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Enfuvirtide

Pronunciation

(en FYOO vir tide)

Index Terms

  • T-20

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Kit, Subcutaneous:

Fuzeon: 90 mg [DSC]

Solution Reconstituted, Subcutaneous:

Fuzeon: 90 mg (1 ea)

Brand Names: U.S.

  • Fuzeon

Pharmacologic Category

  • Antiretroviral, Fusion Protein Inhibitor (Anti-HIV)

Pharmacology

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

Absorption

SubQ: Absorption is comparable when injected into abdomen, arm, or thigh

Distribution

Vd: 5.5 ± 1.1 L; CSF concentrations (2-18 hours after administration; n=4): nondetectable (<0.025 mcg/mL)

Metabolism

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.

Excretion

Clearance:

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)

Half-Life Elimination

3.8 ± 0.6 hours

Protein Binding

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

Contraindications

Hypersensitivity to enfuvirtide or any component of the formulation

Dosage

HIV treatment:

Children and Adolescents 6 to 16 years: SubQ: 2 mg/kg twice daily (maximum dose: 90 mg twice daily)

Adolescents >16 years and Adults: SubQ: 90 mg twice daily

Dosage adjustment in renal impairment: No dosage adjustment necessary.

Dosage adjustment in hepatic impairment: No dosage adjustment necessary (has not been studied).

Reconstitution

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.

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).

Storage

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.

Drug Interactions

Protease Inhibitors: May increase the serum concentration of Enfuvirtide. Enfuvirtide may increase the serum concentration of Protease Inhibitors. Monitor therapy

Adverse Reactions

>10%:

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, 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, suicide attempt, taste disturbances, thrombocytopenia, toxic hepatitis, triglycerides increased, tubular necrosis, weakness

Warnings/Precautions

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.

Disease-related concerns:

• 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.

Monitoring Parameters

Viral load; CD4 count; hypersensitivity and injection site reactions; pediatric weight (periodically; adjust dose accordingly); signs and symptoms of pneumonia

Pregnancy Risk Factor

B

Pregnancy Considerations

Teratogenic effects were not observed in animal studies. Enfuvirtide has minimal to low transfer across the human placenta. The DHHS Perinatal HIV Guidelines note that data are insufficient to recommend use during pregnancy.

Regardless of CD4 count or HIV RNA copy number, all HIV-infected pregnant women should receive a combination antiretroviral (ARV) drug regimen. A combination of antepartum, intrapartum, and infant ARV prophylaxis is recommended. ARV therapy should be started as soon as possible in women with symptomatic infection. Although earlier initiation may be more effective in reducing the perinatal transmission of HIV, initiation may be delayed until after 12 weeks gestation in women who do not require immediate treatment after careful consideration of maternal conditions (eg, nausea and vomiting) and the potential risks of first trimester fetal exposure for specific agents. A scheduled cesarean delivery at 38 weeks gestation is recommended for all women with HIV RNA >1000 copies/mL or unknown concentrations near delivery in order to decrease transmission. If ARV therapy must be interrupted for <24 hours during the peripartum period, 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 ARV medications. In couples who want to conceive, the HIV-infected partner should attain maximum viral suppression prior to conception.

Healthcare providers are encouraged to enroll pregnant women exposed to antiretroviral medications in the Antiretroviral Pregnancy Registry (1-800-258-4263 or www.APRegistry.com). Healthcare providers caring for HIV-infected women and their infants may contact the National Perinatal HIV Hotline (888-448-8765) for clinical consultation (HHS [perinatal], 2014).

Patient Education

• 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, dyspepsia, asthenia, lack of appetite, weight loss, or myalgia. Have patient report immediately to prescriber signs of infection, signs of pancreatitis, severe injection site irritation, hematuria, paresthesia, significant dizziness, syncope, dyspnea, edema of extremities, enlarged lymph nodes, skin infection, 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.

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