Maraviroc is an antiretroviral medication indicated for use in combination with other antiretroviral agents to treat CCR5-tropic human immunodeficiency virus type 1 (HIV-1) infections in adult and pediatric patients weighing at least 2 kg. It was the first antiretroviral approved that blocked HIV entry into human cells via its predominant entry route, the CCR5 co-receptor. There are 2 co-receptors that allow HIV entry into CD4 cells: CCR5 and CXCR4. 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 therefore, a tropism assay of the HIV strain is necessary prior to treatment. Hepatotoxicity has been reported with the use of maraviroc and may be accompanied by signs or symptoms of a systemic allergic reaction. In clinical trials, adult patients who were at increased risk of cardiovascular events experienced such events including myocardial ischemia and infarction. Maraviroc is a substrate of CYP3A and dosing is reliant upon concurrently administered drugs.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific 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.
Severe and life-threatening hepatotoxicity has been reported in patients receiving maraviroc, with some patients experiencing a drug reaction with eosinophilia and systemic symptoms (DRESS) prior to the development of hepatotoxicity. Systemic allergic reactions include severe rash, pyrexia, eosinophilia, elevated IgE, or other systemic symptoms and occur approximately 1 month after treatment initiation. Immediately evaluate, and consider discontinuing maraviroc, in any patient with signs or symptoms of hepatitis or with elevated hepatic enzymes accompanied by rash or other systemic symptoms. During clinical trials, an increase in hepatic adverse effects were observed in less than 2% of patients, including cases of hepatic cirrhosis, hepatic failure, portal vein thrombosis, hypertransaminasemia, and cholestatic jaundice. Elevated hepatic enzymes were also reported during clinical trials, with 4.8% of treatment-experienced patients and 4% of treatment-naive patients experiencing increases in aspartate aminotransferase (AST) more than 5-times the upper limit of normal (ULN). Elevated alanine aminotransferase (ALT) more than 5-times ULN was reported in 2.6% and 3.9% of treatment experienced and treatment-naive patients, respectively. Elevations in total bilirubin more than 2.5-times ULN (hyperbilirubinemia) were observed in 5.5% of treatment-experience patients.
In Phase 3 clinical trials, 11 patients (1.3%) who received maraviroc experienced a cardiovascular event including myocardial infarction and ischemia (total exposure was 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 risk factors or disease prior to treatment with maraviroc, and the relative contribution of the drug to the events is not known. In phase 2b/3 trials in treatment-naive patients, 3 patients (0.8%) had events related to ischemic heart disease. In trials with healthy volunteers at doses higher than recommended, symptomatic orthostatic hypotension was noted in more patients receiving maraviroc than with placebo; however, in HIV trials at recommended doses, orthostatic hypotension rates were similar to placebo (0.5%). Use cautions when administering maraviroc to patients with a known history of orthostatic hypotension or with those on concomitant mediation to lower blood pressure or with severe renal impairment as this may increase the risk of orthostatic hypotension. Vascular hypertensive disorders (hypertension) were noted in 3% of treatment-experience patients in clinical trials. Also during clinical trials, unstable angina, acute heart failure, coronary artery disease, myocardial infarction, myocardial ischemia, and coronary artery occlusion were reported in less than 2% of patients who received maraviroc.
During clinical trials in treatment-experienced patients, dizziness, or postural dizziness, was among the most common adverse reactions reported in patients receiving maraviroc (adults, 8% to 9%; pediatric patients, 3%); 2 patients (0.5%) discontinued therapy (1 due to syncope, 1 due to orthostatic hypotension) versus 1 on placebo (0.5%; due to dizziness). Other treatment-emergent nervous system related adverse reactions reported during clinical trials included paresthesias and dysesthesia (4% to 5%), sensory abnormalities (4%), disturbances in consciousness (4%), memory impairment (3%), insomnia (8%), depression (4%), anxiety (4%) and peripheral neuropathy (4%). Central nervous system adverse events that occurred in less than 2% of patients include cerebrovascular accident (stroke), convulsions (seizures) and epilepsy, tremor (excluding congenital), facial palsy, hemianopia, loss of consciousness, and visual field defect (visual impairment).
Increased cough was among the most common adverse reactions reported in patients receiving maraviroc during clinical trials (14%). Other treatment-emergent respiratory adverse reactions included rhinitis, nasal congestion and inflammation (4%), dyspnea or breathing abnormalities (4%), paranasal sinus disorders (3%), and unspecified upper respiratory tract disorders (6% to 9%).
During clinical trials, fever (pyrexia) was among the most common adverse reactions reported in patients receiving maraviroc twice daily compared to placebo (13% vs. 9%, respectively). Pain and discomfort occurred in 4% of patients in treatment-experienced clinical trials. Problems with body temperature perception occurred in 3% of patients in treatment-naive trials.
