Fuzeon

Fuzeon in combination with other antiretroviral agents is indicated for the treatment of HIV-1 infection in treatment-experienced patients with evidence of HIV-1 replication despite ongoing antiretroviral therapy. This indication is based on results from two controlled studies of 48 weeks duration. Subjects enrolled were treatment-experienced adults; many had advanced disease. There are no studies of Fuzeon in antiretroviral naive subjects.

Enfuvirtide interferes with the entry of HIV-1 into cells by inhibiting fusion of viral and cellular membranes. Enfuvirtide binds to the first heptad-repeat (HR1) in the gp41 subunit of the viral envelope glycoprotein and prevents the conformational changes required for the fusion of viral and cellular membranes.

Injection site reactions Fuzeon causes injection site reactions. Almost all people get injection site reactions with Fuzeon. Reactions are usually mild to moderate but occasionally may be severe.

Reactions on the skin where Fuzeon is injected include:

• itching
• swelling
• redness
• pain or tenderness
• hardened skin
• bumps

These reactions generally happen within the first week of Fuzeon treatment and usually happen again as you keep using Fuzeon. A reaction at one skin injection site usually lasts for less than 7 days. Injection site reactions may be worse when injections are given again in the same place on the body or when the injection is given deeper than it should be (for example, into the muscle).

If you are worried about the reaction you are having, call your healthcare provider to help you decide if you need medical care. If the injection site reaction you are having is severe, call your healthcare provider right away. If you have an injection site reaction, you can discuss with your healthcare provider ways to help the symptoms.

An injection site can get infected. It is important to follow the Fuzeon Injection Instructions that come with your medicine to lower your chances of getting an injection site infection. Call your healthcare provider right away if there are signs of infection at the injection site such as oozing, increasing heat, swelling, redness or pain.

Injection using Biojector 2000

Shooting nerve pain and tingling lasting up to 6 months from injecting close to large nerves or near joints, and bruising and/or collections of blood under the skin have been reported with use of the Biojector 2000 needlefree device to inject Fuzeon.

If you are taking any blood thinners, or have hemophilia or any other bleeding disorder, you may be at higher risk of bruising or bleeding after using the Biojector.

Pneumonia Patients with HIV get bacterial pneumonia more often than patients without HIV. Patients taking Fuzeon with other HIV medicines may get bacterial pneumonia more often than patients not receiving Fuzeon. It is unclear if this is related to the use of Fuzeon.

You should contact your healthcare provider right away if you have a cough, fever or trouble breathing.

Patients are more likely to get bacterial pneumonia if they had 4 a low number of CD4 cells, increased amount of HIV in the blood, intravenous (injected into the vein) drug use, smoking or had experienced lung disease in the past. It is unclear if pneumonia is related to Fuzeon.

Allergic reactions Fuzeon can cause serious allergic reactions. Symptoms of a serious allergic reaction with Fuzeon can include:

• trouble breathing
• fever with vomiting and a skin rash
• blood in your urine
• swelling of your feet

Call your healthcare provider right away if you get any of these symptoms. Other side effects The following side effects were seen more often in patients using Fuzeon with their other anti-HIV medicines than in patients not using Fuzeon with their other anti-HIV medicines:

• pain and numbness in feet or legs
• loss of sleep
• depression
• decreased appetite
• sinus problems
• enlarged lymph nodes
• weight decrease
• weakness or loss of strength
• muscle pain
• constipation
• pancreas problems

These are not all the side effects of Fuzeon. For more information, ask your healthcare provider or pharmacist. If you have questions about side effects, ask your healthcare provider. Report any new or continuing symptoms to your healthcare provider. Your healthcare provider will tell you what to do and may be able to help you with these side effects.

Adults

The recommended dose of Fuzeon is 90 mg (1 mL) twice daily injected subcutaneously into the upper arm, anterior thigh or abdomen. Each injection should be given at a site different from the preceding injection site, and only where there is no current injection site reaction from an earlier dose. Fuzeon should not be injected near any anatomical areas where large nerves course close to the skin, such as near the elbow, knee, groin or the inferior or medial section of the buttocks, skin abnormalities, including directly over a blood vessel, into moles, scar tissue, bruises, or near the navel, surgical scars, tattoos or burn sites. Additional detailed information regarding the administration of Fuzeon is described in the Fuzeon Injection Instructions.

Pediatric Patients

Insufficient data are available to establish a dose recommendation of Fuzeon in pediatric patients below the age of 6 years. In pediatric patients 6 years through 16 years of age, the recommended dosage of Fuzeon is 2 mg/kg twice daily up to a maximum dose of 90 mg twice daily injected subcutaneously into the upper arm, anterior thigh or abdomen. Each injection should be given at a site different from the preceding injection site and only where there is no current injection site reaction from an earlier dose. Fuzeon should not be injected into moles, scar tissue, bruises or the navel. Table 1 contains dosing guidelines for Fuzeon based on body weight. Weight should be monitored periodically and the Fuzeon dose adjusted accordingly.

Potential for Fuzeon to Affect Other Drugs

Based on the results from an in vitro human microsomal study, enfuvirtide is not an inhibitor of CYP450 enzymes. In an in vivo human metabolism study (N=12), Fuzeon at the recommended dose of 90 mg twice daily did not alter the metabolism of CYP3A4, CYP2D6, CYP1A2, CYP2C19 or CYP2E1 substrates.

Potential for Other Drugs to Affect Enfuvirtide

Based on the available data, co-administration of Fuzeon and other drugs which are inducers or inhibitors of CYP450 is not expected to alter the pharmacokinetics of enfuvirtide. No dose adjustments are needed when Fuzeon is co-administered with other antiretroviral and non-antiretroviral drugs.

Pregnancy

Pregnancy Category B Reproduction studies have been performed in rats and rabbits at doses up to 27 times and 3.2 times the adult human dose on a m2 basis and have revealed no evidence of impaired fertility or harm to the fetus due to enfuvirtide. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Antiretroviral Pregnancy Registry To monitor maternal-fetal outcomes of pregnant women exposed to Fuzeon and other antiretroviral drugs, an Antiretroviral Pregnancy Registry has been established. Physicians are encouraged to register patients by calling 1-800-258-4263.

Nursing Mothers

The Centers for Disease Control and Prevention recommends that HIV-infected mothers not breast-feed their infants to avoid the risk of postnatal transmission of HIV. It is not known whether enfuvirtide is excreted in human milk. Because of both the potential for HIV transmission and the potential for serious adverse reactions in nursing infants, mothers should be instructed not to breast-feed if they are receiving Fuzeon. Studies where radio-labeled 3 H-enfuvirtide was administered to lactating rats indicated that radioactivity was present in the milk. It is not known whether the radioactivity in the milk was from radio-labeled enfuvirtide or from radio-labeled metabolites of enfuvirtide (i.e., amino acids and peptide fragments).