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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

Medically reviewed on Sep 3, 2018

Warning

  • 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

See also: Atripla

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, adolescents, and children ≥2 years of age infected with CCR5-tropic HIV-1;1 used in conjunction with other antiretrovirals.1

Not recommended in patients with dual/mixed-tropic or CXC chemokine receptor 4 (CXCR4)-tropic HIV-1 infection.1 (See General under Dosage and Administration.) Outgrowth of preexisting low levels of dual/mixed-tropic or CXCR4-tropic HIV-1 not detected during initial screening has been associated with virologic failure in patients receiving maraviroc.1

Not recommended for initial treatment regimens in antiretroviral-naive adults and adolescents because coreceptor tropism testing must be performed, there is no virologic benefit compared with other recommended regimens, and a twice-daily dosing regimen is required.200

Not recommended for initial treatment in antiretroviral-naive pediatric patients because insufficient data available.201

Postexposure Prophylaxis following Occupational Exposure to HIV

Postexposure prophylaxis of HIV infection following occupational exposure (PEP) in health-care personnel and others exposed via percutaneous injury (e.g., needlestick, cut with sharp object) or mucous membrane or nonintact skin (e.g., chapped, abraded, dermatitis) contact with blood, tissue, or other body fluids that might contain HIV.199

USPHS recommends a 3-drug regimen of raltegravir in conjunction with emtricitabine and tenofovir disoproxil fumarate (tenofovir DF) as the preferred regimen for PEP following occupational exposures to HIV.199 Maraviroc is one of several alternative agents that may be used in conjunction with other antiretrovirals for PEP, but use only with expert consultation.199

Management of occupational exposures to HIV is complex and evolving; consult infectious disease specialist, clinician with expertise in administration of antiretroviral agents, and/or National Clinicians’ Postexposure Prophylaxis Hotline (PEPline at 888-448-4911) whenever possible.199 Do not delay initiation of PEP while waiting for expert consultation.199

Postexposure Prophylaxis following Nonoccupational Exposure to HIV (nPEP)

Postexposure prophylaxis of HIV infection following nonoccupational exposure (nPEP) in individuals exposed to blood, genital secretions, or other potentially infectious body fluids that might contain HIV when the exposure represents a substantial risk for HIV transmission.198 Used in conjunction with other antiretrovirals.198

When nPEP indicated in adults and adolescents ≥13 years of age with normal renal function, CDC states preferred regimen is either raltegravir or dolutegravir used in conjunction with emtricitabine and tenofovir DF (given as emtricitabine/tenofovir DF);198 recommended alternative in these patients is ritonavir-boosted darunavir used in conjunction with emtricitabine/tenofovir DF.198

CDC states maraviroc is an alternative antiretroviral that can be used in nPEP regimens, but use in such regimens only with expert consultation.198

Consult infectious disease specialist, clinician with expertise in administration of antiretroviral agents, and/or the National Clinicians’ Postexposure Prophylaxis Hotline (PEPline at 888-448-4911) if nPEP indicated in certain exposed individuals (e.g., pregnant women, children, those with medical conditions such as renal impairment) or if considering a regimen not included in CDC guidelines, source virus is known or likely to be resistant to antiretrovirals, or healthcare provider is inexperienced in prescribing antiretrovirals.198 Do not delay initiation of nPEP while waiting for expert consultation.198

Maraviroc Dosage and Administration

General

  • Prior to initiation of maraviroc, test all patients for CCR5 tropism using a highly sensitive tropism assay.1 (See Coreceptor Tropism Assay under Cautions.)

  • Determine serum concentrations of AST, ALT, and bilirubin prior to initiation of maraviroc and monitor as clinically indicated during treatment with the drug.1 (See Hepatic Effects under Cautions.)

Administration

Oral Administration

Administer orally twice daily without regard to food.1

Oral Solution

Administer using press-in bottle adapter and oral dosing syringe supplied by the manufacturer.1

After inserting press-in bottle adapter into bottle of oral solution, draw recommended dose into dosing syringe and administer orally at the inside of the cheek.1

Rinse dosing syringe with water and air dry after each use.1

Consult manufacturer's information for more specific information regarding administration of the oral solution.1

Tablet

Swallow whole;1 do not chew.1

Assess children for ability to swallow tablets;1 use oral solution instead of tablets in those unable to reliably swallow tablets.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

Pediatric dosage is based on weight and should not exceed recommended adult dosage.1

Treatment of HIV Infection
Pediatric Patients ≥2 Years of Age Receiving a Potent CYP3A Inhibitor (with or without a CYP3A Inducer)
Oral

Pediatric patients ≥2 years of age weighing ≥10 kg receiving concomitant therapy with a potent CYP3A inhibitor (e.g., a protease inhibitor [PI] [except ritonavir-boosted tipranavir], delavirdine, ketoconazole, itraconazole, clarithromycin, other potent CYP3A inhibitors [nefazodone, telithromycin]) with or without a potent CYP3A inducer: Dosage based on weight.1 (See Table 1.)

