PDR MEMBER LOGIN:
  • PDR Search

    Required field
  • Advertisement
  • CLASSES

    HIV-1 Entry Inhibitors/Fusion Inhibitors

    BOXED WARNING

    Fever, hepatic disease, hepatitis, hepatitis B and HIV coinfection, hepatitis C and HIV coinfection, hepatotoxicity, serious rash

    Hepatotoxicity has been reported in patients receiving maraviroc, and evidence of a systemic allergic reaction (e.g., fever, serious rash, eosinophilia, or elevated IgE) prior to the development of hepatotoxicity may occur. These events have appeared approximately 1 month after starting therapy. However, cases of hepatitis have developed without allergic features and in patients without pre-existing hepatic impairment. Health care providers are advised to perform liver function tests before initiation therapy and at other points during treatment as clinically indicated. Instruct patients to discontinue maraviroc and seek immediate medical attention if signs or symptoms of hepatitis, allergic reaction, rash with fever, or other systemic symptoms develop; delaying treatment discontinuation may result in life-threatening reactions. Patients with moderate hepatic impairment who are receiving a concomitant potent CYP3A4 inhibitor should be monitored closely for adverse events as maraviroc concentrations are higher when 150 mg PO twice daily is administered with a potent CYP3A4 inhibitor as compared to 300 mg PO twice daily without a CYP3A4 inhibitor. Of note, maraviroc has not been studied in patients with severe hepatic disease, including patients coinfected with hepatitis and HIV; therefore, it is recommended to administer maraviroc cautiously to patients with pre-existing liver dysfunction. HIV treatment guidelines recommend all patients presenting with HIV infection undergo testing for hepatitis C, with continued annual screening advised for those persons considered high risk for acquiring hepatitis C. If hepatitis C and HIV coinfection is identified, consider treating both viral infections concurrently. For most patients, the benefits of concurrent therapy outweigh the potential risks (i.e., drug-induced hepatic injury, complex drug interactions, overlapping toxicities); therefore, it is recommended to initiate a fully suppressive antiretroviral (ARV) therapy and a hepatitis C regimen in all coinfected patients regardless of CD4 count. However, for antiretroviral naive patients with CD4 counts greater than 500 cells/mm3, consideration may be given to deferring ARV until the hepatitis C treatment regimen has been completed. Conversely, for patients with CD4 counts less than 200 cells/mm3, consider delaying initiation of the hepatitis C treatment regimen until the patient is stable on fully suppressive ARV regimen. Patients presenting with HIV infection should also be screened for hepatitis B virus (HBV) to assure appropriate treatment. Patients with hepatitis B and HIV coinfection should be started on a fully suppressive ARV regimen with activity against both viruses (regardless of CD4 counts and HBV DNA concentrations). HIV treatment guidelines recommend these patients receive an ARV regimen that contains a dual NRTI backbone of tenofovir alafenamide or tenofovir disoproxil fumarate with either emtricitabine or lamivudine. If tenofovir cannot be used, entecavir should be used in combination with a fully suppressive ARV regimen (note: entecavir should not be considered part of the ARV regimen). Avoid using single-drug therapy to treat HBV (i.e., lamivudine, emtricitabine, tenofovir, or entecavir as the only active agent) as this may result in HIV resistant strains. Further, HBV treatment regimens that include adefovir or telbivudine should also be avoided, as these regimens are associated with a higher incidence of toxicities and increased rates of HBV treatment failure. Most coinfected patients should continue treatment indefinitely with the goal of maximal HIV suppression and prevention of HBV relapse. If treatment must be discontinued, monitor transaminase concentrations every 6 weeks for the first 3 months, and every 3 to 6 months thereafter. For patients who refuse a fully suppressive ARV regimen, but still requires treatment for HBV, consider 48 weeks of peginterferon alfa; do not administer HIV-active medications in the absence of a fully suppressive ARV regimen. Instruct coinfected patients to avoid consuming alcohol, and offer vaccinations against hepatitis A and hepatitis B as appropriate. [46638] [33473] [34362]

    DEA CLASS

    Rx

    DESCRIPTION

    Entry inhibitor
    Used for treatment of CCR5-tropic human immunodeficiency virus (HIV) infection in combination with other antiretroviral agents
    Tropism assay of the HIV strain required prior to treatment

    COMMON BRAND NAMES

    Selzentry

    HOW SUPPLIED

    Maraviroc/Selzentry Oral Sol: 1mL, 20mg
    Maraviroc/Selzentry Oral Tab: 25mg, 75mg, 150mg, 300mg

    DOSAGE & INDICATIONS

    For the treatment of CCR5-tropic human immunodeficiency virus (HIV) infection in combination with other antiretroviral agents.
    Oral dosage (tablets)
    Adults taking a medication regimen that does not include any potent CYP3A inducers or inhibitors

    300 mg PO twice daily. NOTE: Concomitant drugs that do not require a dosage change include dolutegravir, enfuvirtide, nevirapine, all nucleoside reverse transcriptase inhibitors (NRTIs), raltegravir, and tipranavir with ritonavir.

    Adults receiving concomitant potent CYP3A inhibitors (with or without a potent CYP3A inducer)

    150 mg PO twice daily. NOTE: Drug interaction examples include clarithromycin, cobicistat, elvitegravir with ritonavir, itraconazole, ketoconazole, nefazodone, protease inhibitors (except tipranavir with ritonavir), and telithromycin.

    Adults receiving concomitant potent or moderate CYP3A inducers (without a potent CYP3A inhibitor)

    600 mg PO twice daily. NOTE: Drug interaction examples include carbamazepine, efavirenz, etravirine, phenobarbital, phenytoin, and rifampin.

    Children and Adolescents weighing 30 kg or more taking a medication regimen that does not include any potent CYP3A inducers or inhibitors

    300 mg PO twice daily. NOTE: Concomitant drugs that do not require a dosage change include dolutegravir, enfuvirtide, nevirapine, all nucleoside reverse transcriptase inhibitors (NRTIs), raltegravir, and tipranavir with ritonavir.

    Children 2 to 12 years weighing 14 to 29 kg taking a medication regimen that does not include any potent CYP3A inducers or inhibitors

    200 mg PO twice daily. NOTE: Concomitant drugs that do not require a dosage change include dolutegravir, enfuvirtide, nevirapine, all nucleoside reverse transcriptase inhibitors (NRTIs), raltegravir, and tipranavir with ritonavir.

    Children 2 to 12 years weighing 10 to 13 kg taking a medication regimen that does not include any potent CYP3A inducers or inhibitors

    150 mg PO twice daily. NOTE: Concomitant drugs that do not require a dosage change include dolutegravir, enfuvirtide, nevirapine, all nucleoside reverse transcriptase inhibitors (NRTIs), raltegravir, and tipranavir with ritonavir.

    Children and Adolescents weighing 40 kg or more receiving concomitant potent CYP3A inhibitors (with or without a potent CYP3A inducer)

    150 mg PO twice daily. NOTE: Drug interaction examples include clarithromycin, cobicistat, elvitegravir with ritonavir, itraconazole, ketoconazole, nefazodone, protease inhibitors (except tipranavir with ritonavir), and telithromycin.

    Children and Adolescents weighing 30 to 39 kg receiving concomitant potent CYP3A inhibitors (with or without a potent CYP3A inducer)

    100 mg PO twice daily. NOTE: Drug interaction examples include clarithromycin, cobicistat, elvitegravir with ritonavir, itraconazole, ketoconazole, nefazodone, protease inhibitors (except tipranavir with ritonavir), and telithromycin.

    Children 2 to 12 years weighing 20 to 29 kg receiving concomitant potent CYP3A inhibitors (with or without a potent CYP3A inducer)

    75 mg PO twice daily. NOTE: Drug interaction examples include clarithromycin, cobicistat, elvitegravir with ritonavir, itraconazole, ketoconazole, nefazodone, protease inhibitors (except tipranavir with ritonavir), and telithromycin.

    Children 2 to 12 years weighing 10 to 19 kg receiving concomitant potent CYP3A inhibitors (with or without a potent CYP3A inducer)

    50 mg PO twice daily. NOTE: Drug interaction examples include clarithromycin, cobicistat, elvitegravir with ritonavir, itraconazole, ketoconazole, nefazodone, protease inhibitors (except tipranavir with ritonavir), and telithromycin.

    Children and Adolescents 2 to 17 years receiving concomitant potent or moderate CYP3A inducers (without a potent CYP3A inhibitor)

    Use not recommended. NOTE: Drug interaction examples include carbamazepine, efavirenz, etravirine, phenobarbital, phenytoin, and rifampin.

    Oral dosage (solution)
    Adults taking a medication regimen that does not include any potent CYP3A inducers or inhibitors

    300 mg PO twice daily. NOTE: Concomitant drugs that do not require a dosage change include dolutegravir, enfuvirtide, nevirapine, all nucleoside reverse transcriptase inhibitors (NRTIs), raltegravir, and tipranavir with ritonavir.

    Adults receiving concomitant potent CYP3A inhibitors (with or without a potent CYP3A inducer)

    150 mg PO twice daily. NOTE: Drug interaction examples include clarithromycin, cobicistat, elvitegravir with ritonavir, itraconazole, ketoconazole, nefazodone, protease inhibitors (except tipranavir with ritonavir), and telithromycin.

    Adults receiving concomitant potent or moderate CYP3A inducers (without a potent CYP3A inhibitor)

    600 mg PO twice daily. NOTE: Drug interaction examples include carbamazepine, efavirenz, etravirine, phenobarbital, phenytoin, and rifampin.

    Children and Adolescents weighing 30 kg or more taking a medication regimen that does not include any potent CYP3A inducers or inhibitors

    300 mg PO twice daily. NOTE: Concomitant drugs that do not require a dosage change include dolutegravir, enfuvirtide, nevirapine, all nucleoside reverse transcriptase inhibitors (NRTIs), raltegravir, and tipranavir with ritonavir.

    Children weighing 14 to 29 kg taking a medication regimen that does not include any potent CYP3A inducers or inhibitors

    200 mg PO twice daily. NOTE: Concomitant drugs that do not require a dosage change include dolutegravir, enfuvirtide, nevirapine, all nucleoside reverse transcriptase inhibitors (NRTIs), raltegravir, and tipranavir with ritonavir.

    Children weighing 10 to 13 kg taking a medication regimen that does not include any potent CYP3A inducers or inhibitors

    150 mg PO twice daily. NOTE: Concomitant drugs that do not require a dosage change include dolutegravir, enfuvirtide, nevirapine, all nucleoside reverse transcriptase inhibitors (NRTIs), raltegravir, and tipranavir with ritonavir.

    Infants and Children weighing 6 to 9 kg taking a medication regimen that does not include any potent CYP3A inducers or inhibitors

    100 mg PO twice daily. NOTE: Concomitant drugs that do not require a dosage change include dolutegravir, enfuvirtide, nevirapine, all nucleoside reverse transcriptase inhibitors (NRTIs), raltegravir, and tipranavir with ritonavir.

    Neonates and Infants weighing 4 to 5 kg taking a medication regimen that does not include any potent CYP3A inducers or inhibitors

    40 mg PO twice daily. NOTE: Concomitant drugs that do not require a dosage change include dolutegravir, enfuvirtide, nevirapine, all nucleoside reverse transcriptase inhibitors (NRTIs), raltegravir, and tipranavir with ritonavir.

    Neonates and Infants weighing 2 to 3 kg taking a medication regimen that does not include any potent CYP3A inducers or inhibitors

    30 mg PO twice daily. NOTE: Concomitant drugs that do not require a dosage change include dolutegravir, enfuvirtide, nevirapine, all nucleoside reverse transcriptase inhibitors (NRTIs), raltegravir, and tipranavir with ritonavir.

    Children and Adolescents weighing 40 kg or more receiving concomitant potent CYP3A inhibitors (with or without a potent CYP3A inducer)

    150 mg PO twice daily. NOTE: Drug interaction examples include clarithromycin, cobicistat, elvitegravir with ritonavir, itraconazole, ketoconazole, nefazodone, protease inhibitors (except tipranavir with ritonavir), and telithromycin.

    Children and Adolescents weighing 30 to 39 kg receiving concomitant potent CYP3A inhibitors (with or without a potent CYP3A inducer)

    100 mg PO twice daily. NOTE: Drug interaction examples include clarithromycin, cobicistat, elvitegravir with ritonavir, itraconazole, ketoconazole, nefazodone, protease inhibitors (except tipranavir with ritonavir), and telithromycin.

    Children weighing 20 to 29 kg receiving concomitant potent CYP3A inhibitors (with or without a potent CYP3A inducer)

    80 mg PO twice daily. NOTE: Drug interaction examples include clarithromycin, cobicistat, elvitegravir with ritonavir, itraconazole, ketoconazole, nefazodone, protease inhibitors (except tipranavir with ritonavir), and telithromycin.

    Children weighing 10 to 19 kg receiving concomitant potent CYP3A inhibitors (with or without a potent CYP3A inducer)

    50 mg PO twice daily. NOTE: Drug interaction examples include clarithromycin, cobicistat, elvitegravir with ritonavir, itraconazole, ketoconazole, nefazodone, protease inhibitors (except tipranavir with ritonavir), and telithromycin.

    Neonates, Infants, and Children weighing 2 to 9 kg receiving concomitant potent CYP3A inhibitors (with or without a potent CYP3A inducer)

    Use not recommended. NOTE: Drug interaction examples include clarithromycin, cobicistat, elvitegravir with ritonavir, itraconazole, ketoconazole, nefazodone, protease inhibitors (except tipranavir with ritonavir), and telithromycin.

    Neonates, Infants, Children, and Adolescents receiving concomitant potent or moderate CYP3A inducers (without a potent CYP3A inhibitor)

    Use not recommended. NOTE: Drug interaction examples include carbamazepine, efavirenz, etravirine, phenobarbital, phenytoin, and rifampin.

    For human immunodeficiency virus (HIV) prophylaxis† after occupational HIV exposure.
    Oral dosage
    Adults without concomitant CYP3A4 inducers or inhibitors

    The US Public Health Service guidelines suggest maraviroc 300 mg PO twice daily in combination with one of the following backbones (in order of preference) as acceptable alternative regimens for HIV post-exposure prophylaxis (PEP): tenofovir plus emtricitabine; tenofovir plus lamivudine; zidovudine plus lamivudine; zidovudine plus emtricitabine. Prior to administering a maraviroc containing regimen, the US Public Health Service and the New York State Department of Health AIDS Institute (NYSDOH AI) recommend consultation with a clinician experienced in the management of PEP. This recommendation is due to the drugs lack of activity against potential CXCR4 tropic virus. According to PEP guidelines, individuals potentially exposed to HIV should receive a 3-drug regimen for a total of 28 days; however if tolerability is a concern, use of a 2-drug regimen may be considered and is preferred to prophylaxis discontinuation. Begin prophylaxis as soon as possible, ideally within 2 hours of exposure. If initiation of prophylaxis is delayed (beyond 36 hours or 72 hours after exposure), efficacy of the antiretroviral regimen may be diminished and treatment should be determined on a case-by-case basis. Exposures for which PEP is indicated include: skin puncture by a sharp object that has been contaminated with blood, body fluid, or other infectious material; bite from a patient with visible bleeding in the mouth which causes bleeding by the exposed worker; splash of blood, body fluid, or other infectious material onto the workers mouth, nose, or eyes; exposure of blood, body fluid, or other infectious material on a workers non-intact skin (i.e., open wound, chapped skin, abrasion, dermatitis).

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    600 mg/day PO; 1,200 mg/day PO if taking a potent or moderate CYP3A inducer; 300 mg/day PO if taking a potent CYP3A inhibitor.

    Geriatric

    600 mg/day PO; 1,200 mg/day PO if taking a potent or moderate CYP3A inducer; 300 mg/day PO if taking a potent CYP3A inhibitor.

    Adolescents

    weighing 40 kg or more: 600 mg/day PO; 300 mg/day PO if taking a potent CYP3A inhibitor; use not recommended with potent or moderate CYP3A inducers.
    weighing 30 to 39 kg: 600 mg/day PO; 200 mg/day PO if taking a potent CYP3A inhibitor; use not recommended with potent or moderate CYP3A inducers.

    Children

    weighing 40 kg or more: 600 mg/day PO; 300 mg/day PO if taking a potent CYP3A inhibitor; use not recommended with potent or moderate CYP3A inducers.
    weighing 30 to 39 kg: 600 mg/day PO; 200 mg/day PO if taking a potent CYP3A inhibitor; use not recommended with potent or moderate CYP3A inducers.
    weighing 20 to 29 kg: 400 mg/day PO; 150 mg/day PO for tablets and 160 mg/day PO for solution if taking a potent CYP3A inhibitor; use not recommended with potent or moderate CYP3A inducers.
    weighing 14 to 19 kg: 400 mg/day PO; 100 mg/day PO if taking a potent CYP3A inhibitor; use not recommended with potent or moderate CYP3A inducers.
    weighing 10 to 13 kg: 300 mg/day PO; 100 mg/day PO if taking a potent CYP3A inhibitor; use not recommended with potent or moderate CYP3A inducers.
    weighing 6 to 9 kg: 200 mg/day PO for solution; use not recommended with potent or moderate CYP3A inducers or potent CYP3A inhibitors.

    Infants

    weighing 6 to 9 kg: 200 mg/day PO for solution; use not recommended with potent or moderate CYP3A inducers or potent CYP3A inhibitors.
    weighing 4 to 5 kg: 80 mg/day for solution; use not recommended with potent or moderate CYP3A inducers or potent CYP3A inhibitors.
    weighing 2 to 3 kg: 60 mg/day for solution; use not recommended with potent or moderate CYP3A inducers or potent CYP3A inhibitors.

    Neonates

    weighing 4 to 5 kg: 80 mg/day for solution; use not recommended with potent or moderate CYP3A inducers or potent CYP3A inhibitors.
    weighing 2 to 3 kg: 60 mg/day for solution; use not recommended with potent or moderate CYP3A inducers or potent CYP3A inhibitors.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Specific guidelines for dosage adjustments in hepatic impairment are not available; however, because maraviroc is metabolized by the liver, concentrations are likely to be increased in such patients; use with caution and monitor patients frequently. In adult patients, maraviroc concentrations are higher when the 150 mg PO twice daily dose is administered with a potent CYP3A4 inhibitor as compared to the administration of the 300 mg PO twice daily dose without a CYP3A4 inhibitor; closely monitor patients with moderate hepatic impairment also receiving a concomitant potent CYP3A4 inhibitor for adverse events. Maraviroc has not been studied in patients with severe hepatic impairment or pediatric patients with any degree of hepatic impairment.

