dupilumab

Action and Spectrum

Dupilumab is a fully human IgG4 monoclonal antibody that works by blocking the interleukin-4 receptor alpha (IL-4Rα) subunit, thereby disrupting the downstream JAK-STAT signaling pathway. By targeting IL-4Rα — which is shared by both IL-4 and IL-13 receptor complexes — dupilumab inhibits the actions of these key pro-inflammatory cytokines that drive immune and inflammatory responses in conditions like atopic dermatitis, asthma, allergic diseases, and chronic rhinosinusitis. This blockade helps address three core aspects of atopic dermatitis pathology: impaired skin barrier integrity, the immune system’s class switch to IgE production, and Th2 cell-driven inflammation. 

Drug Interaction

Adverse Reaction

Frequency defined:  

>10% 

Antibody development 

1% to 10% 

Headache 

Pharyngitis 

Fever 

Post-marketing  

Angioedema 

Hypersensitivity reaction 

Black Box Warning

There is no blackbox warning for this drug 

Contraindication / Caution

Contraindications 

Hypersensitivity 

Cautions 

Serious Allergic Reactions: Rare cases of anaphylaxis, serum sickness-like reactions, angioedema, and severe rashes have occurred. Stop treatment if severe hypersensitivity happens and provide appropriate care. 

Eye Problems: Conjunctivitis and keratitis are more common, especially in atopic dermatitis. Patients should report any new or worsening eye issues; an eye exam may be needed if symptoms persist. 

Eosinophilic Conditions: Conditions like eosinophilic pneumonia or EGPA (vasculitis) can occur, especially if oral steroids are tapered. Watch for worsening breathing, rashes, or organ involvement. Pause dupilumab if suspected. 

Not for Acute Attacks: Do not use dupilumab to treat sudden asthma/COPD attacks or status asthmaticus. Patients must seek urgent care if their breathing suddenly worsens. 

Corticosteroid Tapering: Do not stop corticosteroids abruptly when starting dupilumab. Taper slowly under medical supervision to avoid withdrawal or flare-ups of other conditions. 

Asthma Patients: Those with asthma should not change their regular asthma meds without consulting their doctor. 

Pregnancy / Lactation

Pregnancy consideration: only preferred if conventional therapies do not work to treat asthma in pregnancy. 

Lactation: Dupilumab excretion in breast milk is not known. 

Pregnancy category: 

• Category A: Satisfactory and well-controlled studies show no risk to the fetus in the first or later trimester. 

• Category B: There is no evidence of risk to the fetus found in animal reproduction studies and there are not enough studies on pregnant women. 

• Category C: Adverse effects on the fetus found with evidence in animal reproduction studies and no adequate evidence for an effect in humans, care must be taken for potential risks in pregnant women 

• Category D: There is adequate data available with sufficient evidence of human fetal risk from various platforms, but despite potential risks may be used only in emergency cases for potential benefits. 

• Category X: Drugs listed in this category outweigh risks over benefits These category drugs should be prohibited for pregnant women. 

• Category N: There is no data available for the drug under this category. 

Pharmacology

 Pharmacology 

Dupilumab is a fully human IgG4 monoclonal antibody that works by binding to the IL-4 receptor alpha (IL-4Rα) subunit, which is a component shared by both the IL-4 and IL-13 receptor complexes. This binding blocks IL-4 signaling through the Type I receptor and blocks both IL-4 and IL-13 signaling through the Type II receptor. By doing so, dupilumab reduces the actions driven by these cytokines, such as the production of pro-inflammatory cytokines, chemokines, and IgE. 

Pharmacodynamics 

As expected with its receptor-blocking action, treatment with dupilumab leads to higher blood levels of IL-4 and IL-13. However, how these changes in cytokine levels relate to its overall clinical benefits is not fully understood. 

Pharmacokinetics 

Absorption
After a subcutaneous injection, dupilumab reaches its peak blood concentration (Cmax) in about one week. Steady-state levels are generally achieved by around the 16th week of regular dosing. Its bioavailability is consistent across conditions like atopic dermatitis, asthma, CRSwNP, EoE, and peanut allergy, typically ranging between 61% and 64%. 

Distribution
The estimated volume of distribution for dupilumab is about 4.8 liters, with some variability. 

Metabolism
Although its exact metabolic pathway hasn’t been fully defined, dupilumab, like other human IgG4 antibodies, is expected to break down through normal protein catabolism into smaller peptides and amino acids. 

Elimination/Excretion
In adults and adolescents (12–17 years), the drug typically becomes undetectable in the blood about 9–13 weeks after the last dose. In younger children, this period can be longer: up to 19 weeks for ages 6–11 and up to 32 weeks for those 6 months to 5 years old. Age does not appear to affect drug clearance in individuals 6–17 years old and adults, but clearance is faster in the youngest age group. The development of anti-drug antibodies can reduce blood levels of dupilumab. 

Adminstartion

Before using dupilumab, allow the prefilled pen or syringe to reach room temperature for 30 to 45 minutes while keeping the cap on. Always check the solution — it should appear clear to pale yellow and free of any particles; do not use it if it looks cloudy or contains debris. Since the medication does not contain preservatives, discard any leftover product after use. Dupilumab is for subcutaneous (under the skin) injection only. Prefilled pens can be used by adults and children aged 2 years and older, with self-injection permitted for those 12 years and above under supervision.  

Prefilled syringes are suitable for children 6 months and older, but injections for those under 12 years should be given by a caregiver. The injection can be given in the thigh or abdomen, but avoid the 2-inch area around the belly button; the upper arm is an option if administered by a caregiver. For initial doses, use different injection sites, and always rotate sites with each injection. Do not inject into skin that is sore, bruised, or scarred, and ensure patients or caregivers are properly trained to administer the injection. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: Dupilumab 

Pronounced: dupil-zu-mab 

Why do we use dupilumab? 

Dupilumab is used to treat asthma, eczema, long-term sinus problems, and eosinophilic esophagitis. 

For asthma attack use a rescue inhaler and talk with your doctor.