Dupilumab (Dupixent) is a fully human monoclonal antibody that belongs to the subclass of immunoglobulins called IgG4. It is a dual inhibitor of Interleukin 4 and Interleukin 13. It is primarily used to treat moderate to severe uncontrolled asthma.

Dupilumab (Dupixent) Uses:

• Asthma:

  • Adults and children under the age of 12 who have moderate to severe asthma with an eosinophilic phenotype or asthma that is corticosteroid dependent should receive additional maintenance medication.
  • Restrictions on use: Not recommended for the treatment of status asthmaticus or acute bronchospasm.

• Atopic dermatitis:

  • Treatment of moderate to severe atopic dermatitis in adults and children under the age of 12 whose condition cannot be successfully controlled by topical prescription medications or in situations where conventional therapies are not recommended.

Other monoclonal antibodies developed for the treatment of asthma include:

• Omalizumab (Xolair)
• Mepolizumab (Nucala)
• Benralizumab

Dupilumab (Dupixent) Dose in Adults

Dupilumab (Dupixent) Dose in the treatment of moderate to severe Asthma: SubQ:

• Initial: 400 mg (given as two 200 mg injections) or 600 mg (given as two 300 mg injections)
• Maintenance: 200 mg (following 400 mg initial dose) or 300 mg (following 600 mg initial dose) once every other week

Dupilumab (Dupixent) Dose in the treatment of Asthma, oral corticosteroid dependent or with comorbid moderate to severe atopic dermatitis: SubQ:

• Initial: 600 mg (given as two 300 mg injections)
• Maintenance: 300 mg once every other week

Dupilumab (Dupixent) Dose in the treatment of Atopic dermatitis: SubQ:

• Initial: 600 mg (given as two 300 mg injections)
• Maintenance: 300 mg once every other week

• Missed doses:

  • If a dose is missed, administer within 7 days from the missed dose, and then resume the original schedule.
  • Wait until the next dose on the original schedule, in case the missed dose is not administered within 7 days.

Dupilumab (Dupixent) Dose in Children

Dupilumab (Dupixent) Dose in the maintenance treatment of moderate to severe Asthma:

• Children ≥12 years and Adolescents:

  • SubQ: Initial: 400 mg once (administered as two 200 mg injections), which is followed by a maintenance dose of 200 mg every other week or
  • 600 mg once (administered as two 300 mg injections), followed by a maintenance dose of 300 mg every other week.

  • Corticosteroid-dependent asthma or comorbid atopic dermatitis (moderate to severe in patients ≥18 years):

    • SubQ: Initial: 600 mg once (administered as two 300 mg injections), which is followed by a maintenance dose of 300 mg every other week.

Dupilumab (Dupixent) Dose in the treatment of moderate to severe Atopic dermatitis (AD):

• Children ≥12 years and Adolescents ≤17 years:

  • <60 kg:
    • SubQ: Initial: 400 mg once (administered as two 200 mg injections), followed by a maintenance dose of 200 mg every other week.
  • ≥60 kg:
    • SubQ: Initial: 600 mg once (administered as two 300 mg injections), which is followed by a maintenance dose of 300 mg every other week.

• Adolescents ≥18 years:

  • SubQ: Initial: 600 mg once (administered as two 300 mg injections), followed by a maintenance dose of 300 mg every other week.

Dupilumab (Dupixent) Pregnancy Risk Category: N

• Dupilumab, a monoclonal IgG anti-IgG antibody, is possible to be exposed to the fetus in pregnancy.
• Uncontrolled asthma can lead to adverse pregnancy events (increased preeclampsia risk, preterm births, low birth weight infants).
• Pregnant women should be monitored for asthma.
• Continuous data collection is underway to monitor the outcomes of Dupilumab exposure in pregnancy and infants.

Dupilumab use during breastfeeding:

• Although it is not known if Dupilumab may be present in breastmilk, there are maternal IgG molecules present in breastmilk.
• According to the manufacturer breastfeeding during therapy is a decision that should be made after considering the risks to infants and the benefits to mothers.

Dose in Kidney disease:

• No dosage adjustments 

Dose in Liver disease:

• No dosage adjustments are provided in the manufacturer's labeling (has not been studied).