    Renal Impairment

    Adult patients
    In combination with strong CYP3A inhibitors with or without a CYP3A inducer:
    CrCl 30 mL/minute or more: No dosage adjustment needed; 150 mg PO twice daily.
    CrCl less than 30 mL/minute: Use is contraindicated.
    In combination with strong CYP3A inducers without a strong CYP3A inhibitor:
    CrCl 30 mL/minute or more: No dosage adjustment needed; 600 mg PO twice daily.
    CrCl less than 30 mL/minute: Use is contraindicated.
    For patients taking a medication regimen that does NOT include any strong CYP3A inducers or inhibitors:
    CrCl 30 mL/minute or more: No dosage adjustment needed; 300 mg PO twice daily.
    CrCl less than 30 mL/minute: No dosage adjustment is needed; however, in patients with symptoms of postural hypotension, reduce the dose to 150 mg PO twice daily.
     
    Pediatric patients
    Data are unavailable to recommend specific doses of maraviroc in pediatric patients with mild or moderate renal impairment. Maraviroc is contraindicated in pediatric patients with severe renal impairment or end-stage renal disease on regular hemodialysis who are receiving potent CYP3A inhibitors or inducers.
     
    Hemodialysis
    For adult patients taking a medication regimen that does NOT include any CYP3A inducers or inhibitors, normal doses of 300 mg PO twice daily should be used; however, in patients with any symptoms of postural hypotension, reduce the dose to 150 mg PO twice daily. Data are not available and use is contraindicated in patients taking concomitant CYP3A4 inducers or inhibitors.

    ADMINISTRATION

    Oral Administration

    May be administered without regard to meals.

    Oral Solid Formulations

    Swallow tablets whole. Do not chew.

    Oral Liquid Formulations

    Administer oral solution using the manufacturer provided press-in bottle adapter and oral dosing syringe.

    STORAGE

    Selzentry:
    - See package insert for detailed storage information
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Unplanned antiretroviral therapy interruption may be necessary for specific situations, such as serious drug toxicity, intercurrent illness or surgery precluding oral intake (e.g., gastroenteritis or pancreatitis), severe hyperemesis gravidarum unresponsive to antiemetics, or drug non-availability. If short-term treatment interruption (i.e., less than 1 to 2 days) is necessary, in general, it is recommended that all antiretroviral agents be discontinued simultaneously, especially if the interruption occurs in a pregnant patient or is because of a serious toxicity. However, if a short-term treatment interruption is anticipated in the case of elective surgery, the pharmacokinetic properties and food requirements of specific drugs should be considered; as stopping all simultaneously in a regimen containing drugs with differing half-lives may result in functional monotherapy of the drug with the longest half-life and may increase the risk for resistant mutations. Health care providers are advised to reinitiate a complete and effective antiretroviral regimen as soon as possible after an interruption of therapy. Planned long-term treatment interruptions are not recommended due to the potential for HIV disease progression (i.e., declining CD4 counts, viral rebound, acute viral syndrome), development of minor HIV-associated manifestations or serious non-AIDS complications, development of drug resistance, increased risk of HIV transmission, and increased risk for opportunistic infections. If therapy must be discontinued, counsel patient on the potential risks and closely monitor for any clinical or laboratory abnormalities. [46638] [42452]

    Infection

    Because maraviroc antagonizes the CCR5 co-receptor located on some immune cells it could potentially increase the risk of developing infection. During Phase 3 clinical trials of treatment-experienced adult patients, the overall incidence and severity of infection, including AIDS-defining infections, was comparable in the treatment groups. There was a higher reported rate of certain upper respiratory tract infections in the maraviroc arm compared to placebo (23% versus 13%), but there was a lower rate of pneumonia (2 % vs 5%) reported in the maraviroc arm. A higher incidence of Herpes virus infections (11 per 100 patient-years) was reported in the maraviroc arm when adjusted for exposure compared to placebo (8 per 100 patient-years). In Phase 2b/3 trials of treatment-naive adult patients, the incidence of infection was similar to comparator. Patients should be monitored closely for evidence of infections while receiving maraviroc.

    Fever, hepatic disease, hepatitis, hepatitis B and HIV coinfection, hepatitis C and HIV coinfection, hepatotoxicity, serious rash

    Hepatotoxicity has been reported in patients receiving maraviroc, and evidence of a systemic allergic reaction (e.g., fever, serious rash, eosinophilia, or elevated IgE) prior to the development of hepatotoxicity may occur. These events have appeared approximately 1 month after starting therapy. However, cases of hepatitis have developed without allergic features and in patients without pre-existing hepatic impairment. Health care providers are advised to perform liver function tests before initiation therapy and at other points during treatment as clinically indicated. Instruct patients to discontinue maraviroc and seek immediate medical attention if signs or symptoms of hepatitis, allergic reaction, rash with fever, or other systemic symptoms develop; delaying treatment discontinuation may result in life-threatening reactions. Patients with moderate hepatic impairment who are receiving a concomitant potent CYP3A4 inhibitor should be monitored closely for adverse events as maraviroc concentrations are higher when 150 mg PO twice daily is administered with a potent CYP3A4 inhibitor as compared to 300 mg PO twice daily without a CYP3A4 inhibitor. Of note, maraviroc has not been studied in patients with severe hepatic disease, including patients coinfected with hepatitis and HIV; therefore, it is recommended to administer maraviroc cautiously to patients with pre-existing liver dysfunction. HIV treatment guidelines recommend all patients presenting with HIV infection undergo testing for hepatitis C, with continued annual screening advised for those persons considered high risk for acquiring hepatitis C. If hepatitis C and HIV coinfection is identified, consider treating both viral infections concurrently. For most patients, the benefits of concurrent therapy outweigh the potential risks (i.e., drug-induced hepatic injury, complex drug interactions, overlapping toxicities); therefore, it is recommended to initiate a fully suppressive antiretroviral (ARV) therapy and a hepatitis C regimen in all coinfected patients regardless of CD4 count. However, for antiretroviral naive patients with CD4 counts greater than 500 cells/mm3, consideration may be given to deferring ARV until the hepatitis C treatment regimen has been completed. Conversely, for patients with CD4 counts less than 200 cells/mm3, consider delaying initiation of the hepatitis C treatment regimen until the patient is stable on fully suppressive ARV regimen. Patients presenting with HIV infection should also be screened for hepatitis B virus (HBV) to assure appropriate treatment. Patients with hepatitis B and HIV coinfection should be started on a fully suppressive ARV regimen with activity against both viruses (regardless of CD4 counts and HBV DNA concentrations). HIV treatment guidelines recommend these patients receive an ARV regimen that contains a dual NRTI backbone of tenofovir alafenamide or tenofovir disoproxil fumarate with either emtricitabine or lamivudine. If tenofovir cannot be used, entecavir should be used in combination with a fully suppressive ARV regimen (note: entecavir should not be considered part of the ARV regimen). Avoid using single-drug therapy to treat HBV (i.e., lamivudine, emtricitabine, tenofovir, or entecavir as the only active agent) as this may result in HIV resistant strains. Further, HBV treatment regimens that include adefovir or telbivudine should also be avoided, as these regimens are associated with a higher incidence of toxicities and increased rates of HBV treatment failure. Most coinfected patients should continue treatment indefinitely with the goal of maximal HIV suppression and prevention of HBV relapse. If treatment must be discontinued, monitor transaminase concentrations every 6 weeks for the first 3 months, and every 3 to 6 months thereafter. For patients who refuse a fully suppressive ARV regimen, but still requires treatment for HBV, consider 48 weeks of peginterferon alfa; do not administer HIV-active medications in the absence of a fully suppressive ARV regimen. Instruct coinfected patients to avoid consuming alcohol, and offer vaccinations against hepatitis A and hepatitis B as appropriate. [46638] [33473] [34362]

    Cardiac disease, myocardial infarction

    Use maraviroc cautiously in patients who are at increased risk for cardiovascular events, such as those with preexisting cardiac disease. In Phase 3 clinical trials of treatment-experienced adult patients, 11 patients (1.3%) who received maraviroc experienced a cardiovascular event including myocardial infarction and/or ischemia (total exposure 609 patient-years); no events were reported in patients who received placebo (total exposure 111 patient-years). The patients who experienced a cardiac event generally had cardiac disease or cardiac risk factors prior to maraviroc use, and the relative contribution of the drug to the events is not known. In Phase 2b/3 trials of treatment-naive adult patients, 3 patients (0.8%) who received maraviroc experienced events related to ischemic heart disease (total exposure 506 patient-years).

    Orthostatic hypotension

    Administer maraviroc cautiously to patients with a history of or risk factors for postural hypotension, or who are receiving treatment with a medication known to lower blood pressure. During clinical trials, when maraviroc was administered to healthy adult volunteers at doses higher than the recommended dose, symptomatic postural hypotension (orthostatic hypotension) was observed at a greater frequency than in the placebo group. However, during Phase 3 trials, postural hypotension was seen at a rate similar to placebo (approximately 0.5%) when maraviroc was given at recommended doses to adults with HIV. An increased risk of postural hypertension may occur in patients with severe renal insufficiency or in those with end-stage disease due to increased maraviroc exposure.

    Dialysis, renal failure, renal impairment

    Maraviroc is contraindicated in patients who are taking concomitant potent CYP3A4 inhibitors or inducers and have severe renal impairment (CrCl less than 30 mL/minute), end-stage renal disease (renal failure), or are on regular dialysis (hemodialysis). No studies have been performed in these patients. If no other HIV treatment options are available in patients taking a CYP3A4 inhibitor or inducer, maraviroc can be considered, although no dosing recommendations are available from the manufacturer. For adult patients with renal impairment taking a medication regimen that does NOT include any CYP3A inducers or inhibitors, normal doses should be used based on a pharmacokinetic study in healthy subjects with varying degrees of renal function. However, in adult patients taking normal doses who have renal impairment and experience any symptoms of postural hypotension, a reduced dose may be necessary. Patients with impaired renal function may have cardiovascular co-morbidities and could be at risk of cardiovascular events triggered by postural hypotension. An increased risk of postural hypertension may occur in patients with severe renal insufficiency or in those with end-stage renal disease due to increased maraviroc exposure. There are no data available to recommend dosing adjustments in pediatric patients with mild or moderate renal impairment.

    Children, infants, neonates

    Maraviroc is not recommended for use in preterm neonates or pediatric patients weighing less than 2 kg. In addition, there are insufficient data to make dosing recommendations in pediatric patients weighing less than 10 kg who are receiving concurrent treatment with a potent CYP3A4 inhibitor, or in any pediatric patient (neonates, infants, children, or adolescents) concurrently receiving a potent or moderate CYP3A4 inducer (without a potent CYP3A4 inhibitor).

    Geriatric

    Clinical studies of maraviroc did not include sufficient numbers of patients aged 65 years or over to determine whether they respond differently from younger patients. In general, dose selection for a geriatric patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy.

    Autoimmune disease, Graves' disease, Guillain-Barre syndrome, immune reconstitution syndrome

    Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy. During the initial phase of HIV treatment, patients whose immune system responds to antiretroviral therapy may develop an inflammatory response to indolent or residual opportunistic infections (such as progressive multifocal leukoencephalopathy (PML), mycobacterium avium complex (MAC), cytomegalovirus (CMV), Pneumocystis pneumonia (PCP), tuberculosis (TB), herpes simplex or herpes zoster), which may necessitate further evaluation and treatment. In addition, autoimmune disease (including Graves' disease, Guillain-Barre syndrome, and polymyositis) may also develop; the time to onset is variable and may occur months after treatment initiation.

    Human immunodeficiency virus (HIV) infection resistance

    Testing for human immunodeficiency virus (HIV) infection resistance is recommended in all antiretroviral treatment-naive patients at the time of HIV diagnosis, regardless of whether treatment will be initiated. Additionally, perform resistance testing prior to initiating or changing any HIV treatment regimen. Transmission of drug-resistant HIV strains has been both well documented and associated with suboptimal virologic response to initial antiretroviral therapy. In high-income countries (e.g., US, some European countries, Australia, Japan), approximately 10% to 17% of treatment-naive individuals have resistance mutations to at least 1 antiretroviral drug; up to 8% (but generally less than 5%) of transmitted viruses will exhibit resistance to drugs from more than 1 class. Therefore, resistance testing at baseline can help optimize treatment and, thus, virologic response. In the absence of therapy, resistant viruses may decline over time to less than the detection limit of standard resistance tests, but may still increase the risk of treatment failure when therapy is eventually initiated. Thus, if therapy is deferred, resistance testing should still be performed during acute HIV infection with the genotypic resistance test result kept in the patient's medical record until it becomes clinically useful. Additionally, because of the possibility of acquisition of another drug-resistant virus before treatment initiation, repeat resistance testing at the time therapy is initiated would be prudent.

    Pregnancy

    Antiretroviral therapy should be provided to all women during pregnancy, regardless of HIV RNA concentrations or CD4 cell count. Using highly active antiretroviral combination therapy (HAART) to maximally suppress viral replication is the most effective strategy to prevent the development of resistance and to minimize the risk of perinatal transmission. In treatment-naive women, begin HAART as soon as pregnancy is recognized or HIV is diagnosed, without waiting for the results of resistance testing; subsequent modifications to the treatment regimen should be made once the test results are available. Women who are currently receiving antiretroviral treatment when pregnancy is recognized should continue their treatment regimen if it is currently effective in suppressing viral replication; consider resistance testing if HIV RNA concentrations are more than 500 copies/mL. For women not currently receiving HAART, but who have previously received treatment, obtain a complete and accurate history of all prior antiretroviral regimens used and results of prior resistance testing, and perform resistance testing if HIV RNA concentrations are greater than 500 copies/mL; treatment should be initiated prior to receiving resistance test results. Data regarding administration of maraviroc during pregnancy are too limited to rule out any potential association with birth defects (i.e., 30 first trimester exposures); therefore, maraviroc-containing regimens should not be initiated in pregnant women. However, it may be appropriate to continue use of the drug in some virally suppressed pregnant women. Regular laboratory monitoring is recommended to determine antiretroviral efficacy. Monitor CD4 counts at the initial visit. Women who have been on HAART for at least 2 years and have consistent viral suppression and CD4 counts consistently greater than 300 cells/mm3 do not need CD4 counts monitored after the initial visit during the pregnancy. However, CD4 counts should be monitored every 3 months during pregnancy for women on HAART less than 2 years, women with CD4 count less than 300 cells/mm3, or women with inconsistent adherence or detectable viral loads. Monitor plasma HIV RNA at the initial visit, 2 to 4 weeks after initiating or changing therapy, monthly until undetectable, then at least every 3 months during pregnancy, and at 34 to 36 weeks gestation. Perform antiretroviral resistance assay (genotypic testing, and if indicated, phenotypic testing) at baseline in all women with HIV RNA concentrations greater than 500 copies/mL, unless they have already been tested for resistance. First trimester ultrasound is recommended to confirm gestational age and provide an accurate estimation of gestational age at delivery. A second trimester ultrasound can be used for both anatomical survey and determination of gestational age in those patients not seen until later in gestation. Perform standard glucose screening in women receiving antiretroviral therapy at 24 to 28 weeks gestation, although it should be noted that some experts would perform earlier screening with ongoing chronic protease inhibitor-based therapy initiated prior to pregnancy, similar to recommendations for women with high-risk factors for glucose intolerance. Liver function testing is recommended within 2 to 4 weeks after initiating or changing antiretroviral therapy, and approximately every 3 months thereafter during pregnancy (or as needed). All pregnant women should be counseled about the importance of adherence to their antiretroviral regimen to reduce the potential for development of resistance and perinatal transmission. It is strongly recommended that antiretroviral therapy, once initiated, not be discontinued. If a woman decides to discontinue therapy, a consultation with an HIV specialist is recommended. There is a pregnancy exposure registry that monitors outcomes in pregnant patients exposed to maraviroc; information about the registry can be obtained at www.apregistry.com or by calling 1-800-258-4263.[27468] [23512] [33473]

    Breast-feeding

    To reduce the risk of postnatal transmission, mothers with HIV within the United States are advised by the Centers for Disease Control and Prevention to avoid breast-feeding. This recommendation applies to both untreated women and women who are receiving antiretroviral therapy. If a mother with HIV opts to breast-feed, the infant should undergo immediate diagnostic and virologic HIV testing. Testing should continue throughout breast-feeding and up to 6 months after cessation of breast-feeding. For expert consultation, health care workers may contact the Perinatal HIV Hotline (888-448-8765).[42452] There are limited data regarding maraviroc use during breast-feeding, and excretion into human breast milk is unknown. Antiretroviral medications whose passage into human breast milk have been evaluated include nevirapine, zidovudine, lamivudine, and nelfinavir.[33473] [46675] [46679] [46680] [46682]

    Asian patients

    Population pharmacokinetic analysis of pooled Phase 1/2a data indicated exposure was 26.5% higher in Asian patients (n = 95) as compared to non-Asian patients (n = 318). However, a study designed to evaluate pharmacokinetic differences between White patients (n = 12) and Singaporeans (n = 12) showed no difference between these two populations. At this point, no dosage adjustment based on race is indicated.

