Maraviroc Prescribing Information
Hepatotoxicity with allergic features including life-threatening events has been reported in clinical trials and postmarketing. Severe rash or evidence of systemic allergic reaction including drug-related rash with fever, eosinophilia, elevated IgE, or other systemic symptoms have been reported in conjunction with hepatotoxicity [
Appropriate laboratory testing including ALT, AST, and bilirubin should be conducted prior to initiating therapy with maraviroc and at other time points during treatment as clinically indicated. Hepatic laboratory parameters should be obtained in any patient who develops rash, or signs or symptoms of hepatitis, or allergic reaction. Discontinuation of maraviroc should be considered in any patient with signs or symptoms of hepatitis, or with increased liver transaminases combined with rash or other systemic symptoms.
When administering maraviroc to patients with pre-existing liver dysfunction or who are co-infected with hepatitis B and/or C virus, additional monitoring may be warranted. The safety and efficacy of maraviroc have not been specifically studied in patients with significant underlying liver disorders.
Maraviroc tablets are indicated in combination with other antiretroviral agents for the treatment of only CCR5-tropic human immunodeficiency virus type 1 (HIV-1) infection in adult and pediatric patients 2 years of age and older weighing at least 10 kg.
Limitations of Use:
• Maraviroc tablets are not recommended in patients with dual/mixed- or CXCR4-tropic HIV-1 [
Maraviroc is a member of a therapeutic class called CCR5 co-receptor antagonists. Maraviroc selectively binds to the human chemokine receptor CCR5 present on the cell membrane, preventing the interaction of HIV-1 gp120 and CCR5 necessary for CCR5-tropic HIV-1 to enter cells. CXCR4-tropic and dual-tropic HIV-1 entry is not inhibited by maraviroc.
Maraviroc inhibits the replication of CCR5-tropic laboratory strains and primary isolates of HIV-1 in models of acute peripheral blood leukocyte infection. The mean EC50value (50% effective concentration) for maraviroc against HIV-1 group M isolates (subtypes A to J and circulating recombinant form AE) and group O isolates ranged from 0.1 to 4.5 nM (0.05 to 2.3 ng per mL) in cell culture.
When used with other antiretroviral agents in cell culture, the combination of maraviroc was not antagonistic with non-nucleoside reverse transcriptase inhibitors (NNRTIs: efavirenz and nevirapine), NRTIs (abacavir, didanosine, emtricitabine, lamivudine, stavudine, tenofovir, zalcitabine, and zidovudine), or protease inhibitors (PIs: amprenavir, atazanavir, darunavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, and tipranavir). Maraviroc was not antagonistic with the HIV-1 gp41 fusion inhibitor enfuvirtide. Maraviroc was not active against CXCR4-tropic and dual-tropic viruses (EC50value greater than 10 μM). The antiviral activity of maraviroc against HIV-2 has not been evaluated.
Fifteen of these viruses were sequenced in the gp120 encoding region and multiple amino acid substitutions with unique patterns in the heterogeneous V3 loop region were detected. Changes at either amino acid position 308 or 323 (HXB2 numbering) were seen in the V3 loop in 7 of the subjects with decreased maraviroc susceptibility. Substitutions outside the V3 loop of gp120 may also contribute to reduced susceptibility to maraviroc.
Maraviroc | Efavirenz | |
| Total N in dataset (as-treated) | 273 | 241 |
| Total virologic failures (as-treated) | 85 (31%) | 56 (23%) |
| Evaluable virologic failures with post baseline genotypic and phenotypic data | 73 | 43 |
| Lamivudine resistance | 39 (53%) | 13 (30%) |
| Zidovudine resistance | 2 (3%) | 0 |
| Efavirenz resistance | - | 23 (53%) |
| Phenotypic resistance to maraviroca | 19 (26 % ) | - |
aIncludes subjects failing with CXCR4- or dual/mixed-tropism because these viruses are not intrinsically susceptible to maraviroc.
In an as-treated analysis of treatment-naive subjects at 96 weeks, 32 subjects failed a maraviroc-containing regimen with CCR5-tropic virus and had a tropism result at failure; 7 of these subjects had evidence of maraviroc phenotypic resistance defined as concentration-response curves that did not reach 95% inhibition. One additional subject had a greater than or equal to 3-fold shift in the EC50value for maraviroc at the time of failure. A clonal analysis of the V3 loop amino acid envelope sequences was performed from 6 of the 7 subjects. Changes in V3 loop amino acid sequence differed between each of these different subjects, even for those infected with the same virus clade, suggesting that there are multiple diverse pathways to maraviroc resistance. The subjects who failed with CCR5-tropic virus and without a detectable maraviroc shift in susceptibility were not evaluated for genotypic resistance.