Maraviroc antagonizes the CCR5 co-receptor located on some immune cells; therefore, it could potentially increase the risk of developing infection. During Phase 3 clinical trials, the overall incidence and severity of infection, including AIDS-defining infections, was comparable in the treatment groups. Of 426 patients who received maraviroc twice daily, 233 (55%) reported an infection compared to 84 of 209 patients who received placebo (40%); however, there was a longer duration of exposure on maraviroc compared to placebo and the exposure-adjusted frequency (rate per 100 subject-years) of these events was similar: 133 for both maraviroc and placebo. Upper respiratory tract infections were among the most common adverse reactions reported in patients receiving maraviroc twice daily (23% to 32%); such infections included sinusitis (7%), bronchitis (7% to 13%), and otitis media (2%). Lower respiratory tract infections occurred in 3% of patients, including pneumonia (2%). There was a higher incidence of herpes virus infections (7% to 8%) and herpes zoster or varicella infections (5%) reported with maraviroc. Other viral infections occurred in 3% of patients. Folliculitis (4%), condyloma acuminatum (2%), tinea infections (4%), and influenza (2%) were also reported. Esophageal candidiasis also occurred in patients receiving maraviroc therapy. Bacterial infections occurred in 6% of patients, including Neisseria infections (3%). Other adverse events that occurred in less than 2% of maraviroc patients include Clostridium difficile colitis (pseudomembranous colitis), endocarditis, infective myositis, meningitis, viral meningitis, pneumonia, treponema infections, and septic shock.
During clinical trials, musculoskeletal symptoms were reported in patients receiving maraviroc. Joint related signs and symptoms, such as arthralgia, (6% to 7%) and muscle pain or myalgia (3%) were also reported. Myositis, osteonecrosis, rhabdomyolysis, and increased creatinine kinase concentrations all occurred in less than 2% of patients.
Gastrointestinal (GI) adverse reactions in adult patients receiving maraviroc included constipation (6%), appetite disorders (8%), gastrointestinal atonic and hypomotility disorders (9%), and other gastrointestinal signs and symptoms (3%). Flatulence, bloating, and distention occurred in 10% of patients receiving maraviroc. Diarrhea also occurred at a higher rate than placebo. In treatment-experienced pediatric patients 2 to 17 years receiving maraviroc in an open-label study (n = 103), GI adverse reactions were the most common adverse events and included vomiting (12%), abdominal pain (4%), diarrhea (4%), and nausea (4%). Maraviroc-related GI adverse events through 48 weeks (nausea, vomiting, diarrhea, constipation, and abdominal pain or cramps) were noted more commonly in patients who received maraviroc oral solution (21%) compared with those who received maraviroc tablets (16%).
During clinical trials, treatment-emergent adverse reactions in patients receiving maraviroc, compared to placebo, included new primary malignancy, such as benign skin neoplasms (3%). Additionally, during clinical trials, neoplasms (benign, malignant, and unspecified) occurred in less than 2% of patients receiving maraviroc. They included: abdominal neoplasm, anal cancer, basal cell carcinoma, Bowen's disease, cholangiocarcinoma, diffuse large B-cell lymphoma, lymphoma, metastases to liver, esophageal carcinoma, nasopharyngeal carcinoma, squamous cell carcinoma, squamous cell carcinoma of the skin, tongue neoplasm (malignant stage unspecified), anaplastic large cell lymphomas T-cell and null-cell types, bile duct neoplasms (malignant), and endocrine neoplasms (malignant and unspecified).
While more commonly associated with protease inhibitor therapy, a lipodystrophy syndrome consisting of redistribution or accumulation of body fat including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, accumulation of facial fat, lipomas, gynecomastia and other cushingoid features has been reported in 3% to 4% of patients receiving maraviroc in clinical trials.
During clinical trials, rash and edema were among the most common adverse reactions reported in patients receiving maraviroc twice daily compared to placebo. Treatment-emergent skin and subcutaneous tissue adverse reactions in patients receiving maraviroc included rash (unspecified) (11%), apocrine and eccrine gland disorders (5%), pruritus (4%), erythema (2%), acne(s) or acne vulgaris (3%), alopecia (2%), and nail or nail bed conditions (excluding infections) (6%). In addition, severe skin and hypersensitivity reactions, including cases of Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms (DRESS), have been noted in post-marketing reports; however, because these reactions are reported voluntarily, it is not possible to estimate frequency or establish a causal relationship to maraviroc. It is recommended to immediately discontinue use of the drug if signs or symptoms of a severe skin or hypersensitivity reaction develop. Continued treatment in these patients may result in life-threatening reactions.