    ADVERSE REACTIONS

    Severe

    new primary malignancy / Delayed / 0-3.0
    thrombosis / Delayed / 0-2.0
    cirrhosis / Delayed / 0-2.0
    hepatic failure / Delayed / 0-2.0
    heart failure / Delayed / 0-2.0
    visual impairment / Early / 0-2.0
    seizures / Delayed / 0-2.0
    stroke / Early / 0-2.0
    rhabdomyolysis / Delayed / 0-2.0
    osteonecrosis / Delayed / 0-2.0
    myocardial infarction / Delayed / 0.8-1.3
    Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) / Delayed / Incidence not known
    hepatotoxicity / Delayed / Incidence not known
    toxic epidermal necrolysis / Delayed / Incidence not known
    Stevens-Johnson syndrome / Delayed / Incidence not known

    Moderate

    anemia / Delayed / 0-8.0
    constipation / Delayed / 6.0-6.0
    hyperamylasemia / Delayed / 4.3-5.7
    neutropenia / Delayed / 4.3-5.7
    hyperbilirubinemia / Delayed / 5.5-5.5
    elevated hepatic enzymes / Delayed / 2.6-4.8
    depression / Delayed / 4.0-4.0
    peripheral neuropathy / Delayed / 4.0-4.0
    dyspnea / Early / 4.0-4.0
    lipodystrophy / Delayed / 3.0-4.0
    hypertension / Early / 3.0-3.0
    memory impairment / Delayed / 3.0-3.0
    ejaculation dysfunction / Delayed / 3.0-3.0
    jaundice / Delayed / 0-2.0
    angina / Early / 0-2.0
    meningitis / Delayed / 0-2.0
    pseudomembranous colitis / Delayed / 0-2.0
    erythema / Early / 2.0-2.0
    conjunctivitis / Delayed / 2.0-2.0
    ocular infection / Delayed / 2.0-2.0
    orthostatic hypotension / Delayed / 0.5-0.5
    hepatitis / Delayed / Incidence not known
    eosinophilia / Delayed / Incidence not known
    candidiasis / Delayed / Incidence not known
    edema / Delayed / Incidence not known

    Mild

    infection / Delayed / 55.0-55.0
    cough / Delayed / 14.0-14.0
    fever / Early / 13.0-13.0
    vomiting / Early / 12.0-12.0
    rash / Early / 11.0-11.0
    flatulence / Early / 10.0-10.0
    dizziness / Early / 3.0-9.0
    insomnia / Early / 8.0-8.0
    sinusitis / Delayed / 7.0-7.0
    arthralgia / Delayed / 6.0-7.0
    paresthesias / Delayed / 4.0-5.0
    dysesthesia / Delayed / 4.0-5.0
    anxiety / Delayed / 4.0-4.0
    nasal congestion / Early / 4.0-4.0
    folliculitis / Delayed / 4.0-4.0
    diarrhea / Early / 4.0-4.0
    nausea / Early / 4.0-4.0
    abdominal pain / Early / 4.0-4.0
    pruritus / Rapid / 4.0-4.0
    myalgia / Early / 3.0-3.0
    acne vulgaris / Delayed / 3.0-3.0
    tremor / Early / 0-2.0
    influenza / Delayed / 2.0-2.0
    alopecia / Delayed / 2.0-2.0
    syncope / Early / Incidence not known
    rhinitis / Early / Incidence not known
    gynecomastia / Delayed / Incidence not known
    Cushingoid features / Delayed / Incidence not known

