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Enfuvirtide: Pediatric drug information

Enfuvirtide: Pediatric drug information
(For additional information see "Enfuvirtide: Drug information" and see "Enfuvirtide: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Fuzeon
Brand Names: Canada
  • Fuzeon
Therapeutic Category
  • Antiretroviral Agent;
  • Fusion Inhibitor;
  • HIV Agents (Anti-HIV Agents)
Dosing: Pediatric
HIV-1 infection, treatment

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 (Ref).

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.

Dosing: Kidney Impairment: Pediatric

Children weighing ≥11 kg and Adolescents: No dosage adjustment necessary.

Dosing: Hepatic Impairment: Pediatric

Children weighing ≥11 kg and Adolescents: No dosage adjustment necessary.

Dosing: Adult

(For additional information see "Enfuvirtide: Drug information")

HIV-1 infection, treatment

HIV-1 infection, treatment: SubQ: 90 mg twice daily.

Dosing: Kidney Impairment: Adult

No dosage adjustment necessary.

Dosing: Hepatic Impairment: Adult

No dosage adjustment necessary (has not been studied).

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>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

Contraindications

Hypersensitivity to enfuvirtide or any component of the formulation

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.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Reconstituted, Subcutaneous:

Fuzeon: 90 mg (1 ea)

Generic Equivalent Available: US

No

Pricing: US

Solution (reconstituted) (Fuzeon Subcutaneous)

90 mg (per each): $71.71

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Kit, Subcutaneous:

Fuzeon: 90 mg

Administration: Pediatric

SubQ: Bring refrigerated reconstituted vials to room temperature before injection and visually inspect vial again; solution should be clear, colorless, and without particulate matter or bubbles.

Inject SubQ into upper arm, abdomen, or anterior thigh. Do not inject IM (severity of reactions is increased). Do not inject into skin abnormalities including directly over a blood vessel, into moles, bruises, scar tissue, near the navel, surgical scars, burn sites, or tattoos. Do not inject in or near sites where large nerves are close to the skin including near the elbow, knee, groin, and inferior or medial sections of the buttocks. Rotate injection site (ie, give injections at a site different from the preceding injection site); do not inject into any site where an injection site reaction is present. After injection, apply heat or ice to injection site or gently massage area to better disperse the dose, to minimize local injection reactions (Ref); discard unused portion of the vial (vial is for single use only).

Administration: Adult

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 (Ref).

Storage/Stability

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.

Use

Treatment of HIV-1 infection in combination with other antiretroviral agents in treatment-experienced patients who are failing current antiretroviral therapy (FDA approved in pediatric patients weighing ≥11 kg and adults). Note: HIV regimens consisting of 3 antiretroviral agents from at least 2 classes are strongly recommended. Although FDA approved, contemporary use is uncommon secondary to availability of more preferable options. It is not recommended as initial therapy in patients who are antiretroviral naive (HHS [pediatric] 2018).

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Betibeglogene Autotemcel: Antiretroviral Agents may diminish the therapeutic effect of Betibeglogene Autotemcel. Risk X: Avoid combination

Elivaldogene Autotemcel: Antiretroviral Agents may diminish the therapeutic effect of Elivaldogene Autotemcel. Management: Avoid use of antiretroviral medications for at least one month, or for the amount of time required for elimination of the retroviral medication, prior to stem cell mobilization and until the all apheresis cycles are finished Risk X: Avoid combination

Orlistat: May decrease the serum concentration of Antiretroviral Agents. Risk C: Monitor therapy

Reproductive Considerations

The Health and Human Services (HHS) perinatal HIV guidelines do not recommend enfuvirtide (except in special circumstances) for patients with HIV infection who are not yet pregnant but are trying to conceive.

Viral suppression sustained below the limits of detection with antiretroviral therapy (ART) and modification of therapy (if needed) is recommended in all patients with HIV infection who are planning a pregnancy. Optimization of the health of the person who will become pregnant and a discussion of the potential risks and benefits of ART during pregnancy is also recommended prior to conception. In most cases, recommendations from the HHS perinatal HIV guidelines (based on data obtained from cisgender women) can be applied to transgender and gender diverse people assigned female sex at birth

Health care providers caring for couples planning a pregnancy when one or both partners are diagnosed with HIV infection may contact the National Perinatal HIV Hotline (888-448-8765) for clinical consultation (HHS [perinatal] 2021).

Pregnancy Considerations

Enfuvirtide has minimal to low transfer across the human placenta.

Outcome information specific to enfuvirtide use in pregnancy is no longer being reviewed and updated in the Health and Humans Services (HHS) Perinatal Guidelines. The HHS perinatal HIV guidelines do not recommend enfuvirtide as initial therapy for pregnant patients living with HIV infection; enfuvirtide is not recommended (except in special circumstances) in pregnant patients who have had antiretroviral therapy (ART) therapy in the past but are restarting, or who require a new ART regimen (due to poor tolerance or poor virologic response of current regimen). Patients who become pregnant while taking enfuvirtide may continue if viral suppression is effective and the regimen is well tolerated.

