enfuvirtide (ENF) or T-20
Class: fusion inhibitor (a type of entry inhibitor)
Standard dose: One subcutaneous (under the skin) injection of 90 mg (1 ml) twice daily (every 12 hours) into the upper arm, thigh or abdomen. No food restrictions (take with or without food). Take missed dose as soon as possible, but do not double up on your next dose.
AWP: $2,333.93 / month for 90 mg kit
Manufacturer contact: Roche Pharmaceuticals and Trimeris, www.rocheusa.com, www.trimeris.com,
www.fuzeon.com, 1 (877) 4–FUZEON (438–9366)
1 (800) HIV–0440 (448–0440), www.aidsinfo.nih.gov
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, so report cough, fever, or trouble breathing to your healthcare provider right away. Immune Reconstitution Inflammatory Syndrome (IRIS) may occur as the immune system regains strength; report symptoms of illness, such as shingles and TB, to health care provider.
Potential drug interactions: To date none found clinically significant.
Tips: With other powerful new drugs on the market, the twice-daily injectable Fuzeon has truly become a medicine of last resort. In fact, some specialists are taking patients off Fuzeon and putting them on one of those newer drugs, Isentress. Fuzeon is intended for treatment of HIV in patients who are treatment-experienced. Preparing and injecting the Fuzeon can be complicated, so ask your healthcare provider how to do it. First, the drug needs to be dissolved with sterile water (provided in the kit), which may take 30 to 45 minutes. Never shake the vial with the Fuzeon, it will foam. Instead, roll it gently in your hands. You can store your second dose in the refrigerator, but it must be used within 24 hours (allow it to warm to room temperature before using). Before injecting, it is important to make sure that the Fuzeon powder is completely dissolved. To minimize injection site reactions, inject where you can pinch an inch (upper arm, stomach, or thigh). 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. 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. Study with a bioinjection (needleless injection device) was stopped; patients reported that it “hurts like hell.” Switching to smaller needles, like insulin syringes, may also help with ISRs.
Fuzeon is the first and only anti-HIV compound on the market called a fusion inhibitor. Fusion inhibitors block fusion of HIV with a cell before the virus enters the cell and begins its replication process. Fusion inhibitors are a type of entry inhibitor, another one of which entered the pharmacy last year (see Selzentry). Because of injections, this drug will most likely be used in the heavily-treatment experienced and salvage therapy options. Two large Phase 3 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 three drug classes. (Remember, though, there are now newer drugs on the market, including a newer drug class.) Participants used three to five antivirals in addition to Fuzeon, and both genotype and phenotype tests.
U.S. HIV treatment guidelines support the use of Fuzeon with an active boosted protease inhibitor in patients who are heavily treatment-experienced. The guidelines supported the approach as it resulted in better and more prolonged virologic suppression than other regimens. Evidence included several studies of new boosted protease inhibitors in treatment-experienced patients which found an enhanced virologic response when used in conjunction with Fuzeon. This reinforces the principle of using two or more new active drugs, if possible, when changing therapy, to make it more effective. Please see package insert for more complete potential side effects and interactions.
Fuzeon, the only fusion inhibitor, stops HIV from entering the cell by preventing fusion of the envelope of the virus with the membrane of the cell. The TORO studies showed how effective it was—until TORO, we never expected people with extensive drug resistance to achieve undetectable viral loads. However, Fuzeon has generally been viewed as a temporary bridge to easier forms of “salvage therapy.” It’s given by twice-daily injection and leaves painful bumps under the skin that can last for days and can eventually leave people with thick, leathery skin at the injection sites. People who are currently taking Fuzeon and maintaining undetectable viral loads are switching to other drugs, especially Isentress, now that they’re available. However, there will still be a need for Fuzeon in some patients with highly-resistant virus. For example, people who can’t take Selzentry because they have the wrong tropism and who already have mutations that make them resistant to Prezista, Aptivus, and/or Intelence may need to take Fuzeon along with Isentress. For those of you not currently in need of Fuzeon, think of it as a strong incentive to make your current regimen last!—Joel Gallant, M.D.
As a new class of drug, Fuzeon is unaffected by previous drug resistance. It has very low toxicity. Just two problems. First, it is an injection. Nearly everyone develops painful injection site reactions (ISRs). Over time, people just run out of places to give the injections. Secondly, the drug is horrendously expensive, more than twice the price of any other HIV drug and easily three times the cost of most. Despite the appearance of greed, the high price really is unfortunately a consequence of the extreme difficulty of making the drug. —Martin Delaney