased maraviroc plasma concentrations;1 consider that patients with renal impairment may have cardiovascular co-morbidities and be at increased risk of adverse cardiovascular events triggered by postural hypotension.1 (See Renal Impairment under Cautions.)

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, M. tuberculosis, cytomegalovirus [CMV], Pneumocystis jiroveci [formerly P. carinii], herpes simplex virus, varicella-zoster virus [VZV]); this may necessitate further evaluation and treatment.1

Autoimmune disorders (e.g., Graves' disease, polymyositis, Guillain-Barré syndrome) reported to occur in the setting of immune reconstitution; time to onset is more variable and can occur many months after initiation of antiretroviral therapy.1

Infectious Complications

Possible increased risk of infection with agents that bind to CCR5 receptors (e.g., maraviroc).1 Monitor for infection.1

Malignancies

Possible increased risk of malignancy with agents that bind to CCR5 receptors (e.g., maraviroc).1 Risk not fully evaluated.1

Coreceptor Tropism Assay

Coreceptor tropism testing with a highly sensitive tropism assay is required for appropriate use of maraviroc.1 Also consider such testing in patients who exhibit virologic failure while receiving a CCR5 antagonist.200

Assay detects CCR5- and CXCR4-using virus; results reported as CCR5-tropic, CXCR4-tropic, or dual/mixed-tropic HIV-1.1

Specific Populations

Pregnancy

Category B.1

Antiretroviral Pregnancy Registry at 800-258-4263 or .1 202

Experts state that safety and pharmacokinetic data are insufficient to recommend maraviroc in antiretroviral-naive pregnant women.202 However, in consultation with HIV and obstetric specialists, use can be considered in pregnant women who have failed therapy with several other classes of antiretrovirals.202

Lactation

Distributed into milk in rats; not known whether distributed into human milk.1

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, efficacy, and pharmacokinetics not established in pediatric patients <16 years of age;1 not recommended in this age group.1 201

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether they respond differently than younger adults.1

Use with caution and monitor because of age-related decreases in hepatic, renal, and/or concomitant disease and drug therapy.1

Hepatic Impairment

Use with caution in individuals with hepatic impairment and in those coinfected with HBV or HCV.1

Safety and efficacy not specifically studied in patients with clinically significant underlying liver disorders.1 Insufficient data available to determine whether patients coinfected with HBV or HCV are at increased risk for adverse hepatic effects.1

Monitor closely for maraviroc-associated adverse effects in individuals with moderate hepatic impairment receiving maraviroc 150 mg twice daily and a drug that strongly inhibits CYP3A.1

Renal Impairment

Do not use in patients with severe renal impairment (Clcr <30 mL/minute) or with ESRD receiving concomitant therapy with a potent inhibitor or inducer of CYP3A.1

Plasma maraviroc concentrations may be increased, especially in those receiving concomitant therapy with a CYP3A inhibitor.1

Patients with severe renal insufficiency or ESRD may be at increased risk of postural hypotension because of increased maraviroc concentrations.1 In addition, patients with renal impairment may have cardiovascular co-morbidities and be at increased risk of cardiovascular adverse events triggered by postural hypotension.1

Use in patients with severe renal impairment or ESRD only if they are not receiving concomitant therapy with a potent CYP3A inhibitor or inducer and only when no alternative treatment options are available.1 If used in patients with severe renal impairment or ESRD, decrease dosage if any symptoms of postural hypotension occur.1 (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Cough, pyrexia, upper respiratory tract infections, rash, dizziness.1

Interactions for Maraviroc

Metabolized by CYP3A.1

Does not inhibit CYP1A2, 2B6, 2C8, 2C9, 2C19, or 3A; may inhibit CYP2D6 at higher than recommended dosage.1 Does not induce CYP1A2.1

A p-glycoprotein substrate.1

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Potential pharmacokinetic interactions with drugs that induce or inhibit CYP3A with possible altered metabolism of maraviroc.1