    DRUG INTERACTIONS

    Abrocitinib: (Moderate) Monitor for an increase in maraviroc-related adverse reactions if coadministration with abrocitinib is necessary. Concomitant use may increase maraviroc exposure. Maraviroc is a P-gp substrate; abrocitinib is a P-gp inhibitor.
    Acetaminophen; Propoxyphene: (Moderate) Use caution if coadministration of maraviroc with propoxyphene is necessary, due to a possible increase in maraviroc exposure. Maraviroc is a CYP3A substrate and propoxyphene is a CYP3A4 inhibitor. Monitor for an increase in adverse effects.
    Adefovir: (Moderate) Use caution and closely monitor for increased adverse effects during concurrent administration of maraviroc and adefovir as increased maraviroc concentrations may occur. Maraviroc is a substrate of multidrug resistance-associated protein (MRP2); adefovir is an inhibitor of MRP2. The effects of this transporter on the concentrations of maraviroc are unknown, although an increase in concentrations and thus, toxicity, are possible.
    Aldesleukin, IL-2: (Minor) Use caution if coadministration of maraviroc with aldesleukin is necessary, due to a possible increase in maraviroc exposure. Maraviroc is a CYP3A substrate and aldesleukin is a weak CYP3A4 inhibitor. Monitor for an increase in adverse effects with concomitant use
    Aliskiren; Amlodipine: (Minor) Use caution if coadministration of maraviroc with amlodipine is necessary, due to a possible increase in maraviroc exposure. Maraviroc is a CYP3A substrate and amlodipine is a weak CYP3A4 inhibitor. Monitor for an increase in adverse effects with concomitant use.
    Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (Minor) Use caution if coadministration of maraviroc with amlodipine is necessary, due to a possible increase in maraviroc exposure. Maraviroc is a CYP3A substrate and amlodipine is a weak CYP3A4 inhibitor. Monitor for an increase in adverse effects with concomitant use.
    Amiodarone: (Moderate) Use caution if coadministration of maraviroc with amiodarone is necessary, due to a possible increase in maraviroc exposure. Maraviroc is a CYP3A4/P-glycoprotein (P-gp) substrate and amiodarone is a CYP3A4/P-gp inhibitor. Monitor for an increase in adverse effects with concomitant use.
    Amlodipine: (Minor) Use caution if coadministration of maraviroc with amlodipine is necessary, due to a possible increase in maraviroc exposure. Maraviroc is a CYP3A substrate and amlodipine is a weak CYP3A4 inhibitor. Monitor for an increase in adverse effects with concomitant use.
    Amlodipine; Atorvastatin: (Minor) Use caution if coadministration of maraviroc with amlodipine is necessary, due to a possible increase in maraviroc exposure. Maraviroc is a CYP3A substrate and amlodipine is a weak CYP3A4 inhibitor. Monitor for an increase in adverse effects with concomitant use.
    Amlodipine; Benazepril: (Minor) Use caution if coadministration of maraviroc with amlodipine is necessary, due to a possible increase in maraviroc exposure. Maraviroc is a CYP3A substrate and amlodipine is a weak CYP3A4 inhibitor. Monitor for an increase in adverse effects with concomitant use.
    Amlodipine; Celecoxib: (Minor) Use caution if coadministration of maraviroc with amlodipine is necessary, due to a possible increase in maraviroc exposure. Maraviroc is a CYP3A substrate and amlodipine is a weak CYP3A4 inhibitor. Monitor for an increase in adverse effects with concomitant use.
    Amlodipine; Olmesartan: (Minor) Use caution if coadministration of maraviroc with amlodipine is necessary, due to a possible increase in maraviroc exposure. Maraviroc is a CYP3A substrate and amlodipine is a weak CYP3A4 inhibitor. Monitor for an increase in adverse effects with concomitant use.
    Amlodipine; Valsartan: (Minor) Use caution if coadministration of maraviroc with amlodipine is necessary, due to a possible increase in maraviroc exposure. Maraviroc is a CYP3A substrate and amlodipine is a weak CYP3A4 inhibitor. Monitor for an increase in adverse effects with concomitant use.
    Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Minor) Use caution if coadministration of maraviroc with amlodipine is necessary, due to a possible increase in maraviroc exposure. Maraviroc is a CYP3A substrate and amlodipine is a weak CYP3A4 inhibitor. Monitor for an increase in adverse effects with concomitant use.
    Amoxicillin; Clarithromycin; Omeprazole: (Major) Coadministration of maraviroc (a substrate of CYP3A, P-gp, and OATP1B1) with clarithromycin (a strong CYP3A4 inhibitor and P-gp/OATP1B1 inhibitor) may result in increased maraviroc concentrations. Reduce the dose of maraviroc when coadministered with strong CYP3A inhibitors; coadministration of maraviroc with strong CYP3A inhibitors is contraindicated in patients with CrCl less than 30 mL/min. Adjust the maraviroc dosage as follows when administered with clarithromycin (with or without a concomitant CYP3A inducer): adults and children weighing 40 kg or more: 150 mg PO twice daily; children weighing 30 to 39 kg: 100 mg PO twice daily; children weighing 20 to 29 kg: 75 mg PO twice daily (or 80 mg PO twice daily for solution); children weighing 10 to 19 kg: 50 mg PO twice daily; children weighing 2 to 9 kg: use not recommended.
    Amprenavir: (Major) Coadministration of maraviroc, a CYP3A substrate, with amprenavir, a strong CYP3A4 inhibitor, may result in increased maraviroc concentrations. Reduce the dose of maraviroc when coadministered with strong CYP3A inhibitors; coadministration of maraviroc with strong CYP3A inhibitors is contraindicated in patients with CrCl less than 30 mL/min. Adjust the maraviroc dosage as follows when administered with amprenavir (with or without a concomitant CYP3A inducer): adults and children weighing 40 kg or more: 150 mg PO twice daily; children weighing 30 to 39 kg: 100 mg PO twice daily; children weighing 20 to 29 kg: 75 mg PO twice daily (or 80 mg PO twice daily for solution); children weighing 10 to 19 kg: 50 mg PO twice daily; children weighing 2 to 9 kg: use not recommended.
    Apalutamide: (Major) Increase the adult maraviroc dose to 600 mg PO twice daily if coadministration with apalutamide is necessary without a concomitant strong CYP3A4 inhibitor, as maraviroc concentrations may be expected to decrease. Coadministration of maraviroc and apalutamide is contraindicated in patients with CrCL less than 30 mL/min. For pediatric patients, concomitant use of maraviroc with apalutamide without a strong CYP3A inhibitor is not recommended. If the patient's medication regimen also contains a strong CYP3A inhibitor, the CYP3A inhibitor's actions are expected to exceed that of the inducer; overall, increased maraviroc concentrations are expected. Maraviroc is a CYP3A4 substrate and apalutamide is a strong CYP3A4 inducer.
    Aprepitant, Fosaprepitant: (Moderate) Use caution if maraviroc and aprepitant, fosaprepitant are used concurrently and monitor for an increase in maraviroc-related adverse effects for several days after administration of a multi-day aprepitant regimen. Maraviroc is a CYP3A substrate. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and inducer and may increase plasma concentrations of maraviroc. For example, a 5-day oral aprepitant regimen increased the AUC of another CYP3A4 substrate, midazolam (single dose), by 2.3-fold on day 1 and by 3.3-fold on day 5. After a 3-day oral aprepitant regimen, the AUC of midazolam (given on days 1, 4, 8, and 15) increased by 25% on day 4, and then decreased by 19% and 4% on days 8 and 15, respectively. As a single 125 mg or 40 mg oral dose, the inhibitory effect of aprepitant on CYP3A4 is weak, with the AUC of midazolam increased by 1.5-fold and 1.2-fold, respectively. After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions. However, as a single 150 mg intravenous dose, fosaprepitant only weakly inhibits CYP3A4 for a duration of 2 days; there is no evidence of CYP3A4 induction. Fosaprepitant 150 mg IV as a single dose increased the AUC of midazolam (given on days 1 and 4) by approximately 1.8-fold on day 1; there was no effect on day 4. Less than a 2-fold increase in the midazolam AUC is not considered clinically important.
    Armodafinil: (Minor) Use caution if coadministration of maraviroc with armodafinil is necessary, due to a possible decrease in maraviroc exposure. Maraviroc is a CYP3A substrate and armodafinil is a weak CYP3A4 inducer. Monitor for a decrease in efficacy with concomitant use.
    Atazanavir: (Major) Coadministration of maraviroc, a CYP3A and OATP1B1 substrate, with atazanavir, a strong CYP3A4 inhibitor and in vitro inhibitor of OATP1B1, may result in increased maraviroc concentrations. Reduce the dose of maraviroc when coadministered with strong CYP3A inhibitors; coadministration of maraviroc with strong CYP3A inhibitors is contraindicated in patients with CrCl less than 30 mL/min. Adjust the maraviroc dosage as follows when administered with atazanavir (with or without a concomitant CYP3A inducer): adults and children weighing 40 kg or more: 150 mg PO twice daily; children weighing 30 to 39 kg: 100 mg PO twice daily; children weighing 20 to 29 kg: 75 mg PO twice daily (or 80 mg PO twice daily for solution); children weighing 10 to 19 kg: 50 mg PO twice daily; children weighing 2 to 9 kg: use not recommended.
    Atazanavir; Cobicistat: (Major) Coadministration of maraviroc (a substrate of CYP3A, P-gp, and OATP1B1) with cobicistat (a CYP3A4, P-gp, OATP1B1 inhibitor) may result in increased maraviroc concentrations. Reduce the dose of maraviroc when coadministered with cobicistat; coadministration is contraindicated in patients with CrCl less than 30 mL/min. Adjust the maraviroc dosage as follows when administered with cobicistat (with or without a concomitant CYP3A inducer): adults and children weighing 40 kg or more: 150 mg PO twice daily; children weighing 30 to 39 kg: 100 mg PO twice daily; children weighing 20 to 29 kg: 75 mg PO twice daily (or 80 mg PO twice daily for solution); children weighing 10 to 19 kg: 50 mg PO twice daily; children weighing 2 to 9 kg: use not recommended. (Major) Coadministration of maraviroc, a CYP3A and OATP1B1 substrate, with atazanavir, a strong CYP3A4 inhibitor and in vitro inhibitor of OATP1B1, may result in increased maraviroc concentrations. Reduce the dose of maraviroc when coadministered with strong CYP3A inhibitors; coadministration of maraviroc with strong CYP3A inhibitors is contraindicated in patients with CrCl less than 30 mL/min. Adjust the maraviroc dosage as follows when administered with atazanavir (with or without a concomitant CYP3A inducer): adults and children weighing 40 kg or more: 150 mg PO twice daily; children weighing 30 to 39 kg: 100 mg PO twice daily; children weighing 20 to 29 kg: 75 mg PO twice daily (or 80 mg PO twice daily for solution); children weighing 10 to 19 kg: 50 mg PO twice daily; children weighing 2 to 9 kg: use not recommended.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (Major) Coadministration of maraviroc, a CYP3A/P-glycoprotein (P-gp) substrate, and phenobarbital, a strong CYP3A inducer and P-gp inducer, without a concomitant strong CYP3A inhibitor may decrease maraviroc concentrations, therefore, the adult maraviroc dose should be increased to 600 mg PO twice daily when coadministered with phenobarbital without a concomitant strong CYP3A inhibitor. Coadministration of maraviroc and phenobarbital is contraindicated in patients with CrCl less than 30 mL/min. For pediatric patients, concomitant use of maraviroc with a strong CYP3A inducer, without a strong CYP3A inhibitor, is not recommended. If the patient's medication regimen also contains a strong CYP3A inhibitor, the CYP3A inhibitor's actions are expected to exceed that of the inducer; overall, increased maraviroc concentrations are expected.
    Berotralstat: (Moderate) Monitor for an increase in maraviroc-related adverse reactions if coadministration with berotralstat is necessary. Maraviroc is a P-gp substrate and a sensitive CYP3A substrate; berotralstat is a P-gp inhibitor and a moderate CYP3A4 inhibitor. Coadministration with moderate CYP3A4 inhibitors may result in increased maraviroc concentrations.
    Bexarotene: (Moderate) Use caution if coadministration of maraviroc with bexarotene is necessary, due to a possible decrease in maraviroc exposure. Maraviroc is a CYP3A substrate and bexarotene is a CYP3A4 inducer. Monitor for a decrease in maraviroc efficacy with concomitant use.
    Boceprevir: (Major) Coadministration of maraviroc, a CYP3A/P-gp substrate, with boceprevir, a strong CYP3A4 inhibitor and P-gp inhibitor, may result in increased maraviroc concentrations. Reduce the dose of maraviroc when coadministered with strong CYP3A inhibitors; coadministration of maraviroc with strong CYP3A inhibitors is contraindicated in patients with CrCl less than 30 mL/min. Adjust the maraviroc dosage as follows when administered with boceprevir (with or without a concomitant CYP3A inducer): adults and children weighing 40 kg or more: 150 mg PO twice daily; children weighing 30 to 39 kg: 100 mg PO twice daily; children weighing 20 to 29 kg: 75 mg PO twice daily (or 80 mg PO twice daily for solution); children weighing 10 to 19 kg: 50 mg PO twice daily; children weighing 2 to 9 kg: use not recommended.
    Brigatinib: (Moderate) Monitor for an increase in maraviroc-related adverse reactions if coadministration with brigatinib is necessary. Concurrent use may increase the plasma concentrations of maraviroc. Maraviroc is a P-glycoprotein (P-gp) substrate; brigatinib is a P-gp inhibitor.
    Cabozantinib: (Minor) Monitor for an increase in maraviroc-related adverse reactions if coadministration with cabozantinib is necessary; a dose adjustment of maraviroc may be necessary. Maraviroc is a P-glycoprotein (P-gp) substrate. Cabozantinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates; however, the clinical relevance of this finding is unknown.
    Cannabidiol: (Moderate) Monitor for an increase in maraviroc-related adverse reactions if coadministration with cannabidiol is necessary. Concomitant use may increase maraviroc exposure. Maraviroc is a P-gp substrate; cannabidiol is a P-gp inhibitor.
    Capmatinib: (Moderate) Monitor for an increase in maraviroc-related adverse reactions if coadministration with capmatinib is necessary. Maraviroc is a P-glycoprotein (P-gp) substrate and capmatinib is a P-gp inhibitor. Concomitant use may increase maraviroc exposure.
    Carbamazepine: (Major) Coadministration of maraviroc, a CYP3A/P-glycoprotein (P-gp) substrate, and carbamazepine, a strong CYP3A inducer and P-gp inducer, without a concomitant strong CYP3A inhibitor may decrease maraviroc concentrations, therefore, the adult maraviroc dose should be increased to 600 mg PO twice daily when coadministered with carbamazepine without a concomitant strong CYP3A inhibitor. Coadministration of maraviroc and carbamazepine is contraindicated in patients with CrCl less than 30 mL/min. For pediatric patients, concomitant use of maraviroc with a strong CYP3A inducer, without a strong CYP3A inhibitor, is not recommended. If the patient's medication regimen also contains a strong CYP3A inhibitor, the CYP3A inhibitor's actions are expected to exceed that of the inducer; overall, increased maraviroc concentrations are expected.
    Carvedilol: (Moderate) Increased concentrations of maraviroc may occur if it is coadministered with carvedilol; exercise caution. Carvedilol is a P-glycoprotein (P-gp) inhibitor and maraviroc is a P-gp substrate.
    Ceritinib: (Major) Reduce the dose of maraviroc when coadministered with strong CYP3A inhibitors such as ceritinib; coadministration of maraviroc with strong CYP3A inhibitors is contraindicated in patients with CrCL less than 30 mL/min. Adjust the maraviroc dosage as follows when administered with ceritinib (with or without a concomitant CYP3A inducer): adults and children weighing 40 kg or more: 150 mg PO twice daily; children weighing 30 to 39 kg: 100 mg PO twice daily; children weighing 20 to 29 kg: 75 mg PO twice daily (or 80 mg PO twice daily for solution); children weighing 10 to 19 kg: 50 mg PO twice daily; children weighing 2 to 9 kg: use not recommended. The AUC of maraviroc was increased by up to approximately 10-fold in the presence of strong CYP3A4 inhibitors.
    Chloramphenicol: (Major) Coadministration of maraviroc, a CYP3A substrate, with chloramphenicol, a strong CYP3A4 inhibitor, may result in increased maraviroc concentrations. Reduce the dose of maraviroc when coadministered with strong CYP3A inhibitors; also, coadministration of maraviroc with strong CYP3A inhibitors is contraindicated in patients with CrCl less than 30 mL/min. Adjust the maraviroc dosage as follows when administered with chloramphenicol (with or without a concomitant CYP3A inducer): adults and children weighing 40 kg or more: 150 mg PO twice daily; children weighing 30 to 39 kg: 100 mg PO twice daily; children weighing 20 to 29 kg: 75 mg PO twice daily (or 80 mg PO twice daily for solution); children weighing 10 to 19 kg: 50 mg PO twice daily; children weighing 2 to 9 kg: use not recommended.
    Cidofovir: (Moderate) Use caution and closely monitor for increased adverse effects during concurrent administration of maraviroc and cidofovir as increased maraviroc concentrations may occur. Maraviroc is a substrate of multidrug resistance-associated protein (MRP2); cidofovir is an inhibitor of MRP2. The effects of this transporter on the concentrations of maraviroc are unknown, although an increase in concentrations and thus, toxicity, are possible.
    Cimetidine: (Minor) Use caution if coadministration of maraviroc with cimetidine is necessary, due to a possible increase in maraviroc exposure. Maraviroc is a CYP3A substrate and cimetidine is a weak CYP3A4 inhibitor. Monitor for an increase in adverse effects with concomitant use.
    Ciprofloxacin: (Minor) Use caution if coadministration of maraviroc with ciprofloxacin is necessary, due to a possible increase in maraviroc exposure. Maraviroc is a CYP3A substrate and ciprofloxacin is a weak CYP3A4 inhibitor. Monitor for an increase in adverse effects with concomitant use.
    Clarithromycin: (Major) Coadministration of maraviroc (a substrate of CYP3A, P-gp, and OATP1B1) with clarithromycin (a strong CYP3A4 inhibitor and P-gp/OATP1B1 inhibitor) may result in increased maraviroc concentrations. Reduce the dose of maraviroc when coadministered with strong CYP3A inhibitors; coadministration of maraviroc with strong CYP3A inhibitors is contraindicated in patients with CrCl less than 30 mL/min. Adjust the maraviroc dosage as follows when administered with clarithromycin (with or without a concomitant CYP3A inducer): adults and children weighing 40 kg or more: 150 mg PO twice daily; children weighing 30 to 39 kg: 100 mg PO twice daily; children weighing 20 to 29 kg: 75 mg PO twice daily (or 80 mg PO twice daily for solution); children weighing 10 to 19 kg: 50 mg PO twice daily; children weighing 2 to 9 kg: use not recommended.
    Clobazam: (Minor) Use caution if coadministration of maraviroc with clobazam is necessary, due to a possible decrease in maraviroc exposure. Maraviroc is a CYP3A substrate and clobazam is a weak CYP3A4 inducer. Monitor for a decrease in efficacy with concomitant use.
    Cobicistat: (Major) Coadministration of maraviroc (a substrate of CYP3A, P-gp, and OATP1B1) with cobicistat (a CYP3A4, P-gp, OATP1B1 inhibitor) may result in increased maraviroc concentrations. Reduce the dose of maraviroc when coadministered with cobicistat; coadministration is contraindicated in patients with CrCl less than 30 mL/min. Adjust the maraviroc dosage as follows when administered with cobicistat (with or without a concomitant CYP3A inducer): adults and children weighing 40 kg or more: 150 mg PO twice daily; children weighing 30 to 39 kg: 100 mg PO twice daily; children weighing 20 to 29 kg: 75 mg PO twice daily (or 80 mg PO twice daily for solution); children weighing 10 to 19 kg: 50 mg PO twice daily; children weighing 2 to 9 kg: use not recommended.
    Conivaptan: (Moderate) Monitor for an increase in maraviroc-related adverse reactions if coadministration with conivaptan is necessary. Concomitant use may increase maraviroc exposure. Maraviroc is a CYP3A and P-gp substrate and conivaptan is a moderate CYP3A and P-gp inhibitor.
    Crizotinib: (Moderate) Monitor for an increase in maraviroc-related adverse reactions if concomitant use with crizotinib is necessary. Maraviroc is a sensitive CYP3A substrate and crizotinib is a moderate CYP3A4 inhibitor. Coadministration with moderate CYP3A4 inhibitors may result in increased maraviroc concentrations.
    Cyclosporine: (Moderate) Use caution and closely monitor for increased adverse effects during concurrent administration of maraviroc and cyclosporine as increased maraviroc concentrations may occur. Maraviroc is a substrate of CYP3A, P-glycoprotein (P-gp), organic anion-transporting polypeptide (OATP1B), and multidrug resistance-associated protein (MRP2). Cyclosporine is a CYP3A4, P-gp, OATP1B1, and MRP2 inhibitor. Monitor for an increase in adverse effects with concomitant use.
    Dabrafenib: (Major) The concomitant use of dabrafenib and maraviroc may lead to decreased maraviroc concentrations and loss of efficacy. Use of an alternative agent is recommended. If concomitant use of these agents together is unavoidable, monitor patients for loss of maraviroc efficacy. Dabrafenib is a moderate CYP3A4 inducer and maraviroc is a sensitive CYP3A4 substrate. Concomitant use of dabrafenib with a single dose of another sensitive CYP3A4 substrate decreased the AUC value of the sensitive CYP3A4 substrate by 65%.
    Daclatasvir: (Moderate) Use caution and closely monitor for increased adverse effects during concurrent administration of maraviroc and daclatasvir as increased maraviroc concentrations may occur. Maraviroc is a substrate of P-glycoprotein (P-gp) and organic anion-transporting polypeptide (OATP1B1); daclatasvir is an inhibitor of P-gp and OATP1B1. The effects of these transporters on the concentrations of maraviroc are unknown, although an increase in concentrations and thus, toxicity, are possible.
    Danazol: (Moderate) Use caution if coadministration of maraviroc with danazol is necessary, due to a possible increase in maraviroc exposure. Maraviroc is a CYP3A substrate and danazol is a CYP3A4 inhibitor. Monitor for an increase in adverse effects with concomitant use.
    Darolutamide: (Moderate) Monitor for an increase in maraviroc-related adverse reactions if coadministration with darolutamide is necessary. Concurrent use may increase the plasma concentrations of maraviroc. Maraviroc is an OATP1B1 substrate; darolutamide is an OATP1B1 inhibitor.
    Darunavir: (Major) Reduce the dose of maraviroc when coadministered with strong CYP3A inhibitors such as darunavir; coadministration of maraviroc with strong CYP3A inhibitors is contraindicated in patients with CrCL less than 30 mL/min. Adjust the maraviroc dosage as follows when administered with darunavir (with or without a concomitant CYP3A inducer): adults and children weighing 40 kg or more: 150 mg PO twice daily; children weighing 30 to 39 kg: 100 mg PO twice daily; children weighing 20 to 29 kg: 75 mg PO twice daily (or 80 mg PO twice daily for solution); children weighing 10 to 19 kg: 50 mg PO twice daily; children weighing 2 to 9 kg: use not recommended.
    Darunavir; Cobicistat: (Major) Coadministration of maraviroc (a substrate of CYP3A, P-gp, and OATP1B1) with cobicistat (a CYP3A4, P-gp, OATP1B1 inhibitor) may result in increased maraviroc concentrations. Reduce the dose of maraviroc when coadministered with cobicistat; coadministration is contraindicated in patients with CrCl less than 30 mL/min. Adjust the maraviroc dosage as follows when administered with cobicistat (with or without a concomitant CYP3A inducer): adults and children weighing 40 kg or more: 150 mg PO twice daily; children weighing 30 to 39 kg: 100 mg PO twice daily; children weighing 20 to 29 kg: 75 mg PO twice daily (or 80 mg PO twice daily for solution); children weighing 10 to 19 kg: 50 mg PO twice daily; children weighing 2 to 9 kg: use not recommended. (Major) Reduce the dose of maraviroc when coadministered with strong CYP3A inhibitors such as darunavir; coadministration of maraviroc with strong CYP3A inhibitors is contraindicated in patients with CrCL less than 30 mL/min. Adjust the maraviroc dosage as follows when administered with darunavir (with or without a concomitant CYP3A inducer): adults and children weighing 40 kg or more: 150 mg PO twice daily; children weighing 30 to 39 kg: 100 mg PO twice daily; children weighing 20 to 29 kg: 75 mg PO twice daily (or 80 mg PO twice daily for solution); children weighing 10 to 19 kg: 50 mg PO twice daily; children weighing 2 to 9 kg: use not recommended.
    Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Coadministration of maraviroc (a substrate of CYP3A, P-gp, and OATP1B1) with cobicistat (a CYP3A4, P-gp, OATP1B1 inhibitor) may result in increased maraviroc concentrations. Reduce the dose of maraviroc when coadministered with cobicistat; coadministration is contraindicated in patients with CrCl less than 30 mL/min. Adjust the maraviroc dosage as follows when administered with cobicistat (with or without a concomitant CYP3A inducer): adults and children weighing 40 kg or more: 150 mg PO twice daily; children weighing 30 to 39 kg: 100 mg PO twice daily; children weighing 20 to 29 kg: 75 mg PO twice daily (or 80 mg PO twice daily for solution); children weighing 10 to 19 kg: 50 mg PO twice daily; children weighing 2 to 9 kg: use not recommended. (Major) Reduce the dose of maraviroc when coadministered with strong CYP3A inhibitors such as darunavir; coadministration of maraviroc with strong CYP3A inhibitors is contraindicated in patients with CrCL less than 30 mL/min. Adjust the maraviroc dosage as follows when administered with darunavir (with or without a concomitant CYP3A inducer): adults and children weighing 40 kg or more: 150 mg PO twice daily; children weighing 30 to 39 kg: 100 mg PO twice daily; children weighing 20 to 29 kg: 75 mg PO twice daily (or 80 mg PO twice daily for solution); children weighing 10 to 19 kg: 50 mg PO twice daily; children weighing 2 to 9 kg: use not recommended.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Major) Coadministration of maraviroc (a substrate of CYP3A, P-gp, MRP2) with ritonavir (a strong CYP3A4 inhibitor and P-gp/MRP2 inhibitor) has been reported to significantly increase maraviroc concentrations. Reduce the dose of maraviroc when coadministered with strong CYP3A inhibitors; coadministration of maraviroc with strong CYP3A inhibitors is contraindicated in patients with CrCl less than 30 mL/min. Adjust the maraviroc dosage as follows when administered with ritonavir (with or without a concomitant CYP3A inducer): adults and children weighing 40 kg or more: 150 mg PO twice daily; children weighing 30 to 39 kg: 100 mg PO twice daily; children weighing 20 to 29 kg: 75 mg PO twice daily (or 80 mg PO twice daily for solution); children weighing 10 to 19 kg: 50 mg PO twice daily; children weighing 2 to 9 kg: use not recommended. (Moderate) Use caution and closely monitor for increased adverse effects during concurrent administration of maraviroc and paritaprevir as increased maraviroc concentrations may occur. Maraviroc is a substrate of organic anion-transporting polypeptide (OATP1B1); paritaprevir is an inhibitor of OATP1B1. The effects of this transporter on the concentrations of maraviroc are unknown, although an increase in concentrations and thus, toxicity, are possible.
    Deferasirox: (Moderate) Use caution if coadministration of maraviroc with deferasirox is necessary, due to a possible decrease in maraviroc exposure. Maraviroc is a CYP3A substrate and deferasirox is a CYP3A4 inducer. Monitor for a decrease in maraviroc efficacy with concomitant use.
    Delavirdine: (Major) Coadministration of maraviroc, a CYP3A substrate, with delavirdine, a strong CYP3A4 inhibitor, may result in increased maraviroc concentrations. Reduce the dose of maraviroc when coadministered with strong CYP3A inhibitors; coadministration of maraviroc with strong CYP3A inhibitors is contraindicated in patients with CrCl less than 30 mL/min. Adjust the maraviroc dosage as follows when administered with delavirdine (with or without a concomitant CYP3A inducer): adults and children weighing 40 kg or more: 150 mg PO twice daily; children weighing 30 to 39 kg: 100 mg PO twice daily; children weighing 20 to 29 kg: 75 mg PO twice daily (or 80 mg PO twice daily for solution); children weighing 10 to 19 kg: 50 mg PO twice daily; children weighing 2 to 9 kg: use not recommended.
    Dexamethasone: (Moderate) Use caution if coadministration of maraviroc with dexamethasone is necessary, due to a possible decrease in maraviroc exposure. Maraviroc is a CYP3A substrate and dexamethasone is a CYP3A4 inducer. Monitor for a decrease in maraviroc efficacy with concomitant use.
    Dextromethorphan; Quinidine: (Moderate) Use caution and careful monitoring with the coadministration of maraviroc and quinidine as increased maraviroc concentrations may occur. Maraviroc is a substrate of P-glycoprotein (P-gp); quinidine is an inhibitor of P-gp. The effects of P-gp on the concentrations of maraviroc are unknown, although an increase in concentrations and thus, toxicity, are possible.
    Diltiazem: (Moderate) Monitor for an increase in maraviroc adverse effects with concomitant use of diltiazem due to a possible increase in maraviroc exposure. Maraviroc is a CYP3A substrate and diltiazem is a CYP3A4 inhibitor.
    Dronedarone: (Moderate) Use caution if coadministration of maraviroc with dronedarone is necessary, due to a possible increase in maraviroc exposure. Maraviroc is a CYP3A and P-glycoprotein (P-gp) substrate and dronedarone is a CYP3A4/P-gp inhibitor. Monitor for an increase in adverse effects with concomitant use.
    Duvelisib: (Moderate) Monitor for increased toxicity of maraviroc if coadministered with duvelisib. Coadministration may increase the exposure of maraviroc. Maraviroc is a sensitive CYP3A substrate; duvelisib is a moderate CYP3A inhibitor.
    Efavirenz: (Major) Coadministration of maraviroc, a CYP3A substrate, and efavirenz, a strong CYP3A inducer, without a concomitant strong CYP3A inhibitor, significantly decreases maraviroc concentrations, therefore, the adult maraviroc dose should be increased to 600 mg PO twice daily when coadministered with efavirenz without a concomitant strong CYP3A inhibitor. Coadministration of maraviroc and efavirenz is contraindicated in patients with CrCl less than 30 mL/min. For pediatric patients, concomitant use of maraviroc with a strong CYP3A inducer, without a strong CYP3A inhibitor, is not recommended. If the patient's medication regimen also contains a strong CYP3A inhibitor, the CYP3A inhibitor's actions are expected to exceed that of the inducer; overall, increased maraviroc concentrations are expected.
    Efavirenz; Emtricitabine; Tenofovir: (Major) Coadministration of maraviroc, a CYP3A substrate, and efavirenz, a strong CYP3A inducer, without a concomitant strong CYP3A inhibitor, significantly decreases maraviroc concentrations, therefore, the adult maraviroc dose should be increased to 600 mg PO twice daily when coadministered with efavirenz without a concomitant strong CYP3A inhibitor. Coadministration of maraviroc and efavirenz is contraindicated in patients with CrCl less than 30 mL/min. For pediatric patients, concomitant use of maraviroc with a strong CYP3A inducer, without a strong CYP3A inhibitor, is not recommended. If the patient's medication regimen also contains a strong CYP3A inhibitor, the CYP3A inhibitor's actions are expected to exceed that of the inducer; overall, increased maraviroc concentrations are expected.
    Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Coadministration of maraviroc, a CYP3A substrate, and efavirenz, a strong CYP3A inducer, without a concomitant strong CYP3A inhibitor, significantly decreases maraviroc concentrations, therefore, the adult maraviroc dose should be increased to 600 mg PO twice daily when coadministered with efavirenz without a concomitant strong CYP3A inhibitor. Coadministration of maraviroc and efavirenz is contraindicated in patients with CrCl less than 30 mL/min. For pediatric patients, concomitant use of maraviroc with a strong CYP3A inducer, without a strong CYP3A inhibitor, is not recommended. If the patient's medication regimen also contains a strong CYP3A inhibitor, the CYP3A inhibitor's actions are expected to exceed that of the inducer; overall, increased maraviroc concentrations are expected.
    Elbasvir; Grazoprevir: (Minor) Use caution if coadministration of maraviroc with grazoprevir is necessary, due to a possible increase in maraviroc exposure. Maraviroc is a CYP3A substrate and grazoprevir is a weak CYP3A inhibitor. Monitor for an increase in adverse effects with concomitant use.
    Elexacaftor; tezacaftor; ivacaftor: (Moderate) Monitor for maraviroc-related adverse reactions during coadministration of elexacaftor; tezacaftor; ivacaftor as concurrent use may increase exposure of maraviroc. Maraviroc is a substrate for the transporter OATP1B1; elexacaftor; tezacaftor; ivacaftor may inhibit uptake of OATP1B1. (Minor) Use caution if coadministration of maraviroc with ivacaftor is necessary, due to a possible increase in maraviroc exposure. Maraviroc is a CYP3A and P-glycoprotein (Pgp) substrate and ivacaftor is a weak CYP3A4/Pgp inhibitor. Monitor for an increase in adverse effects with concomitant use.
    Eliglustat: (Moderate) Use caution and closely monitor for increased adverse effects with the coadministration of maraviroc and eliglustat as increased maraviroc concentrations may occur. Maraviroc is a substrate of P-glycoprotein (P-gp); eliglustat is an inhibitor of P-gp. The effects of P-gp on the concentrations of maraviroc are unknown, although an increase in concentrations and thus, toxicity, are possible.
    Eltrombopag: (Moderate) Use caution and closely monitor for increased adverse effects during concurrent administration of maraviroc and eltrombopag as increased maraviroc concentrations may occur. Maraviroc is a substrate of organic anion-transporting polypeptide (OATP1B1); eltrombopag is an inhibitor of OATP1B1. The effects of this transporter on the concentrations of maraviroc are unknown, although an increase in concentrations and thus, toxicity, are possible.
    Elvitegravir: (Major) Coadministration of maraviroc, a CYP3A substrate, with elvitegravir boosted with ritonavir, a strong CYP3A4 inhibitor, may result in increased maraviroc concentrations. Reduce the dose of maraviroc when coadministered with strong CYP3A inhibitors; coadministration of maraviroc with strong CYP3A inhibitors is contraindicated in patients with CrCl less than 30 mL/min. Adjust the maraviroc dosage as follows when administered with elvitegravir boosted with ritonavir (with or without a concomitant CYP3A inducer): adults and children weighing 40 kg or more: 150 mg PO twice daily; children weighing 30 to 39 kg: 100 mg PO twice daily; children weighing 20 to 29 kg: 75 mg PO twice daily (or 80 mg PO twice daily for solution); children weighing 10 to 19 kg: 50 mg PO twice daily; children weighing 2 to 9 kg: use not recommended.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Coadministration of maraviroc (a substrate of CYP3A, P-gp, and OATP1B1) with cobicistat (a CYP3A4, P-gp, OATP1B1 inhibitor) may result in increased maraviroc concentrations. Reduce the dose of maraviroc when coadministered with cobicistat; coadministration is contraindicated in patients with CrCl less than 30 mL/min. Adjust the maraviroc dosage as follows when administered with cobicistat (with or without a concomitant CYP3A inducer): adults and children weighing 40 kg or more: 150 mg PO twice daily; children weighing 30 to 39 kg: 100 mg PO twice daily; children weighing 20 to 29 kg: 75 mg PO twice daily (or 80 mg PO twice daily for solution); children weighing 10 to 19 kg: 50 mg PO twice daily; children weighing 2 to 9 kg: use not recommended. (Major) Coadministration of maraviroc, a CYP3A substrate, with elvitegravir boosted with ritonavir, a strong CYP3A4 inhibitor, may result in increased maraviroc concentrations. Reduce the dose of maraviroc when coadministered with strong CYP3A inhibitors; coadministration of maraviroc with strong CYP3A inhibitors is contraindicated in patients with CrCl less than 30 mL/min. Adjust the maraviroc dosage as follows when administered with elvitegravir boosted with ritonavir (with or without a concomitant CYP3A inducer): adults and children weighing 40 kg or more: 150 mg PO twice daily; children weighing 30 to 39 kg: 100 mg PO twice daily; children weighing 20 to 29 kg: 75 mg PO twice daily (or 80 mg PO twice daily for solution); children weighing 10 to 19 kg: 50 mg PO twice daily; children weighing 2 to 9 kg: use not recommended.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Coadministration of maraviroc (a substrate of CYP3A, P-gp, and OATP1B1) with cobicistat (a CYP3A4, P-gp, OATP1B1 inhibitor) may result in increased maraviroc concentrations. Reduce the dose of maraviroc when coadministered with cobicistat; coadministration is contraindicated in patients with CrCl less than 30 mL/min. Adjust the maraviroc dosage as follows when administered with cobicistat (with or without a concomitant CYP3A inducer): adults and children weighing 40 kg or more: 150 mg PO twice daily; children weighing 30 to 39 kg: 100 mg PO twice daily; children weighing 20 to 29 kg: 75 mg PO twice daily (or 80 mg PO twice daily for solution); children weighing 10 to 19 kg: 50 mg PO twice daily; children weighing 2 to 9 kg: use not recommended. (Major) Coadministration of maraviroc, a CYP3A substrate, with elvitegravir boosted with ritonavir, a strong CYP3A4 inhibitor, may result in increased maraviroc concentrations. Reduce the dose of maraviroc when coadministered with strong CYP3A inhibitors; coadministration of maraviroc with strong CYP3A inhibitors is contraindicated in patients with CrCl less than 30 mL/min. Adjust the maraviroc dosage as follows when administered with elvitegravir boosted with ritonavir (with or without a concomitant CYP3A inducer): adults and children weighing 40 kg or more: 150 mg PO twice daily; children weighing 30 to 39 kg: 100 mg PO twice daily; children weighing 20 to 29 kg: 75 mg PO twice daily (or 80 mg PO twice daily for solution); children weighing 10 to 19 kg: 50 mg PO twice daily; children weighing 2 to 9 kg: use not recommended.
    Enasidenib: (Moderate) Monitor for an increase in maraviroc-related adverse reactions if coadministration with enasidenib is necessary. Concomitant use may increase maraviroc exposure. Maraviroc is a P-gp and OATP1B1 substrate; enasidenib is a P-gp and OATP1B1 inhibitor.
    Encorafenib: (Moderate) Coadministration of encorafenib with maraviroc may result in increased toxicity or decreased efficacy of maraviroc. Maraviroc is a sensitive CYP3A4 substrate. In vitro studies with encorafenib showed time-dependent inhibition of CYP3A4 and induction of CYP3A4. The clinical relevance of the in vivo effect of encorafenib on CYP3A4 is not established.
    Enzalutamide: (Major) Coadministration of maraviroc, a CYP3A substrate, and enzalutamide, a strong CYP3A inducer, without a concomitant strong CYP3A inhibitor may decrease maraviroc concentrations, therefore, the adult maraviroc dose should be increased to 600 mg PO twice daily when coadministered with enzalutamide without a concomitant strong CYP3A inhibitor. Coadministration of maraviroc and enzalutamide is contraindicated in patients with CrCl less than 30 mL/min. For pediatric patients, concomitant use of maraviroc with a strong CYP3A inducer, without a strong CYP3A inhibitor, is not recommended. If the patient's medication regimen also contains a strong CYP3A inhibitor, the CYP3A inhibitor's actions are expected to exceed that of the inducer; overall, increased maraviroc concentrations are expected.
    Erythromycin: (Moderate) Use caution and closely monitor for increased adverse effects during concurrent administration of maraviroc and eythromycin as increased maraviroc concentrations may occur. Maraviroc is a substrate of CYP3A, P-glycoprotein (P-gp), and organic anion-transporting polypeptide (OATP1B). Erythromycin is a CYP3A4, P-gp, and OATP1B1 inhibitor. Monitor for an increase in adverse effects with concomitant use.
    Erythromycin; Sulfisoxazole: (Moderate) Use caution and closely monitor for increased adverse effects during concurrent administration of maraviroc and eythromycin as increased maraviroc concentrations may occur. Maraviroc is a substrate of CYP3A, P-glycoprotein (P-gp), and organic anion-transporting polypeptide (OATP1B). Erythromycin is a CYP3A4, P-gp, and OATP1B1 inhibitor. Monitor for an increase in adverse effects with concomitant use.
    Eslicarbazepine: (Moderate) Use caution if coadministration of maraviroc with eslicarbazepine is necessary, due to a possible decrease in maraviroc exposure. Maraviroc is a CYP3A substrate and eslicarbazepine is a CYP3A4 inducer. Monitor for a decrease in maraviroc efficacy with concomitant use.
    Ethanol: (Minor) Maraviroc treatment should not be interrupted if alcohol is consumed. Counsel patients to continue their antiviral treatment to avoid potential for viral resistance. In a pharmacokinetic study, healthy adults were administered alcohol (1 gram/kg) and placebo, with data collected before and after 7 days of maraviroc administration. Alcohol concentrations increased by 12% when patients were taking maraviroc. Adverse symptoms were mild and included increased drowsiness and nausea during sessions of alcohol administration. Maraviroc pharmacokinetics were unaffected by alcohol.
    Etravirine: (Major) Coadministration of maraviroc, a CYP3A substrate, and etravirine, a strong CYP3A inducer, without a concomitant strong CYP3A inhibitor significantly decreases maraviroc concentrations, therefore, the adult maraviroc dose should be increased to 600 mg PO twice daily when coadministered with etravirine without a concomitant strong CYP3A inhibitor. Coadministration of maraviroc and etravirine is contraindicated in patients with CrCl less than 30 mL/min. For pediatric patients, concomitant use of maraviroc with a strong CYP3A inducer, without a strong CYP3A inhibitor, is not recommended. If the patient's medication regimen also contains a strong CYP3A inhibitor, the CYP3A inhibitor's actions are expected to exceed that of the inducer; overall, increased maraviroc concentrations are expected.
    Felbamate: (Minor) Use caution if coadministration of maraviroc with felbamate is necessary, due to a possible decrease in maraviroc exposure. Maraviroc is a CYP3A substrate and felbamate is a CYP3A4 inducer. Monitor for a decrease in maraviroc efficacy with concomitant use.
    Flibanserin: (Moderate) Use caution and closely monitor for increased adverse effects with the coadministration of maraviroc and flibanserin as increased maraviroc concentrations may occur. Maraviroc is a substrate of P-glycoprotein (P-gp); flibanserin is an inhibitor of P-gp. The effects of P-gp on the concentrations of maraviroc are unknown, although an increase in concentrations and thus, toxicity, are possible.
    Fluconazole: (Moderate) Use caution if coadministration of maraviroc with fluconazole is necessary, due to a possible increase in maraviroc exposure. Maraviroc is a CYP3A substrate and fluconazole is a CYP3A4 inhibitor. Monitor for an increase in adverse effects with concomitant use.
    Fluoxetine: (Minor) Use caution if coadministration of maraviroc with fluoxetine is necessary, due to a possible increase in maraviroc exposure. Maraviroc is a CYP3A substrate and fluoxetine is a weak CYP3A4 inhibitor. Monitor for an increase in adverse effects with concomitant use.
    Flutamide: (Moderate) Use caution if coadministration of maraviroc with flutamide is necessary, due to a possible decrease in maraviroc exposure. Maraviroc is a CYP3A substrate. Flutamide is an inducer of CYP3A4 in vitro but the clinical significance of this finding is unknown. Monitor for a decrease in maraviroc efficacy with concomitant use.
    Fosamprenavir: (Major) Coadministration of maraviroc, a CYP3A substrate, with fosamprenavir, a strong CYP3A4 inhibitor, may result in increased maraviroc concentrations. Reduce the dose of maraviroc when coadministered with strong CYP3A inhibitors; coadministration of maraviroc with strong CYP3A inhibitors is contraindicated in patients with CrCl less than 30 mL/min. Adjust the maraviroc dosage as follows when administered with fosamprenavir (with or without a concomitant CYP3A inducer): adults and children weighing 40 kg or more: 150 mg PO twice daily; children weighing 30 to 39 kg: 100 mg PO twice daily; children weighing 20 to 29 kg: 75 mg PO twice daily (or 80 mg PO twice daily for solution); children weighing 10 to 19 kg: 50 mg PO twice daily; children weighing 2 to 9 kg: use not recommended.
    Fosphenytoin: (Major) Coadministration of maraviroc, a CYP3A substrate, and fosphenytoin, a strong CYP3A inducer, without a concomitant strong CYP3A inhibitor may decrease maraviroc concentrations, therefore, the adult maraviroc dose should be increased to 600 mg PO twice daily when coadministered with fosphenytoin without a concomitant strong CYP3A inhibitor. Coadministration of maraviroc and fosphenytoin is contraindicated in patients with CrCl less than 30 mL/min. For pediatric patients, concomitant use of maraviroc with a strong CYP3A inducer, without a strong CYP3A inhibitor, is not recommended. If the patient's medication regimen also contains a strong CYP3A inhibitor, the CYP3A inhibitor's actions are expected to exceed that of the inducer; overall, increased maraviroc concentrations are expected.
    Fostamatinib: (Moderate) Monitor for maraviroc toxicities that may require maraviroc dose reduction if given concurrently with fostamatinib. Concomitant use of fostamatinib with a P-gp substrate may increase the concentration of the P-gp substrate. Fostamatinib is a P-gp inhibitor; maraviroc is a substrate for P-gp. Coadministration of fostamatinib with another P-gp substrate increased the P-gp substrate AUC by 37% and Cmax by 70%.
    Furosemide: (Moderate) Use caution and closely monitor for increased adverse effects during concurrent administration of maraviroc and furosemide as increased maraviroc concentrations may occur. Maraviroc is a substrate of multidrug resistance-associated protein (MRP2); furosemide is an inhibitor of MRP2. The effects of this transporter on the concentrations of maraviroc are unknown, although an increase in concentrations and thus, toxicity, are possible.
    Gemfibrozil: (Moderate) Use caution and closely monitor for increased adverse effects during concurrent administration of maraviroc and gemfibrozil as increased maraviroc concentrations may occur. Maraviroc is a substrate of organic anion-transporting polypeptide (OATP1B1); gemfibrozil is an inhibitor of OATP1B1. The effects of this transporter on the concentrations of maraviroc are unknown, although an increase in concentrations and thus, toxicity, are possible.
    Gilteritinib: (Moderate) Monitor for an increase in maraviroc-related adverse reactions if coadministration with gilteritinib is necessary. Concomitant use may increase maraviroc exposure. Maraviroc is a P-gp substrate; gilteritinib is a P-gp inhibitor.
    Glecaprevir; Pibrentasvir: (Moderate) Use caution and closely monitor for increased adverse effects during concurrent administration of maraviroc and glecaprevir as increased maraviroc concentrations may occur. Maraviroc is a substrate of P-glycoprotein (P-gp) and organic anion-transporting polypeptide (OATP1B1); glecaprevir is an inhibitor of P-gp and OATP1B1. The effects of these transporters on the concentrations of maraviroc are unknown, although an increase in concentrations and thus, toxicity, are possible. (Moderate) Use caution and closely monitor for increased adverse effects during concurrent administration of maraviroc and pibrentasvir as increased maraviroc concentrations may occur. Maraviroc is a substrate of P-glycoprotein (P-gp) and organic anion-transporting polypeptide (OATP1B1); pibrentasvir is an inhibitor of P-gp and OATP1B1. The effects of these transporters on the concentrations of maraviroc are unknown, although an increase in concentrations and thus, toxicity, are possible.
    Grapefruit juice: (Major) Advise patients to avoid grapefruit and grapefruit juice during maraviroc therapy. Coadministration of maraviroc, a CYP3A substrate, with grapefruit juice, a strong CYP3A4 inhibitor, may result in increased maraviroc concentrations and increased side effects. Reduce the dose of maraviroc when it is used with other strong CYP3A inhibitors; coadministration of maraviroc with strong CYP3A inhibitors is contraindicated in patients with CrCl less than 30 mL/minute.
    Idelalisib: (Major) Coadministration of idelalisib, a strong CYP3A4 inhibitor, and maraviroc, a CYP3A4 substrate, may result in elevated maraviroc concentrations. According to the manufacturer of idelalisib, concomitant use of idelalisib and CYP3A substrates should be avoided. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. According to the manufacturer of maraviroc, a reduced adult maraviroc dose of 150 mg PO twice daily is recommended when it is administered in the presence of a CYP3A inhibitor, with or without a concomitant CYP3A inducer. Coadministration of maraviroc with strong CYP3A inhibitors is contraindicated in patients with CrCl less than 30 mL/min. Dose recommendations in pediatrics are: 150 mg PO twice daily for children weighing 40 kg or more, 100 mg PO twice daily for children weighing 30 to 39 kg, 75 mg PO twice daily (or 80 mg PO twice daily for solution) for children weighing 20 to 29 kg, 50 mg PO twice daily for children weighing 10 to 19 kg, and use is not recommended in children weighing 2 to 9 kg.
    Imatinib: (Moderate) Use caution if coadministration of maraviroc with imatinib is necessary, due to a possible increase in maraviroc exposure. Maraviroc is a CYP3A substrate and imatinib is a CYP3A4 inhibitor. Monitor for an increase in adverse effects with concomitant use.