Table 1. Dosage of Maraviroc Oral Solution or Tablets in Pediatric Patients ≥2 Years of Age Weighing ≥10 kg Receiving a Potent CYP3A Inhibitor (with or without a CYP3A Inducer)

Body Weight (kg)

Dosage of Oral Solution Containing 100 mg/5 mL

Dosage of Tablets

10 to <20

50 mg (2.5 mL) twice daily

50 mg twice daily

20 to <30

80 mg (4 mL) twice daily

75 mg twice daily

30 to <40

100 mg (5 mL) twice daily

100 mg twice daily

≥40

150 mg (7.5 mL) twice daily

150 mg twice daily

Pediatric Patients ≥2 Years of Age Receiving Drugs that are not CYP3A Inhibitors or Inducers
Oral

Pediatric patients ≥2 years of age weighing ≥10 kg receiving concomitant therapy with ritonavir-boosted tipranavir, nevirapine, nucleoside reverse transcriptase inhibitors (NRTIs), enfuvirtide, raltegravir, or other drugs that are not potent CYP3A inhibitors or inducers: Dosage based on weight.1 (See Table 2.)

Table 2. Dosage of Maraviroc Oral Solution or Tablets in Pediatric Patients ≥2 Years of Age Weighing ≥10 kg Receiving Drugs that are not CYP3A Inhibitors or Inducers

Body Weight (kg)

Dosage of Oral Solution Containing 100 mg/5 mL

Dosage of Tablets

10 to <20

Not recommended

Not recommended

20 to <30

Not recommended

Not recommended

30 to <40

300 mg (15 mL) twice daily

300 mg twice daily

≥40

300 mg (15 mL) twice daily

300 mg twice daily

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, cobicistat-boosted elvitegravir, 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

Postexposure Prophylaxis following Occupational Exposure to HIV
Oral

300 mg twice daily, provided patient is not receiving a potent CYP3A inducer.199 Use in conjunction with other antiretrovirals.199 (See Postexposure Prophylaxis following Occupational Exposure to HIV under Uses.)

Initiate PEP as soon as possible following occupational exposure to HIV (preferably within hours); continue for 4 weeks, if tolerated.199

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

Adults with mild or moderate renal impairment (Clcr ≥30 mL/minute): Dosage adjustments not needed.1

Adults with severe renal impairment (Clcr <30 mL/minute) or with 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.)

Adults with severe renal impairment or with ESRD on regular hemodialysis 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): Contraindicated.1

Adults with severe renal impairment or with ESRD on regular hemodialysis receiving concomitant therapy with a potent CYP3A inducer, such as efavirenz, etravirine, rifampin, carbamazepine, phenobarbital, or phenytoin: Contraindicated.1

Pediatric patients with mild or moderate renal impairment (Clcr ≥30 mL/minute): Data not available to make dosage recommendations.1

Pediatric patients with severe renal impairment or with ESRD on hemodialysis receiving a potent CYP3A inhibitor: Contraindicated.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

Warnings

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

Perform appropriate laboratory testing (e.g., ALT, AST, bilirubin) prior to and as clinically indicated during maraviroc therapy.1

Safety and efficacy not specifically studied in patients with clinically important underlying liver disease.1 (See Hepatic Impairment under Cautions.) If used in patients with preexisting liver dysfunction or in those with HBV or HCV infection, additional monitoring may be necessary.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

Sensitivity Reactions

Severe Dermatologic and Hypersensitivity Reactions

Severe, potentially life-threatening skin and hypersensitivity reactions reported, usually in patients receiving maraviroc and concomitant therapy with other drugs associated with such reactions.1 Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug rash with eosinophilia and systemic symptoms (DRESS) reported;1 cases usually involved rash, constitutional findings, and sometimes organ dysfunction, including hepatic failure.1