During clinical trials, laboratory abnormalities reported in patients receiving maraviroc, included hyperamylasemia (with amylase more than 2-times the upper limit of normal, ULN) (4.3% to 5.7%), and lipase more than 2-times ULN (4.9%).
During clinical trials, laboratory abnormalities reported in patients receiving maraviroc included absolute neutrophil count less than 750/mm3 (neutropenia) in 4.3% to 5.7% of patients and hemoglobin concentrations of less than 7 g/dL in 2.9% of patients. Cases of anemia were reported in 8% of patients during clinical trials. Bone marrow depression and hypoplastic anemia were reported in less than 2% of patients receiving maraviroc. Decreased hemoglobin was the most common adverse reaction in HIV-exposed neonates who received at least 1 dose of maraviroc during clinical trials, occurring in 14% of drug recipients.
Genitourinary symptoms occurred in maraviroc trials. During clinical trials, urinary abnormalities were among the most common adverse reactions reported in patients receiving maraviroc twice daily compared to placebo. Bladder and urethral symptoms occurred in 4% to 5% of patients, while urinary tract signs and symptoms occurred in 3% of patients. Erection and ejaculation conditions and disorders (ejaculation dysfunction) was noted in 3% of patients.
Eye and ear disorders were reported in patients receiving maraviroc in clinical trials. Conjunctivitis occurred in 2% of patients. Ocular infection, inflammation, and associated manifestations were also reported in 2% of patients in clinical trials. Ear disorders (unspecified) occurred in 3% of patients.
During baseline evaluation of people with HIV, discuss risk reduction measures and the need for status disclosure to sexual or needle-sharing partners, especially with untreated patients who are still at high risk of HIV transmission. Include the importance of adherence to therapy to achieve and maintain a plasma HIV RNA less than 200 copies/mL. Maintaining a plasma HIV RNA less than 200 copies/mL, including any measurable value below this threshold, with antiretroviral therapy prevents sexual transmission of HIV to their partners. Patients may recognize this concept as Undetectable = Untransmittable or U=U. Instruct patients to achieve sustained viral suppression (i.e., 2 recorded measurements of plasma viral loads that are below the limits of detection and taken at least 3 months apart) before attempting to conceive a child in order to maximize their health, prevent HIV sexual transmission, and minimize the risk of HIV transmission to the infant once conception occurs. For partners with different HIV status when the person with HIV is on antiretroviral therapy and has achieved sustained viral suppression, sexual intercourse without a condom allows conception without sexual HIV transmission to the person without HIV. Expert consultation is recommended.
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. Healthcare 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.
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.
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. Healthcare 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 with hepatitis and HIV coinfection; therefore, it is recommended to administer maraviroc cautiously to patients with pre-existing liver dysfunction. Patients presenting with HIV infection should 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 antiretroviral (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 patients with coinfection 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 patients with coinfection to avoid consuming alcohol, and offer vaccinations against hepatitis A and hepatitis B as appropriate.
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).
HIV treatment guidelines recommend all patients presenting with HIV infection undergo routine screening for hepatitis C virus (HCV). For HCV seronegative individuals who are at continued high risk of acquiring hepatitis C, specifically men who have sex with men (MSM) or persons who inject drugs, additional HCV screening is recommended annually or as indicated by clinical presentation (e.g., unexplained ALT elevation), risk activities, or exposure. Similarly, the AASLD/IDSA HCV guidelines and the CDC preexposure prophylaxis (PrEP) guidelines recommend HCV serologic testing at baseline and every 12 months for MSM, transgender women, and persons who inject drugs. Use an FDA-approved immunoassay licensed for detection of HCV antibodies (anti-HCV); in settings where acute HCV infection is suspected or in persons with known prior infection that cleared spontaneously or after treatment, use of nucleic acid testing for HCV RNA is recommended. If hepatitis C and HIV coinfection is identified, consider treating both viral infections concurrently. It is recommended to use a fully suppressive antiretroviral therapy and an HCV regimen in all patients with coinfection regardless of CD4 count, as lower CD4 counts do not appear to compromise the efficacy of HCV treatment. In most patients, a simplified pangenotypic HCV regimen (i.e., glecaprevir; pibrentasvir or sofosbuvir; velpatasvir) may be an appropriate choice; however, these regimens are NOT recommended for use in persons with HCV and HIV coinfection who: are treatment-experience with HCV relapse (reinfection after successful therapy is not an exclusion); have decompensated cirrhosis; on a tenofovir disoproxil fumarate containing regimen with eGFR less than 60 mL/minute; on efavirenz, etravirine, nevirapine, or boosted protease inhibitor; have untreated chronic hepatitis B; are pregnant. Patients with HCV and HIV coinfection who meet these exclusion criteria should be treated for HCV following standard approaches as described in the AASLD/IDSA HCV guidelines. Treatment of HCV infection in children younger than 3 years is not usually recommended; however, treatment should be considered for all children 3 years and older with HCV and HIV coinfection who have no contraindications to treatment. Instruct patients with coinfection to avoid consuming alcohol, limit ingestion of potentially hepatotoxic medications, avoid iron supplementation in the absence of documented iron deficiency, and receive vaccinations against hepatitis A and hepatitis B as appropriate.
