Enfuvirtide (Monograph)

Brand name: Fuzeon
Drug class: HIV Entry and Fusion Inhibitors

Medically reviewed by Drugs.com on Oct 26, 2023. Written by ASHP.

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Introduction

Antiretroviral; HIV fusion inhibitor.

Uses for Enfuvirtide

Treatment of HIV Infection

Treatment of HIV-1 infection in antiretroviral-experienced (previously treated) patients with evidence of HIV-1 replication despite ongoing antiretroviral therapy; used in conjunction with other antiretrovirals.

Enfuvirtide is not recommended as initial therapy and is usually used as part of an optimized antiretroviral regimen in the management of patients with virologic failure. Selection of an optimized regimen should be individualized based on factors such as virologic efficacy, toxicity, current and previous drug-resistance test results, and availability of antiretrovirals with a high barrier to resistance.

Not included in any recommended or alternative regimens for initial treatment in antiretroviral-naive adults and adolescents. Not recommended for initial treatment in antiretroviral-naive children. Not recommended in pregnancy except under special circumstances.

Postexposure Prophylaxis following Occupational Exposure to HIV

Only recommended for use in postexposure prophylaxis of HIV infection following occupational exposure (PEP)^{† [off-label]} in health-care personnel and other individuals after expert consultation.

US Public Health Service (USPHS) recommends a 3-drug regimen of raltegravir in conjunction with emtricitabine and tenofovir disoproxil fumarate (tenofovir DF) as the preferred regimen for PEP following occupational exposures to HIV. Enfuvirtide is one of several alternative agents that may be used in conjunction with other antiretrovirals for PEP, but only with expert consultation. Do not delay initiation of PEP while waiting for expert consultation.

Postexposure Prophylaxis following Nonoccupational Exposure to HIV (nPEP)

Only recommended for use in postexposure prophylaxis of HIV infection following nonoccupational exposure (nPEP)^{† [off-label]} after sexual, injection drug use, or other nonoccupational exposures in individuals after expert consultation.

When nPEP indicated in adults and adolescents ≥13 years of age with normal renal function, CDC states preferred regimen is either raltegravir or dolutegravir used in conjunction with emtricitabine and tenofovir DF (given as emtricitabine/tenofovir DF); recommended alternative in these patients is ritonavir-boosted darunavir used in conjunction with emtricitabine/tenofovir DF.

Consult infectious disease specialist, clinician with expertise in administration of antiretroviral agents, and/or the National Clinicians’ Postexposure Prophylaxis Hotline (PEPline at 888-448-4911) if nPEP indicated in certain exposed individuals (e.g., pregnant women, children, those with medical conditions such as renal impairment) or if considering a regimen not included in CDC guidelines, source virus is known or likely to be resistant to antiretrovirals, or healthcare provider is inexperienced in prescribing antiretrovirals. Do not delay initiation of nPEP while waiting for expert consultation.

Related/similar drugs

Biktarvy, Descovy, Truvada, Atripla, Epzicom, Stribild, Complera

Enfuvirtide Dosage and Administration

General

Pretreatment Screening

• Evaluate patient use of anticoagulants or presence of coagulation disorders. Risk of post-injection bleeding is higher in these patients.

Patient Monitoring

• Monitor for injection site reactions including signs or symptoms of cellulitis or local infection.

• Monitor for signs and symptoms of pneumonia.

Administration

Available as a single-dose lyophilized powder or as a kit containing 108 mg of enfuvirtide.

Sub-Q Administration

Administer by sub-Q injection into upper arm, anterior thigh, or abdomen (avoid the navel).

Rotate injection sites with each injection (i.e., inject at a site different from preceding injection site).

Do not inject into areas where skin shows signs of a previous injection site reaction and do not inject near anatomical areas where large nerve tracts lie close to the skin (e.g., near elbow, knee, groin, inferior or medial section of the buttocks). Do not inject directly over blood vessels, near the navel, or into skin abnormalities, moles, scars (including surgical scars), bruises, tattoos, or burn sites.

Allow refrigerated reconstituted solution to come to room temperature before injection.

May be self-administered if clinician determines that the patient and/or their caregiver is competent to safely administer the drug.

Reconstitution

Add 1 mL of sterile water for injection diluent (provided by the manufacturer in the convenience kit) to vial containing 108 mg; tap vial gently with a fingertip for 10 seconds and then gently roll between the hands (avoid foaming) to ensure that drug is in contact with diluent. Let vial stand until all of the powder goes into solution; reconstitution can take up to 45 minutes.

Reconstituted solution contains 90 mg/mL.

Dosage

Must be given in conjunction with other antiretrovirals.

Pediatric Patients

Treatment of HIV Infection

Sub-Q

Children weighing at least 11 kg: 2 mg/kg (maximum 90 mg) twice daily. See Table for specific dose and injection volume.

