Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Subcutaneous:
Fuzeon: 90 mg (1 ea)
Pharmacology
Mechanism of Action
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
Pharmacokinetics/Pharmacodynamics
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.
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 and Administration
Dosing: Adult
HIV-1 infection, treatment: SubQ: 90 mg twice daily
Dosing: Geriatric
Refer to adult dosing.
Dosing: Pediatric
HIV-1 infection, treatment: Note: Gene mutation and antiretroviral (ARV) resistance patterns should be evaluated (refer to https://www.iasusa.org/ for more information) when necessary. Although FDA approved, contemporary use is uncommon secondary to availability of more preferable options. The role in therapy is typically reserved when other options are not available; it is not recommended as initial therapy in patients who are ARV naive (HHS [pediatric] 2018).
Children weighing ≥11 kg and Adolescents:
Weight-directed dosing: SubQ: 2 mg/kg/dose twice daily; maximum dose: 90 mg/dose
Fixed dosing (weight-band): SubQ:
11 to 15.5 kg: 27 mg twice daily
15.6 to 20 kg: 36 mg twice daily
20.1 to 24.5 kg: 45 mg twice daily
24.6 to 29 kg: 54 mg twice daily
29.1 to 33.5 kg: 63 mg twice daily
33.6 to 38 kg: 72 mg twice daily
38.1 to 42.5 kg: 81 mg twice daily
≥42.6 kg: 90 mg twice daily
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
SubQ: 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
Orlistat: May decrease the serum concentration of Antiretroviral Agents. Monitor therapy
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 reaction (98%; may include cyst at injection site, erythema at injection site, induration at injection site, injection site ecchymosis, injection site nodule, injection site pruritus, pain at injection site), injection site infection (children: 11%, adults: 2%)
1% to 10%:
Dermatologic: Folliculitis (2%)
Endocrine & metabolic: Weight loss (7%)
Gastrointestinal: Abdominal pain (4%), decreased appetite (3%), pancreatitis (3%), anorexia (2%), xerostomia (2%)
Hematologic & oncologic: Eosinophilia (2% to 9%)
Hepatic: Increased serum transaminases (4%, grade 4: 1%)
Infection: Infection (4% to 6%), herpes simplex infection (4%)
Neuromuscular & skeletal: Increased creatine phosphokinase (3% to 7%), limb pain (3%), myalgia (3%)
Ophthalmic: Conjunctivitis (2%)
Respiratory: Sinusitis (6%), cough (4%), bacterial pneumonia (3%), flu-like symptoms (2%)
<1%, postmarketing, and/or case reports: Amyloidosis (cutaneous; at the injection site), angina pectoris, anxiety, constipation, depression, dysgeusia, glomerulonephritis, Guillain-Barré syndrome, hyperglycemia; hypersensitivity exacerbation (to abacavir), hypersensitivity reaction (symptoms may include fever, hypotension, increased serum transaminases, nausea, skin rash, vomiting); increased amylase, increased gamma-glutamyl transferase, insomnia, increased serum lipase, increased serum triglycerides, liver steatosis, lymphadenopathy, neutropenia, peripheral neuropathy, pulmonary disease, renal failure, renal insufficiency, renal tubular necrosis, respiratory distress, sepsis, sixth nerve palsy, suicidal tendencies, thrombocytopenia, toxic hepatitis, 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). Additionally, immune mediated reactions (eg, glomerulonephritis, Guillain-Barré syndrome, primary immune complex reaction, respiratory distress) have been reported. 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
Pregnancy Considerations
Enfuvirtide has minimal to low transfer across the human placenta.
Data collected by the antiretroviral pregnancy registry are insufficient to evaluate human teratogenic risk. Maternal antiretroviral therapy (ART) may be associated with adverse pregnancy outcomes, including preterm delivery, stillbirth, low birth weight, and small for gestational age infants. Actual risks may be influenced by maternal factors, such as disease severity, gestational age at initiation of therapy, and specific ART regimen; therefore, close fetal monitoring is recommended. Because there is clear benefit to appropriate treatment, maternal ART should not be withheld due to concerns for adverse neonatal outcomes. Long-term follow-up is recommended for all infants exposed to antiretroviral medications; children without HIV but who were exposed to ART in utero and develop significant organ system abnormalities of unknown etiology (particularly of the CNS or heart) should be evaluated for potential mitochondrial dysfunction.
The Health and Human Services (HHS) perinatal HIV guidelines do not recommend enfuvirtide as initial therapy for patients living with HIV (including pregnant females); enfuvirtide is not recommended (except in special circumstances) in pregnant females who have had ART therapy in the past but are restarting, who require a new ART regimen (due to poor tolerance or poor virologic response of current regimen), and who are not yet pregnant but are trying to conceive. Females who become pregnant while taking enfuvirtide may continue if viral suppression is effective and the regimen is well tolerated. Pharmacokinetic data are insufficient to make dosing recommendations during pregnancy.
In general, ART is recommended for all pregnant females living with HIV to keep the viral load below the limit of detection and reduce the risk of perinatal transmission. Therapy should be individualized following a discussion of the potential risks and benefits of treatment during pregnancy. Monitoring of pregnant females is more frequent than in nonpregnant adults. ART should be continued postpartum for all females living with HIV and can be modified after delivery.
Health care providers are encouraged to enroll pregnant females exposed to antiretroviral medications as early in pregnancy as possible in the Antiretroviral Pregnancy Registry (1-800-258-4263 or http://www.APRegistry.com). Health care providers caring for pregnant females living with HIV and their infants may contact the National Perinatal HIV Hotline (888-448-8765) for clinical consultation (HHS [perinatal] 2019).
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 abdominal pain, diarrhea, loss of strength and energy, lack of appetite, flu-symptoms, dry mouth, painful extremities, sinus irritation, weight loss, or muscle pain. Have patient report immediately to prescriber signs of infection, signs of kidney problems (unable to pass urine, blood in the urine, change in amount of urine passed, or weight gain), signs of pancreatitis (severe abdominal pain, severe back pain, severe nausea, or vomiting), severe injection site irritation, chills, severe nausea, vomiting, weakness, burning or numbness feeling, severe dizziness, passing out, cough, fast breathing, eye irritation, difficulty breathing, or shortness of breath (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 health care 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.
