Approval of novel anti-HIV drug offers patients hope

April 21, 2003

Healthcare providers can now treat HIV-infected patients with an antiretroviral drug that is unlike any other. The FDA recently granted accelerated approval of enfuvirtide (Fuzeon, Roche/Trimeris) to be used in combination with other antiretroviral agents for the treatment of HIV-1 infection in treatment-experienced patients with evidence of HIV-1 infection despite ongoing antiretroviral therapy. Enfuvirtide is approved for use in adults and children ages 6 years and older. It is currently available in pharmacies.

 

Rx CARE

Approval of novel anti-HIV drug offers patients hope

Healthcare providers can now treat HIV-infected patients with an antiretroviral drug unlike any other. The Food & Drug Administration recently granted accelerated approval of enfuvirtide (Fuzeon, Roche/Trimeris) for use in combination with other antiretroviral agents for the treatment of HIV-1 infection in treatment-experienced patients with evidence of HIV-1 infection despite ongoing antiretroviral therapy. Enfuvirtide is approved for use in adults and children ages six years and older.

Enfuvirtide is the first fusion inhibitor approved for the treatment of HIV infection worldwide. Fusion inhibitors are the first new class of antiretroviral drugs to receive FDA approval in seven years.

Enfuvirtide inhibits the entry of HIV-1 into CD4+ cells by binding to the gp41 subunit of the viral envelope and preventing the conformational changes required for the fusion of the viral and cellular membranes, said Michelle Sherman, R.Ph., a pharmacist at Garden Grove Pharmacy, Garden Grove, Calif. And, according to John Lalezari, M.D., director, Quest Clinical Research of Mount Zion Hospital at the University of California, San Francisco, this unique mechanism of action means that enfuvirtide is less likely to have cross-resistance with current antiretroviral therapies, which target viral processes once the virus has entered the cell. In addition, he believes that the drug may be safer compared with current antiretroviral therapies—or at least have a better toxicity profile—because it does not exert its effect inside the cell.

The recommended dose of enfuvirtide is 90 mg injected subcutaneously twice per day into the upper arm, anterior thigh, or abdomen. The recommended dosage for children between the ages of six and 16 years is 2 mg/kg injected subcutaneously twice per day, to a maximum dose of 90 mg.

Roche and Trimeris expect initial demand for enfuvirtide to exceed supply, so they have developed a special U.S. distribution plan for the drug. Chronimed recently announced it has contracted with Roche to be the exclusive U.S. distributor of enfuvirtide. The firm will distribute the drug primarily from its mail-service operation and its StatScript pharmacy network. The term of the contract is for one year beyond the enfuvirtide launch date, at which time Roche has the option to extend the agreement or expand distribution to multiple distributors. The price of the drug has been set at approximately $20,000 per year.

The package insert for enfuvirtide carries warnings about local injection-site reactions, pneumonia, and hypersensitivity reactions. Injection-site reactions are the most common adverse reactions associated with enfuvirtide therapy, according to the manufacturer. The reactions can include the formation of nodules or cysts. Injection-site reactions may also include pain and discomfort, induration, erythema, pruritus, and ecchymosis.

Nodules can form because the molecule being injected is very large, said Sherman. They can be short-lived or long-lived, Lalezari added. Persons who have long-lived nodules can develop continuous nodule formation over time, he said, and could run out of subcutaneous space.

Lalezari and Sherman both pointed out that during phase III clinical trials, an increased incidence of bacterial pneumonia was observed in patients treated with enfuvirtide compared with those in the control group. Although it is uncertain if the increased rate of pneumonia was associated with enfuvirtide use, the manufacturer recommends that HIV-infected patients be carefully monitored for signs and symptoms of pneumonia. Risk factors for pneumonia include low initial CD4+ cell count, high initial viral load, intravenous drug use, smoking, and a prior history of lung disease.

Hypersensitivity reactions have been associated with enfuvirtide use and may recur with rechallenge, according to Lalezari and Sherman. Hypersensitivity reactions may include, individually and in combination: rash, fever, nausea and vomiting, chills, rigors, hypotension, and elevated serum liver transaminases.

Patients must know how to properly reconstitute and inject enfuvirtide and monitor themselves carefully for signs of cellulitis or local infection. This information is provided in an injection instruction guide for patients, who should notify a healthcare professional immediately if they develop signs or symptoms indicative of pneumonia or hypersensitivity.

Enfuvirtide is classified under Pregnancy Category B and should be used during pregnancy only if absolutely necessary. Women should not breast-feed if they are taking enfuvirtide.

Charlotte LoBuono

TIPS TO REMEMBER: Fuzeon

  • Massaging the injection site and diluting the injection correctly may help prevent the formation of nodules at the injection site.

  • Fuzeon must be taken in combination with other antiretroviral drugs to which the patient is not resistant.

  • Dosage adjustment is not necessary on the basis of weight or gender.



Charlotte LoBuono. Approval of novel anti-HIV drug offers patients hope.

Drug Topics

Apr. 21, 2003;147:20.