Of the 32 maraviroc virologic failures failing with CCR5-tropic virus, 20 (63%) also had genotypic and/or phenotypic resistance to background drugs in the regimen (lamivudine, zidovudine).
Detection of CXCR4-using virus prior to initiation of therapy has been associated with a reduced virological response to maraviroc. Furthermore, subjects failing twice-daily maraviroc at Week 48 with CXCR4-using virus had a lower median increase in CD4+ cell counts from baseline (+41 cells per mm3) than those subjects failing with CCR5-tropic virus (+162 cells per mm3). The median increase in CD4+ cell count in subjects failing in the placebo arm was +7 cells per mm3.
Subjects who had only CCR5-tropic virus at baseline and failed maraviroc therapy with CXCR4-using virus had a median increase in CD4+ cell counts from baseline of +113 cells per mm3while those subjects failing with CCR5-tropic virus had an increase of +135 cells per mm3. The median increase in CD4+ cell count in subjects failing in the efavirenz arm was +95 cells per mm3.
• Prior to initiation of maraviroc tablets for treatment of HIV-1 infection, test all patients for CCR5 tropism using a highly sensitive tropism assay. (
Prior to initiation of maraviroc tablets for treatment of HIV-1 infection, test all patients for CCR5 tropism using a highly sensitive tropism assay. Maraviroc tablets are recommended for patients with only CCR5-tropic HIV-1 infection. Outgrowth of pre-existing low-level CXCR4- or dual/mixed-tropic HIV-1 not detected by tropism testing at screening has been associated with virologic failure on maraviroc tablets [
Monitor patients for ALT, AST, and bilirubin prior to initiation of maraviroc tablets and at other time points during treatment as clinically indicated
• Maraviroc tablets are taken twice daily by mouth and may be taken with or without food. Maraviroc tablets must be given in combination with other antiretroviral medications. (
• Maraviroc tablets are taken twice daily by mouth and may be taken with or without food.
• Maraviroc tablets must be given in combination with other antiretroviral medications.
• The recommended dosage of maraviroc tablets differs based on concomitant medications due to drug interactions.
Recommended Dosage in Adult Patients: (
Table 1 displays oral dosage of maraviroc tablets based on different concomitant medications [
Concomitant Medications | Dosage of Maraviroc Tablets |
Potent cytochrome P450 (CYP)3A inhibitors (with or without a potent CYP3A inducer)a | 150 mg twice daily |
Noninteracting concomitant medicationsb | 300 mg twice daily |
Potent and moderate CYP3A inducers (without a potent CYP3A inhibitor)c | 600 mg twice daily |
aPotent CYP3A inhibitors (with or without a potent CYP3A inducer) including: clarithromycin, cobicistat, elvitegravir/ritonavir, itraconazole, ketoconazole, nefazodone, protease inhibitors (except tipranavir/ritonavir), telithromycin.
bNoninteracting concomitant medications include all medications that are not potent CYP3A inhibitors or inducers such as: dolutegravir, enfuvirtide, nevirapine, all nucleoside reverse transcriptase inhibitors (NRTIs), raltegravir, and tipranavir/ritonavir.
cPotent and moderate CYP3A inducers (without a potent CYP3A inhibitor) including: carbamazepine, efavirenz, etravirine, phenobarbital, phenytoin, and rifampin.
