Enfuvirtide (Fuzeon) is a fusion inhibitor. It inhibits the binding of the HIV-1 virus to CD4 cells blocking its entry into the cells. It is used in combination with other antiretroviral drugs to treat HIV-1 infection.

Enfuvirtide Uses:

• HIV-1 infection:

  • It in indicated in treatment of HIV-1 infection in treatment-experienced patients with evidence of HIV-1 replication despite ongoing antiretroviral therapy.

Enfuvirtide (Fuzeon) Dose in Adults

Enfuvirtide (Fuzeon) Dose in the treatment of HIV-1 infection:

• Subcutaneous: 90 mg twice a day

Enfuvirtide (Fuzeon) Dose in the treatment of HIV-1 infection:

Note: It is not recommended as initial therapy in ARV naive patients, and reserved when other options are not available. Gene mutation and antiretroviral (ARV) resistance patterns should be evaluated when necessary. FDA approved, contemporary use is uncommon secondary to the availability of more preferable options.

• Children weighing ≥11 kg and Adolescents:

  • Weight-directed dosing:
    • Subcutaneous: 2 mg/kg/dose twice a day; maximum dose: 90 mg/dose

  • Fixed dosing (weight-band): Subcutaneous

    • 11 - 15.5 kg: 27 mg twice a day
    • 6 - 20 kg: 36 mg twice a day
    • 1 - 24.5 kg: 45 mg twice a day
    • 6 - 29 kg: 54 mg twice a day
    • 1 - 33.5 kg: 63 mg twice a day
    • 6 - 38 kg: 72 mg twice a day
    • 1 - 42.5 kg: 81 mg twice a day
    • ≥42.6 kg: 90 mg twice a day

Enfuvirtide Pregnancy Category: B

• It is capable of transferring very little to no placenta.
• Preterm birth may be more likely in a pregnant woman, although some studies (not all of them) show an increase in stillbirth, low birth weight and small gestational infants.
• Maternal ART has a clear advantage and should not be avoided due to the potential for adverse neonatal outcomes. ART is generally recommended for all pregnant women.
• A mother who has used ART should continue to monitor her infants. If any of her children develop an organ system abnormality of unknown origin, they should be evaluated for mitochondrial dysfunction.
• Health and Human Services (HHS), Perinatal HIV Guidelines
  • Recommend not to use enfuvirtide in pregnant HIV-infected females
  • In special cases, pregnant women can receive enfuvirtide
    • Have you tried ART therapy before?
    • A patient may require a new regimen of ART if they have poor virologic response or tolerance to the current regimen.
    • People who aren't yet pregnant, but are trying to conceive.
• If enfuvirtide is well tolerated and effective in viral suppression, females who are pregnant while on enfuvirtide can continue to take the drug.

Enfuvirtide use during breastfeeding:

• It is unknown if breast milk contains enfuvirtide.
• HIV-infected women should stop breastfeeding. There are still chances for HIV transmission. Antiretroviral treatment does not eliminate all risk.
• The multi-class-resistant virus has been detected in breastfeeding infants despite maternal therapy.

Dose in Kidney disease:

No dosage adjustment required.

Dose in Liver disease:

No dosage adjustment required

Common Side Effects of Enfuvirtide (Fuzeon):

• Central nervous system:

  • Fatigue
  • Insomnia

• Gastrointestinal:

  • Diarrhea
  • Nausea

• Local:

  • Injection site reaction 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

Less Common Side Effects of Enfuvirtide (Fuzeon):

• Dermatologic:

  • Folliculitis

• Endocrine & Metabolic:

  • Weight Loss

• Gastrointestinal:

  • Abdominal Pain
  • Decreased Appetite
  • Pancreatitis
  • Anorexia
  • Xerostomia

• Hematologic & Oncologic:

  • Eosinophilia

• Hepatic:

  • Increased Serum Transaminases

• Infection:

  • Infection
  • Herpes Simplex Infection

• Neuromuscular & Skeletal:

  • Increased Creatine Phosphokinase
  • Limb Pain
  • Myalgia

• Ophthalmic:

  • Conjunctivitis

• Respiratory:

  • Sinusitis
  • Cough
  • Bacterial Pneumonia
  • Flu-Like Symptoms

Contraindication to Enfuvirtide (Fuzeon):

Hypersensitivity reactions

Warnings and precautions

• Hypersensitivity reactions

  • There are many types of hypersensitivity reactions, from mild reactions like rash or fever to severe anaphylaxis.
  • For example, immune-mediated reactions may occur. Guillain Barre syndrome and glomerulonephritis are some examples of immune-mediated reactions.
  • In the event of systemic reactions, discontinue use immediately and permanently.

• Immune reconstitution syndrome:

  • Patients may develop immune reconstitution syndrome
  • An activation of an autoimmune disorder, e.g. GBS, graves disease, or polymyositis may be present.

• Injection site reactions:

  • Local injection site reactions can be common.
  • You can administer it using the needle-free tool, which is also associated to nerve pain (including paresthesia and neuralgia)
  • Do not administer to large nerves.

• Pneumonia:

  • Clinical trials have shown an increase in the incidence of pneumonia. Risk factors include low CD4 count, high viral load, IV drug usage, smoking, and history of lung disease.
  • Monitorization is recommended for any signs or symptoms of pneumonia.

• Bleeding disorders:

  • Patients at high risk of bleeding (e.g., coagulation disorder) should be cautious when injecting. coagulation disorder

• Use it in the right way:

  • It shouldn't be used on antiretroviral treatment-naive patients.

Enfuvirtide: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring parameters:

• Viral load
• CD4 count
• Hypersensitivity and injection site reactions
• Pediatric weight (periodically; adjust dose accordingly)
• Signs and symptoms of pneumonia

How to administer Enfuvirtide (Fuzeon)?

Subcutaneous: Into upper arm, abdomen, or anterior thigh.

Don'ts of administration:

• Do not inject into moles, navel, over a blood vessel, or skin abnormalities such as scars, bruises, tattoos, or burn sites.
• Do not inject at sites near large nerves.
• Do not inject into any site where an injection site reaction is evident

Do's of administration:

• Rotate injection site
• Inject at the site different from the preceding injection site.

Bioequivalence was similar in a study comparing standard administration using a needle versus a needle-free device

Mechanism of action of Enfuvirtide:

• It acts as a fusion inhibitor. 
• It blocks the confrontational change, gp41 that is required for membrane fusion and entry to CD4 cells.

Absorption:

• Subcutaneous: Similar absorption when injected under the skin, arm or thigh.

Protein binding:

• 92% of the protein is protein-bound to albumin, but also alpha-1 acids glycoprotein in a lesser degree.

Metabolism: Hydrolysis

• It undergoes catabolism by peptidases and proteinases in liver and kidneys to amino acids; hydrolysis produces deaminated metabolite (with 20% activity compared to parent drug).

Half-life elimination:

• 3.8 ± 0.6 hours

Time to peak: Subcutaneous:

• Single-dose: Median: 8 hours (range: 3 to 12 hours)
• Multiple dosing: Median: 4 hours (range: 4 to 8 hours)

International Brand Names of Enfuvirtide:

• Fuzeon

Enfuvirtide Brand Names in Pakistan:

No Brands Available in Pakistan.