Adults

Treatment of HIV Infection

Sub-Q

90 mg twice daily.

Special Populations

Hepatic Impairment

Dosage adjustments not necessary.

Renal Impairment

Dosage adjustments not necessary.

Geriatric Use

No specific dosage recommendations at this time.

Cautions for Enfuvirtide

Contraindications

• Known hypersensitivity to enfuvirtide or any ingredient in the formulation.

Warnings/Precautions

Local Injection Site Reactions

Sub-Q enfuvirtide associated with injection site reactions (e.g., mild to moderate pain/discomfort, induration, erythema, presence of nodules or cysts, pruritus, ecchymosis). Infection at injection site (including abscess and cellulitis) occurs rarely. Postmarketing reports of cutaneous amyloidosis at injection site.

May occur throughout course of treatment and often occur at more than one injection site. Most patients in clinical studies had at least 1 local injection site reaction. Such reactions persisted for >7 days in some patients. Inject each dose at a different site from the preceding injection site. Do not inject into areas where skin shows signs of a previous injection site reaction.

Administration with Biojector 2000

When administered using a Biojector 2000 needle-free device, neuralgia and/or paresthesia, sometimes lasting up to 6 months, reported when injections were given into anatomical sites where large nerve tracts lie close to the skin. Bruising and hematomas also reported when this device used.

Post-Injection Bleeding

Patients receiving anticoagulants and those with hemophilia or other coagulation disorders may be at higher risk for post-injection bleeding.

Hypersensitivity Reactions

Hypersensitivity reactions (e.g., rash, fever, nausea and vomiting, chills, rigors, hypotension, elevated serum liver transaminase concentrations) reported; these hypersensitivity reactions have recurred on rechallenge.

Other adverse events that may be immune-mediated include primary immune complex reactions, respiratory distress, glomerulonephritis, and Guillain-Barré syndrome.

If hypersensitivity reaction occurs, discontinue and seek immediate medical evaluation.

Do not reinitiate enfuvirtide in patients who have experienced a hypersensitivity reaction.

Pneumonia

Increased incidence of bacterial pneumonia reported in clinical studies; has not been directly attributed to the drug. Risk factors included low initial CD4⁺ T-cell counts, high initial viral load, IV drug abuse, smoking, and history of lung disease.

Monitor patients (especially those with underlying conditions that may predispose them to pneumonia) carefully for signs and symptoms of pneumonia.

Non-HIV Infected Individuals

Although enfuvirtide has not been studied in non-HIV-infected individuals, the possibility exists that administration could lead to production of anti-enfuvirtide antibodies that could cross react with HIV glycoprotein 41(gp41), resulting in a false-positive HIV test using an enzyme-linked immunosorbent assay (ELISA); a confirmatory test (i.e., Western blot) would be expected to be negative.

Immune Reconstitution Syndrome

During initial treatment, patients who respond to antiretroviral therapy may develop an inflammatory response to indolent or residual opportunistic infections (e.g., Mycobacterium avium, M. tuberculosis, cytomegalovirus [CMV], Pneumocystis jirovecii [formerly P. carinii]); may necessitate further evaluation and treatment.

Autoimmune disorders (e.g., Graves' disease, polymyositis, Guillain-Barré syndrome) reported to occur in the setting of immune reconstitution; time to onset is more variable and can occur many months after initiation of antiretroviral therapy.

Specific Populations

Pregnancy

Register patients in Antiretroviral Pregnancy Registry at 800-258-4263. The number of human pregnancy exposures to enfuvirtide is insufficient to make a risk assessment compared to a reference population. No adverse developmental effects were observed in animal reproduction studies at exposures ≥ 2 times higher than human exposures at the recommended human dose.

Experts state enfuvirtide not recommended for initial treatment regimens in antiretroviral-naive pregnant women. Can be considered for pregnant women when therapy with several other classes of antiretroviral agents has failed; however, safety and pharmacokinetic data insufficient to recommend an appropriate dosage for pregnant women and experts state undertake such use only after consultation with HIV and obstetric specialists.

Lactation

Enfuvirtide or its metabolites distributed into milk in animals; not known whether distributed into human milk.

Instruct HIV-infected women not to breast-feed because of risk of HIV transmission and risk of adverse effects in the infant.

Pediatric Use

Safety and pharmacokinetics evaluated in pediatric patients weighing ≥11 kg; use is supported by adequate and well-controlled adult and pediatric studies; median ages of patients in 2 pediatric studies were 9 and 12 years.

Adverse effects in pediatric patients similar to those in adults; however, infections at the injection site (cellulitis, abscess) reported more frequently in adolescents than adults.

Geriatric Use

Insufficient experience in those ≥65 years of age to determine whether they respond differently than younger adults.