Maternal 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 not diagnosed with HIV infection but who were exposed to ART in utero or as a neonate and develop significant organ system abnormalities of unknown etiology (particularly of the CNS or heart) should be evaluated for potential metabolic dysfunction.

ART is recommended for all pregnant people with HIV infection to maximize their health, maintain 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. Patients on fully suppressive regimens prior to pregnancy generally may continue the same regimen considering known pregnancy outcomes and pharmacokinetic data. Monitoring of patients who are pregnant is more frequent than in patients who are not pregnant. ART initiated during pregnancy can be modified after delivery. In most cases, recommendations from the HHS perinatal HIV guidelines (based on data obtained from cisgender women) can be applied to transgender and gender diverse people assigned female sex at birth.

Data collection to monitor pregnancy and infant outcomes following exposure to ART is ongoing. Health care providers are encouraged to enroll patients who are pregnant 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 pregnant patients with HIV infection and their infants may contact the National Perinatal HIV Hotline (888-448-8765) for clinical consultation (HHS [perinatal] 2021).

Monitoring Parameters

HIV: General recommendations: Management of HIV infection requires extensive monitoring; refer to current guidelines (https://clinicalinfo.hiv.gov/en/guidelines) for additional guidance. Antiretroviral drug-resistance testing is recommended before initiation of therapy in treatment-naive patients. After initiation of or change in antiretroviral therapy regimen, pediatric patients should be evaluated for clinical adverse effects and treatment adherence at 1 to 2 weeks, and laboratory testing for drug toxicity should occur at 2 to 4 weeks; monitor for therapy adherence, effectiveness, and toxicities every 3 to 4 months.

Drug-specific monitoring: Frequency may vary based on several factors including age, concomitant therapy, and clinical response; refer to current guidelines for additional information.

Monitor injection site for cellulitis (more common in pediatric patients) and sign/symptoms of hypersensitivity reactions; signs/symptoms of bacterial pneumonia.

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 (Adult Data Unless Noted)

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)

Protein binding: 92%; primarily to albumin, but also to alpha-1 acid glycoprotein (to a lesser extent)

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.

Bioavailability: SubQ: Absolute: 84.3% ± 15.5%; Note: Bioequivalence was found to be similar in a study comparing standard administration using a needle versus a needle-free device.

Half-life elimination: 3.8 ± 0.6 hours

Time to peak: SubQ: Single dose: Median: 8 hours (range: 3 to 12 hours); Multiple dosing: Median: 4 hours (range: 4 to 8 hours)

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (CH) Switzerland: Fuzeon;
  • (MX) Mexico: Thidezu
  1. Church JA, Cunningham C, Hughes M, et al. Safety and antiretroviral activity of chronic subcutaneous administration of T-20 in human immunodeficiency virus 1-infected children. Pediatr Infect Dis J. 2002;21(7):653-659. [PubMed 12237598]
  2. Fuzeon (enfuvirtide) [prescribing information]. South San Francisco, CA: Genentech USA, Inc; December 2019.
  3. Hardy H, Skolnik PR. Enfuvirtide, a new fusion inhibitor for therapy of human immunodeficiency virus infection. Pharmacotherapy. 2004;24(2):198-211. [PubMed 14998221]
  4. HHS Panel on Antiretroviral Therapy and Medical Management of HIV-Infected Children. Guidelines for the use of antiretroviral agents in pediatric HIV infection. 2018. Available at http://aidsinfo.nih.gov.
  5. Morris JL, Kraus DM. New antiretroviral therapies for pediatric HIV infection. J Pediatr Pharmacol Ther. 2005;10:215-247.
  6. Soy D, Aweeka FT, Church JA, et al. Population pharmacokinetics of enfuvirtide in pediatric patients with human immunodeficiency virus: searching for exposure-response relationships. Clin Pharmacol Ther. 2003;74(6):569-580. [PubMed 14663459]
  7. True AL, Chiu YY, Demasi RA, et al, “Pharmacokinetic Bioequivalence of Enfuvirtide Using a Needle-Free Device Versus Standard Needle Administration,” Pharmacotherapy, 2006, 26(12):1679-86. [PubMed 17125431]
  8. US Department of Health and Human Services (HHS) Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents, Department of Health and Human Services. 2018. http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf
  9. US Department of Health and Human Services (HHS) Panel on Antiretroviral Therapy and Medical Management of HIV-Infected Children. Guidelines for the use of antiretroviral agents in pediatric HIV infection. 2018. Available at http://aidsinfo.nih.gov
  10. US Department of Health and Human Services (HHS) Panel on Treatment of HIV During Pregnancy and Prevention of Perinatal Transmission. Recommendations for the use of antiretroviral drugs during pregnancy and interventions to reduce perinatal HIV transmission in the United States. https://clinicalinfo.hiv.gov/en/guidelines/perinatal/whats-new. Updated December 30, 2021. Accessed January 3, 2022.
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