Immediately discontinue maraviroc and other suspected agents if signs or symptoms of severe skin or hypersensitivity reactions occur (e.g., severe rash or rash accompanied by fever, malaise, muscle or joint aches, blisters, oral lesions, conjunctivitis, facial edema, lip swelling, and/or eosinophilia).1 Life-threatening reactions could occur if discontinuance of maraviroc or other suspect agents is delayed after onset of rash.1

Monitor clinical status, including liver aminotransferases, and initiate appropriate therapy.1

Other Warnings and Precautions

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

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

Patients with cardiovascular comorbidities or risk factors for postural hypotension and patients receiving concomitant therapy with drugs with hypotensive effects could be at increased risk of adverse cardiovascular events triggered by postural hypotension.1 Additional monitoring may be warranted in such patients.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 jirovecii [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) also reported 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

Specific Populations

Pregnancy

Limited data on use in pregnant women.1 In animals, no evidence of adverse developmental outcomes observed with systemic exposures in rats or rabbits approximately 20 or 5 times higher, respectively, than systemic exposures in humans at recommended dosages.1

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

Experts state maraviroc not recommended for initial treatment regimens in antiretroviral-naive pregnant women.202 Can be considered for pregnant women when therapy with several other classes of antiretroviral agents has failed; however, safety and pharmacokinetic data insufficient to recommend an appropriate dosage for pregnant women and experts state undertake such use only after consultation with HIV and obstetric specialists.202

Low concentrations cross the placenta in humans.23

Lactation

Distributed into milk in rats.1 Not known whether distributed into human milk, affects human milk production, or affects breast-fed infant.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 <2 years of age or <10 kg.1

Insufficient data to make dosage recommendations for use in pediatric patients ≥2 years of age weighing <30 kg receiving drugs that are not CYP3A inhibitors or inducers or in any pediatric patient receiving a potent CYP3A inducer without a potent CYP3A inhibitor.1

Not recommended in pediatric patients receiving concomitant therapy with a potent CYP3A inducer, such as efavirenz, etravirine, rifampin, carbamazepine, phenobarbital, or phenytoin, without a potent CYP3A inhibitor.1

Not studied in pediatric patients with renal impairment.1 (See Renal Impairment under Cautions.)

Geriatric Use

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

Use with caution 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 important 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 who are receiving a drug that strongly inhibits CYP3A.1

Renal Impairment

Adults with severe renal impairment (Clcr <30 mL/minute) or with ESRD receiving concomitant therapy with a potent CYP3A inhibitor or inducer: Contraindicated.1

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

Pediatric patients with renal impairment: Insufficient data to recommend dosage in those with mild or moderate renal impairment.1 Contraindicated in those with severe renal impairment or with ESRD on regular hemodialysis who are receiving a potent CYP3A inhibitor or inducer.1

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 (P-gp) inhibitors or inducers with possible altered metabolism of maraviroc.1

In vitro studies suggest maraviroc could inhibit P-gp in the gut, but in vivo studies indicate the drug may not inhibit or induce P-gp to any clinically important extent.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

Isavuconazonium (prodrug of isavuconazole): Possible increased maraviroc concentrations200

Itraconazole: Possible increased maraviroc concentrations 200

Ketoconazole: Increased maraviroc concentrations1 21 200

Posaconazole: Possible increased maraviroc concentrations200

Voriconazole: Possible increased maraviroc concentrations 200

Isavuconazonium: Consider using maraviroc dosage 150 mg twice daily200

Itraconazole: Recommended maraviroc dosage is 150 mg twice daily1 200

Ketoconazole: Recommended maraviroc dosage is 150 mg twice daily1 200

Posaconazole: Recommended maraviroc dosage is 150 mg twice daily200

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: Concomitant use not recommended;200 if concomitant use considered necessary, recommended maraviroc dosage is 600 mg twice daily if regimen does not include a potent CYP3A inhibitor1 16 200 or 300 mg twice daily if regimen includes a potent CYP3A inhibitor200

Rifapentine: Concomitant use not recommended 200

Atazanavir

Cobicistat-boosted, ritonavir-boosted, or unboosted atazanavir: Increased maraviroc concentrations and AUC1 200

No in vitro evidence of antagonistic antiretroviral effects1

Cobicistat-boosted, ritonavir-boosted, or unboosted 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

 

Daclatasvir

Pharmacokinetic interaction not expected200

Experts state dosage adjustments not needed200

Darunavir

Cobicistat-boosted or ritonavir-boosted darunavir: Increased maraviroc concentrations and AUC1 200

No in vitro evidence of antagonistic antiretroviral effects1

Cobicistat-boosted or ritonavir-boosted darunavir: Recommended maraviroc dosage is 150 mg twice daily1 200