| Concomitant Medications | Dosage of Maraviroc tablets | ||||||||
When given with potent cytochrome P450 (CYP)3A inhibitors (with or without potent CYP3A inducers) including PIs (except tipranavir/ritonavir) (Table 1 displays oral dosage of maraviroc tablets based on different concomitant medications [ see Drug Interactions ].Table 1. Recommended Dosage in Adults
aPotent CYP3A inhibitors (with or without a potent CYP3A inducer) including: clarithromycin, cobicistat, elvitegravir/ritonavir, itraconazole, ketoconazole, nefazodone, protease inhibitors (except tipranavir/ritonavir), telithromycin. Maraviroc is metabolized by CYP3A and is also a substrate for P-glycoprotein (P-gp), organic anion-transporting polypeptide (OATP)1B1, and multidrug resistance-associated protein (MRP)2. The pharmacokinetics of maraviroc are likely to be modulated by inhibitors and inducers of CYP3A and P-gp and may be modulated by inhibitors of OATP1B1 and MRP2. Therefore, a dosage adjustment may be required when maraviroc is coadministered with those drugs [ see Dosage and Administration ].Concomitant use of maraviroc and St. John's wort ( Hypericum perforatum ) or products containing St. John's wort is not recommended. Coadministration of maraviroc with St. John's wort is expected to substantially decrease maraviroc concentrations and may result in suboptimal levels of maraviroc and lead to loss of virologic response and possible resistance to maraviroc.Additional drug interaction information is available [ see Clinical Pharmacology ]. | 150 mg twice daily | ||||||||
With NRTIs, tipranavir/ritonavir, nevirapine, raltegravir, and other drugs that are not potent CYP3A inhibitors or CYP3A inducers (Table 1 displays oral dosage of maraviroc tablets based on different concomitant medications [ see Drug Interactions ].Table 1. Recommended Dosage in Adults
aPotent CYP3A inhibitors (with or without a potent CYP3A inducer) including: clarithromycin, cobicistat, elvitegravir/ritonavir, itraconazole, ketoconazole, nefazodone, protease inhibitors (except tipranavir/ritonavir), telithromycin. Maraviroc is metabolized by CYP3A and is also a substrate for P-glycoprotein (P-gp), organic anion-transporting polypeptide (OATP)1B1, and multidrug resistance-associated protein (MRP)2. The pharmacokinetics of maraviroc are likely to be modulated by inhibitors and inducers of CYP3A and P-gp and may be modulated by inhibitors of OATP1B1 and MRP2. Therefore, a dosage adjustment may be required when maraviroc is coadministered with those drugs [ see Dosage and Administration ].Concomitant use of maraviroc and St. John's wort ( Hypericum perforatum ) or products containing St. John's wort is not recommended. Coadministration of maraviroc with St. John's wort is expected to substantially decrease maraviroc concentrations and may result in suboptimal levels of maraviroc and lead to loss of virologic response and possible resistance to maraviroc.Additional drug interaction information is available [ see Clinical Pharmacology ]. | 300 mg twice daily | ||||||||
With potent and moderate CYP3A inducers including efavirenz (without a potent CYP3A inhibitor) (Table 1 displays oral dosage of maraviroc tablets based on different concomitant medications [ see Drug Interactions ].Table 1. Recommended Dosage in Adults
aPotent CYP3A inhibitors (with or without a potent CYP3A inducer) including: clarithromycin, cobicistat, elvitegravir/ritonavir, itraconazole, ketoconazole, nefazodone, protease inhibitors (except tipranavir/ritonavir), telithromycin. Maraviroc is metabolized by CYP3A and is also a substrate for P-glycoprotein (P-gp), organic anion-transporting polypeptide (OATP)1B1, and multidrug resistance-associated protein (MRP)2. The pharmacokinetics of maraviroc are likely to be modulated by inhibitors and inducers of CYP3A and P-gp and may be modulated by inhibitors of OATP1B1 and MRP2. Therefore, a dosage adjustment may be required when maraviroc is coadministered with those drugs [ see Dosage and Administration ].Concomitant use of maraviroc and St. John's wort ( Hypericum perforatum ) or products containing St. John's wort is not recommended. Coadministration of maraviroc with St. John's wort is expected to substantially decrease maraviroc concentrations and may result in suboptimal levels of maraviroc and lead to loss of virologic response and possible resistance to maraviroc.Additional drug interaction information is available [ see Clinical Pharmacology ]. | 600 mg twice daily |
A more complete list of coadministered drugs is listed in
• Prior to initiation of maraviroc tablets for treatment of HIV-1 infection, test all patients for CCR5 tropism using a highly sensitive tropism assay.
• Maraviroc tablets are taken twice daily by mouth and may be taken with or without food. Maraviroc tablets must be given in combination with other antiretroviral medications.
