(mah RAV er rock)
HIV infection: Treatment of only CCR5-tropic HIV-1 infection, in combination with other antiretroviral agents
Patients with severe renal impairment (CrCl <30 mL/minute) or end-stage renal disease (ESRD) who are taking potent CYP3A inhibitors or inducers
Canadian labeling: Additional contraindications (not in U.S. labeling): Hypersensitivity to maraviroc or any component of the formulation
Hepatotoxicity has been reported with maraviroc use. Severe rash or evidence of a systemic allergic reaction (eg, eosinophilia, elevated immunoglobulin E [Ige], fever) prior to the development of hepatotoxicity may occur. Immediately evaluate patients with signs or symptoms of hepatitis or allergic reactions following use of maraviroc.
HIV infection: Oral: 300 mg twice daily; dose recommended when maraviroc administered concomitantly with other medications, including tipranavir/ritonavir, nevirapine, raltegravir, all NRTIs and enfuvirtide.
Dosage adjustment for concomitant CYP3A inhibitors/inducers:
CYP3A inhibitors (with or without a potent CYP3A inducer): 150 mg twice daily; dose recommended when maraviroc administered concomitantly with potent CYP3A inhibitors including (but not limited to) protease inhibitors (excluding tipranavir/ritonavir), delavirdine, elvitegravir/ritonavir, ketoconazole, itraconazole, clarithromycin, nefazodone, telithromycin, and boceprevir.
CYP3A inducers (without a potent CYP3A inhibitor): 600 mg twice daily; dose recommended when maraviroc administered concomitantly with potent CYP3A inducers including (but not limited to) efavirenz, etravirine, rifampin, carbamazepine, phenobarbital, and phenytoin
HIV infection: Oral:
Alternate dosing: Adolescents ≥16 years: Refer to adult dosing (HHS [pediatric], 2014).
CrCl ≥30 mL/minute:
CrCl ≥30 mL/minute and concomitant potent CYP3A inhibitors (with or without a potent CYP3A inducer): 150 mg twice daily
CrCl ≥30 mL/minute and concomitant potent CYP3A inducer (without a potent CYP3A inhibitor): 600 mg twice daily
CrCl ≥30 mL/minute and other concomitant medications (eg, tipranavir/ritonavir, nevirapine, raltegravir, all NRTIs, and enfuvirtide): 300 mg twice daily
CrCl <30 mL/minute:
CrCl <30 mL/minute and concomitant potent CYP3A inhibitors (with or without a potent CYP3A inducer) or concomitant potent CYP3A inducer (without a potent CYP3A inhibitor): Use is contraindicated
CrCl <30 mL/minute and other concomitant medications (eg, tipranavir/ritonavir, nevirapine, raltegravir, all NRTIs, and enfuvirtide): 300 mg twice daily. If postural hypotension occurs, reduce dose to 150 mg twice daily
CrCl <30 mL/minute and experiencing postural hypotension: Reduce dose to 150 mg twice daily
ESRD requiring intermittent hemodialysis (IHD):Note: Hemodialysis has minimal effect on clearance
With concomitant potent CYP3A inhibitors (with or without a potent CYP3A inducer) or concomitant potent CYP3A inducer (without a potent CYP3A inhibitor): Use is contraindicated
With other concomitant medications (eg, tipranavir/ritonavir, nevirapine, raltegravir, all NRTIs, and enfuvirtide): 300 mg twice daily. If postural hypotension occurs, reduce dose to 150 mg twice daily.
Mild to moderate impairment: There are no dosage adjustments provided in the manufacturers labeling; however, maraviroc concentrations are increased in mild to moderate impairment; use caution.
Moderate impairment (with concomitant potent CYP3A inhibitor): There are no dosage adjustments provided in the manufacturer's labeling; however, maraviroc concentrations are increased moderate impairment; use caution and monitor closely for adverse events.
Severe impairment: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Administer without regards to meals.