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.
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.
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).
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.
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.
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. The prevalence of transmitted drug resistance (TDR) in high-income countries ranges from 9% to 14% and varies by country. In most TDR surveys, non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance and nucleoside reverse transcriptase inhibitor (NRTI) resistance are the most common mutation class types detected, followed by protease inhibitor (PI) and integrase strand transfer inhibitor (INSTI) resistance mutations, respectively. 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.
Antiretroviral therapy should be provided to all patients 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. Begin HAART as soon as pregnancy is recognized, or HIV is diagnosed. Data regarding administration of maraviroc during pregnancy are too limited to rule out any potential association with birth defects (i.e., 31 first trimester exposures); therefore, maraviroc-containing regimens should not be initiated in pregnant patients. However, it may be appropriate to continue use of the drug in some virally suppressed pregnant patients. Regular laboratory monitoring is recommended to determine antiretroviral efficacy. Monitor CD4 counts at the initial visit. Patients who have been on HAART for at least 2 years and have consistent viral suppression and CD4 counts consistently greater than or equal to 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 patients on HAART less than 2 years and have CD4 counts less than 300 cells/mm3, patients with inconsistent adherence, or patients with detectable viral loads. For patients on HAART less than 2 years but have CD4 counts greater than or equal to 300 cells/mm3, monitor CD4 counts every 6 months. Monitor plasma HIV RNA at the initial visit (with review of prior levels), 2 to 4 weeks after initiating or changing therapy, monthly until undetectable, and then at least every 3 months during pregnancy. Viral load should also be assessed at approximately 36 weeks gestation, or within 4 weeks of planned delivery, to inform decisions regarding mode of delivery and optimal treatment for newborns. Patients whose HIV RNA levels are above the threshold for resistance testing (usually greater than 500 copies/mL but may be possible for levels greater than 200 copies/mL in some laboratories) should undergo antiretroviral resistance testing (genotypic testing, and if indicated, phenotypic testing). Resistance testing should be conducted before starting therapy in treatment-naive patients who have not been previously tested, starting therapy in treatment-experienced patients (including those who have received pre-exposure prophylaxis), modifying therapy in patients who become pregnant while receiving treatment, or modifying therapy in patients who have suboptimal virologic response to treatment that was started during pregnancy. DO NOT delay initiation of antiretroviral therapy while waiting on the results of resistance testing; treatment regimens can be modified, if necessary, once the testing results are known. 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 patients 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 patients 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 patients 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 patient 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.
HIV treatment guidelines recommend clinicians provide mothers with evidence-based, patient-centered counseling to support shared decision-making regarding infant feeding. Inform patients that use of replacement feeding (i.e., formula or banked pasteurized donor human milk) eliminates the risk of HIV transmission. Advise patients who receive a diagnosis of HIV infection while breast-feeding (acute HIV) to immediately discontinue breast-feeding and switch to replacement feeding in order to reduce the risk of postnatal HIV transmission to the infant. Replacement feeding is also recommended for use when mothers with HIV are not on antiretroviral therapy (ART) or do not have suppressed viral load during pregnancy, as well as at delivery. For patients on ART who have achieved and maintained viral suppression during pregnancy (at minimum throughout the third trimester) and postpartum, the transmission risk from breast-feeding is less than 1%, but not zero. Virologically suppressed mothers who choose to breast-feed should be supported in this decision. If breast-feeding is chosen, counsel the patient about the importance of adherence to therapy and recommend that the infant be exclusively breast-fed for up to 6 months of age, as exclusive breast-feeding has been associated with a lower rate of HIV transmission as compared to mixed feeding (i.e., breast milk and formula). Promptly identify and treat mastitis, thrush, and cracked or bleeding nipples, as these conditions may increase the risk of HIV transmission through breast-feeding. Breast-fed infants 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, healthcare workers may contact the Perinatal HIV Hotline (888-448-8765). 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.
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.
Maraviroc must ONLY be used in patients with CCR5-tropic HIV infection. Tropism testing conducted on a current sample should guide treatment; do not use in patients with dual or CXCR4-tropic HIV, as efficacy was not demonstrated in a phase 2 study of this patient group.
NOTE: As compared to treatment with efavirenz, treatment-naive adults treated with maraviroc experienced more virologic failure and lamivudine resistance.
