(en FYOO vir tide)
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Subcutaneous:
Fuzeon: 90 mg (1 ea)
Brand Names: U.S.
- Antiretroviral, Fusion Protein Inhibitor (Anti-HIV)
Binds to the first heptad-repeat (HR1) in the gp41 subunit of the viral envelope glycoprotein. Inhibits the fusion of HIV-1 virus with CD4 cells by blocking the conformational change in gp41 required for membrane fusion and entry into CD4 cells
SubQ: Absorption is comparable when injected into abdomen, arm, or thigh
Vd: 5.5 ± 1.1 L; CSF concentrations (2-18 hours after administration; n=4): nondetectable (<0.025 mcg/mL)
Expected to undergo catabolism via peptidases and proteinases in the liver and kidneys to amino acids; amino acids would then be recycled in the body pool. A deaminated metabolite (with 20% activity compared to parent drug) was formed via hydrolysis during in vitro human microsomal and hepatocyte studies.
Plasma clearance is decreased in adults with lower body weight and in females after adjusting for body weight (clearance in adults females is 20% lower compared to adults males). However, no adjustment in dose is recommended for gender or weight.
Compared to patients with normal renal function, enfuvirtide clearance is decreased by 38% in patients with severe renal impairment (CrCl 11 to 35 mL/minute) and by 14% to 28% in patients with end-stage renal disease who are maintained on dialysis. However, no adjustment in dose is recommended for patients with renal impairment.
Apparent clearance: Multiple dosing: Children: 40 ± 17 mL/hour/kg; Adults: 30.6 ± 10.6 mL/hour/kg
Time to Peak
SubQ: Single dose: Median: 8 hours (range: 3 to 12 hours); Multiple dosing: Median: 4 hours (range: 4 to 8 hours)
3.8 ± 0.6 hours
92%; primarily to albumin, but also to alpha-1 acid glycoprotein (to a lesser extent)
Use: Labeled Indications
HIV-1 infection: Treatment of HIV-1 infection in combination with other antiretroviral agents in treatment-experienced patients with evidence of HIV-1 replication despite ongoing antiretroviral therapy
Hypersensitivity to enfuvirtide or any component of the formulation
HIV treatment: SubQ: 90 mg twice daily
Refer to adult dosing.
Children and Adolescents 6 to 16 years: SubQ: 2 mg/kg twice daily (maximum dose: 90 mg twice daily)
Adolescents >16 years: SubQ: Refer to adult dosing.
Dosing: Renal Impairment
No dosage adjustment necessary.
Dosing: Hepatic Impairment
No dosage adjustment necessary (has not been studied).
Reconstitute with 1 mL SWFI; tap vial for 10 seconds and roll gently between the hands to avoid foaming and to ensure contact with diluent; then allow vial to stand until complete dissolution. May require up to 45 minutes to form solution; allow more time if solution is foamy or jelled. Use immediately or refrigerate reconstituted solution and use within 24 hours; bring refrigerated solution to room temperature before administration.
Inject subcutaneously into upper arm, abdomen, or anterior thigh. Do not inject into moles, the navel, over a blood vessel or skin abnormalities such as scar tissue, surgical scars, bruises, tattoos, or burn sites. In addition, do not inject in or near sites where large nerves are close to the skin including the elbow, knee, groin, or buttocks. Rotate injection site, give injections at a site different from the preceding injection site; do not inject into any site where an injection site reaction is evident. Bioequivalence was found to be similar in a study comparing standard administration using a needle versus a needle-free device (True, 2006).
Store intact vials at 25°C (77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F). Store reconstituted solution in the original vial at 2°C to 8°C (36°F to 46°F); use within 24 hours. Vials are for single use only; discard unused portion.
Protease Inhibitors: May increase the serum concentration of Enfuvirtide. Enfuvirtide may increase the serum concentration of Protease Inhibitors. Monitor therapy
Central nervous system: Fatigue (20%), insomnia (11%)
Gastrointestinal: Diarrhea (32%), nausea (23%)
Local: Injection site infection (children 11%), injection site reactions (98%; may include pain, erythema, induration, pruritus, ecchymosis, nodule or cyst formation)
1% to 10%:
Dermatologic: Folliculitis (2%)
Gastrointestinal: Weight loss (7%), abdominal pain (4%), appetite decreased (3%), pancreatitis (3%), anorexia (2%), xerostomia (2%)
Hematologic: Eosinophilia (2% to 9%)
Hepatic: Transaminases increased (4%, grade 4: 1%)
Local: Injection site infection (adults 2%)
Neuromuscular & skeletal: CPK increased (3% to 7%), limb pain (3%), myalgia (3%)
Ocular: Conjunctivitis (2%)
Respiratory: Sinusitis (6%), cough (4%), bacterial pneumonia (3%)
Miscellaneous: Infections (4% to 6%), herpes simplex (4%), flu-like syndrome (2%)
<1% (Limited to important or life-threatening): Abacavir hypersensitivity worsening, amylase increased, amyloidosis (cutaneous; at the injection site), angina, anxiety, constipation, depression, GGT increased, glomerulonephritis, Guillain-Barré syndrome, hepatic steatosis, hyperglycemia; hypersensitivity reactions (symptoms may include rash, fever, nausea, vomiting, hypotension, and transaminase increases); insomnia, lipase increased, lymphadenopathy, neutropenia, peripheral neuropathy, pneumopathy, renal failure, renal insufficiency, respiratory distress, sepsis, sixth nerve palsy, suicidal tendencies, taste disturbances, thrombocytopenia, toxic hepatitis, triglycerides increased, tubular necrosis, weakness
Concerns related to adverse effects:
• Hypersensitivity reactions: May cause hypersensitivity reactions (symptoms may include rash, fever, nausea, vomiting, chills, rigors, hypotension, and/or elevated liver transaminases). Discontinue therapy immediately if systemic reactions occur; do not rechallenge patient.