Dasabuvir, ombitasvir, paritaprevir, and ritonavir

Fixed combination of dasabuvir, ombitasvir, paritaprevir, and ritonavir (dasabuvir/ombitasvir/paritaprevir/ritonavir) or fixed combination of ombitasvir, paritaprevir, and ritonavir (ombitasvir/paritaprevir/ritonavir) copackaged with dasabuvir (ombitasvir/paritaprevir/ritonavir with dasabuvir): Increased maraviroc concentrations200

Dasabuvir/ombitasvir/paritaprevir/ritonavir (fixed combination) or ombitasvir/paritaprevir/ritonavir with dasabuvir (copackaged): Experts state do not use concomitantly with maraviroc200

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

Dolutegravir

No in vitro evidence of antagonistic antiretroviral effects236

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

Elbasvir and grazoprevir

Fixed combination of elbasvir and grazoprevir (elbasvir/grazoprevir): Data not available200

Elvitegravir and cobicistat

Fixed combination of elvitegravir, cobicistat, emtricitabine, and either tenofovir alafenamide (EVG/c/FTC/TAF) or tenofovir disoproxil fumarate (EVG/c/FTC/TDF): Possible increased maraviroc concentrations200

EVG/c/FTC/TAF or EVG/c/FTC/TDF: Experts state use maraviroc 150 mg twice daily200

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

No in vitro evidence of antagonistic 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: Experts state dosage adjustments not needed200

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 with or without low-dose ritonavir: Increased maraviroc concentrations and AUC; decreased amprenavir (active metabolite of fosamprenavir) concentrations and AUC1 205

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

Fosamprenavir with low-dose ritonavir: Recommended maraviroc dosage is 150 mg twice daily with usual dosage of ritonavir-boosted fosamprenavir1 205

Fosamprenavir without low-dose ritonavir: Do not use with maraviroc1 205

Glecaprevir and pibrentasvir

Fixed combination of glecaprevir and pibrentasvir (glecaprevir/pibrentasvir): Pharmacokinetic interaction not expected200

Experts state dosage adjustments not needed200

Indinavir

No in vitro evidence of antagonistic antiretroviral effects1

Recommended maraviroc dosage is 150 mg twice daily1

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

Ledipasvir and sofosbuvir

Fixed combination of ledipasvir and sofosbuvir (ledipasvir/sofosbuvir): Pharmacokinetic interaction not expected200

Experts state dosage adjustments not needed200

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 maraviroc and decreased raltegravir concentrations and AUC;1 200 inferior virologic outcomes reported with 2-drug regimen of maraviroc and raltegravir in antiretroviral-experienced patients200

Some experts state concomitant use not recommended200

Manufacturer of maraviroc states pharmacokinetic interaction not clinically important;1 if used concomitantly in regimen that does not include a potent CYP3A inhibitor or inducer, recommended maraviroc dosage is 300 mg twice daily1

Rilpivirine

Clinically important pharmacokinetic interactions not expected226

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

St. John’s wort (Hypericum perforatum)

Potential decreased maraviroc concentrations and loss of virologic response1

Concomitant use not recommended1 200

Saquinavir

Ritonavir-boosted saquinavir: Increased maraviroc concentrations and AUC1

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

Saquinavir: No in vitro evidence of antagonistic antiretroviral effects 1

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

Simeprevir

Clinically important interactions not expected200

Experts state dosage adjustments not needed200

Sofosbuvir

Pharmacokinetic interaction not expected200

Experts state dosage adjustments not needed200

Sofosbuvir and velpatasvir

Fixed combination of sofosbuvir and velpatasvir (sofosbuvir/velpatasvir): Pharmacokinetic interaction not expected200

Experts state dosage adjustments not needed200

Sofosbuvir, velpatasvir, and voxilaprevir

Fixed combination of sofosbuvir, velpatasvir, and voxilaprevir (sofosbuvir/velpatasvir/voxilaprevir): Pharmacokinetic interaction not expected200

Experts state dosage adjustments not needed200

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

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

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

Adults with severe hepatic impairment: Not studied.1

Pediatric patients with hepatic impairment: Not studied.1

Adults with mild or moderate renal impairment: Pharmacokinetics similar to adults with normal renal function.1

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

Pediatric patients 2 to <18 years of age: Exposures in those receiving a potent CYP3A inhibitor (with or without a potent CYP3A inducer) and in those weighing >30 kg receiving drugs that are not CYP3A inhibitors or inducers are similar to exposures in adults.1