Common Side Effects of Dupilumab (Dupixent):

• Immunologic:

  • Antibody development

• Local:

  • Injection site reaction

Less Common Side Effects of Dupilumab (Dupixent):

• Gastrointestinal:

  • Oral herpes simplex infection

• Hematologic & oncologic:

  • Eosinophilia

• Infection:

  • Herpes simplex infection

• Ophthalmic:

  • Conjunctivitis
  • Sye pruritus

• Respiratory:

  • Oropharyngeal pain

Contraindications to Dupilumab (Dupixent):

• Hypersensitivity to Dupilumab and any component of the formulation

Warnings and precautions

• Hypersensitivity

  • However, hypersensitivity reactions that underpin urticaria and rash, erythema nodosum, serum sickness, or similar reactions have been reported in rare cases.
  • If you notice signs/symptoms that a severe hypersensitivity reaction is developing, stop using it immediately and seek appropriate treatment.

• Eosinophilia, vasculitis:

  • Rare cases of severe systemic eosinophilia may be present. Patients can also present with vasculitis or clinical signs of eosinophilic pneumonia.
  • This condition is commonly treated with systemic corticosteroid treatment.
  • You should monitor for signs such as eosinophilia and vasculitic skin rash, worsening of pulmonary symptoms, cardiac complications, and/or neuropathy, especially after reducing oral corticosteroids.
  • It has been proven that there is no causal relationship between Dupilumab, these conditions, and Dupilumab.

• Ocular effects

  • There have been reports of conjunctivitis, keratitis, and other skin conditions.
  • You must notify your healthcare provider if you notice any new or worsening symptoms.

• Asthma

  • Patients with atopic dermatitis and comorbid asthma should consult their healthcare provider before discontinuing or adjusting asthma medication.

• Infections with Helminth

  • Although it is not known whether Dupilumab administration will affect a patient's response to parasitic infections, patients with known helminthic infections were not studied.
  • Patients with helminth infection must be treated before Dupilumab treatment can begin.
  • Patients infected with helminths during treatment should discontinue the use of Dupilumab until the infection is resolved.

Why Does Dupixent Hurt So Much?

Dupilumab: 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:

• Monitor for signs/symptoms of hypersensitivity reactions and ocular adverse effects;
• signs of infection;
• pulmonary function in patients treated for asthma

How to administer Dupilumab (Dupixent)?

• Subcutaneous injections into the thigh or lower abdomen should be administered; however, the caregiver may inject the medication into the upper arm.
• Rotate injection sites, that add in initial doses (administer 600 mg initial dose as two 300 mg injections; administer 400 mg initial dose as two 200 mg injections).
• Avoid administering the drug to skin that is tender, damaged, bruised, or scarred.
• Patients may self-administer injections after proper training.
• Allow the solution to reach room temperature for 45 minutes (300 mg prefilled syringe) or 30 minutes (200 mg prefilled syringe) before its use; however, there is no need to remove the needle cap while allowing the product to reach room temperature.
• If the solution is cloudy or includes particles, don't shake it, and don't use it either.
• There is no preservative in a prefilled syringe; discard any unused medication.

Mechanism of action of Dupilumab (Dupixent):

• Interleukin-4 and interleukin-13 signaling are inhibited by the monoclonal IgG4 human antibody Dupilumab by binding the IL-4Ra subunit.
• Dupilumab blocks IL-4Ra and inhibits IL-4Ra and IL13 cytokine-induced inflammatory reactions, which include proinflammatory cytokines and chemokines as well as IgE.
• The mechanism of Dupilumab's action in asthma is not yet fully understood.

Metabolism:

• Monoclonal antibodies are first degraded by catabolism into small peptides or amino acids.

Bioavailability:

• 61% to 64%

Time to peak:

• ~1 week

Excretion: Clearance:

• The median time to non-detectable concentrations is:
  • 10 to 11 weeks for 300 mg every 2 weeks,
  • 13 weeks for 300 mg weekly, and
  • 9 weeks (for 200 mg every 2 weeks).
• Though, age did not affect clearance.

International Brand Names of Dupilumab:

• Dupixent

Dupilumab Brand Names in Pakistan:

No Brands are Available in Pakistan.