Store at 25 ‚ °C (77 ‚ °F); excursions permitted to 15 ‚ °C to 30 ‚ °C (59 ‚ °F to 86 ‚ °F).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Selzentry: 150 mg, 300 mg [contains fd&c blue #2 aluminum lake, soybean lecithin]
Aprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Bosentan: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Avoid combination
CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
CYP3A4 Inducers (Strong): May decrease the serum concentration of Maraviroc. Management: Increase maraviroc adult dose to 600 mg twice daily when used with strong CYP3A4 inducers. This does not apply to patients also receiving strong CYP3A4 inhibitors. Do not use maraviroc with strong CYP3A4 inducers in patients with CrCl less than 30 mL/min. Consider therapy modification
CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Monitor therapy
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Maraviroc. Management: Reduce the adult dose of maraviroc to 150 mg twice daily when used with a strong CYP3A4 inhibitor. Do not use maraviroc with strong CYP3A4 inhibitors in patients with Clcr less than 30 mL/min. Consider therapy modification
Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates. Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification
Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Efavirenz: May decrease the serum concentration of Maraviroc. Of note, this effect only applies in the absence of a strong CYP3A4 inhibitor Management: Increase maraviroc adult dose to 600 mg twice daily if used with efavirenz. This does not apply to patients also receiving strong CYP3A4 inhibitors. This combination is contraindicated in patients with CrCl less than 30 mL/min. Consider therapy modification
Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates. Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Consider therapy modification
Etravirine: May decrease the serum concentration of Maraviroc. Of note, this effect only applies in the absence of a strong CYP3A4 inhibitor Management: Increase maraviroc adult dose to 600 mg twice daily if used with etravirine. This does not apply to patients also receiving strong CYP3A4 inhibitors. This combination is contraindicated in patients with CrCl less than 30 mL/min. Consider therapy modification
Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates. Avoid combination
Idelalisib: May increase the serum concentration of CYP3A4 Substrates. Avoid combination
Ivacaftor: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Luliconazole: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
MiFEPRIStone: May increase the serum concentration of CYP3A4 Substrates. Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. Consider therapy modification
Mitotane: May decrease the serum concentration of CYP3A4 Substrates. Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Consider therapy modification
Netupitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Osimertinib: May increase the serum concentration of CYP3A4 Substrates. Osimertinib may decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Palbociclib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Siltuximab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Simeprevir: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
St Johns Wort: May decrease the serum concentration of Maraviroc. Avoid combination
Stiripentol: May increase the serum concentration of CYP3A4 Substrates. Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Viral load, CD4 count, transaminases and bilirubin (prior to initiation and periodically during treatment); signs/symptoms of infection, rash, severe skin reactions, hepatitis and/or allergic reaction; postural hypotension; tropism testing (prior to initiation)
>10%:
Central nervous system: Fever (13%)
Dermatologic: Skin rash (11%)
Respiratory: Upper respiratory tract infection (23%), cough (14%)
2% to 10%:
Cardiovascular: Vascular hypertensive disorder (3%)
Central nervous system: Dizziness (9%; including postural dizziness), insomnia (8%), paresthesia (5%), anxiety (4%), impaired consciousness (4%), depression (4%), pain (4%), peripheral neuropathy (4%), sensory disturbance (4%), amnesia (3%)
Dermatologic: Folliculitis (4%), pruritus (4%), acne vulgaris (3%), skin neoplasm (benign; 3%), alopecia (2%), erythema (2%), tinea (4%)
Endocrine & metabolic: Lipodystrophy (4%)
Gastrointestinal: Decreased gastrointestinal motility (9%), change in appetite (8%), constipation (6%)
Genitourinary: Genitourinary complaint (urinary tract/bladder symptoms, 3% to 5%), warts (genital, 2%)
Hematologic & oncologic: Neutropenia (grades 3/4: 4%)
Hepatic: Increased serum AST (grades 3/4: 5%), increased serum ALT (grades 3/4: 3%), increased serum bilirubin (grades 3/4: 6%)
Infection: Herpes infection (8%), bacterial infection (3%), Neisseria, (3%),
Neuromuscular & skeletal: Arthralgia (7%), myalgia (3%)
Ophthalmic: Conjunctivitis (2%), eye infection (2%)
Otic: Otitis media (2%)
Respiratory: Bronchitis (7%), sinusitis (7%), paranasal sinus disease (3% to 6%), irregular breathing (4%), nasal congestion (4%), lower respiratory tract infection (3%)
Miscellaneous: Sweat gland disturbances (5%), flu-like symptoms (2%)
<2% (Limited to important or life-threatening): Anal cancer, angina pectoris, basal cell carcinoma, bile duct neoplasm, bone marrow depression, carcinoma in situ of esophagus, cardiac failure, cerebrovascular accident, cholestatic jaundice, coronary artery disease, coronary artery occlusion, endocarditis, endocrine neoplasm, hepatic cirrhosis, hepatic failure, hepatotoxicity, hypoplastic anemia, immune reconstitution syndrome, increased creatine kinase, ischemic heart disease, liver metastases, lymphoma, meningitis (viral), multiorgan hypersensitivity, myocardial infarction, myositis, osteonecrosis, pneumonia, portal vein thrombosis, rhabdomyolysis, seizure, septic shock, squamous cell carcinoma, Stevens-Johnson syndrome, syncope, T-cell lymphoma, tongue neoplasm, toxic epidermal necrolysis, tremor
In a single 300 mg dose study in patients with severe renal impairment (CrCl <30 mL/minute) and ESRD, Cmax and AUC were 2.4- and 3.2-fold higher, respectively, for patients with severe renal impairment, and 1.7- and 2-fold higher, respectively, for ESRD patients.