Drugs Affecting or Affected by P-Glycoprotein Transport

Pharmacokinetic interactions likely with drugs that are p-glycoprotein inhibitors or inducers with possible altered metabolism of maraviroc.1

Inhibits the P-glycoprotein transport system; may affect bioavailability of certain other drugs.1

Specific Drugs

Drug

Interaction

Comments

Abacavir

No in vitro evidence of antagonistic antiretroviral effects 1

Recommended maraviroc dosage is 300 mg twice daily when used in conjunction with NRTIs, provided regimen does not include a potent CYP3A inhibitor or inducer1 16

Anticonvulsants (carbamazepine, phenobarbital, phenytoin)

Possible decreased maraviroc concentrations200

Carbamazepine, phenobarbital, phenytoin: Recommended maraviroc dosage is 600 mg twice daily, provided regimen does not include a potent CYP3A inhibitor;1 16 200 consider alternative anticonvulsants200

Antifungals, azoles (itraconazole, ketoconazole, voriconazole)

Itraconazole: Possible increased maraviroc concentrations 200

Ketoconazole: Increased maraviroc concentrations1 21 200

Voriconazole: Possible increased maraviroc concentrations 200

Itraconazole: Recommended maraviroc dosage is 150 mg twice daily1 200

Ketoconazole: Recommended maraviroc dosage is 150 mg twice daily1 200

Voriconazole: Consider using maraviroc dosage 150 mg twice daily200

Antimycobacterials (rifabutin, rifampin, rifapentine)

Rifabutin: Possible decreased maraviroc concentrations200

Rifampin: Decreased maraviroc concentrations1 22 200

Rifapentine: Possible decreased maraviroc concentrations200

Rifabutin: Recommended maraviroc dosage is 300 mg twice daily if regimen does not include a potent CYP3A inducer or inhibitor;200 recommended maraviroc dosage is 150 mg twice daily if regimen includes a potent CYP3A inhibitor200

Rifampin: Recommended maraviroc dosage is 600 mg twice daily if regimen does not include a potent CYP3A inhibitor;1 16 200 recommended maraviroc dosage is 300 mg twice daily if regimen includes a potent CYP3A inhibitor200

Rifapentine: Concomitant use not recommended 200

Atazanavir

Atazanavir or ritonavir-boosted atazanavir: Increased maraviroc concentrations and AUC1 200

No in vitro evidence of antagonistic antiretroviral effects1

Atazanavir or ritonavir-boosted atazanavir: Recommended maraviroc dosage is 150 mg twice daily1 200

Clarithromycin

Possible increased maraviroc concentrations200

Recommended maraviroc dosage is 150 mg twice daily1 200

Co-trimoxazole

No effect on maraviroc pharmacokinetics1

 

Darunavir

Ritonavir-boosted darunavir: Increased maraviroc concentrations and AUC1 200

No in vitro evidence of antagonistic antiretroviral effects1

Ritonavir-boosted darunavir: Recommended maraviroc dosage is 150 mg twice daily1 200

Delavirdine

No in vitro evidence of antagonistic antiretroviral effects1

Recommended maraviroc dosage is 150 mg twice daily1 200

Didanosine

No in vitro evidence of antagonistic antiretroviral effects1

Recommended maraviroc dosage is 300 mg twice daily when used in conjunction with NRTIs, provided regimen does not include a potent CYP3A inhibitor or inducer1 16

Efavirenz

Efavirenz: Decreased maraviroc concentrations and AUC1 22 200

Efavirenz and lopinavir/ritonavir: Increased maraviroc concentrations and AUC1 16 200

Efavirenz and ritonavir-boosted saquinavir: Increased maraviroc concentrations and AUC1 200

Efavirenz: No in vitro evidence of antagonistic antiretroviral effects1

Recommended maraviroc dosage is 600 mg twice daily when used with efavirenz, provided regimen does not include a potent CYP3A inhibitor1 200