Recommended Dosage in Adult Patients:
| Concomitant Medications | Dosage of Maraviroc tablets |
| When given with potent cytochrome P450 (CYP)3A inhibitors (with or without potent CYP3A inducers) including PIs (except tipranavir/ritonavir) | 150 mg twice daily |
| With NRTIs, tipranavir/ritonavir, nevirapine, raltegravir, and other drugs that are not potent CYP3A inhibitors or CYP3A inducers | 300 mg twice daily |
| With potent and moderate CYP3A inducers including efavirenz (without a potent CYP3A inhibitor) | 600 mg twice daily |
A more complete list of coadministered drugs is listed in
Recommended Dosage in Pediatric Patients 2 years and older and weighing at Least 10 kg:
Administer twice daily. Dosage should be based on body weight (kg) and concomitant medications and should not exceed the recommended adult dose.
Recommended Dosage in Patients with Renal Impairment: Dose adjustment may be necessary in adult patients with renal impairment.
Prior to initiation of maraviroc tablets for treatment of HIV-1 infection, test all patients for CCR5 tropism using a highly sensitive tropism assay. Maraviroc tablets are recommended for patients with only CCR5-tropic HIV-1 infection. Outgrowth of pre-existing low-level CXCR4- or dual/mixed-tropic HIV-1 not detected by tropism testing at screening has been associated with virologic failure on maraviroc tablets [
Monitor patients for ALT, AST, and bilirubin prior to initiation of maraviroc tablets and at other time points during treatment as clinically indicated
• Maraviroc tablets are taken twice daily by mouth and may be taken with or without food.
• Maraviroc tablets must be given in combination with other antiretroviral medications.
• The recommended dosage of maraviroc tablets differs based on concomitant medications due to drug interactions.
Table 1 displays oral dosage of maraviroc tablets based on different concomitant medications [
Concomitant Medications | Dosage of Maraviroc Tablets |
Potent cytochrome P450 (CYP)3A inhibitors (with or without a potent CYP3A inducer)a | 150 mg twice daily |
Noninteracting concomitant medicationsb | 300 mg twice daily |
Potent and moderate CYP3A inducers (without a potent CYP3A inhibitor)c | 600 mg twice daily |
aPotent CYP3A inhibitors (with or without a potent CYP3A inducer) including: clarithromycin, cobicistat, elvitegravir/ritonavir, itraconazole, ketoconazole, nefazodone, protease inhibitors (except tipranavir/ritonavir), telithromycin.
bNoninteracting concomitant medications include all medications that are not potent CYP3A inhibitors or inducers such as: dolutegravir, enfuvirtide, nevirapine, all nucleoside reverse transcriptase inhibitors (NRTIs), raltegravir, and tipranavir/ritonavir.
cPotent and moderate CYP3A inducers (without a potent CYP3A inhibitor) including: carbamazepine, efavirenz, etravirine, phenobarbital, phenytoin, and rifampin.
The recommended dosage of maraviroc tablets should be based on body weight (kg) and should not exceed the recommended adult dose. The recommended dosage also differs based on concomitant medications due to drug interactions (Table 2 and Table 3) [
Before prescribing maraviroc tablets, assess children for the ability to swallow tablets. If a child is unable to reliably swallow maraviroc tablets, the oral solution formulation should be prescribed.
The recommended oral dosage of maraviroc tablets in pediatric patients aged 2 years and older weighing at least 10 kg is presented in Table 2.
Concomitant Medications | Dosage of Maraviroc Tablets Based on Weight | ||||
10 kg to <14 kg | 14 kg to <20 kg | 20 kg to <30 kg | 30 kg to <40 kg | ≥40 kg | |
| Potent CYP3A inhibitors (with or without a CYP3A inducer)a | 50 mg twice daily | 50 mg twice daily | 75 mg twice daily | 100 mg twice daily | 150 mg twice daily |
| Noninteracting concomitant medicationsb | 150 mg twice daily | 200 mg twice daily | 200 mg twice daily | 300 mg twice daily | 300 mg twice daily |
| Potent and moderate CYP3A inducers (without a potent CYP3A inhibitor)c | Not recommendedd | ||||
aPotent CYP3A inhibitors (with or without a CYP3A inducer) including: clarithromycin, cobicistat, elvitegravir/ritonavir, itraconazole, ketoconazole, nefazodone, protease inhibitors (except tipranavir/ritonavir), telithromycin.
bNoninteracting concomitant medications including all medications that are not potent CYP3A inhibitors or inducers such as: dolutegravir, enfuvirtide, nevirapine, all NRTIs, raltegravir, and tipranavir/ritonavir.
cPotent and moderate CYP3A inducers (without a potent CYP3A inhibitor) including: carbamazepine, efavirenz, etravirine, phenobarbital, phenytoin, and rifampin.
dInsufficient data are available to recommend use.