Concerns related to adverse effects:
- CNS effects: May cause dizziness. If this occurs, patients should avoid driving or operating machinery.
- Hepatotoxicity: [US Boxed Warning]: Possible drug-induced hepatotoxicity with allergic type features has been reported; hepatotoxicity may be preceded by severe rash or other signs of systemic allergic reactions (eg, pruritic rash, eosinophilia, fever, and/or increased IgE, excluding rash alone or Stevens-Johnson syndrome (HHS [adult], 2015) and/or hepatic adverse events (transaminase increases or signs/symptoms of hepatitis); some cases have been life-threatening; immediately evaluate patients with signs and symptoms of allergic reaction or hepatitis (with or without allergy symptoms). Use with caution in patients with pre-existing hepatic dysfunction or coinfection with HBV and/or HCV, however symptoms have occurred in the absence of pre-existing hepatic conditions. Monitor hepatic function at baseline and as clinically indicated during treatment. Consider discontinuation in any patient with possible hepatitis or with elevated transaminases combined with systemic allergic events. Rechallenge with maraviroc is not recommended (HHS [pediatric], 2014).
- Immune reconstitution syndrome: Patients may develop immune reconstitution syndrome resulting in the occurrence of an inflammatory response to an indolent or residual opportunistic infection during initial HIV treatment or activation of autoimmune disorders (eg, Graves ' disease, polymyositis, Guillain-Barre syndrome) later in therapy; further evaluation and treatment may be required.
- Infections: Monitor closely for signs/symptoms of developing infections; use associated with a small increase of certain upper respiratory tract infections and herpes virus infections during clinical trials.
- Malignancy: May affect immune surveillance and lead to an increased risk of malignancy due to pharmacologic mechanism of action. No increase in malignancy has been observed. Long term follow up needed to assess this risk.
- Postural hypotension: Symptomatic postural hypotension has occurred; use caution in patients at risk due to concomitant medication or history of condition. An increased risk of postural hypotension may occur in patients with severe renal insufficiency or in those with ESRD. Patients with severe renal dysfunction or ESRD who experience postural hypotension should have dose reduced.
- Skin and hypersensitivity reactions: Severe and life-threatening skin and hypersensitivity reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis and drug rash with eosinophilia with systemic symptoms (DRESS), have been reported with use, predominately in patients also receiving concomitant agents associated with these reactions. Rash and constitutional findings (eg, fever, muscle aches, conjunctivitis, oral lesions), with or without organ dysfunction (including hepatic failure), have also accompanied these reports. Discontinue maraviroc and any other suspected agent immediately if symptoms or signs of hypersensitivity occur. Monitor liver function tests and clinical status as appropriate.
Disease-related concerns:
- Cardiovascular disease: Use with caution in patients with cardiovascular disease, or in patients with a history of or current cardiac risk factors for postural hypotension, or receiving concomitant medication known to lower blood pressure. Patients who have cardiovascular comorbidities could be at risk for cardiac adverse events prompted by postural hypotension. During trials, a small increase in cardiovascular events (myocardial ischemia and/or infarction) occurred in treated patients compared to placebo, although a contributory relationship relative to therapy is unknown. Of note, patients experiencing events generally had cardiac disease/risk factors prior to therapy.
- Hepatic impairment: Use caution in patients with HBV and/or HCV coinfection or with mild-to-moderate hepatic impairment; maraviroc concentrations are increased. Maraviroc concentrations are further increased in patients with moderate hepatic impairment receiving concomitant potent CYP3A inhibitors; monitor closely for adverse events. Use in patients with severe hepatic impairment has not been studied.
