Selzentry- Antiretroviral slows advance of HIV

Company:

Pfizer

Pharmacologic class:

Antiretroviral (CCR5 co-receptor antagonist)

Active ingredient:

Maraviroc 150 mg, 300 mg; tabs.

Indication:

HIV-1 infection in treatment-experienced adults infected with only CCR5-tropic HIV-1 detectable, who have evidence of viral replication and HIV-1 strains resistant to multiple antiretrovirals.

Pharmacology:

Maraviroc blocks the interaction between HIV-1 gp120 and the chemokine receptor on the T-cell membrane known as CCR5, thus preventing the virus from entering T cells. It is effective only against those strains of HIV-1 that are CCR5-tropic. The infection of immune cells by dual-tropic and CXCR4-tropic strains of HIV-1 is not inhibited by maraviroc. Therefore, tropism testing should be done and treatment history should be taken into account to evaluate the appropriateness of this drug.

Virologic failure may occur in patients with resistance to maraviroc or with the outgrowth of undetected CXCR4-tropic virus that may have been present before treatment.

Clinical trials:

Two ongoing trials are being conducted with maraviroc in patients with CCR5-tropic HIV-1 infection. At study entry, patients had a viral load of >5,000 copies/mL despite at least six months' therapy with at least one agent from three out of the four classes of antiretrovirals, or documented resistance or intolerance to at least one member of each drug class. They were placed on an optimized background regimen with three to six antiretrovirals, then randomized to either maraviroc 300 mg once daily, maraviroc 300 mg twice daily, or placebo.

Doses were adjusted based on background therapy. After 24 weeks, 61% of maraviroc patients had a viral load of <400 copies/mL, compared with 28% of those given placebo. Increases in T-cell counts were higher in the maraviroc patients than in those given placebo. In a study in patients infected with dual/mixed co-receptor tropic HIV-1, maraviroc was not associated with a significant decrease in viral load.

Adults:

≥16 years: Concomitant CYP3A inhibitors (e.g., protease inhibitors except tipranavir/ritonavir, delavirdine, ketoconazole, itraconazole, clarithromycin, nefazodone, telithromycin) (with or without a CYP3A inducer): 150 mg twice daily. Other concomitant drugs, including tipranavir/ritonavir, nevirapine, nucleoside reverse transcriptase inhibitors, enfuvirtide: 300 mg twice daily.

Concomitant CYP3A inducers (e.g., efavirenz, rifampin, carbamazepine, phenobarbital, phenytoin) (without a strong CYP3A inhibitor): 600 mg twice daily. Renal dysfunction (CrCl <50 mL/min) and CYP3A inhibitors: monitor closely for side effects (e.g., dizziness).

Children:

<16 years: not recommended.

Precautions:

Liver dysfunction or disease. Re-evaluate if hepatitis or elevated LFTs develop. Cardiovascular risk factors. Postural hypotension. Monitor for immune reconstitution syndrome, infections, malignancies. Pregnancy (Cat. B). Nursing mothers: not recommended.

Interactions:

Concomitant St. John's wort: not recommended. May affect, or be affected by, CYP3A inhibitors or inducers and drugs affected by p-glycoprotein (e.g., potentiated by ketoconazole, lopinavir/ritonavir, ritonavir, saquinavir, atazanavir; antagonized by rifampin, efavirenz). Caution with antihypertensives.

Adverse reactions:

Cough, pyrexia, upper respiratory infections, rash, musculoskeletal symptoms, abdominal pain, dizziness; hepatotoxicity (may be preceded by systemic allergic reaction; immediately evaluate if occurs); others (see literature).

How supplied:

Tabs—60

Register pregnant patients exposed to maraviroc by calling 800.258.4263.

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