The recommended oral dosage of maraviroc oral solution in pediatric patients weighing at least 10 kg is presented in Table 3.
Concomitant Medications | Dosage (Volume of Solution) of Maraviroc Tablets Based on Weight | ||||
10 kg to <14 kg | 14 kg to <20 kg | 20 kg to <30 kg | 30 kg to <40 kg | ≥40 kg | |
| Potent CYP3A inhibitors (with or without a CYP3A inducer)a | 50 mg (2.5 mL) twice daily | 50 mg (2.5 mL) twice daily | 80 mg (4 mL) twice daily | 100 mg (5 mL) twice daily | 150 mg (7.5 mL) twice daily |
| Noninteracting concomitant medicationsc | 150 mg (7.5 mL) twice daily | 200 mg (10 mL) twice daily | 200 mg (10 mL) twice daily | 300 mg (15 mL) twice daily | 300 mg (15 mL) twice daily |
| Potent and moderate CYP3A inducers (without a potent CYP3A inhibitor)d | Not recommendedd | ||||
aPotentCYP3A inhibitors(with or without a CYP3A inducer) including:clarithromycin, cobicistat,elvitegravir/ritonavir, itraconazole,ketoconazole,nefazodone,proteaseinhibitors (excepttipranavir/ritonavir), telithromycin.
bInsufficient data areavailable to recommend use.
cNoninteractingconcomitantmedicationsincluding all medicationsthatare not potent CYP3A inhibitorsor inducers such as: dolutegravir, enfuvirtide,nevirapine, all NRTIs,raltegravir, and tipranavir/ritonavir.
dPotent and moderateCYP3A inducers (without a potent CYP3A inhibitor)including:
carbamazepine,efavirenz,etravirine, phenobarbital,phenytoin, and rifampin.
Administer the oral solution using the included press-in bottle adapter and the appropriate oral dosing syringe: for doses of 2.5 mL, use the 3-mL syringe; for doses greater than 2.5 mL, use the 10-mL syringe.
Table 4 provides dosing recommendations for patients based on renal function and concomitant medications.
Concomitant Medications | Dosage of Maraviroc Tablets Based on Renal Function | ||||
Normal (CrCl >80 mL/min) | Mild (CrCl >50 and ≤80 mL/min) | Moderate (CrCl ≥30 and ≤50 mL/min) | Severe (CrCl <30 mL/min) | End-Stage Renal Disease on Regular Hemodialysis | |
| Potent CYP3A inhibitors (with or without a CYP3A inducer)a | 150 mg twice daily | 150 mg twice daily | 150 mg twice daily | Contraindicated | Contraindicated |
| Noninteracting concomitant medicationsb | 300 mg twice daily | 300 mg twice daily | 300 mg twice daily | 300 mg twice daily | 300 mg twice dailyc |
| Potent and moderate CYP3A inducers (without a potent CYP3A inhibitor)d | 600 mg twice daily | 600 mg twice daily | 600 mg twice daily | Contraindicated | Contraindicated |
aPotent CYP3A inhibitors (with or without a CYP3A inducer) including: clarithromycin, cobicistat, elvitegravir/ritonavir, itraconazole, ketoconazole, nefazodone, protease inhibitors (except tipranavir/ritonavir), telithromycin.
bNoninteracting concomitant medications include all medications that are not potent CYP3A inhibitors or inducers such as: dolutegravir, enfuvirtide, nevirapine, all NRTIs, raltegravir, and tipranavir/ritonavir.
cDosage of maraviroc tablets should be reduced to 150 mg twice daily if there are any symptoms of postural hypotension [
dPotent and moderate CYP3A inducers (without a potent CYP3A inhibitor) including: carbamazepine, efavirenz, etravirine, phenobarbital, phenytoin, and rifampin.
There are no data to recommend specific doses of maraviroc tablets in pediatric patients with mild or moderate renal impairment [
Recommended Dosage in Pediatric Patients 2 years and older and weighing at Least 10 kg:
Administer twice daily. Dosage should be based on body weight (kg) and concomitant medications and should not exceed the recommended adult dose. (
The recommended dosage of maraviroc tablets should be based on body weight (kg) and should not exceed the recommended adult dose. The recommended dosage also differs based on concomitant medications due to drug interactions (Table 2 and Table 3) [
Before prescribing maraviroc tablets, assess children for the ability to swallow tablets. If a child is unable to reliably swallow maraviroc tablets, the oral solution formulation should be prescribed.