Emtricitabine

No in vitro evidence of antagonistic antiretroviral effects 1

Recommended maraviroc dosage is 300 mg twice daily when used in conjunction with NRTIs, provided regimen does not include a potent CYP3A inhibitor or inducer1 16

Enfuvirtide

In vitro evidence of additive to synergistic antiretroviral effects1

Recommended maraviroc dosage is 300 mg twice daily when used with enfuvirtide, provided regimen does not include a potent CYP3A inhibitor or inducer1

Estrogens/ Progestins

Oral contraceptives containing ethinyl estradiol and levonorgestrel: No clinically important effect on pharmacokinetics of the oral contraceptive1 200

Oral contraceptives can be used safely with maraviroc200

Etravirine

Decreased maraviroc concentrations and AUC;1 200 214 no clinically importance effect on etravirine concentrations or AUC214

No in vitro evidence of antagonistic antiretroviral effects214

Recommended maraviroc dosage is 600 mg twice daily with usual etravirine dosage, provided regimen does not include a potent CYP3A inhibitor200 214

Fosamprenavir

Fosamprenavir: Possible increased maraviroc concentrations1 200

No in vitro evidence of antagonistic antiretroviral effects between amprenavir and maraviroc1

Fosamprenavir: Recommended maraviroc dosage is 150 mg twice daily200

Indinavir

No in vitro evidence of antagonistic antiretroviral effects1

Recommended maraviroc dosage is 150 mg twice daily1 200

Lamivudine

No effect on lamivudine pharmacokinetics1

No in vitro evidence of antagonistic antiretroviral effects1

Recommended maraviroc dosage is 300 mg twice daily when used in conjunction with NRTIs, provided regimen does not include a potent CYP3A inhibitor or inducer1 16

Lopinavir/ritonavir

Substantially increased maraviroc concentrations and AUC1 21 200

Lopinavir/ritonavir and efavirenz: Increased maraviroc concentrations1 200

No in vitro evidence of antagonistic antiretroviral effects 1

Recommended maraviroc dosage is 150 mg twice daily1 200

Midazolam

No change in the pharmacokinetics of midazolam1

Nefazodone

Possible pharmacokinetic interaction 1

Recommended maraviroc dosage is 150 mg twice daily1

Nelfinavir

No in vitro evidence of antagonistic antiretroviral effects 1

Recommended maraviroc dosage is 150 mg twice daily1

Nevirapine

Increased maraviroc concentrations, but no effect on maraviroc AUC1 200

No in vitro evidence of antagonistic antiretroviral effects1

Recommended maraviroc dosage is 300 mg twice daily when used with nevirapine, provided regimen does not include a PI or other potent CYP3A inhibitor;200 recommended maraviroc dosage is 150 mg twice daily if regimen includes a PI (except ritonavir-boosted tipranavir)200

Raltegravir

Decreased raltegravir concentrations and AUC;1 200 decreased maraviroc concentrations and AUC1 200

Not considered clinically important1

Recommended maraviroc dosage is 300 mg twice daily when used with raltegravir, provided regimen does not include a potent CYP3A inhibitor or inducer1 200

Rilpivirine

Clinically important pharmacokinetic interactions unlikely226

No in vitro evidence of antagonistic antiretroviral effects 226

Ritonavir

Low-dose ritonavir (ritonavir 100 mg twice daily): Increased maraviroc concentrations and AUC1 21 200

No in vitro evidence of antagonistic antiretroviral effects1

Regimens that include low-dose ritonavir (except ritonavir-boosted tipranavir): Recommended maraviroc dosage is 150 mg twice daily1 200

Saquinavir

Ritonavir-boosted saquinavir (saquinavir 1 g twice daily with ritonavir 100 mg twice daily): Substantially increased maraviroc concentrations and AUC21 200

Ritonavir-boosted saquinavir and efavirenz: Increased maraviroc concentrations and AUC1 200

