Maraviroc

Indications

Maraviroc is used for: HIV infection, Allogeneic bone marrow transplantation

Adult Dose

HIV-1 Infection Indicated for combination antiretroviral treatment of CCR5-tropic HIV-1 in patients who have viral replication and HIV-1 strains resistant to multiple antiretroviral agents With NRTIs, tipranavir/ritonavir, nevirapine, raltegravir, and other drugs that are not potent CYP3A inhibitors or CYP3A4 inducers: 300 mg PO q12hr Coadministration with strong CYP3A4 inhibitors (with or without potent CYP3A4 inducers): 150 mg PO q12hr Coadministration with CYP3A inducers including efavirenz (without a strong CYP3A inhibitor): 600 mg PO q12hr Hepatic Impairment Mild to moderate impairment: Maraviroc concentrations increased but dose adjustment not recommended; monitor Moderate impairment and strong CYP 3A4 inhibitor: Use caution; monitor closely for adverse reactions Severe impairment: Not studied

Child Dose

HIV-1 Infection <16 years: Safety and efficacy not established >16 years: As in adults; indicated for combination antiretroviral treatment of CCR5-tropic HIV-1 in patients who have viral replication and HIV-1 strains resistant to multiple antiretroviral agents With NRTIs, tipranavir/ritonavir, nevirapine, raltegravir, and other drugs that are not potent CYP3A4 inhibitors or CYP3A4 inducers: 300 mg PO q12hr Coadministration with strong CYP3A4 inhibitors (with or without potent CYP3A4 inducers): 150 mg PO q12hr Coadministration with CYP3A4 inducers including efavirenz (without a strong CYP3A4 inhibitor): 600 mg PO q12hr

Renal Dose

Renal Impairment CrCl <30 mL/min or hemodialysis Experiencing postural hypotension: 150 mg PO q12hr Concomitantly administraiton with NRTIs and other medications but without concomitant CYP3A inducers or inhibitors: 300 mg PO q12hr; if postural hypotension occurs, reduce dose to 150 mg q12hr With potent CYP3A inducers or inhibitors: Not recommended CrCl>30 mL/min Concomitant administration with potent CYP 3A4 inhibitors with or without a CYP3A4 inducer: 150 mg PO q12hr With potent CYP3A4 inducer without CYP3A4 inhibitor: 600 mg PO q12hr With NRTIs and other medications but without concomitant CYP3A inducers or inhibitors: 300 mg PO q12hr

Administration

May be taken with or without food.

Contra Indications

Patients with severe renal impairment or end-stage renal disease (ESRD) (CrCl < 30 mL/min) who are taking potent CYP3A inhibitors or inducers.

Precautions

Hepatotoxicity Cardiovascular Events Immune Reconstitution Syndrome Potential Risk of Infection Potential Risk of Malignancy Lactation: breastfeeding not recommended in HIV+ mothers

Pregnancy-Lactation

Interactions

Increased or decreased conc w/ CYP3A inhibitors &/or inducers, respectively. Increased metabolic ratio of debrisoquine. Increased conc w/ elvitegravir/ritonavir, delavirdine, boceprevir, telaprevir, HIV PIs (except tipranavir/ritonavir), NNRTI + PI, rifabutin + PI, clarithromycin, telithromycin, ketoconazole, itraconazole. Decreased conc w/ efavirenz, etravirine, rifampicin, St. John's wort.

Adverse Effects

Side effects of Maraviroc : >10% Upper respiratory infections (20%),Arthritis and musculoskeletal S/S (15%),Cough (13%),Pyrexia (12%),Rash (11%),Fever (13%) 2-10% Dizziness (9%),Appetite disorder (8%),Herpes infection (8%),Bronchitis (7%),Sinusitis (7%),Constipation (6%),Apocrine and eccrine gland disorder (5%),Paresthesia/dysesthesia (5%),Renal/urinary disorder (3-5%),Depression (4%),Disturbed consciousness (4%),Periph neuropathies (4%),Pruritus (4%),Sensory abnormalities (4%),Folliculitis (3%),Hypertension (3%),Lipodystrophy (3%),Muscle pain (3%),Influenza (2%),Pneumonia (2%),Condyloma acuminata,Dermatitis/eczema,Dyspepsia,GI pain,Stomatitis/ulceration

Mechanism of Action

Selective antagonist of the interaction between human CCR5 and HIV-1 gp120; blocking this interaction prevents CCR5-tropic HIV-1 entry into cells.