The recommended oral dosage of maraviroc tablets in pediatric patients aged 2 years and older weighing at least 10 kg is presented in Table 2.
Concomitant Medications | Dosage of Maraviroc Tablets Based on Weight | ||||
10 kg to <14 kg | 14 kg to <20 kg | 20 kg to <30 kg | 30 kg to <40 kg | ≥40 kg | |
| Potent CYP3A inhibitors (with or without a CYP3A inducer)a | 50 mg twice daily | 50 mg twice daily | 75 mg twice daily | 100 mg twice daily | 150 mg twice daily |
| Noninteracting concomitant medicationsb | 150 mg twice daily | 200 mg twice daily | 200 mg twice daily | 300 mg twice daily | 300 mg twice daily |
| Potent and moderate CYP3A inducers (without a potent CYP3A inhibitor)c | Not recommendedd | ||||
aPotent CYP3A inhibitors (with or without a CYP3A inducer) including: clarithromycin, cobicistat, elvitegravir/ritonavir, itraconazole, ketoconazole, nefazodone, protease inhibitors (except tipranavir/ritonavir), telithromycin.
bNoninteracting concomitant medications including all medications that are not potent CYP3A inhibitors or inducers such as: dolutegravir, enfuvirtide, nevirapine, all NRTIs, raltegravir, and tipranavir/ritonavir.
cPotent and moderate CYP3A inducers (without a potent CYP3A inhibitor) including: carbamazepine, efavirenz, etravirine, phenobarbital, phenytoin, and rifampin.
dInsufficient data are available to recommend use.
The recommended oral dosage of maraviroc oral solution in pediatric patients weighing at least 10 kg is presented in Table 3.
Concomitant Medications | Dosage (Volume of Solution) of Maraviroc Tablets Based on Weight | ||||
10 kg to <14 kg | 14 kg to <20 kg | 20 kg to <30 kg | 30 kg to <40 kg | ≥40 kg | |
| Potent CYP3A inhibitors (with or without a CYP3A inducer)a | 50 mg (2.5 mL) twice daily | 50 mg (2.5 mL) twice daily | 80 mg (4 mL) twice daily | 100 mg (5 mL) twice daily | 150 mg (7.5 mL) twice daily |
| Noninteracting concomitant medicationsc | 150 mg (7.5 mL) twice daily | 200 mg (10 mL) twice daily | 200 mg (10 mL) twice daily | 300 mg (15 mL) twice daily | 300 mg (15 mL) twice daily |
| Potent and moderate CYP3A inducers (without a potent CYP3A inhibitor)d | Not recommendedd | ||||
aPotentCYP3A inhibitors(with or without a CYP3A inducer) including:clarithromycin, cobicistat,elvitegravir/ritonavir, itraconazole,ketoconazole,nefazodone,proteaseinhibitors (excepttipranavir/ritonavir), telithromycin.
bInsufficient data areavailable to recommend use.
cNoninteractingconcomitantmedicationsincluding all medicationsthatare not potent CYP3A inhibitorsor inducers such as: dolutegravir, enfuvirtide,nevirapine, all NRTIs,raltegravir, and tipranavir/ritonavir.
dPotent and moderateCYP3A inducers (without a potent CYP3A inhibitor)including:
carbamazepine,efavirenz,etravirine, phenobarbital,phenytoin, and rifampin.
Administer the oral solution using the included press-in bottle adapter and the appropriate oral dosing syringe: for doses of 2.5 mL, use the 3-mL syringe; for doses greater than 2.5 mL, use the 10-mL syringe.
Recommended Dosage in Patients with Renal Impairment: Dose adjustment may be necessary in adult patients with renal impairment. (
Table 4 provides dosing recommendations for patients based on renal function and concomitant medications.
