maraviroc (Rx)

>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

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; postural hypotension reported in patients with renal impairment

Monitor for developing infections

When administering to patients with pre-existing liver dysfunction or who are co-infected with hepatitis B and/or C virus, additional monitoring may be warranted

Cardiovascular adverse events triggered by postural hypotension’ additional monitoring may be warranted

Antiretroviral Pregnancy Registry has been established.to monitor maternal-fetal outcomes of pregnant women; register patients by calling 1-800-258-4263

Drug interaction overview

• Drug 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; 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, dosage adjustment may be required when maraviroc is coadministered with those drugs

Pregnancy: Limited data on pregnancy from the APR and case reports are not sufficient to inform a drug-associated risk of birth defects and miscarriage; n animal reproduction studies, no evidence of adverse developmental outcomes observed with maraviroc

Lactation: Centers for Disease Control and Prevention recommend that HIV-1-infected mothers in United States not breastfeed their infants to avoid risking postnatal transmission of HIV-1 infection

There are no data on presence of maraviroc in human milk, effects on breastfed infant, or effects on milk production; when administered to lactating rats, maraviroc was present in milk; because of potential for (1) HIV transmission (in HIV-negative infants), (2) developing viral resistance (in HIV-positive infants), and (3) serious adverse reactions in a breastfed infant similar to those seen in adults, instruct mothers not to breastfeed if they are receiving therapy

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.

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)

Oral Administration

Tablets and oral solution are taken twice daily

May take with or without food

Must be given in combination with other antiretroviral medications

The recommended dosage of maraviroc differs based on concomitant medications owing to drug interactions