A drug with a new mechanism of action is always a welcome addition in the fight against HIV. Maraviroc (Selzentry), from Pfizer
Inc., was recently approved by the Food & Drug Administration and is the first of the chemokine (C-C motif) receptor 5 (CCR5)
antagonists to enter the market.
"Maraviroc works to block the entry of HIV virus into CD4+ T lymphocytes," said Jennifer Cocohoba, Pharm.D., assistant clinical
professor at the University of California San Francisco School of Pharmacy. "In one of the first steps of infection, the HIV
virus binds to the CD4+ receptor and must also bind to a coreceptor—a chemokine receptor," she explained. There are two main
types of coreceptors: CCR5 and CXCR4. "Some HIV viruses predominantly use the CCR5 coreceptor to gain entry, others use the
CXCR4 coreceptor, and some use both. Maraviroc inhibits the CCR5 coreceptors so that the HIV virus cannot attach, and therefore
cannot get into the cells and replicate."
|
According to the manufacturer, use of maraviroc is not recommended in patients with dual/mixed or CXCR4-tropic HIV-1 nor in
treatment-naïve adult or pediatric patients. "Patients who use the drug actually need to be tested to find out if their virus
is a CCR5-tropic virus," Cocohoba pointed out. The prescribing information suggests that tropism testing and treatment history
should guide the use of maraviroc. "Until more data accumulate, this is not likely to be a drug we use as a first-line therapy,"
she said. Maraviroc is indicated for patients with evidence of viral replication and HIV-1 strains resistant to multiple antiretroviral
agents who are infected with only CCR5-tropic HIV.
A black box is contained in the label for maraviroc alerting prescribers to the potential for hepatotoxicity. Evidence of
a systemic allergic reaction prior to the development of liver toxicity may occur, and patients with signs and symptoms of
hepatitis or allergic reaction following administration of maraviroc should be evaluated immediately and discontinuation considered.
The drug should be administered with caution in patients with preexisting liver dysfunction or who are coinfected with viral
hepatitis B or C. In addition, maraviroc should be used with caution in patients at increased risk for cardiovascular events.
According to Pfizer, the most common adverse reactions (>8% incidence) include pyrexia, cough, upper respiratory infections,
rash, abdominal pain, musculoskeletal symptoms, and dizziness. The appropriate dosage of maraviroc is dependent on concomitant medications. For patients taking CYP3A inhibitors (with or
without a CYP3A inducer), 150 mg of maraviroc twice daily is the recommended dose. When tipranavir (Aptivus, Boehringer Ingelheim)
plus ritonavir (Norvir, Abbott), nevirapine (Viramune, Boehringer Ingelheim), any of the nucleoside reverse transcriptase
inhibitors, or enfuvirtide (Fuzeon, Roche) is given, maraviroc should be administered as 300 mg twice daily. When a CYP3A
inducer (without a strong CYP3A inhibitor) is the concomitant drug, the dose of maraviroc should be 600 mg twice daily.
"The advantage of having a drug with a new mechanism of action is that now there is another option for treatment of HIV virus
resistant to the classes of drugs we have currently," Cocohoba believes. This new class of drugs may help some patients with
panresistance achieve viral suppression or increase their CD4 counts to protect them from dangerous opportunistic infections,
she explained.
Pfizer has announced the wholesale cost of maraviroc to be $10,585 per patient per year, or $29 per patient per day. An FDA-approved
Medication Guide should be distributed to patients with the initial prescription and again at each refill. The drug will be
available by September 2007.
TIPS TO REMEMBER Selzentry
- Selzentry is indicated for treatment-experienced patients with only CCR5-tropic HIV-1.
- Selzentry belongs to Pregnancy Category B and should be used in pregnant women only if the potential benefit justifies the
risk to the fetus.
- Selzentry is available as 150-mg and 300-mg blue, oval-shaped, film-coated tablets.
- Tropism testing and treatment history should guide the use of Selzentry.
- Selzentry is not recommended for patients with dual/mixed or CXCR4-tropic HIV-1.
Drug Topics archives are now available on ModernMedicine.com, a new online resource designed to meet the evolving needs of physicians.