Initiation of therapy for HIV treatment:
-For adults, initiation of treatment immediately (or as soon as possible) after HIV diagnosis is recommended in all patients to reduce the risk of disease progression and to prevent the transmission of HIV, including perinatal transmission and transmission to sexual partners. Starting antiretroviral therapy early is particularly important for patients with AIDS-defining conditions, those with acute or recent HIV infection, and individuals who are pregnant; delaying therapy in these subpopulations has been associated with high risks of morbidity, mortality, and HIV transmission.
-Prior to initiating treatment, obtain baseline plasma HIV RNA (viral load) and CD4 count; results do not need to be available before starting therapy.
-Antiretroviral drug-resistance testing:-Genotypic drug-resistance testing is recommended prior to initiation of therapy and prior to changing therapy for treatment failure.
--Standard genotypic drug-resistance testing in treatment-naive people should focus on testing for mutations in reverse transcriptase (RT) and protease (PR) genes.
-Testing for mutations in the integrase gene should also be performed if integrase strand transfer inhibitor (INSTI) resistance is a concern (e.g., people who acquire HIV after pre-exposure prophylaxis with long-acting cabotegravir).
-Phenotypic resistance testing may be used in conjunction with the genotypic test for patients with known or suspected complex drug-resistance mutation patterns.
-HIV-1 proviral DNA resistance testing is available for use in patients with HIV RNA concentrations below the limits of detection or with low-level viremia (i.e., less than 1,000 copies/mL), where genotypic testing is unlikely to be successful; however, the clinical utility of this assay has not been fully determined.
-It is not necessary to delay treatment until resistance test results are available; however, subsequent modifications to the treatment regimen should be made, if needed, once the test results are available.
-Pediatric guidelines are also available.
Place in therapy for HIV treatment:
-For treatment-naive adults, maraviroc is not recommended as part of an initial treatment regimen due to the need for CCR5 tropism testing, inconvenient dosing, and lack of virologic benefit.
-Data are limited regarding use of maraviroc during pregnancy; therefore, the drug cannot be recommended for routine use in pregnant women. However, it may be appropriate to continue use of the drug in some virally suppressed pregnant women.
-Pediatric guidelines are also available.
Per the manufacturer, this drug has been shown to be active against most strains of the following microorganisms either in vitro and/or in clinical infections: human immunodeficiency virus (HIV)
NOTE: The safety and effectiveness in treating clinical infections due to organisms with in vitro data only have not been established in adequate and well-controlled clinical trials.
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).
Therapeutic Drug Monitoring:
The suggested minimum target trough concentration for maraviroc in antiretroviral-experienced patients who have resistant HIV-1 strains is > 50 ng/mL. However, when employing a therapeutic drug monitoring (TDM) strategy for patient management, measured drug concentrations must be integrated with other clinical information. As knowledge of associations between antiretroviral therapy and virologic response continues to accumulate, clinicians should consult the most current literature and recommendations.
Maximum Dosage Limits:
-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.
Patients with Hepatic Impairment Dosing
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.
Patients with Renal Impairment Dosing
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.
*non-FDA-approved indication
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.
Adagrasib: (Major) Reduce the dose of maraviroc when coadministration with adagrasib is necessary, regardless of whether the patient is receiving a concomitant strong CYP3A inducer. The effect of adagrasib on maraviroc exposure is expected to exceed that of the inducer and overall, increased maraviroc concentrations are expected. Coadministration of maraviroc with adagrasib is contraindicated in patients with CrCl less than 30 mL/min. Recommendations for reducing the maraviroc dose when administered with adagrasib (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 adagrasib is a strong CYP3A and P-gp inhibitor. Coadministration with strong CYP3A inhibitors may result in increased maraviroc concentrations.
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.
Amiodarone: (Moderate) Monitor for an increase in maraviroc-related adverse reactions if coadministration with amiodarone is necessary. Concomitant use may increase maraviroc exposure. Maraviroc is a P-gp substrate; amiodarone is a P-gp inhibitor.
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.
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.
Asciminib: (Moderate) Monitor for an increase in maraviroc-related adverse reactions if coadministration with asciminib is necessary. Concomitant use may increase maraviroc exposure. Maraviroc is an OATP1B1 substrate; asciminib is an OATP1B1 inhibitor.
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.
Berotralstat: (Moderate) Monitor for an increase in maraviroc-related adverse reactions if coadministration with berotralstat is necessary. Maraviroc is a sensitive CYP3A substrate and berotralstat is a moderate CYP3A inhibitor. Coadministration with moderate CYP3A 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.
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.
Danicopan: (Moderate) Monitor for an increase in maraviroc-related adverse reactions if coadministration with danicopan is necessary. Concomitant use may increase maraviroc exposure. Maraviroc is a P-gp substrate; danicopan is a P-gp inhibitor.