    Indinavir: (Major) Coadministration of maraviroc, a CYP3A substrate, with indinavir, a strong CYP3A4 inhibitor, may result in increased maraviroc concentrations. Reduce the dose of maraviroc when coadministered with strong CYP3A inhibitors; coadministration of maraviroc with strong CYP3A inhibitors is contraindicated in patients with CrCl less than 30 mL/min. Adjust the maraviroc dosage as follows when administered with indinavir (with or without a concomitant CYP3A inducer): adults and children weighing 40 kg or more: 150 mg PO twice daily; children weighing 30 to 39 kg: 100 mg PO twice daily; children weighing 20 to 29 kg: 75 mg PO twice daily (or 80 mg PO twice daily for solution); children weighing 10 to 19 kg: 50 mg PO twice daily; children weighing 2 to 9 kg: use not recommended.
    Isavuconazonium: (Moderate) Use caution if coadministration of maraviroc with isavuconazonium is necessary, due to a possible increase in maraviroc exposure. Maraviroc is a CYP3A/P-glycoprotein (P-gp) substrate and isavuconazole, the active moiety of isavuconazonium, is a CYP3A4/P-gp inhibitor. Monitor for an increase in adverse effects with concomitant use.
    Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Coadministration of maraviroc, a CYP3A/P-glycoprotein (P-gp) substrate, and rifampin, a strong CYP3A inducer and P-gp inducer, without a concomitant strong CYP3A inhibitor significantly decreases maraviroc concentrations. Consider using rifabutin instead of rifampin in patients receiving maraviroc. However, if rifampin must be used, the adult maraviroc dose should be increased to 600 mg PO twice daily when coadministered with rifampin without a concomitant strong CYP3A inhibitor. Coadministration of maraviroc and rifampin is contraindicated in patients with CrCl less than 30 mL/min. For pediatric patients, concomitant use of maraviroc with a strong CYP3A inducer, without a strong CYP3A inhibitor, is not recommended. If the patient's medication regimen also contains a strong CYP3A inhibitor, the CYP3A inhibitor's actions are expected to exceed that of the inducer; overall, increased maraviroc concentrations are expected.
    Isoniazid, INH; Rifampin: (Major) Coadministration of maraviroc, a CYP3A/P-glycoprotein (P-gp) substrate, and rifampin, a strong CYP3A inducer and P-gp inducer, without a concomitant strong CYP3A inhibitor significantly decreases maraviroc concentrations. Consider using rifabutin instead of rifampin in patients receiving maraviroc. However, if rifampin must be used, the adult maraviroc dose should be increased to 600 mg PO twice daily when coadministered with rifampin without a concomitant strong CYP3A inhibitor. Coadministration of maraviroc and rifampin is contraindicated in patients with CrCl less than 30 mL/min. For pediatric patients, concomitant use of maraviroc with a strong CYP3A inducer, without a strong CYP3A inhibitor, is not recommended. If the patient's medication regimen also contains a strong CYP3A inhibitor, the CYP3A inhibitor's actions are expected to exceed that of the inducer; overall, increased maraviroc concentrations are expected.
    Itraconazole: (Major) Reduce the dose of maraviroc when coadministered with itraconazole; coadministration is contraindicated in patients with CrCl less than 30 mL/min. Coadministration of maraviroc, a CYP3A/P-gp substrate, with itraconazole, a strong CYP3A4 inhibitor and P-gp inhibitor, may result in increased maraviroc concentrations. Maraviroc dosage adjustments are as follows when administered with itraconazole (with or without a concomitant CYP3A inducer): adults and children weighing 40 kg or more: 150 mg PO twice daily; children weighing 30 to 39 kg: 100 mg PO twice daily; children weighing 20 to 29 kg: 75 mg PO twice daily (or 80 mg PO twice daily for solution); children weighing 10 to 19 kg: 50 mg PO twice daily; children weighing 2 to 9 kg: use not recommended.
    Ivacaftor: (Minor) Use caution if coadministration of maraviroc with ivacaftor is necessary, due to a possible increase in maraviroc exposure. Maraviroc is a CYP3A and P-glycoprotein (Pgp) substrate and ivacaftor is a weak CYP3A4/Pgp inhibitor. Monitor for an increase in adverse effects with concomitant use.
    Ixabepilone: (Minor) Ixabepilone is a weak inhibitor of P-glycoprotein (Pgp). Maraviroc is a Pgp substrate, and concomitant use of ixabepilone with a Pgp substrate may cause an increase in maraviroc concentrations. Use caution if ixabepilone is coadministered with a Pgp substrate.
    Ketoconazole: (Major) Coadministration of maraviroc, a CYP3A/P-gp substrate, with ketoconazole, a strong CYP3A4 inhibitor and P-gp inhibitor, may result in increased maraviroc concentrations. Reduce the dose of maraviroc when coadministered with strong CYP3A inhibitors; coadministration of maraviroc with strong CYP3A inhibitors is contraindicated in patients with CrCl less than 30 mL/min. Adjust the maraviroc dosage as follows when administered with ketoconazole (with or without a concomitant CYP3A inducer): adults and children weighing 40 kg or more: 150 mg PO twice daily; children weighing 30 to 39 kg: 100 mg PO twice daily; children weighing 20 to 29 kg: 75 mg PO twice daily (or 80 mg PO twice daily for solution); children weighing 10 to 19 kg: 50 mg PO twice daily; children weighing 2 to 9 kg: use not recommended.
    Lansoprazole; Amoxicillin; Clarithromycin: (Major) Coadministration of maraviroc (a substrate of CYP3A, P-gp, and OATP1B1) with clarithromycin (a strong CYP3A4 inhibitor and P-gp/OATP1B1 inhibitor) may result in increased maraviroc concentrations. Reduce the dose of maraviroc when coadministered with strong CYP3A inhibitors; coadministration of maraviroc with strong CYP3A inhibitors is contraindicated in patients with CrCl less than 30 mL/min. Adjust the maraviroc dosage as follows when administered with clarithromycin (with or without a concomitant CYP3A inducer): adults and children weighing 40 kg or more: 150 mg PO twice daily; children weighing 30 to 39 kg: 100 mg PO twice daily; children weighing 20 to 29 kg: 75 mg PO twice daily (or 80 mg PO twice daily for solution); children weighing 10 to 19 kg: 50 mg PO twice daily; children weighing 2 to 9 kg: use not recommended.
    Lapatinib: (Moderate) Monitor for an increase in maraviroc-related adverse reactions if coadministration with lapatinib is necessary. Maraviroc is a P-glycoprotein (P-gp) substrate and lapatinib is a P-gp inhibitor. Concomitant use may increase maraviroc exposure.
    Ledipasvir; Sofosbuvir: (Minor) Use caution and closely monitor for increased adverse effects with the coadministration of maraviroc and ledipasvir as increased maraviroc concentrations may occur. Maraviroc is a substrate of P-glycoprotein (P-gp); ledipasvir is a weak inhibitor of P-gp. The effects of P-gp on the concentrations of maraviroc are unknown, although an increase in concentrations and thus, toxicity, are possible.
    Leflunomide: (Moderate) Use caution and closely monitor for increased adverse effects during concurrent administration of maraviroc and leflunomide as increased maraviroc concentrations may occur. Maraviroc is a substrate of organic anion-transporting polypeptide (OATP1B1); leflunomide is an inhibitor of OATP1B1. The effects of this transporter on the concentrations of maraviroc are unknown, although an increase in concentrations and thus, toxicity, are possible.
    Lesinurad: (Minor) Use caution if coadministration of maraviroc with lesinurad is necessary, due to a possible decrease in maraviroc exposure. Maraviroc is a CYP3A substrate and lesinurad is a weak CYP3A4 inducer. Monitor for a decrease in efficacy with concomitant use.
    Lesinurad; Allopurinol: (Minor) Use caution if coadministration of maraviroc with lesinurad is necessary, due to a possible decrease in maraviroc exposure. Maraviroc is a CYP3A substrate and lesinurad is a weak CYP3A4 inducer. Monitor for a decrease in efficacy with concomitant use.
    Letermovir: (Moderate) Administering letermovir with maraviroc may increase maraviroc concentration and risk for adverse events. In patients also receiving cyclosporine, reduce maraviroc adult dose to 150 mg twice daily (weight based dose reductions also recommended for pediatric patients), because the magnitude of the interaction may be amplified. In patients with severe renal impairment, use of maraviroc with both letermovir and cyclosporine is contraindicated. Maraviroc is primarily metabolized by CYP3A4 and is a substrate of organic anion-transporting polypeptide (OATP1B). Letermovir is a moderate CYP3A4 and OATP1B1 inhibitor; however, when given with cyclosporine, the combined effect on CYP3A4 substrates may be similar to a strong CYP3A4 inhibitor.
    Levamlodipine: (Minor) Use caution if coadministration of maraviroc with amlodipine is necessary, due to a possible increase in maraviroc exposure. Maraviroc is a CYP3A substrate and amlodipine is a weak CYP3A4 inhibitor. Monitor for an increase in adverse effects with concomitant use.
    Levoketoconazole: (Major) Coadministration of maraviroc, a CYP3A/P-gp substrate, with ketoconazole, a strong CYP3A4 inhibitor and P-gp inhibitor, may result in increased maraviroc concentrations. Reduce the dose of maraviroc when coadministered with strong CYP3A inhibitors; coadministration of maraviroc with strong CYP3A inhibitors is contraindicated in patients with CrCl less than 30 mL/min. Adjust the maraviroc dosage as follows when administered with ketoconazole (with or without a concomitant CYP3A inducer): adults and children weighing 40 kg or more: 150 mg PO twice daily; children weighing 30 to 39 kg: 100 mg PO twice daily; children weighing 20 to 29 kg: 75 mg PO twice daily (or 80 mg PO twice daily for solution); children weighing 10 to 19 kg: 50 mg PO twice daily; children weighing 2 to 9 kg: use not recommended.
    Lomitapide: (Moderate) Concomitant use of lomitapide and maraviroc may result in increased serum concentrations of maraviroc. According to the manufacturer of lomitapide, dose reduction of maraviroc should be considered during concurrent use. Lomitapide is an inhibitor of P-glycoprotein (P-gp) and maraviroc is a P-gp substrate.
    Lonafarnib: (Major) Reduce the dose of maraviroc when coadministration with lonafarnib is necessary, regardless of whether the patient is receiving a concomitant strong CYP3A inducer. The effect of lonafarnib on maraviroc exposure is expected to exceed that of the inducer and overall, increased maraviroc concentrations are expected. Coadministration of maraviroc with lonafarnib is contraindicated in patients with CrCl less than 30 mL/min. Recommendations for reducing the maraviroc dose when administered with lonafarnib (with or without a concomitant CYP3A inducer) are: adults and children weighing 40 kg or more: 150 mg PO twice daily; children weighing 30 to 39 kg: 100 mg PO twice daily; children weighing 20 to 29 kg: 75 mg PO twice daily (or 80 mg PO twice daily for solution); children weighing 10 to 19 kg: 50 mg PO twice daily. Maraviroc is a sensitive CYP3A and P-gp substrate and lonafarnib is a strong CYP3A and P-gp inhibitor.
    Lopinavir; Ritonavir: (Major) Coadministration of maraviroc (a substrate of CYP3A, P-gp, MRP2) with ritonavir (a strong CYP3A4 inhibitor and P-gp/MRP2 inhibitor) has been reported to significantly increase maraviroc concentrations. Reduce the dose of maraviroc when coadministered with strong CYP3A inhibitors; coadministration of maraviroc with strong CYP3A inhibitors is contraindicated in patients with CrCl less than 30 mL/min. Adjust the maraviroc dosage as follows when administered with ritonavir (with or without a concomitant CYP3A inducer): adults and children weighing 40 kg or more: 150 mg PO twice daily; children weighing 30 to 39 kg: 100 mg PO twice daily; children weighing 20 to 29 kg: 75 mg PO twice daily (or 80 mg PO twice daily for solution); children weighing 10 to 19 kg: 50 mg PO twice daily; children weighing 2 to 9 kg: use not recommended. (Major) Coadministration of maraviroc, a substrate of organic anion-transporting polypeptide (OATP1B1), with lopinavir, a OATP1B1 inhibitor, has been reported to increase maraviroc exposure. Adjust the maraviroc dosage as follows when administered with lopinavir; ritonavir (with or without a concomitant CYP3A inducer): adults and children weighing 40 kg or more: 150 mg PO twice daily; children weighing 30 to 39 kg: 100 mg PO twice daily; children weighing 20 to 29 kg: 75 mg PO twice daily (or 80 mg PO twice daily for solution); children weighing 10 to 19 kg: 50 mg PO twice daily; children weighing 2 to 9 kg: use not recommended.
    Lorlatinib: (Moderate) Monitor for a decrease in the efficacy of maraviroc if coadministration with lorlatinib is necessary. Maraviroc is a CYP3A4 substrate and a P-glycoprotein (P-gp) substrate. Lorlatinib is a moderate CYP3A4 inducer as well as a P-gp inducer.
    Lumacaftor; Ivacaftor: (Major) Coadministration of maraviroc, a CYP3A substrate, and lumacaftor; ivacaftor, a strong CYP3A inducer, without a concomitant strong CYP3A inhibitor may decrease maraviroc concentrations, therefore, the adult maraviroc dose should be increased to 600 mg PO twice daily when coadministered with lumacaftor; ivacaftor without a concomitant strong CYP3A inhibitor. Coadministration of maraviroc and lumacaftor; ivacaftor is contraindicated in patients with CrCl less than 30 mL/min. For pediatric patients, concomitant use of maraviroc with a strong CYP3A inducer, without a strong CYP3A inhibitor, is not recommended. If the patient's medication regimen also contains a strong CYP3A inhibitor, the CYP3A inhibitor's actions are expected to exceed that of the inducer; overall, increased maraviroc concentrations are expected.
    Lumacaftor; Ivacaftor: (Minor) Use caution if coadministration of maraviroc with ivacaftor is necessary, due to a possible increase in maraviroc exposure. Maraviroc is a CYP3A and P-glycoprotein (Pgp) substrate and ivacaftor is a weak CYP3A4/Pgp inhibitor. Monitor for an increase in adverse effects with concomitant use.
    Maribavir: (Moderate) Monitor for an increase in maraviroc-related adverse reactions if coadministration with maribavir is necessary. Concomitant use may increase maraviroc exposure. Maraviroc is a P-gp substrate; maribavir is a P-gp inhibitor.
    Mefloquine: (Moderate) Use caution and closely monitor for increased adverse effects with the coadministration of maraviroc and mefloquine as increased maraviroc concentrations may occur. Maraviroc is a substrate of P-glycoprotein (P-gp); mefloquine is an inhibitor of P-gp. The effects of P-gp on the concentrations of maraviroc are unknown, although an increase in concentrations and thus, toxicity, are possible.
    Midostaurin: (Moderate) Monitor for an increase in maraviroc-related adverse reactions if coadministration with midostaurin is necessary. Concurrent use may increase the plasma concentrations of maraviroc. Maraviroc is an OATP1B1 substrate; midostaurin is an OATP1B1 inhibitor.
    Mifepristone: (Moderate) Use caution if coadministration of maraviroc with mifepristone is necessary, due to a possible increase in maraviroc exposure. Maraviroc is a CYP3A/P-glycoprotein (P-gp) substrate and mifepristone is a CYP3A4/P-gp inhibitor. Monitor for an increase in adverse effects with concomitant use.
    Mitapivat: (Moderate) Monitor for an increase in maraviroc-related adverse reactions if coadministration with mitapivat is necessary. Concomitant use may increase maraviroc exposure. Maraviroc is a P-gp substrate; mitapivat is a P-gp inhibitor.
    Mitotane: (Major) Coadministration of maraviroc, a CYP3A substrate, and mitotane, a strong CYP3A inducer, without a concomitant strong CYP3A inhibitor may decrease maraviroc concentrations, therefore, the adult maraviroc dose should be increased to 600 mg PO twice daily when coadministered with mitotane without a concomitant strong CYP3A inhibitor. Coadministration of maraviroc and mitotane is contraindicated in patients with CrCl less than 30 mL/min. For pediatric patients, concomitant use of maraviroc with a strong CYP3A inducer, without a strong CYP3A inhibitor, is not recommended. If the patient's medication regimen also contains a strong CYP3A inhibitor, the CYP3A inhibitor's actions are expected to exceed that of the inducer; overall, increased maraviroc concentrations are expected.
    Modafinil: (Moderate) Use caution if coadministration of maraviroc with modafinil is necessary, due to a possible decrease in maraviroc exposure. Maraviroc is a CYP3A substrate and modafinil is a CYP3A4 inducer. Monitor for a decrease in maraviroc efficacy with concomitant use.
    Nafcillin: (Moderate) Use caution if coadministration of maraviroc with nafcillin is necessary, due to a possible decrease in maraviroc exposure. Maraviroc is a CYP3A substrate and nafcillin is a CYP3A4 inducer. Monitor for a decrease in maraviroc efficacy with concomitant use.
    Nefazodone: (Major) Coadministration of maraviroc, a CYP3A substrate, with nefazodone, a strong CYP3A4 inhibitor, may result in increased maraviroc concentrations. Reduce the dose of maraviroc when coadministered with strong CYP3A inhibitors; coadministration of maraviroc with strong CYP3A inhibitors is contraindicated in patients with CrCl less than 30 mL/min. Adjust the maraviroc dosage as follows when administered with nefazodone (with or without a concomitant CYP3A inducer): adults and children weighing 40 kg or more: 150 mg PO twice daily; children weighing 30 to 39 kg: 100 mg PO twice daily; children weighing 20 to 29 kg: 75 mg PO twice daily (or 80 mg PO twice daily for solution); children weighing 10 to 19 kg: 50 mg PO twice daily; children weighing 2 to 9 kg: use not recommended.
    Nelfinavir: (Major) Coadministration of maraviroc, a CYP3A/P-gp substrate, with nelfinavir, a strong CYP3A4 inhibitor and P-gp inhibitor, may result in increased maraviroc concentrations. Reduce the dose of maraviroc when coadministered with strong CYP3A inhibitors; coadministration of maraviroc with strong CYP3A inhibitors is contraindicated in patients with CrCl less than 30 mL/min. Adjust the maraviroc dosage as follows when administered with nelfinavir (with or without a concomitant CYP3A inducer): adults and children weighing 40 kg or more: 150 mg PO twice daily; children weighing 30 to 39 kg: 100 mg PO twice daily; children weighing 20 to 29 kg: 75 mg PO twice daily (or 80 mg PO twice daily for solution); children weighing 10 to 19 kg: 50 mg PO twice daily; children weighing 2 to 9 kg: use not recommended.
    Neratinib: (Moderate) Monitor for an increase in maraviroc-related adverse reactions if coadministration with neratinib is necessary. Concurrent use may increase the plasma concentrations of maraviroc. Maraviroc is a P-glycoprotein (P-gp) substrate; neratinib is a P-gp inhibitor.
    Netupitant, Fosnetupitant; Palonosetron: (Moderate) Use caution if coadministration of maraviroc with netupitant is necessary, due to a possible increase in maraviroc exposure. Maraviroc is a CYP3A substrate and netupitant is a CYP3A4 inhibitor; the inhibitory effect on CYP3A4 can last for multiple days. Monitor for an increase in adverse effects with concomitant use.
    Nicardipine: (Moderate) Monitor for an increase in adverse effects with concomitant use of maraviroc and nicardipine due to a possible increase in maraviroc exposure. Maraviroc is a CYP3A and nicardipine is a CYP3A4 inhibitor.
    Nifedipine: (Minor) Use caution and careful monitoring with the coadministration of maraviroc and nifedipine as increased maraviroc concentrations may occur. Maraviroc is a substrate of P-glycoprotein (Pgp); nifedipine is a mild inhibitor of Pgp. The effects of Pgp on the concentrations of maraviroc are unknown, although an increase in concentrations and thus, toxicity, are possible.
    Nirmatrelvir; Ritonavir: (Major) Coadministration of maraviroc (a substrate of CYP3A, P-gp, MRP2) with ritonavir (a strong CYP3A4 inhibitor and P-gp/MRP2 inhibitor) has been reported to significantly increase maraviroc concentrations. Reduce the dose of maraviroc when coadministered with strong CYP3A inhibitors; coadministration of maraviroc with strong CYP3A inhibitors is contraindicated in patients with CrCl less than 30 mL/min. Adjust the maraviroc dosage as follows when administered with ritonavir (with or without a concomitant CYP3A inducer): adults and children weighing 40 kg or more: 150 mg PO twice daily; children weighing 30 to 39 kg: 100 mg PO twice daily; children weighing 20 to 29 kg: 75 mg PO twice daily (or 80 mg PO twice daily for solution); children weighing 10 to 19 kg: 50 mg PO twice daily; children weighing 2 to 9 kg: use not recommended.
    Obeticholic Acid: (Moderate) Use caution and closely monitor for increased adverse effects during concurrent administration of maraviroc and obeticholic acid as increased maraviroc concentrations may occur. Maraviroc is a substrate of organic anion-transporting polypeptide (OATP1B1); obeticholic acid is an inhibitor of OATP1B1. The effects of this transporter on the concentrations of maraviroc are unknown, although an increase in concentrations and thus, toxicity, are possible.
    Octreotide: (Moderate) Use caution if coadministration of maraviroc with octreotide is necessary, due to a possible increase in maraviroc exposure. Maraviroc is a CYP3A substrate and octreotide is a CYP3A4 inhibitor. Monitor for an increase in adverse effects with concomitant use.
    Olanzapine; Fluoxetine: (Minor) Use caution if coadministration of maraviroc with fluoxetine is necessary, due to a possible increase in maraviroc exposure. Maraviroc is a CYP3A substrate and fluoxetine is a weak CYP3A4 inhibitor. Monitor for an increase in adverse effects with concomitant use.
    Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Minor) Use caution if coadministration of maraviroc with amlodipine is necessary, due to a possible increase in maraviroc exposure. Maraviroc is a CYP3A substrate and amlodipine is a weak CYP3A4 inhibitor. Monitor for an increase in adverse effects with concomitant use.
    Ombitasvir; Paritaprevir; Ritonavir: (Major) Coadministration of maraviroc (a substrate of CYP3A, P-gp, MRP2) with ritonavir (a strong CYP3A4 inhibitor and P-gp/MRP2 inhibitor) has been reported to significantly increase maraviroc concentrations. Reduce the dose of maraviroc when coadministered with strong CYP3A inhibitors; coadministration of maraviroc with strong CYP3A inhibitors is contraindicated in patients with CrCl less than 30 mL/min. Adjust the maraviroc dosage as follows when administered with ritonavir (with or without a concomitant CYP3A inducer): adults and children weighing 40 kg or more: 150 mg PO twice daily; children weighing 30 to 39 kg: 100 mg PO twice daily; children weighing 20 to 29 kg: 75 mg PO twice daily (or 80 mg PO twice daily for solution); children weighing 10 to 19 kg: 50 mg PO twice daily; children weighing 2 to 9 kg: use not recommended. (Moderate) Use caution and closely monitor for increased adverse effects during concurrent administration of maraviroc and paritaprevir as increased maraviroc concentrations may occur. Maraviroc is a substrate of organic anion-transporting polypeptide (OATP1B1); paritaprevir is an inhibitor of OATP1B1. The effects of this transporter on the concentrations of maraviroc are unknown, although an increase in concentrations and thus, toxicity, are possible.
    Omeprazole; Amoxicillin; Rifabutin: (Moderate) Use caution if coadministration of maraviroc with rifabutin is necessary, due to a possible decrease in maraviroc exposure. Maraviroc is a CYP3A substrate and rifabutin is a CYP3A4 inducer. Monitor for a decrease in maraviroc efficacy with concomitant use.
    Oritavancin: (Minor) Use caution if coadministration of maraviroc with oritavancin is necessary, due to a possible decrease in maraviroc exposure. Maraviroc is a CYP3A substrate and oritavancin is a weak CYP3A4 inducer. Monitor for a decrease in maraviroc efficacy with concomitant use.
    Osimertinib: (Moderate) Monitor for an increase in maraviroc-related adverse reactions if coadministration with osimertinib is necessary. Maraviroc is a P-glycoprotein (P-gp) substrate and osimertinib is a P-gp inhibitor. Concomitant use may increase maraviroc exposure.
    Oxcarbazepine: (Moderate) Use caution if coadministration of maraviroc with oxcarbazepine is necessary, due to a possible decrease in maraviroc exposure. Maraviroc is a CYP3A substrate and oxcarbazepine is a CYP3A4 inducer. Monitor for a decrease in maraviroc efficacy with concomitant use.
    Pacritinib: (Moderate) Monitor for an increase in maraviroc-related adverse reactions if coadministration with pacritinib is necessary. Concomitant use may increase maraviroc exposure. Maraviroc is a P-gp substrate; pacritinib is a P-gp inhibitor.
    Pazopanib: (Minor) Use caution if coadministration of maraviroc with pazopanib is necessary, due to a possible increase in maraviroc exposure. Maraviroc is a CYP3A substrate and pazopanib is a weak CYP3A4 inhibitor. Monitor for an increase in adverse effects with concomitant use.
    Perampanel: (Minor) Use caution if coadministration of maraviroc with perampanel is necessary, due to a possible decrease in maraviroc exposure. Maraviroc is a CYP3A substrate and perampanel is a weak CYP3A4 inducer. Monitor for a decrease in efficacy with concomitant use.
    Perindopril; Amlodipine: (Minor) Use caution if coadministration of maraviroc with amlodipine is necessary, due to a possible increase in maraviroc exposure. Maraviroc is a CYP3A substrate and amlodipine is a weak CYP3A4 inhibitor. Monitor for an increase in adverse effects with concomitant use.