Use with caution because of age-related decreases in hepatic, renal, and/or cardiac function and potential for concomitant disease and drug therapy.

Hepatic Impairment

Pharmacokinetics not studied; dosage adjustments not considered necessary.

Renal Impairment

No significant changes in pharmacokinetics observed with renal impairment or hemodialysis. Dosage adjustments not considered necessary.

Common Adverse Effects

Most common adverse reactions: local injection site reactions, diarrhea, nausea, fatigue.

Drug Interactions

Does not inhibit CYP-450 isoenzymes.

Does not affect metabolism of CYP3A4, CYP2D6, CYP1A2, CYP2C19, or CYP2E1 substrates.

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Based on available data, pharmacokinetic interactions unlikely.

Specific Drugs and Laboratory Tests

Enfuvirtide Pharmacokinetics

Absorption

Bioavailability

Almost completely absorbed following sub-Q administration; absolute bioavailability is 84.3%.

Systemic absorption is comparable following injection into the abdomen, thigh, or arm.

Systemic absorption in adults is comparable following sub-Q injection using the Biojector 2000 needle-free device or a 27-gauge ½-inch needle and syringe.

Special Populations

Plasma concentrations in children 5–16 years of age receiving enfuvirtide 2 mg/kg twice daily (maximum 90 mg twice daily) similar to those reported in adults receiving the recommended dosage.

Distribution

Extent

Enfuvirtide or its metabolites distributed into milk in animals; not known whether distributed into human milk.

Plasma Protein Binding

92%; bound mainly to albumin and, to a lesser extent, α-1 acid glycoprotein.

Elimination

Metabolism/Elimination

Expected to undergo catabolism to its constituent amino acids, with subsequent recycling of the amino acids in the body pool.

Hemodialysis does not have a clinically important effect on enfuvirtide clearance.

Half-life

3.8 hours.

Special Populations

Pharmacokinetics not evaluated in hepatic impairment.

No clinically significant changes in pharmacokinetics at any level of renal impairment or hemodialysis.

Stability

Storage

Parenteral

Powder for Injection

25°C (excursions permitted between 15–30°C).

Store reconstituted solution under refrigeration at 2–8°C; discard 24 hours after reconstitution.

Actions and Spectrum

• Pharmacologically and structurally different from other currently available antiretrovirals.

• Active against HIV-1; inactive against HIV-2.

• Interferes with entry of HIV-1 into target cells by inhibiting fusion of the viral and cellular membranes.

• HIV-1 with reduced susceptibility to enfuvirtide has been selected in vitro and has emerged during therapy with the drug.

• Cross-resistance between enfuvirtide and nucleoside reverse transcriptase inhibitors (NRTIs), nonnucleoside reverse transcriptase inhibitors (NNRTIs), or HIV protease inhibitors (PIs) is highly unlikely since HIV-1 isolates resistant to these agents were susceptible to enfuvirtide in cell culture.

Advice to Patients

• Advise patients of the critical nature of compliance with HIV therapy and importance of remaining under the care of a clinician. Importance of taking as prescribed; do not alter or discontinue antiretroviral regimen without consulting clinician.

• Inform patients of the importance of using in conjunction with other antiretrovirals—not for monotherapy.

• Advise patients that antiretroviral therapy is not a cure for HIV infection; opportunistic infections and other complications associated with HIV disease may still occur.

• Provide appropriate instruction on use of enfuvirtide to patients and/or their caregivers who are allowed to administer the drug in the home setting.

• Advise patient and/or caregiver of the importance of administering enfuvirtide into the preferred sites (i.e., upper arm, abdomen, anterior thigh). Injections should not be made near anatomical areas where large nerve tracts lie close to the skin (e.g., near the elbow, knee, groin, inferior or medial section of the buttocks), directly over a blood vessel, near the navel, or into skin abnormalities, moles, scars (including surgical scars), bruises, tattoos, or burn sites.

• Importance of monitoring for signs and symptoms of injection site reactions (e.g., cellulitis, local infections) and contacting clinician if such reactions occur.

• Advise patients that an increased rate of bacterial pneumonia has been reported. Importance of immediately seeking medical evaluation if signs and symptoms of pneumonia (cough with fever, rapid breathing, shortness of breath) occur.

• Advise patients that hypersensitivity reactions may occur. Importance of discontinuing enfuvirtide and immediately seeking medical evaluation if signs or symptoms of systemic hypersensitivity (e.g., combinations of rash, fever, nausea, vomiting, chills, rigors, and/or hypotension) occur.

• Advise patients if dizziness occurs, necessity of exercising caution when driving or operating machinery.

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal products, and any concomitant illnesses.

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed. Advise HIV-infected women not to breast-feed.

• Importance of advising patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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