• Immune reconstitution syndrome: Patients may develop immune reconstitution syndrome resulting in the occurrence of an inflammatory response to an indolent or residual opportunistic infection during initial HIV treatment or activation of autoimmune disorders (eg, Graves’ disease, polymyositis, Guillain-Barré syndrome) later in therapy; further evaluation and treatment may be required.
• Injection site reactions: Local injection site reactions are common. Administration using a needle-free device has been associated with nerve pain (including neuralgia and/or paresthesia lasting up to 6 months), bruising, and hematomas when administered at sites where large nerves are close to the skin; only administer medication in recommended sites.
• Pneumonia: Monitor closely for signs/symptoms of pneumonia; associated with an increased incidence during clinical trials, particularly in patients with a low CD4 cell count, high initial viral load, IV drug use, smoking, or a history of lung disease.
• Bleeding disorders: Use with caution in patients with coagulation disorders (eg, hemophilia) or receiving anticoagulants; increased risk of bleeding at injection site.
• Appropriate use: Use is not recommended in antiretroviral therapy-naive patients.
Viral load; CD4 count; hypersensitivity and injection site reactions; pediatric weight (periodically; adjust dose accordingly); signs and symptoms of pneumonia
Pregnancy Risk Factor
Teratogenic effects were not observed in animal studies; data collected by the antiretroviral pregnancy registry is insufficient to evaluate human teratogenic risk. Enfuvirtide has minimal to low transfer across the human placenta. The HHS Perinatal HIV Guidelines note that there are insufficient data to recommend use of enfuvirtide in antiretroviral-naive pregnant women; pharmacokinetic data are insufficient to make dosing recommendations during pregnancy.
Combination antiretroviral therapy (cART) therapy is recommended for all HIV-infected pregnant women. The goal of therapy is to keep the viral load below the limit of detection and prevent perinatal transmission. Therapy must be individualized. In general, women who become pregnant on a stable cART regimen may continue that regimen if viral suppression is effective, contraindications for use in pregnancy are not present, and the regimen is well tolerated. For HIV infected couples planning a pregnancy, maximum viral suppression with cART is recommended prior to conception for the HIV-infected partner(s). When HIV is diagnosed during pregnancy in a woman who has never received antiretroviral therapy, cART should be considered as soon as possible after diagnosis to reduce the risk of perinatal transmission. If antiretroviral drug-resistance testing is done, treatment may be started prior to obtaining results, then adjusted accordingly. Monitoring during pregnancy is more frequent than in non-pregnant adults. If cART must be interrupted for <24 hours, stop then restart all medications simultaneously in order to decrease the chance of developing resistance. Long-term follow-up is recommended for all infants exposed to antiretroviral medications; children who develop significant organ system abnormalities (particularly of the CNS or heart) should be evaluated for potential mitochondrial dysfunction.
HIV infected women not planning a pregnancy may use any available type of contraception, considering possible drug interactions and contraindications of the specific method. In addition, consistent use of condoms is also recommended (even during pregnancy) to prevent transmission of HIV or other sexually transmitted diseases.
Health care providers are encouraged to enroll pregnant women exposed to antiretroviral medications as early in pregnancy as possible in the Antiretroviral Pregnancy Registry (1-800-258-4263 or www.APRegistry.com). Health care providers caring for HIV-infected women and their infants may contact the National Perinatal HIV Hotline (888-448-8765) for clinical consultation (HHS [perinatal] 2015).
• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience insomnia, diarrhea, nausea, loss of strength and energy, lack of appetite, weight loss, or muscle pain. Have patient report immediately to prescriber signs of infection, signs of skin infection, signs of pancreatitis (severe abdominal pain, severe back pain, severe nausea, or vomiting), severe injection site irritation, hematuria, burning or numbness feeling, severe dizziness, passing out, shortness of breath, swelling of arms or legs, enlarged lymph nodes, or depression (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.
More about enfuvirtide
- Other brands: Fuzeon