The United States Food and Drug Administration (FDA) approved changes last week in the prescription information for Selzentry (maraviroc) 150 mg and 300 mg tablets.

The new information states that Selzentry is contraindicated and should not be taken by individuals with severe kidney impairment or end-stage renal (kidney) disease (ESRD) who are taking strong CYP3A inhibitors or inducers, which includes the antiretroviral Norvir (ritonavir).

The FDA also recommends that patients with severe kidney impairment or ESRD not take Selzentry unless no alternative treatments are available.

CYP3A is a family of enzymes that break down Selzentry in the body. CYP3A inhibitors and inducers can affect the amount of Selzentry in the bloodstream.

Inducers include Norvir; carbamazepine (Tegretol), an anticonvulsant and mood stabilizer; the antibiotics rifampin and Mycobutin (rifabutin); and St. John’s wort.

Inhibitors include ketoconazole (Nizoral), itraconazole (Sporanox), and fluconazole (Diflucan), used to treat fungal infections; Tagamet or Tagamet HB (cimetidine), used to treat heartburn and stomach ulcers; the antibiotics clarithromycin (Biaxin), erythromycin, and troleandomycin; and grapefruit juice.

In addition, the FDA noted that individuals taking Selzentry who have impaired kidney function are at greater risk of postural hypotension, a drop in blood pressure due to a change in body position.

Postural hypotension could increase risk of heart problems, so the FDA recommends that these patients not take Selzentry unless other options are not available. If Selzentry is necessary, any patients experiencing symptoms of postural hypotension should have their dosage reduced to 150 mg twice daily.

The new label is the result of a study examining the effects of Selzentry in people with kidney impairment.

According to its prescribing information (pdf), the kidneys account for 25 percent of the total clearance of Selzentry by the body. As a result, in individuals with kidney impairment, Selzentry concentrations may increase in the bloodstream.

In addition to the new information for people with severe kidney impairment or ESRD, Pfizer, the manufacturer of Selzentry, also studied the effects of Selzentry in people with mild or moderate kidney impairment.

These results were similar to those of individuals with normal kidney function. The FDA made no new recommendations on dosage adjustment for individuals with mild or moderate kidney impairment, even if they are also taking strong CYP3A inhibitors or inducers.

Selzentry is a member of a relatively new class of antiretrovirals called entry inhibitors. Entry inhibitors work by preventing HIV from attaching to and entering healthy T cells in the body.

Generally, Selzentry is used by individuals who have been previously treated for HIV infection and have formed resistance to other antiretroviral medications.

For more information, please see the updated label for Selzentry, which will be available soon on the FDA website.