Potential side effects and toxicity: The most common are Injection Site Reactions (ISRs), which occur in virtually all patients. The severity of reactions is variable, and for most is mild to moderate. Symptoms could include itching, swelling, redness, pain or tenderness, hardened skin or bumps; others include headache and fever. Bumps termed “nodules” seem to occur more frequently and severely in areas of high muscle mass (most notably the center of the stomach—the abs—and the legs). They will hurt with movement. Allergic reactions are possible. In studies, pneumonia happened more often in the patients on Fuzeon. It is unclear if this was related to the use of Fuzeon. Report cough, fever or trouble breathing to your healthcare provider right away.
Potential drug interactions: To date none that require dose adjustment have been reported.
Tips: To minimize injection site reactions, inject where you can pinch an inch. If not, then be sure to use half the length of the needle. Inject slowly and apply a gentle massage after injection. Try using vibrating devices after injections. Careful reconstitution of drug is also helpful. The drug must be carefully reconstituted for 30–45 minutes (for the two daily doses—refrigerate the dose—after reconstitution—that will be taken later, and then allow it to warm to room temperature before using). Never shake—it will foam. Follow instructions to avoid infection. ISR may worsen when injection is repeated in the same spot or given deeper than intended, for example, into the muscle. Fuzeon can be taken at the same time as other anti-HIV drugs. Always rotate injection sites frequently. Never inject into moles, scars, bruises, nodules or the navel. New bioinjection (needleless injection device) is being studied and is available in limited distribution; however, patients report that it “hurts like hell,” but doesn’t cause as severe injection site reactions.
Fuzeon is the first in a new class of anti-HIV compounds called fusion inhibitors. Fusion inhibitors block fusion of HIV with host cells before the virus enters the cell and begins its replication process. Because of injections, this drug will most likely be used in the heavily-treatment experienced and salvage therapy options. However, because the drug is so good, it should be studied (and used more) in people with earlier disease or those on their second or third regimen. Two large Phase III studies showed good viral load decrease when added to an optimized antiviral combination in heavily treatment-experienced people, including those with protease inhibitor-resistant virus and those who’ve taken all three current drug classes. Participants used three to five antivirals in addition to Fuzeon, and both genotype and phenotype tests.
Recently updated DHHS guidelines support the use of Fuzeon with an active boosted protease inhibitor in patients with three-class virologic failure. DHHS supported the approach as it resulted in better and more prolonged virologic suppression than other regimens. Evidence included several recent clinical trials of new boosted protease inhibitors in treatment-experienced patients that found an enhanced virologic response when used in conjunction with Fuzeon.
Doctor
Enfuvirtide (T-20) is the first in a new class of antiretroviral agents, fusion entry inhibitor. It works at a different part of the viral replication cycle: it blocks entry into target cells (such as T-cells). It is administered as a subcutaneous injection twice a day. A new needleless delivery device is being marketed which may make use of this drug easier for some patients. Currently it is indicated for use in salvage situations. It is usually combined with whatever other HIV drugs may still be effective in patients with highly resistant virus. It is generally very well tolerated; the main side effect is irritation and nodule formation at the site of injection. If not for the inconvenience and difficulty of twice-daily injections and high cost, this drug might best be used as a first-line agent. Newer entry inhibitors which will be taken orally are currently in development; FDA approval is not anticipated until 2007.—Chad J. Zawitz, MD
Activist
This injectable product has had a difficult uptake in the community due to fear of needles, injection site reactions, and the fear that it is a “last resort drug before you die.” Studies have shown the obvious: starting Fuzeon with at least one more active agent may improve the duration of response. Unfortunately, most people who started it after approval did not have any other active agent left in their genotype, so they had to start it on top of a failing regimen, which only provided viral control for a few weeks. We have now seen the Aptivus RESIST and the TMC-114 POWER studies say the same thing: those who used these products with Fuzeon did better. I am happy to see that those who are running out of options can start Fuzeon with Aptivus or TMC-114, and possibly entry inhibitors soon. To minimize ISRs, people stopped using the needles provided in the kit and went for smaller insulin syringes. Also, a bioinjector needle-free device which is expected to be launched soon may help some people. Fuzeon is the most expensive single drug in the market at $26,000 a year (Aptivus plus Norvir is the highest boosted PI at $28,000). A very huge problem has been access for patients who do not have insurance in states with ADAP systems that have a cap on the number of people who can get Fuzeon. Roche would not give free drugs to those who apply after the cap has been met in those states.
Fuzeon is here to stay as a backbone to new drugs in the pipeline. But its price, administration and difficult access need to improve for it to be accepted as part of standard of care in the U.S.—Nelson Vergel
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