- Renal impairment: Renal impairment may increase maraviroc concentrations. Use with caution in patients with mild-to-moderate renal impairment. An increased risk of postural hypotension may occur in patients with severe renal impairment or in those with ESRD. Patients with severe renal dysfunction or ESRD who experience postural hypotension should have dose reduced. Do not use maraviroc in patients with severe renal impairment or ESRD who are receiving CYP3A inhibitors or inducers unless no alternative treatment options are available.
Concurrent drug therapy issues:
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
Other warnings/precautions:
- Appropriate use: Prior to therapy, coreceptor tropism testing should be performed for presence of CCR5-tropic only virus HIV-1 infection. Therapy not recommended for use in patients with CXCR4- or dual/mixed tropic HIV-1 infection; efficacy not demonstrated in this population. In studies with treatment-naive patients, virologic failure and emergent lamivudine resistance was more common in maraviroc-treated patients compared to patients receiving efavirenz.
B
Adverse effects have not been observed in animal reproduction studies; data collected by the antiretroviral pregnancy registry is insufficient to evaluate human teratogenic risk. Maraviroc has minimal to low transfer across the human placenta. The HHS Perinatal HIV Guidelines note there is insufficient data to recommend use of maraviroc in antiretroviral-naive pregnant women; pharmacokinetic data are insufficient to make dosing recommendations during pregnancy.
Combination antiretroviral therapy (cART) therapy is recommended for all HIV-infected pregnant women. The goal of therapy is to keep the viral load below the limit of detection and prevent perinatal transmission. Therapy must be individualized. In general, women who become pregnant on a stable cART regimen may continue that regimen if viral suppression is effective, contraindications for use in pregnancy are not present, and the regimen is well tolerated. For HIV-infected couples planning a pregnancy, maximum viral suppression with cART is recommended prior to conception for the HIV-infected partner(s). When HIV is diagnosed during pregnancy in a woman who has never received antiretroviral therapy, cART should be considered as soon as possible after diagnosis to reduce the risk of perinatal transmission. If antiretroviral drug-resistance testing is done, treatment may be started prior to obtaining results, then adjusted accordingly. Monitoring during pregnancy is more frequent than in non-pregnant adults. If cART must be interrupted for <24 hours, stop then restart all medications simultaneously in order to decrease the chance of developing resistance. Long-term follow-up is recommended for all infants exposed to antiretroviral medications; children who develop significant organ system abnormalities (particularly of the CNS or heart) should be evaluated for potential mitochondrial dysfunction.
HIV-infected women not planning a pregnancy may use any available type of contraception, considering possible drug interactions and contraindications of the specific method. In addition, consistent use of condoms is also recommended (even during pregnancy) to prevent transmission of HIV or other sexually transmitted diseases.
Health care providers are encouraged to enroll pregnant women exposed to antiretroviral medications as early in pregnancy as possible in the Antiretroviral Pregnancy Registry (1-800-258-4263 or www.APRegistry.com). Health care providers caring for HIV-infected women and their infants may contact the National Perinatal HIV Hotline (888-448-8765) for clinical consultation (HHS [perinatal] 2016).
Maraviroc, a CCR5 antagonist, selectively and reversibly binds to the chemokine (C-C motif receptor 5 [CCR5]) coreceptors located on human CD4 cells. CCR5 antagonism prevents interaction between the human CCR5 coreceptor and the gp120 subunit of the viral envelope glycoprotein, thereby inhibiting gp120 conformational change required for CCR5-tropic HIV-1 fusion with the CD4 cell and subsequent cell entry.
Vd: ~194 L
Hepatic, via CYP3A to inactive metabolites
Urine (~20%, 8% as unchanged drug); feces (76%, 25% as unchanged drug)
Plasma: 0.5 to 4 hours
14 to 18 hours
~76%
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience constipation, diarrhea, rhinorrhea, rhinitis, abdominal pain, flatulence, joint pain, or insomnia. Have patient report immediately to prescriber signs of liver problems (dark urine, feeling tired, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes), signs of infection, severe dizziness, passing out, burning or numbness feeling, angina, urinary retention, change in amount of urine passed, loss of strength and energy, swelling of arms or legs, or signs of Stevens-Johnson syndrome/toxic epidermal necrolysis (red, swollen, blistered, or peeling skin [with or without fever]; red or irritated eyes; or sores in mouth, throat, nose, or eyes) (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.