Dosing and uses of Selzentry (maraviroc)
Adult dosage forms and strengths
tablet
- 150mg
- 300mg
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
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
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
Pediatric dosage forms and strengths
tablet
- 150mg
- 300mg
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
Selzentry (maraviroc) adverse (side) effects
>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
<2% (critical ADRs)
CBn
Cardiac disorder
CVA
Hepatic cirrhosis
Hepatic failure
Neoplasms
C. difficile colitis
Viral meningitis
Pneumonia
Septic shock
Myositis
Osteonecrosis
Rhabdomyolysis
Warnings
Black box warnings
Hepatotoxicity reported; may be preceded by systemic allergic reaction (eg, pruritic rash, eosinophilia, elevated IgE)
Immediately evaluate if signs or symptoms of hepatitis or allergic reaction occur
Contraindications
Hypersensitivity
Severe renal impairment or end-stage renal disease (CrCl <30 mL/min) in patients taking potent CYP3A4 inhibitors or inducers
Cautions
Risks of hepatotoxicity
Risk of immune reconstitution syndrome if used in combination with other antiretroviral drugs
Autoimmune disorders (eg, Graves’ disease, polymyositis, Guillain-Barré syndrome) reported in the setting of immune reconstitution, however, the time to onset is more variable, and can occur many months after initiation of treatment
Do not use in treatment-naïve patients; more likely to experienced virologic failure and developed lamivudine resistance compared to efavirenz
Tropism testing with a highly sensitive tropism assay is required for the appropriate use
Evaluate if signs/symptoms of hepatitis, increase LFTs, or rash develop
Preexisting liver dysfunction or viral hepatitis B or C coinfection
Patient history of increased risk for cardiovascular events
History of postural hypotension or concomitant use of blood pressure lowering medication
Caution in renal and hepatic impairment
Monitor for developing infections
Antiretroviral Pregnancy Registry has been established.to monitor maternal-fetal outcomes of pregnant women; register patients by calling 1-800-258-4263
Pregnancy and lactation
Pregnancy category: B
Lactation: breastfeeding not recommended in HIV+ mothers
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Selzentry (maraviroc)
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
Absorption
Bioavailability: 23-33%
Peak plasma time: 0.5-4 hr
Peak plasma concentration: 333 ng/mL (330 mg BID)
Distribution
Protein bound: 76%
Vd: 194 L
Metabolism
Metabolized by cytochrome P450 system, with CYP3A as major enzyme of metabolism
Elimination
Half-life: 14-18 hr
Excretion: 76% (feces); 20% (urine)