Saquinavir: No in vitro evidence of antagonistic antiretroviral effects 1

Ritonavir-boosted saquinavir: Recommended maraviroc dosage is 150 mg twice daily1 200

Stavudine

No in vitro evidence of antagonistic antiretroviral effects1

Recommended maraviroc dosage is 300 mg twice daily when used in conjunction with NRTIs, provided regimen does not include a potent CYP3A inhibitor or inducer1 16

St. John’s wort (Hypericum perforatum)

Potential decreased maraviroc concentrations and loss of virologic response1

Concomitant use not recommended1 200

Telithromycin

Possible pharmacokinetic interaction 1

Recommended maraviroc dosage is 150 mg twice daily1

Tenofovir

No effect on maraviroc pharmacokinetics1

No in vitro evidence of antagonistic antiretroviral effects 1

Recommended maraviroc dosage is 300 mg twice daily when used in conjunction with NRTIs, provided regimen does not include a potent CYP3A inhibitor or inducer16 1

Tipranavir

Ritonavir-boosted tipranavir: No clinically important effect on maraviroc pharmacokinetics1 200

No in vitro evidence of antagonistic antiretroviral effects1

Ritonavir-boosted tipranavir: Recommended maraviroc dosage is 300 mg twice daily, provided regimen does not include a potent CYP3A inhibitor or inducer1 16 200

Zidovudine

No effect on zidovudine pharmacokinetics1

No in vitro evidence of antagonistic antiretroviral effects 1

Recommended maraviroc dosage is 300 mg twice daily when used in conjunction with NRTIs, provided regimen does not include a potent CYP3A inhibitor or inducer1 16

Maraviroc Pharmacokinetics

Absorption

Bioavailability

Absolute bioavailability of a 100-mg oral dose is 23%; absolute bioavailability of a 300-mg dose predicted to be 33%.1 20

Following oral administration, peak plasma concentrations attained in 0.5–4 hours.1

Food

When a 300-mg tablet was administered with a high fat meal, AUC was decreased by 33%.1

Special Populations

Increased plasma concentrations and AUC in patients with severe renal impairment (Clcr<30 mL/minute) or ESRD, especially in those receiving concomitant therapy with a potent CYP3A inhibitor.1

Increased plasma concentrations and AUC in individuals with mild or moderate hepatic impairment, especially in those with moderate hepatic impairment receiving concomitant therapy with a potent CYP3A inhibitor.1

Distribution

Extent

Distributed into milk in rats; not known whether distributed into human milk.1

Plasma Protein Binding

76%.1

Elimination

Metabolism

Principally metabolized by CYP3A to inactive metabolites.1

Elimination Route

Approximately 20% eliminated in urine (8% as unchanged maraviroc) and 76% excreted in feces (25% as unchanged maraviroc).1

Half-life

14–18 hours.1 20

Special Populations

Pharmacokinetics not studied in patients with severe hepatic impairment.1

Stability

Storage

Oral

Tablets

25°C (may be exposed to 15–30°C).1

Actions

  • Active against HIV-1;1 activity against HIV-2 not evaluated.1

  • CCR5 antagonist;1 6 8 200 CCR5 is a co-receptor for the most commonly transmitted HIV-1 strains that predominate during the early stages of infection6 200 and remains the dominant form in many patients with late-stage infection.6

  • Selectively binds to CCR5 on the cell membrane and prevents the interaction of HIV-1 glycoprotein 120 and CCR5 necessary for CCR5-tropic HIV-1 to enter cells.1 6

  • Does not inhibit CXCR4-tropic and dual/mixed-tropic HIV-1 entry into cells.1

  • Active against some strains of HIV-1 resistant to NRTIs, nonnucleoside reverse transcriptase inhibitors (NNRTIs), PIs, and HIV entry and fusion inhibitors (enfuvirtide).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