Concomitant Medications | Dosage of Maraviroc Tablets Based on Renal Function | ||||
Normal (CrCl >80 mL/min) | Mild (CrCl >50 and ≤80 mL/min) | Moderate (CrCl ≥30 and ≤50 mL/min) | Severe (CrCl <30 mL/min) | End-Stage Renal Disease on Regular Hemodialysis | |
| Potent CYP3A inhibitors (with or without a CYP3A inducer)a | 150 mg twice daily | 150 mg twice daily | 150 mg twice daily | Contraindicated | Contraindicated |
| Noninteracting concomitant medicationsb | 300 mg twice daily | 300 mg twice daily | 300 mg twice daily | 300 mg twice daily | 300 mg twice dailyc |
| Potent and moderate CYP3A inducers (without a potent CYP3A inhibitor)d | 600 mg twice daily | 600 mg twice daily | 600 mg twice daily | Contraindicated | Contraindicated |
aPotent CYP3A inhibitors (with or without a CYP3A inducer) including: clarithromycin, cobicistat, elvitegravir/ritonavir, itraconazole, ketoconazole, nefazodone, protease inhibitors (except tipranavir/ritonavir), telithromycin.
bNoninteracting concomitant medications include all medications that are not potent CYP3A inhibitors or inducers such as: dolutegravir, enfuvirtide, nevirapine, all NRTIs, raltegravir, and tipranavir/ritonavir.
cDosage of maraviroc tablets should be reduced to 150 mg twice daily if there are any symptoms of postural hypotension [
dPotent and moderate CYP3A inducers (without a potent CYP3A inhibitor) including: carbamazepine, efavirenz, etravirine, phenobarbital, phenytoin, and rifampin.
There are no data to recommend specific doses of maraviroc tablets in pediatric patients with mild or moderate renal impairment [
• 150 mg white to off-white colored, oval, biconvex, film coated tablets debossed with ‘J’ on one side and ‘62’ on the other side.
• 300 mg white to off-white colored, oval, biconvex, film coated tablets debossed with ‘J’ on one side and ‘63’ on the other side.
• Lactation: Women infected with HIV should be instructed not to breastfeed due to the potential for HIV transmission. (
The Centers for Disease Control and Prevention recommend that HIV-1–infected mothers in the United States not breastfeed their infants to avoid risking postnatal transmission of HIV-1 infection.
There are no data on the presence of maraviroc in human milk, the effects on the breastfed infant, or the effects on milk production. When administered to lactating rats, maraviroc was present in milk (
Maraviroc (and related metabolites) was excreted into the milk of lactating rats following a single oral dose of maraviroc (100 mg per kg) on lactation Day 12, with a maximal milk concentration achieved one hour post-administration at a milk concentration approximately 2.5 times that of maternal plasma concentrations.
Maraviroc tablets are contraindicated in patients with severe renal impairment or ESRD (CrCl less than 30 mL per minute) who are concomitantly taking potent CYP3A inhibitors or inducers [
Eleven subjects (1.3%) who received maraviroc had cardiovascular events, including myocardial ischemia and/or infarction, during the Phase 3 trials in treatment-experienced subjects (total exposure 609 patient-years [300 on maraviroc once daily + 309 on maraviroc twice daily]), while no subjects who received placebo had such events (total exposure 111 patient-years). These subjects generally had cardiac disease or cardiac risk factors prior to use of maraviroc, and the relative contribution of maraviroc to these events is not known.
In the Phase 2b/3 trial in treatment-naive adult subjects, 3 subjects (0.8%) who received maraviroc had events related to ischemic heart disease and 5 subjects (1.4%) who received efavirenz had such events (total exposure 506 and 508 patient-years for maraviroc and efavirenz, respectively).
When maraviroc was administered to healthy volunteers at doses higher than the recommended dose, symptomatic postural hypotension was seen at a greater frequency than in placebo. However, when maraviroc was given at the recommended dose in HIV-1-infected adult subjects in Phase 3 trials, postural hypotension was seen at a rate similar to placebo (approximately 0.5%).
Patients with cardiovascular comorbidities, risk factors for postural hypotension, or receiving concomitant medication known to lower blood pressure, could be at increased risk of cardiovascular adverse events triggered by postural hypotension. Additional monitoring may be warranted.
An increased risk of postural hypotension may occur in patients with severe renal insufficiency or in those with ESRD due to increased maraviroc exposure in some patients. Maraviroc should be used in patients with severe renal impairment or ESRD only if they are not receiving a concomitant potent CYP3A inhibitor or inducer. However, the use of maraviroc in these patients should only be considered when no alternative treatment options are available. If adult patients with severe renal impairment or ESRD experience any symptoms of postural hypotension while taking 300 mg twice daily, the dose should be reduced to 150 mg twice daily [