Daridorexant: (Moderate) Monitor for an increase in maraviroc-related adverse reactions if coadministration with daridorexant is necessary. Concomitant use may increase maraviroc exposure. Maraviroc is a P-gp substrate; daridorexant is a P-gp inhibitor.
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.
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.
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 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.
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.
Elacestrant: (Moderate) Monitor for an increase in maraviroc-related adverse reactions if coadministration with elacestrant is necessary. Concomitant use may increase maraviroc exposure. Maraviroc is a P-gp substrate; elacestrant is a P-gp inhibitor.
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 an increase in maraviroc-related adverse reactions if coadministration with elexacaftor is necessary. Concomitant use may increase maraviroc exposure. Maraviroc is an OATP1B1 substrate; elexacaftor is an OATP1B1 inhibitor. (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; 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: (Major) Coadministration of maraviroc with encorafenib may result in decreased maraviroc efficacy or an increased risk of maraviroc-related adverse reactions; a dose adjustment may be needed. Maraviroc is a sensitive CYP3A and OATP1B1 substrate and encorafenib is both a strong CYP3A inducer and OATP1B1 inhibitor. The net effect on maraviroc exposure is unknown. When administered with a strong CYP3A inducer, without a concomitant strong CYP3A inhibitor, it is recommended to increase the adult dose of maraviroc to 600 mg PO twice daily. Coadministration of maraviroc and encorafenib is contraindicated in patients with CrCl less than 30 mL/min. For pediatric patients, the concomitant use of maraviroc with encorafenib without also taking a strong CYP3A inhibitor is not recommended. If the adult or pediatric patient's medication regimen also contains a strong CYP3A inhibitor, the CYP3A inhibitor's actions are expected to exceed that of encorafenib; overall, increased maraviroc concentrations are expected (see recommended dose adjustments for use of maraviroc with the strong inhibitor).
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.
Erdafitinib: (Moderate) Monitor for an increase in maraviroc-related adverse reactions if coadministration with erdafitinib is necessary. Concomitant use may increase maraviroc exposure. Maraviroc is a P-gp substrate; erdafitinib is a P-gp inhibitor.
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.
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.
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.
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: (Moderate) Monitor for an increase in maraviroc-related adverse reactions if coadministration with fosamprenavir is necessary. Maraviroc is a sensitive CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor. Coadministration with moderate CYP3A inhibitors may result in increased maraviroc concentrations.
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.
Futibatinib: (Moderate) Monitor for an increase in maraviroc-related adverse reactions if coadministration with futibatinib is necessary. Concomitant use may increase maraviroc exposure. Maraviroc is a P-gp substrate; futibatinib is a P-gp inhibitor.
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.
Ketoconazole: (Major) Reduce the dose of maraviroc when coadministration with ketoconazole is necessary, regardless of whether the patient is receiving a concomitant strong CYP3A4 inducer. The effect of ketoconazole on maraviroc exposure is expected to exceed that of the inducer and overall, increased maraviroc concentrations are expected. Coadministration of maraviroc with ketoconazole is contraindicated in patients with CrCl less than 30 mL/minute. Recommendations for reducing the maraviroc dose when administered with ketoconazole (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 substrate and ketoconazole is a strong CYP3A inhibitor. Coadministration with strong CYP3A4 inhibitors may result in increased maraviroc concentrations.
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.
Lasmiditan: (Moderate) Monitor for an increase in maraviroc-related adverse reactions if coadministration with lasmiditan is necessary. Concomitant use may increase maraviroc exposure. Maraviroc is a P-gp substrate; lasmiditan is a P-gp inhibitor.
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.
Lenacapavir: (Moderate) Monitor for an increase in maraviroc-related adverse reactions if coadministration with lenacapavir is necessary. Maraviroc is a CYP3A and P-gp substrate and lenacapavir is a moderate CYP3A and P-gp inhibitor. Coadministration with moderate CYP3A inhibitors may result in increased maraviroc concentrations.
Leniolisib: (Moderate) Monitor for an increase in maraviroc-related adverse reactions if coadministration with leniolisib is necessary. Concomitant use may increase maraviroc exposure. Maraviroc is an OATP1B1 substrate; leniolisib is an OATP1B1 inhibitor.
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) Reduce the dose of maraviroc when coadministration with ketoconazole is necessary, regardless of whether the patient is receiving a concomitant strong CYP3A4 inducer. The effect of ketoconazole on maraviroc exposure is expected to exceed that of the inducer and overall, increased maraviroc concentrations are expected. Coadministration of maraviroc with ketoconazole is contraindicated in patients with CrCl less than 30 mL/minute. Recommendations for reducing the maraviroc dose when administered with ketoconazole (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 substrate and ketoconazole is a strong CYP3A inhibitor. Coadministration with strong CYP3A4 inhibitors may result in increased maraviroc concentrations.