Pregnant women: Exposures 28–30% lower during third trimester compared with postpartum exposures.23

Distribution

Extent

Low concentrations cross placenta in humans.23

Distributed into milk in rats;1 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% of a dose eliminated in urine (8% as unchanged maraviroc) and 76% of a dose excreted in feces (25% as unchanged maraviroc).1

Hemodialysis has only minimal effect on maraviroc clearance in patients with ESRD.1

Half-life

14–18 hours.1 20

Special Populations

Severe hepatic impairment: Pharmacokinetics not studied.1

Stability

Storage

Oral

Solution

20–25°C (may be exposed to 15–30°C).1

Tablets, film-coated

20–25°C (may be exposed to 15–30°C).1

Actions and Spectrum

  • Active against HIV-1;1 may be active against some HIV-2 isolates.200

  • 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.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Maraviroc

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film-coated

25 mg

Selzentry

ViiV

75 mg

Selzentry

ViiV

150 mg

Selzentry

ViiV

300 mg

Selzentry

ViiV

Oral solution

100 mg/5 mL

Selzentry

ViiV

AHFS DI Essentials™. © Copyright 2018, Selected Revisions September 3, 2018. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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

References

1. ViiV Healthcare. Selzentry (maraviroc) tablets and oral solution prescribing information. Research Triangle Park, NC; 2016 Nov.

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. http://www.ncbi.nlm.nih.gov/pubmed/19432546?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/16251317?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=1280117&blobtype=pdf

7. Stephenson J. Researchers buoyed by novel HIV drugs: will expand drug arsenal against resistant virus. JAMA. 2007; 297:1535-6. http://www.ncbi.nlm.nih.gov/pubmed/17426263?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/16905787?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/20151839?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/18832244?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=3078519&blobtype=pdf

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. http://www.ncbi.nlm.nih.gov/pubmed/18333867?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=2311408&blobtype=pdf

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. http://www.ncbi.nlm.nih.gov/pubmed/18333863?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=2311406&blobtype=pdf

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. http://www.ncbi.nlm.nih.gov/pubmed/18333864?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=2311410&blobtype=pdf

23. Colbers A, Best B, Schalkwijk S et al. Maraviroc Pharmacokinetics in HIV-1-Infected Pregnant Women. Clin Infect Dis. 2015; 61:1582-9. http://www.ncbi.nlm.nih.gov/pubmed/26202768?dopt=AbstractPlus

24. Giaquinto C, Mawela MP, Chokephaibulkit K et al. Pharmacokinetics, Safety, and Efficacy of Maraviroc in Treatment-Experienced Pediatric Patients Infected With CCR5-Tropic HIV-1. Pediatr Infect Dis J. 2017; http://www.ncbi.nlm.nih.gov/pubmed/29023357?dopt=AbstractPlus

198. Centers for Disease Control and Prevention. Updated guidelines for antiretroviral postexposure prophylaxis after sexual, injection drug use, or other nonoccupational exposure to HIV – United States, 2016. From HHS AIDS Information (AIDSinfo) website. http://www.aidsinfo.nih.gov

199. Kuhar DT, Henderson DK, Struble KA et al. Updated US Public Health Service guidelines for the management of occupational exposures to human immunodeficiency virus and recommendations for postexposure prophylaxis. Infect Control Hosp Epidemiol. 2013; 34:875-92. http://www.ncbi.nlm.nih.gov/pubmed/23917901?dopt=AbstractPlus

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 (October 17, 2017). Updates may be available at HHS AIDS Information (AIDSinfo) website. http://www.aidsinfo.nih.gov

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 (April 27, 2017). Updates may be available at HHS AIDS Information (AIDSinfo) website. http://www.aidsinfo.nih.gov

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 (November 17, 2017). Updates may be available at HHS AIDS Information (AIDSinfo) website. http://www.aidsinfo.nih.gov

205. ViiV Healthcare. Lexiva (fosamprenavir calcium) tablets and oral suspension prescribing information. Research Triangle Park, NC; 2016 Sep.

214. Janssen Therapeutics. Intelence (etravirine) tablets prescribing information. Titusville, NJ; 2014 Aug.

226. Janssen Therapeutics. Edurant (rilpivirine) tablets prescribing information. Titusville, NJ; 2015 Aug.

236. ViiV Healthcare. Tivicay (dolutegravir) tablets prescribing information. Research Triangle Park, NC; 2017 Mar.

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