  • 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.200

  • Importance of reading patient information provided by the manufacturer.1

  • If a dose is missed and it is more than 6 hours before the next scheduled dose, the dose should be taken as soon as possible and the next dose taken at the regularly scheduled time.1 If there are less than 6 hours before the next scheduled dose when the missed dose is remembered, omit the dose and take the next dose at the regularly scheduled time.1

  • Advise patients that liver problems, including life-threatening reactions, have occurred.1 Importance of immediately discontinuing maraviroc and seeking medical attention if signs or symptoms of hepatitis or allergic reactions (e.g., rash, yellow skin or eyes, dark urine, vomiting, abdominal pain) occur.1

  • Possibility of dizziness,1 especially in those with a history of postural hypotension or receiving drugs known to lower BP.1 Advise patients to avoid driving a motor vehicle or operating hazardous machinery if they experience dizziness.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and herbal products (e.g., St. John’s wort), and any concomitant illnesses.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.

Maraviroc

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film-coated

150 mg

Selzentry

ViiV

300 mg

Selzentry

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.

Selzentry 150MG Tablets (VIIV HEALTHCARE): 30/$530.00 or 90/$1,529.94

Selzentry 300MG Tablets (VIIV HEALTHCARE): 30/$570.98 or 90/$1,671.95

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions September 15, 2012. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

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

4. Saag M, Goodrich J, Fätkenheuer G et al. A double-blind, placebo-controlled trial of maraviroc in treatment-experienced patients infected with non-R5 HIV-1. J Infect Dis. 2009; 199:1638-47. [PubMed 19432546]

6. Dorr P, Westby M, Dobbs S et al. Maraviroc (UK-427,857), a potent, orally bioavailable, and selective small-molecule inhibitor of chemokine receptor CCR5 with broad-spectrum anti-human immunodeficiency virus type 1 activity. Antimicrob Agents Chemother. 2005; 49:4721-32. [PubMed 16251317]

7. Stephenson J. Researchers buoyed by novel HIV drugs: will expand drug arsenal against resistant virus. JAMA. 2007; 297:1535-6. [PubMed 17426263]

8. Lederman MM, Penn-Nicholson A, Cho M et al. Biology of CCR5 and its role in HIV infection and treatment. JAMA. 2006; 296:815-26. [PubMed 16905787]

15. Cooper DA, Heera J, Goodrich J et al. Maraviroc versus efavirenz, both in combination with zidovudine-lamivudine, for the treatment of antiretroviral-naive subjects with CCR5-tropic HIV-1 infection. J Infect Dis. 2010; 201:803-13. [PubMed 20151839]

16. Pfizer, New York, NY: Personal communication.

17. Gulick RM, Lalezari J, Goodrich J et al. Maraviroc for previously treated patients with R5 HIV-1 infection. N Engl J Med. 2008; 359:1429-41. [PubMed 18832244]

18. Sierra-Madero J, Di Perri G, Wood R et al. Efficacy and safety of maraviroc versus efavirenz, both with zidovudine/lamivudine: 96-week results from the MERIT study. HIV Clin Trials. 2010 May-Jun; 11:125-32.

20. Abel S, Russell D, Whitlock LA et al. Assessment of the absorption, metabolism and absolute bioavailability of maraviroc in healthy male subjects. Br J Clin Pharmacol. 2008; 65(Suppl 1):60-7. [PubMed 18333867]

21. Abel S, Russell D, Taylor-Worth RJ et al. Effects of CYP3A4 inhibitors on the pharmacokinetics of maraviroc in healthy volunteers. Br J Clin Pharmacol. 2008; 65(Suppl 1):27-37. [PubMed 18333863]

22. Abel S, Jenkins TM, Whitlock LA et al. Effects of CYP3A4 inducers with and without CYP3A4 inhibitors on the pharmacokinetics of maraviroc in healthy volunteers. Br J Clin Pharmacol. 2008; 65(Suppl 1):38-46. [PubMed 18333864]

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.

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

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

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