    Pexidartinib: (Moderate) Be aware of the potential for decreased plasma concentrations of maraviroc if coadministration with pexidartinib is necessary, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Maraviroc is a sensitive CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer.
    Phenobarbital: (Major) Coadministration of maraviroc, a CYP3A/P-glycoprotein (P-gp) substrate, and phenobarbital, a strong CYP3A inducer and P-gp inducer, without a concomitant strong CYP3A inhibitor may decrease maraviroc concentrations, therefore, the adult maraviroc dose should be increased to 600 mg PO twice daily when coadministered with phenobarbital without a concomitant strong CYP3A inhibitor. Coadministration of maraviroc and phenobarbital is contraindicated in patients with CrCl less than 30 mL/min. For pediatric patients, concomitant use of maraviroc with a strong CYP3A inducer, without a strong CYP3A inhibitor, is not recommended. If the patient's medication regimen also contains a strong CYP3A inhibitor, the CYP3A inhibitor's actions are expected to exceed that of the inducer; overall, increased maraviroc concentrations are expected.
    Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Coadministration of maraviroc, a CYP3A/P-glycoprotein (P-gp) substrate, and phenobarbital, a strong CYP3A inducer and P-gp inducer, without a concomitant strong CYP3A inhibitor may decrease maraviroc concentrations, therefore, the adult maraviroc dose should be increased to 600 mg PO twice daily when coadministered with phenobarbital without a concomitant strong CYP3A inhibitor. Coadministration of maraviroc and phenobarbital is contraindicated in patients with CrCl less than 30 mL/min. For pediatric patients, concomitant use of maraviroc with a strong CYP3A inducer, without a strong CYP3A inhibitor, is not recommended. If the patient's medication regimen also contains a strong CYP3A inhibitor, the CYP3A inhibitor's actions are expected to exceed that of the inducer; overall, increased maraviroc concentrations are expected.
    Phentermine; Topiramate: (Minor) Use caution if coadministration of maraviroc with topiramate is necessary, due to a possible decrease in maraviroc exposure. Maraviroc is a CYP3A substrate and topiramate is a CYP3A4 inducer. Monitor for a decrease in maraviroc efficacy with concomitant use.
    Phenytoin: (Major) Coadministration of maraviroc, a CYP3A substrate, and phenytoin, a strong CYP3A inducer, without a concomitant strong CYP3A inhibitor may decrease maraviroc concentrations, therefore, the adult maraviroc dose should be increased to 600 mg PO twice daily when coadministered with phenytoin without a concomitant strong CYP3A inhibitor. Coadministration of maraviroc and phenytoin is contraindicated in patients with CrCl less than 30 mL/min. For pediatric patients, concomitant use of maraviroc with a strong CYP3A inducer, without a strong CYP3A inhibitor, is not recommended. If the patient's medication regimen also contains a strong CYP3A inhibitor, the CYP3A inhibitor's actions are expected to exceed that of the inducer; overall, increased maraviroc concentrations are expected.
    Pirfenidone: (Minor) Use caution and closely monitor for increased adverse effects with the coadministration of maraviroc and pirfenidone as increased maraviroc concentrations may occur. Maraviroc is a substrate of CYP3A and P-glycoprotein (P-gp); pirfenidone is a weak inhibitor of CYP3A4 and P-gp. The effects of P-gp on the concentrations of maraviroc are unknown, although an increase in concentrations and thus, toxicity, are possible.
    Posaconazole: (Major) Coadministration of maraviroc, a CYP3A/P-gp substrate, with posaconazole, a strong CYP3A4 inhibitor and P-gp inhibitor, may result in increased maraviroc concentrations. Reduce the dose of maraviroc when coadministered with strong CYP3A inhibitors; coadministration of maraviroc with strong CYP3A inhibitors is contraindicated in patients with CrCl less than 30 mL/min. Adjust the maraviroc dosage as follows when administered with posaconazole (with or without a concomitant CYP3A inducer): adults and children weighing 40 kg or more: 150 mg PO twice daily; children weighing 30 to 39 kg: 100 mg PO twice daily; children weighing 20 to 29 kg: 75 mg PO twice daily (or 80 mg PO twice daily for solution); children weighing 10 to 19 kg: 50 mg PO twice daily; children weighing 2 to 9 kg: use not recommended.
    Primidone: (Major) Coadministration of maraviroc, a CYP3A/P-glycoprotein (P-gp) substrate, and primidone, a strong CYP3A inducer and P-gp inducer, without a concomitant strong CYP3A inhibitor may decrease maraviroc concentrations, therefore, the adult maraviroc dose should be increased to 600 mg PO twice daily when coadministered with primidone without a concomitant strong CYP3A inhibitor. Coadministration of maraviroc and primidone is contraindicated in patients with CrCl less than 30 mL/min. For pediatric patients, concomitant use of maraviroc with a strong CYP3A inducer, without a strong CYP3A inhibitor, is not recommended. If the patient's medication regimen also contains a strong CYP3A inhibitor, the CYP3A inhibitor's actions are expected to exceed that of the inducer; overall, increased maraviroc concentrations are expected.
    Probenecid: (Moderate) Use caution and closely monitor for increased adverse effects during concurrent administration of maraviroc and probenecid as increased maraviroc concentrations may occur. Maraviroc is a substrate of multidrug resistance-associated protein (MRP2); probenecid is an inhibitor of MRP2. The effects of this transporter on the concentrations of maraviroc are unknown, although an increase in concentrations and thus, toxicity, are possible.
    Probenecid; Colchicine: (Moderate) Use caution and closely monitor for increased adverse effects during concurrent administration of maraviroc and probenecid as increased maraviroc concentrations may occur. Maraviroc is a substrate of multidrug resistance-associated protein (MRP2); probenecid is an inhibitor of MRP2. The effects of this transporter on the concentrations of maraviroc are unknown, although an increase in concentrations and thus, toxicity, are possible.
    Propafenone: (Moderate) Use caution and careful monitoring with the coadministration of maraviroc and propafenone as increased maraviroc concentrations may occur. Maraviroc is a substrate of P-glycoprotein (P-gp); propafenone is an inhibitor of P-gp. The effects of P-gp on the concentrations of maraviroc are unknown, although an increase in concentrations and thus, toxicity, are possible.
    Propoxyphene: (Moderate) Use caution if coadministration of maraviroc with propoxyphene is necessary, due to a possible increase in maraviroc exposure. Maraviroc is a CYP3A substrate and propoxyphene is a CYP3A4 inhibitor. Monitor for an increase in adverse effects.
    Quinidine: (Moderate) Use caution and careful monitoring with the coadministration of maraviroc and quinidine as increased maraviroc concentrations may occur. Maraviroc is a substrate of P-glycoprotein (P-gp); quinidine is an inhibitor of P-gp. The effects of P-gp on the concentrations of maraviroc are unknown, although an increase in concentrations and thus, toxicity, are possible.
    Quinine: (Moderate) Use caution if coadministration of maraviroc with quinine is necessary as altered maraviroc concentrations may occur. Maraviroc is a substrate of CYP3A; quinine is an inhibitor and inducer of CYP3A4. Monitor for decreased efficacy and/or an increase in adverse effects with concomitant use.
    Ranolazine: (Moderate) Use caution and careful monitoring with the coadministration of maraviroc and ranolazine as increased maraviroc concentrations may occur. Maraviroc is a substrate of P-glycoprotein (P-gp) and CYP3A; ranolazine is an inhibitor of P-gp and a weak in vitro inhibitor of CYP3A. The effects of P-gp on the concentrations of maraviroc are unknown, although an increase in concentrations and thus, toxicity, are possible.
    Ribociclib: (Major) Reduce the dose of maraviroc when coadministered with strong CYP3A inhibitors such as ribociclib; coadministration of maraviroc with strong CYP3A inhibitors is contraindicated in patients with CrCL less than 30 mL/min. Adjust the maraviroc dosage as follows when administered with ribociclib (with or without a concomitant CYP3A inducer): adults and children weighing 40 kg or more: 150 mg PO twice daily; children weighing 30 to 39 kg: 100 mg PO twice daily; children weighing 20 to 29 kg: 75 mg PO twice daily (or 80 mg PO twice daily for solution); children weighing 10 to 19 kg: 50 mg PO twice daily; children weighing 2 to 9 kg: use not recommended.
    Ribociclib; Letrozole: (Major) Reduce the dose of maraviroc when coadministered with strong CYP3A inhibitors such as ribociclib; coadministration of maraviroc with strong CYP3A inhibitors is contraindicated in patients with CrCL less than 30 mL/min. Adjust the maraviroc dosage as follows when administered with ribociclib (with or without a concomitant CYP3A inducer): adults and children weighing 40 kg or more: 150 mg PO twice daily; children weighing 30 to 39 kg: 100 mg PO twice daily; children weighing 20 to 29 kg: 75 mg PO twice daily (or 80 mg PO twice daily for solution); children weighing 10 to 19 kg: 50 mg PO twice daily; children weighing 2 to 9 kg: use not recommended.
    Rifabutin: (Moderate) Use caution if coadministration of maraviroc with rifabutin is necessary, due to a possible decrease in maraviroc exposure. Maraviroc is a CYP3A substrate and rifabutin is a CYP3A4 inducer. Monitor for a decrease in maraviroc efficacy with concomitant use.
    Rifampin: (Major) Coadministration of maraviroc, a CYP3A/P-glycoprotein (P-gp) substrate, and rifampin, a strong CYP3A inducer and P-gp inducer, without a concomitant strong CYP3A inhibitor significantly decreases maraviroc concentrations. Consider using rifabutin instead of rifampin in patients receiving maraviroc. However, if rifampin must be used, the adult maraviroc dose should be increased to 600 mg PO twice daily when coadministered with rifampin without a concomitant strong CYP3A inhibitor. Coadministration of maraviroc and rifampin is contraindicated in patients with CrCl less than 30 mL/min. For pediatric patients, concomitant use of maraviroc with a strong CYP3A inducer, without a strong CYP3A inhibitor, is not recommended. If the patient's medication regimen also contains a strong CYP3A inhibitor, the CYP3A inhibitor's actions are expected to exceed that of the inducer; overall, increased maraviroc concentrations are expected.
    Rifapentine: (Major) The HIV guidelines recommend avoiding coadministration of maraviroc and rifapentine as decreased concentrations of maraviroc are expected. Maraviroc is a substrate of CYP3A and rifapentine is a CYP3A4 inducer. However, if the patient's medication regimen also contains a strong CYP3A inhibitor, the CYP3A inhibitor's actions are expected to exceed that of the inducer; overall, increased maraviroc concentrations are expected. Monitor for decreased efficacy if coadministration is necessary.
    Rifaximin: (Minor) Use caution and closely monitor for increased adverse effects with the coadministration of maraviroc and rifaximin as increased maraviroc concentrations may occur. Maraviroc is a substrate of P-glycoprotein (P-gp); rifaximin is a mild inhibitor of P-gp. The effects of P-gp on the concentrations of maraviroc are unknown, although an increase in concentrations and thus, toxicity, are possible.
    Ritonavir: (Major) Coadministration of maraviroc (a substrate of CYP3A, P-gp, MRP2) with ritonavir (a strong CYP3A4 inhibitor and P-gp/MRP2 inhibitor) has been reported to significantly increase maraviroc concentrations. Reduce the dose of maraviroc when coadministered with strong CYP3A inhibitors; coadministration of maraviroc with strong CYP3A inhibitors is contraindicated in patients with CrCl less than 30 mL/min. Adjust the maraviroc dosage as follows when administered with ritonavir (with or without a concomitant CYP3A inducer): adults and children weighing 40 kg or more: 150 mg PO twice daily; children weighing 30 to 39 kg: 100 mg PO twice daily; children weighing 20 to 29 kg: 75 mg PO twice daily (or 80 mg PO twice daily for solution); children weighing 10 to 19 kg: 50 mg PO twice daily; children weighing 2 to 9 kg: use not recommended.
    Rolapitant: (Moderate) Use caution and closely monitor for increased adverse effects with the coadministration of maraviroc and rolapitant as increased maraviroc concentrations may occur. Maraviroc is a substrate of P-glycoprotein (P-gp); rolapitant is an inhibitor of P-gp. The effects of P-gp on the concentrations of maraviroc are unknown, although an increase in concentrations and thus, toxicity, are possible.
    Saquinavir: (Major) Coadministration of maraviroc, a CYP3A/P-gp substrate, with saquinavir, a strong CYP3A4 inhibitor and P-gp inhibitor, has been reported to increase maraviroc concentrations by 9.8-fold. Reduce the dose of maraviroc when coadministered with strong CYP3A inhibitors; coadministration of maraviroc with strong CYP3A inhibitors is contraindicated in patients with CrCl less than 30 mL/min. Adjust the maraviroc dosage as follows when administered with saquinavir (with or without a concomitant CYP3A inducer): adults and children weighing 40 kg or more: 150 mg PO twice daily; children weighing 30 to 39 kg: 100 mg PO twice daily; children weighing 20 to 29 kg: 75 mg PO twice daily (or 80 mg PO twice daily for solution); children weighing 10 to 19 kg: 50 mg PO twice daily; children weighing 2 to 9 kg: use not recommended.
    Simeprevir: (Moderate) Use caution and closely monitor for increased adverse effects during concurrent administration of maraviroc and simprevir as increased maraviroc concentrations may occur. Maraviroc is a substrate of CYP3A, P-glycoprotein (P-gp), and organic anion-transporting polypeptide (OATP1B). Simeprevir is a CYP3A4, P-gp, and OATP1B1 inhibitor. Monitor for an increase in adverse effects with concomitant use.
    Sofosbuvir; Velpatasvir: (Moderate) Use caution and closely monitor for increased adverse effects during concurrent administration of maraviroc and velpatasvir as increased maraviroc concentrations may occur. Maraviroc is a substrate of P-glycoprotein (P-gp) and organic anion-transporting polypeptide (OATP1B1); velpatasvir is an inhibitor of P-gp and OATP1B1. The effects of these transporters on the concentrations of maraviroc are unknown, although an increase in concentrations and thus, toxicity, are possible.
    Sofosbuvir; Velpatasvir; Voxilaprevir: (Moderate) Use caution and closely monitor for increased adverse effects during concurrent administration of maraviroc and velpatasvir as increased maraviroc concentrations may occur. Maraviroc is a substrate of P-glycoprotein (P-gp) and organic anion-transporting polypeptide (OATP1B1); velpatasvir is an inhibitor of P-gp and OATP1B1. The effects of these transporters on the concentrations of maraviroc are unknown, although an increase in concentrations and thus, toxicity, are possible. (Moderate) Use caution and closely monitor for increased adverse effects during concurrent administration of maraviroc and voxilaprevir as increased maraviroc concentrations may occur. Maraviroc is a substrate of P-glycoprotein (P-gp) and organic anion-transporting polypeptide (OATP1B1); voxilaprevir is an inhibitor of P-gp and OATP1B1. The effects of these transporters on the concentrations of maraviroc are unknown, although an increase in concentrations and thus, toxicity, are possible.
    Sorafenib: (Moderate) Monitor for an increase in maraviroc-related adverse reactions if coadministration with sorafenib is necessary. Maraviroc is a P-glycoprotein (P-gp) substrate. Sorafenib inhibits P-gp in vitro and may increase the concentrations of concomitantly administered drugs that are P-gp substrates.
    Sotorasib: (Major) Avoid concurrent use of sotorasib and maraviroc due to unpredictable effects. Coadministration may alter the exposure of maraviroc resulting in decreased efficacy or increased toxicity. Maraviroc is a CYP3A4 and P-gp substrate; sotorasib is a moderate CYP3A4 inducer and P-gp inhibitor.
    St. John's Wort, Hypericum perforatum: (Major) Concomitant use of maraviroc and St. John's wort, Hypericum perforatum or products containing St. John's wort is not recommended. St. John's wort is expected to substantially decrease maraviroc concentrations; reductions in plasma concentrations could lead to HIV treatment failures or the development of viral-resistance. St. John's wort in all forms, including teas, should be avoided in HIV-infected patients treated with maraviroc.
    Tacrolimus: (Minor) Use caution and careful monitoring with the coadministration of maraviroc and tacrolimus as increased maraviroc concentrations may occur. Maraviroc is a substrate of P-glycoprotein (P-gp); tacrolimus may be an inhibitor of P-gp. Conflicting data exist regarding any interaction between tacrolimus and P-gp. The effects of P-gp on the concentrations of maraviroc are unknown, although an increase in concentrations and thus, toxicity, are possible.
    Telaprevir: (Major) Coadministration of maraviroc, a CYP3A substrate, with telaprevir, a strong CYP3A4 inhibitor, may result in increased maraviroc concentrations. Reduce the dose of maraviroc when coadministered with strong CYP3A inhibitors; coadministration of maraviroc with strong CYP3A inhibitors is contraindicated in patients with CrCl less than 30 mL/min. Adjust the maraviroc dosage as follows when administered with telaprevir (with or without a concomitant CYP3A inducer): adults and children weighing 40 kg or more: 150 mg PO twice daily; children weighing 30 to 39 kg: 100 mg PO twice daily; children weighing 20 to 29 kg: 75 mg PO twice daily (or 80 mg PO twice daily for solution); children weighing 10 to 19 kg: 50 mg PO twice daily; children weighing 2 to 9 kg: use not recommended.
    Telithromycin: (Major) Coadministration of maraviroc (a substrate of CYP3A, P-gp, and OATP1B1) with telithromycin (a strong CYP3A4 inhibitor and P-gp/OATP1B1 inhibitor) may result in increased maraviroc concentrations. Reduce the dose of maraviroc when coadministered with strong CYP3A inhibitors; coadministration of maraviroc with strong CYP3A inhibitors is contraindicated in patients with CrCl less than 30 mL/min. Adjust the maraviroc dosage as follows when administered with telithromycin (with or without a concomitant CYP3A inducer): adults and children weighing 40 kg or more: 150 mg PO twice daily; children weighing 30 to 39 kg: 100 mg PO twice daily; children weighing 20 to 29 kg: 75 mg PO twice daily (or 80 mg PO twice daily for solution); children weighing 10 to 19 kg: 50 mg PO twice daily; children weighing 2 to 9 kg: use not recommended.
    Telmisartan; Amlodipine: (Minor) Use caution if coadministration of maraviroc with amlodipine is necessary, due to a possible increase in maraviroc exposure. Maraviroc is a CYP3A substrate and amlodipine is a weak CYP3A4 inhibitor. Monitor for an increase in adverse effects with concomitant use.
    Temsirolimus: (Moderate) Monitor for an increase in maraviroc-related adverse reactions if coadministration with temsirolimus is necessary; a dose adjustment of maraviroc may be necessary. Maraviroc is a P-glycoprotein (P-gp) substrate and temsirolimus is a P-gp inhibitor. Concomitant use is likely to lead to increased concentrations of maraviroc.
    Tepotinib: (Moderate) Monitor for an increase in maraviroc-related adverse reactions if coadministration with tepotinib is necessary. Concomitant use may increase maraviroc exposure. Maraviroc is a P-gp substrate; tepotinib is a P-gp inhibitor.
    Teriflunomide: (Moderate) Use caution and closely monitor for increased adverse effects during concurrent administration of maraviroc and teriflunomide as increased maraviroc concentrations may occur. Maraviroc is a substrate of organic anion-transporting polypeptide (OATP1B1); teriflunomide is an inhibitor of OATP1B1. The effects of this transporter on the concentrations of maraviroc are unknown, although an increase in concentrations and thus, toxicity, are possible.
    Tezacaftor; Ivacaftor: (Minor) Use caution if coadministration of maraviroc with ivacaftor is necessary, due to a possible increase in maraviroc exposure. Maraviroc is a CYP3A and P-glycoprotein (Pgp) substrate and ivacaftor is a weak CYP3A4/Pgp inhibitor. Monitor for an increase in adverse effects with concomitant use.
    Ticagrelor: (Minor) Use caution if coadministration of maraviroc with ticagrelor is necessary due to a possible increase in maraviroc exposure. Maraviroc is a CYP3A4 and P-glycoprotein substrate (P-gp) and ticagrelor is a weak CYP3A4 and P-gp inhibitor. Monitor for an increase in adverse effects with concomitant use.
    Topiramate: (Minor) Use caution if coadministration of maraviroc with topiramate is necessary, due to a possible decrease in maraviroc exposure. Maraviroc is a CYP3A substrate and topiramate is a CYP3A4 inducer. Monitor for a decrease in maraviroc efficacy with concomitant use.
    Trandolapril; Verapamil: (Moderate) Use caution if coadministration of maraviroc with verapamil is necessary, due to a possible increase in maraviroc exposure. Maraviroc is a CYP3A4/P-glycoprotein (P-gp) substrate and verapamil is a CYP3A4/P-gp inhibitor. Monitor for an increase in adverse effects with concomitant use.
    Tucatinib: (Major) Reduce the dose of maraviroc when coadministered with tucatinib; coadministration is contraindicated in patients with CrCl less than 30 mL/minute. Coadministration of maraviroc, a CYP3A/P-gp substrate, with tucatinib, a strong CYP3A4 inhibitor and P-gp inhibitor, may result in increased maraviroc concentrations. Maraviroc dosage adjustments are as follows when administered with tucatinib (with or without a concomitant CYP3A inducer): adults and children weighing 40 kg or more: 150 mg PO twice daily; children weighing 30 to 39 kg: 100 mg PO twice daily; children weighing 20 to 29 kg: 75 mg PO twice daily (or 80 mg PO twice daily for solution); children weighing 10 to 19 kg: 50 mg PO twice daily; children weighing 2 to 9 kg: use not recommended.
    Valproic Acid, Divalproex Sodium: (Minor) Use caution and closely monitor for decreased efficacy and/or increased adverse effects with the coadministration of maraviroc and valproic acid as altered maraviroc concentrations may occur. Maraviroc is a substrate of CYP3A and P-glycoprotein (P-gp); valproic acid is a weak CYP3A4 inhibitor/inducer, as well as a weak P-gp inducer. The effects of P-gp on the concentrations of maraviroc are unknown, although a decrease in concentrations and thus, decreased efficacy, are possible.
    Vemurafenib: (Moderate) Concomitant use of vemurafenib and maraviroc may result in altered concentrations of maraviroc. Vemurafenib is an inhibitor of P-glycoprotein (P-gp) and a weak inducer of CYP3A4. Maraviroc is a substrate of P-gp and CYP3A4. Use caution and monitor patients for toxicity and efficacy.
    Verapamil: (Moderate) Use caution if coadministration of maraviroc with verapamil is necessary, due to a possible increase in maraviroc exposure. Maraviroc is a CYP3A4/P-glycoprotein (P-gp) substrate and verapamil is a CYP3A4/P-gp inhibitor. Monitor for an increase in adverse effects with concomitant use.
    Voclosporin: (Moderate) Monitor for an increase in maraviroc-related adverse reactions if coadministration with voclosporin is necessary. Concomitant use may increase maraviroc exposure. Maraviroc is a P-gp and OATP1B1 substrate; voclosporin is a P-gp and OATP1B1 inhibitor.
    Voriconazole: (Major) Reduce the dose of maraviroc when coadministered with strong CYP3A inhibitors such as voriconazole; coadministration of maraviroc with strong CYP3A inhibitors is contraindicated in patients with CrCL less than 30 mL/min. Adjust the maraviroc dosage as follows when administered with voriconazole (with or without a concomitant CYP3A inducer): adults and children weighing 40 kg or more: 150 mg PO twice daily; children weighing 30 to 39 kg: 100 mg PO twice daily; children weighing 20 to 29 kg: 75 mg PO twice daily (or 80 mg PO twice daily for solution); children weighing 10 to 19 kg: 50 mg PO twice daily; children weighing 2 to 9 kg: use not recommended.
    Voxelotor: (Moderate) Monitor for an increase in maraviroc-related adverse reactions if coadministration with voxelotor is necessary. Maraviroc is a sensitive CYP3A substrate and voxelotor is a moderate CYP3A inhibitor. Coadministration with moderate CYP3A inhibitors may result in increased maraviroc concentrations.
    Zafirlukast: (Minor) Use caution if coadministration of maraviroc with zafirlukast is necessary, due to a possible increase in maraviroc exposure. Maraviroc is a CYP3A substrate and zafirlukast is a weak CYP3A4 inhibitor. Monitor for an increase in adverse effects with concomitant use.
    Zonisamide: (Minor) Zonisamide is a weak inhibitor of P-glycoprotein (P-gp), and maraviroc is a substrate of P-gp. There is theoretical potential for zonisamide to affect the pharmacokinetics of drugs that are P-gp substrates. Use caution when starting or stopping zonisamide or changing the zonisamide dosage in patients also receiving drugs which are P-gp substrates.

