Trade Names:Selzentry- Tablets 150 mg, 300 mgCelsentri (Canada)
Selectively binds to CCR5 present on the cell membrane, preventing CCR5-tropic HIV-1 to enter cells.
After oral dosing, C max attained in 0.5 to 4 h. Bioavailability is 23% at a 100 mg dose and 33% at a 300 mg dose. Maraviroc is a substrate for the efflux transporter P-glycoprotein.
Approximately 76% bound to human plasma protein and shows moderate affinity for albumin and alpha-1 acid glycoprotein. Vd is approximately 194 L.
Primarily metabolized by CYP3A to inactive metabolites.
Terminal t ½ is 14 to 18 h. Elimination is approximately 76% and 20% in the feces and urine, respectively, over 168 h. Maraviroc is the major component excreted and the remainder are metabolites.
Not sufficiently studied; however, renal Cl accounts for approximately 25% of total Cl.Hepatic Function Impairment
Not sufficiently studied; however, maraviroc is metabolized by the liver.Gender
Does not affect concentrations.Race
Dosage adjustment based on race is not needed.
In combination with other antiretroviral agents for treatment-experienced patients infected with only CCR5-tropic HIV-1 detectable, who have evidence of HIV-1 replication despite ongoing antiretroviral therapy.
PO 150 mg twice daily.Concomitant Enfuvirtide, Nevirapine, all NRTIs, Tipranavir/RitonavirAdults and Adolescents 16 yr of age and older
PO 300 mg twice daily.Concomitant CYP3A inducers (without a CYP3A inhibitor)Adults and Adolescents 16 yr of age and older
PO 600 mg twice daily.
Store at 59° to 86°F.
Maraviroc concentrations may be reduced. Determine dosage selection based on concurrent medications.CYP3A and/or P-glycoprotein inhibitors (eg, atazanavir, atazanavir/ritonavir, ketoconazole, lopinavir/ritonavir, ritonavir, saquinavir)
Maraviroc concentrations may be elevated. Determine dosage selection based on concurrent medications.CYP3A and/or P-glycoprotein inhibitors plus inducers (eg, lopinavir/ritonavir plus efavirenz, tipranavir/ritonavir)
Maraviroc concentrations may be altered. Determine dosage selection based on concurrent medications.St. John's wort
Coadministration is not recommended. Maraviroc concentrations may be reduced, which may result in suboptimal levels of maraviroc and lead to loss of virologic response and possible resistance.
None well documented.
Vascular hypotension disorders (3%); acute cardiac failure, coronary artery disease and occlusion, MI, myocardial ischemia, unstable angina (less than 2%).
Dizziness/postural dizziness (8%); disturbances in initiating and maintaining sleep (7%); paresthesias and dysesthesias (5%); depressive disorders, disturbances in consciousness, sensory abnormalities (4%); peripheral nephropathies (3%); cerebrovascular accident (less than 2%).
Rash (10%); apocrine and eccrine gland disorders (5%); pruritus (4%); benign skin neoplasms, dermatitis and eczema, lipodystrophies (3%); squamous cell carcinoma of skin (less than 2%).
GI and abdominal pain (8%); constipation (5%); dyspeptic signs and symptoms, stomatitis, ulceration (3%); anal cancer, esophageal carcinoma, tongue neoplasm (less than 2%).
Bladder and urethral symptoms (5%); urinary tract signs and symptoms (3%).
Cholestatic jaundice, hepatic cirrhosis or failure, metastases to liver (less than 2%).
Increased blood CK (less than 2%).
Elevated amylase or total bilirubin (6%); elevated AST or lipase (5%); decreased absolute neutrophil count (4%); elevated ALT (2%).
Appetite disorders (7%).
Musculoskeletal and connective tissue signs and symptoms (9%); joint-related signs and symptoms (6%); muscle pains (3%); myositis, osteonecrosis, rhabdomyolysis (less than 2%).
Upper respiratory tract infection (20%); coughing and associated symptoms (13%); bronchitis, sinusitis (6%); breathing abnormalities (3%); bronchospasm and obstruction, paranasal sinus disorders, pneumonia, respiratory tract disorders (2%).
Pyrexia (12%); herpes infection (7%); pain and discomfort (4%); folliculitis (3%); condyloma acuminatum, influenza (2%); abdominal neoplasm, basal cell carcinoma, Bowen disease, cholangiocarcinoma, Clostridium difficile colitis, lymphoma, septic shock, viral meningitis (less than 2%).
Hepatotoxicity has been reported. Evidence of a systemic allergic reaction (eg, pruritic rash, eosinophilia or elevated Immunoglobulin E) prior to development of hepatotoxicity may occur. Patients with signs or symptoms of hepatitis or allergic reaction to the drug should be evaluated immediately.
Category B .
Undetermined; however, HIV-infected mothers should not breast-feed in order to avoid risking potential transmission of HIV to infant.
Safety and efficacy not established in patients younger than 16 years of age.
Use with caution because of the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant diseases or other drug therapy.
Use with caution; patients with a CrCl of less than 50 mL/min should receive maraviroc and a CYP3A inhibitor only if the potential benefit outweighs the risk.
Use with caution in patients at increased risk of CV event and in patients with history of postural hypotension or receiving medication known to lower BP.
Has been reported; during initial phase of combination antiretroviral treatment, patients whose immune system responds may develop an inflammatory response to indolent or residual opportunistic infections (eg, Mycobacterium avium , cytomegalovirus, Mycobacterium tuberculosis ) and may require additional evaluation and treatment.
Because the CCR5 coreceptor located on some immune cells is antagonized, there can be an increased risk of developing infections.
May increase risk of malignancy.
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