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. (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.
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.
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.
Mavacamten: (Major) Increase the adult dose of maraviroc to 600 mg PO twice daily when coadministered with mavacamten without a concomitant strong CYP3A inhibitor. Coadministration of maraviroc and mavacamten is contraindicated in patients with CrCl less than 30 mL/min. For pediatric patients, the concomitant use of maraviroc with mavacamten without also taking a strong CYP3A inhibitor is not recommended. If the adult or pediatric patient's medication regimen also contains a strong CYP3A inhibitor, the CYP3A inhibitor's actions are expected to exceed that of mavacamten; overall, increased maraviroc concentrations are expected (see recommended dose adjustments for use of maraviroc with the strong inhibitor). Maraviroc is a sensitive CYP3A substrate and mavacamten is a moderate CYP3A inducer.
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.
Nirogacestat: (Moderate) Monitor for an increase in maraviroc-related adverse reactions if coadministration with nirogacestat is necessary. Maraviroc is a sensitive CYP3A substrate and nirogacestat is a moderate CYP3A inhibitor. Coadministration with moderate CYP3A inhibitors may result in increased maraviroc concentrations.
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.
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.
Pirtobrutinib: (Moderate) Monitor for an increase in maraviroc-related adverse reactions if coadministration with pirtobrutinib is necessary. Concomitant use may increase maraviroc exposure. Maraviroc is a P-gp substrate; pirtobrutinib is a P-gp inhibitor.
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.
Pretomanid: (Moderate) Monitor for an increase in maraviroc-related adverse reactions if coadministration with pretomanid is necessary. Concomitant use may increase maraviroc exposure. Maraviroc is a P-gp substrate; pretomanid is a P-gp inhibitor.
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.
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.
Repotrectinib: (Major) Increase the adult dose of maraviroc to 600 mg PO twice daily when coadministered with repotrectinib without a concomitant strong CYP3A inhibitor. Coadministration of maraviroc and repotrectinib is contraindicated in patients with CrCl less than 30 mL/min. For pediatric patients, the concomitant use of maraviroc with repotrectinib without also taking a strong CYP3A inhibitor is not recommended. If the adult or pediatric patient's medication regimen also contains a strong CYP3A inhibitor, the CYP3A inhibitor's actions are expected to exceed that of repotrectinib; overall, increased maraviroc concentrations are expected (see recommended dose adjustments for use of maraviroc with the strong inhibitor). Maraviroc is a sensitive CYP3A substrate and repotrectinib is a moderate CYP3A inducer.
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.
Ritlecitinib: (Moderate) Monitor for an increase in maraviroc-related adverse reactions if coadministration with ritlecitinib is necessary. Maraviroc is a sensitive CYP3A substrate and ritlecitinib is a moderate CYP3A inhibitor. Coadministration with moderate CYP3A inhibitors may result in increased maraviroc concentrations.
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.
Selpercatinib: (Moderate) Monitor for an increase in maraviroc-related adverse reactions if coadministration with selpercatinib is necessary. Concomitant use may increase maraviroc exposure. Maraviroc is a P-gp substrate; selpercatinib is a P-gp inhibitor.
Sodium Phenylbutyrate; Taurursodiol: (Moderate) Monitor for an increase in maraviroc-related adverse reactions if coadministration with taurursodiol is necessary. Concomitant use may increase maraviroc exposure. Maraviroc is a P-gp substrate; taurursodiol is a P-gp inhibitor.
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.
Sparsentan: (Moderate) Monitor for an increase in maraviroc-related adverse reactions if coadministration with sparsentan is necessary. Concomitant use may increase maraviroc exposure. Maraviroc is a P-gp substrate; sparsentan is a 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.
Stiripentol: (Moderate) Consider a dose adjustment of maraviroc when coadministered with stiripentol. Coadministration may alter plasma concentrations of maraviroc resulting in an increased risk of adverse reactions and/or decreased efficacy. Maraviroc is a sensitive CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
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.
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.
Trofinetide: (Moderate) Monitor for an increase in maraviroc-related adverse reactions if coadministration with trofinetide is necessary. Concomitant use may increase maraviroc exposure. Maraviroc is an OATP1B1 substrate; trofinetide is an OATP1B1 inhibitor.
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.
Vonoprazan; 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.
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.
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.
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.
-Route-Specific Pharmacokinetics
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.
-Special Populations
Hepatic Impairment
While pharmacokinetic parameters have not been sufficiently studied in patients with hepatic impairment, because maraviroc is metabolized by the liver, concentrations are likely to be increased in such patients; use with caution and monitor patients frequently.