    PREGNANCY AND LACTATION

    Pregnancy

    Antiretroviral therapy should be provided to all women during pregnancy, regardless of HIV RNA concentrations or CD4 cell count. Using highly active antiretroviral combination therapy (HAART) to maximally suppress viral replication is the most effective strategy to prevent the development of resistance and to minimize the risk of perinatal transmission. In treatment-naive women, begin HAART as soon as pregnancy is recognized or HIV is diagnosed, without waiting for the results of resistance testing; subsequent modifications to the treatment regimen should be made once the test results are available. Women who are currently receiving antiretroviral treatment when pregnancy is recognized should continue their treatment regimen if it is currently effective in suppressing viral replication; consider resistance testing if HIV RNA concentrations are more than 500 copies/mL. For women not currently receiving HAART, but who have previously received treatment, obtain a complete and accurate history of all prior antiretroviral regimens used and results of prior resistance testing, and perform resistance testing if HIV RNA concentrations are greater than 500 copies/mL; treatment should be initiated prior to receiving resistance test results. Data regarding administration of maraviroc during pregnancy are too limited to rule out any potential association with birth defects (i.e., 30 first trimester exposures); therefore, maraviroc-containing regimens should not be initiated in pregnant women. However, it may be appropriate to continue use of the drug in some virally suppressed pregnant women. Regular laboratory monitoring is recommended to determine antiretroviral efficacy. Monitor CD4 counts at the initial visit. Women who have been on HAART for at least 2 years and have consistent viral suppression and CD4 counts consistently greater than 300 cells/mm3 do not need CD4 counts monitored after the initial visit during the pregnancy. However, CD4 counts should be monitored every 3 months during pregnancy for women on HAART less than 2 years, women with CD4 count less than 300 cells/mm3, or women with inconsistent adherence or detectable viral loads. Monitor plasma HIV RNA at the initial visit, 2 to 4 weeks after initiating or changing therapy, monthly until undetectable, then at least every 3 months during pregnancy, and at 34 to 36 weeks gestation. Perform antiretroviral resistance assay (genotypic testing, and if indicated, phenotypic testing) at baseline in all women with HIV RNA concentrations greater than 500 copies/mL, unless they have already been tested for resistance. First trimester ultrasound is recommended to confirm gestational age and provide an accurate estimation of gestational age at delivery. A second trimester ultrasound can be used for both anatomical survey and determination of gestational age in those patients not seen until later in gestation. Perform standard glucose screening in women receiving antiretroviral therapy at 24 to 28 weeks gestation, although it should be noted that some experts would perform earlier screening with ongoing chronic protease inhibitor-based therapy initiated prior to pregnancy, similar to recommendations for women with high-risk factors for glucose intolerance. Liver function testing is recommended within 2 to 4 weeks after initiating or changing antiretroviral therapy, and approximately every 3 months thereafter during pregnancy (or as needed). All pregnant women should be counseled about the importance of adherence to their antiretroviral regimen to reduce the potential for development of resistance and perinatal transmission. It is strongly recommended that antiretroviral therapy, once initiated, not be discontinued. If a woman decides to discontinue therapy, a consultation with an HIV specialist is recommended. There is a pregnancy exposure registry that monitors outcomes in pregnant patients exposed to maraviroc; information about the registry can be obtained at www.apregistry.com or by calling 1-800-258-4263.[27468] [23512] [33473]

    To reduce the risk of postnatal transmission, mothers with HIV within the United States are advised by the Centers for Disease Control and Prevention to avoid breast-feeding. This recommendation applies to both untreated women and women who are receiving antiretroviral therapy. If a mother with HIV opts to breast-feed, the infant should undergo immediate diagnostic and virologic HIV testing. Testing should continue throughout breast-feeding and up to 6 months after cessation of breast-feeding. For expert consultation, health care workers may contact the Perinatal HIV Hotline (888-448-8765).[42452] There are limited data regarding maraviroc use during breast-feeding, and excretion into human breast milk is unknown. Antiretroviral medications whose passage into human breast milk have been evaluated include nevirapine, zidovudine, lamivudine, and nelfinavir.[33473] [46675] [46679] [46680] [46682]

    MECHANISM OF ACTION

    Maraviroc interferes with the entry of HIV-1 into host cells by inhibiting the fusion of the virus and cell membranes. In order for HIV-1 to enter and infect a human cell, the viral surface glycoprotein gp120 binds to the host CD4+ cell receptor, along with a chemokine co-receptor CCR5 or CXCR4 (both expressed on lymphocytes and mononuclear cells). Then, the viral transmembrane glycoprotein gp41 undergoes a conformational change facilitating the fusion of cellular and viral membranes. Maraviroc blocks the CCR5 receptor and prevents the functional viral envelope protein-co-receptor interaction required for membrane fusion and subsequent viral entry into target cells.
     
    Maraviroc is only effective at reducing viral load in patients with CCR5-tropic HIV strains; it is not effective against viruses targeting the CXCR4 co-receptor (i.e., CXCR4-tropic HIV) and has a limited effect against viruses with the ability to target both receptors (i.e., dual-tropic HIV). CXCR4-tropic and dual-tropic HIV strains are common in patients with HIV for several years. Because the target population for maraviroc is treatment-experienced patients, who have likely been infected with HIV for several years, tropism assay of the HIV strain is necessary prior to treatment. In the majority of cases, treatment failure on maraviroc was associated with the detection of CXCR4-using (i.e., CXCR4- or dual-tropic) virus which was not detected by the tropism assay prior to treatment. CXCR4-using virus was detected at failure in approximately 55% of patients who failed treatment on maraviroc, as compared to 9% who experienced treatment failure in the placebo arm. To investigate the likely origin of the on-treatment CXCR4-using virus, a detailed clonal analysis was conducted on viruses from 20 representative subjects (16 subjects from the maraviroc arms and 4 subjects from the placebo arm) in whom CXCR4-using virus was detected at treatment failure. From an analysis of amino acid sequence differences and phylogenetic data, CXCR4-using virus in these subjects emerged from a low level of pre-existing CXCR4-using virus not detected by the tropism assay (which is population-based) prior to treatment rather than from a co-receptor switch from CCR5-tropic virus to CXCR4-using virus resulting from a mutation in the virus.

    PHARMACOKINETICS

    Maraviroc is administered orally. It is bound (approximately 76%) to human plasma proteins, and shows moderate affinity for albumin and alpha-1 acid glycoprotein. After a single 300 mg dose of 14C-maraviroc, maraviroc is the major circulating component (approximately 42% drug related radioactivity) and the most significant circulating metabolite is a secondary amine (approximately 22% radioactivity) formed by N-dealkylation; this metabolite has no significant pharmacological activity. The terminal half-life following oral dosing to steady-state in healthy subjects was 14 to 18 hours. Maraviroc was the major component present in urine (mean of 8% dose) and feces (mean of 25% dose); the remainder was excreted as metabolites.
     
    Affected cytochrome P450 isoenzymes and drug transporters: CYP3A, CYP2D6, P-gp, OATP1B1, MRP2
    Maraviroc is a substrate of CYP3A, P-glycoprotein (P-gp), organic anion-transporting polypeptide (OATP1B1), and multidrug resistance-associated protein (MRP2). The pharmacokinetic parameters of maraviroc are likely to be modulated by inhibitors and inducers of CYP3A4 and P-gp, and may be modulated by inhibitors of OATP1B1 and MRP2. The recommended dose of maraviroc differs based on concurrently administered medications and their influence on CYP3A. Carefully asses each medications' potential for CYP3A influence prior to coadministration, and adjust the maraviroc dose accordingly. Based on in vitro data, maraviroc is unlikely to inhibit the actions of CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, or CYP3A enzymes. In addition, maraviroc does not inhibit the CYP2D6 enzyme in vitro until concentrations are more than 100 microM, which correlate with low or normal doses (i.e., 150 mg or 300 mg twice daily); there is potential inhibition at higher doses (i.e., 600 mg twice daily). In vitro studies suggest that maraviroc could inhibit P-gp in the gut; however, it did not significantly affect the pharmacokinetics of digoxin in vivo, suggesting maraviroc may not significantly inhibit or induce P-gp clinically. Maraviroc does not inhibit the uptake of OATP1B1 or the export of MRP2.

    Oral Route

    The absolute bioavailability is 23% for maraviroc 100 mg and is predicted to be 33% for maraviroc 300 mg. In volunteers without HIV, peak plasma concentrations were attained 0.5 to 4 hours after single oral doses of 1 to 1,200 mg. The pharmacokinetics are not dose-proportional over the dose range. Administration of a 300 mg tablet with a high-fat breakfast reduced the Cmax and AUC by 33% in healthy volunteers; coadministration of 75 mg of the oral solution with a high-fat breakfast reduced the AUC by 73%. There were no food restrictions in the studies that demonstrated the efficacy and safety; therefore, maraviroc can be administered with or without food. In healthy volunteers receiving 300 mg twice daily, the Cmax was 888 ng/mL, the Cmin was 43.1 ng/mL, and the AUC12 was 2,908 ng x hour/mL. In asymptomatic HIV patients receiving 300 mg twice daily in phase 2 trials, the Cmax was 618 ng/mL, the Cmin was 33.6 ng/mL, and the AUC12 was 2,550 ng x hour/mL. In treatment-experienced HIV patients receiving 300 mg twice daily, the Cmax was 266 ng/mL, the Cmin was 37.2 ng/mL, and the AUC12 was 1,513 ng x hour/mL. In treatment-experienced HIV patients receiving 150 mg twice daily with a CYP3A4 inhibitor, the Cmax was 332 ng/mL, the Cmin was 101 ng/mL, and the AUC12 was 2,463 ng x hour/mL. In treatment-naive HIV patients receiving 300 mg twice daily, the Cmax was 287 ng/mL, the Cmin was 60 ng/mL, and the AUC12 was 1,865 ng x hour/mL.