Renal Impairment
A single-dose maraviroc (300 mg) pharmacokinetic study compared healthy volunteers with severe renal impairment (CrCl less than 30 mL/minute; n = 6) and end-stage renal disease (ESRD) (n = 6) to those with normal renal function. The mean Cmax was 2.4-fold higher in patients with severe renal impairment and 1.7-fold higher in patients with ESRD. The mean AUC was 3.2-fold higher in patients with severe renal impairment and 2-fold higher in patients with ESRD. Hemodialysis had minimal effect on maraviroc exposure. Maraviroc concentrations in patients with severe renal impairment or ESRD were comparable to concentrations noted in patients with normal renal function in previously completed studies; however, maraviroc concentrations in patients with normal renal function in the current study were 50% lower compared to previous studies. Based on the current study, the FDA-approved product label does not recommend dosage changes in adult patients with severe renal impairment or ESRD for patients not receiving concomitant potent CYP3A4 inducers or inhibitors. However, if patients experience any symptoms of postural hypotension, the maraviroc dose should be reduced to 150 mg PO twice daily. No studies are available in pediatric patients with any degree of renal impairment.
A multiple dose maraviroc pharmacokinetic study with concomitant saquinavir; ritonavir (1,000 mg; 100 mg PO twice daily for 7 days), a potent CYP3A4 inhibitor, compared healthy volunteers (n = 6) with normal renal function to those with mild renal impairment (CrCl more than 50 and 80 mL/minute or less; n = 6) and moderate renal impairment (CrCl 30 or more and 50 mL/minute or less; n = 6). Patients with normal renal function received maraviroc 150 mg PO every 12 hours. Patients with mild renal impairment received maraviroc 150 mg PO every 24 hours. Patients with moderate renal impairment received maraviroc 150 mg PO every 48 hours. As compared to patients with normal renal function, the mean AUC was 50% higher in patients with mild renal impairment and 16% higher in patients with moderate renal impairment. The mean Cmax was 20% higher in patients with mild renal impairment and 29% higher in patients with moderate renal impairment. The mean Cmin was 43% lower in patients with mild renal impairment and 85% lower in patients with moderate renal impairment. Based on this study, the FDA-approved product label does not recommend dosage changes in adult patients on concomitant potent CYP3A4 inhibitors with mild or moderate renal impairment. No studies are available in these patients with severe renal impairment or pediatric patients with any degree of renal impairment.
Pediatrics
In a study of CCR5-tropic, treatment-experienced pediatric patients (2 to 17 years; n = 98), maraviroc pharmacokinetics in patients receiving potent CYP3A inhibitors (with or without a potent CYP3A inducer) were comparable to those observed in adult patients. Clinical pharmacokinetic data in pediatric patients aged 2 to 17 years receiving non-interacting concomitant medications are limited. In another study, the pharmacokinetics of maraviroc were evaluated in 38 neonates with HIV (ages birth to 6 weeks) who received either single (n = 13) or multiple doses (n = 25) of maraviroc. Data from this study showed the pharmacokinetic of maraviroc in neonates weighing at least 2 kg at birth were similar to those observed in adults. Clinical pharmacokinetic data in pediatric patients between 6 weeks and 2 years of age are not available; however, population pharmacokinetic modeling and simulations suggest the recommended dosing regimen will result in maraviroc exposures comparable to those observed in adults.
Geriatric
There was an insufficient number of patients aged 65 years or older to determine a difference in response compared to younger patients. In general, use caution when administering maraviroc to elderly patients, especially in regard to the potential for decreased hepatic and renal function, concomitant disease, and other drug therapy.
Other
Pregnancy
The pharmacokinetic parameters of maraviroc during pregnancy were evaluated in 13 women with HIV. This study found a 21% reduction in plasma drug exposure (AUC) during the third trimester compared to postpartum (p = 0.083). In addition, maraviroc trough concentrations (Cmin) were also decreased during the third trimester; however, these reductions were not deemed significant (90% CI: 0.72, 1.01). Of note, observed Cmin values for 2 women fell below the therapeutic target of 50 ng/mL. In another study involving 18 women, the pharmacokinetics of maraviroc were evaluated during the third trimester and at least 2 weeks postpartum. In this study, the mean ratio for third trimester AUC versus postpartum AUC was 0.72 and the mean ratio for peak concentration (Cmax) in the third trimester versus postpartum was 0.7. Despite an overall 30% decrease in the AUC during pregnancy and a 15% decrease in the Cmin, the Cmin exceeded the minimum target concentration of 50 ng/mL in all but 1 subject. According to HIV guidelines, these data suggest the standard dose (adjusted for concomitant antiretroviral medications) is appropriate for pregnant patients. There is moderate placental transfer rate to the fetus.