Dupilumab (Monograph)

Brand name: Dupixent
Drug class:

Medically reviewed by Drugs.com on Mar 10, 2024. Written by ASHP.

Introduction

Recombinant human IgG₄ monoclonal antibody that binds specifically to the interleukin-4 receptor alpha subunit (IL-4Rα) of interleukin-4 (IL-4) and interleukin-13 (IL-13) and inhibits activity of proinflammatory cytokines.

Uses for Dupilumab

Atopic Dermatitis

Treatment of moderate to severe atopic dermatitis in adults and pediatric patients ≥6 months of age who have had an inadequate response to topical therapy (e.g., topical corticosteroids) or in whom such therapy is inadvisable; may be used with or without topical corticosteroids.

Asthma

Add-on maintenance therapy in adults and pediatric patients ≥6 years of age with moderate-to-severe asthma characterized by an eosinophilic phenotype or oral corticosteroid dependence.

Not indicated for relief of acute bronchospasm or status asthmaticus.

Several clinical practice guidelines on asthma management are available, including the Global Initiative for Asthma (GINA) guidelines. In GINA, stepwise approach to treatment is recommended where specific drugs are added or adjusted up or down through a series of steps (1 through 5) to achieve symptom control while keeping the patient on the lowest effective treatment.

Biologic agents such as dupilumab are generally recommended as add-on therapy for severe asthma.

Chronic Rhinosinusitis with Nasal Polyposis

Add-on maintenance treatment of inadequately treated chronic rhinosinusitis with nasal polyposis (CRSwNP) in adults.

Eosinophilic Esophagitis

Treatment of eosinophilic esophagitis in adults and pediatric patients (≥1 year of age) weighing at least 15 kg.

Prurigo Nodularis

Treatment of prurigo nodularis in adults.

Related/similar drugs

Fasenra, Nucala, Trelegy Ellipta, prednisone, hydroxyzine, fluticasone, fluticasone nasal

Dupilumab Dosage and Administration

General

Pretreatment Screening

• Screen for pre-existing parasitic helminth infections and treat infections, prior to initiation of dupilumab.

• Consider completion of all age-appropriate vaccinations as recommended by current immunization guidelines, prior to initiation of dupilumab.

Patient Monitoring

• Monitor for new onset or worsening eye symptoms specific to conjunctivitis and keratitis throughout treatment with dupilumab.

• Monitor patients being treated for asthma for signs of eosinophilic conditions, including vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy.

• Monitor patients for new onset or worsening joint symptoms.

Other General Considerations

• In the treatment of atopic dermatitis, dupilumab can be used with or without concomitant topical corticosteroid therapy. Although topical calcineurin inhibitors may also be used concomitantly with dupilumab, these topical agents should be reserved for use only on the face, neck, and intertriginous or genital areas.

• Do not use dupilumab to treat acute bronchospasm or status asthmaticus.

• Do not abruptly discontinue systemic, topical, or inhaled corticosteroids upon initiation of therapy with dupilumab.

Administration

Administer by sub-Q injection using pre-filled syringe or pre-filled pen.

The pre-filled pen is indicated for use only in adults and pediatric patients ≥2 years of age.

The pre-filled syringe is indicated for use in adults and pediatric patients ≥6 months of age.

Intended for use under supervision of a clinician, but may be self-administered after appropriate training provided.

Administration by or under the supervision of an adult is recommended in adolescent patients ≥12 years of age. Self-administration in pediatric patients 6 months to 11 years of age is not recommended.

Prior to injection, remove the appropriate number of pre-filled syringes or pens from refrigerator and allow to sit at room temperature for 30–45 minutes based on the dosage strength. Do not expose the drug to heat or to direct sunlight. Do not remove needle cap while warming to room temperature. Do not shake.

Discard and do not use if solution is cloudy, discolored, or contains particulates.

Sub-Q Administration

Inject sub-Q into upper arm, thigh, or abdomen (except within 2 inches of the navel). Only a clinician or caregiver should administer sub-Q injections into upper arm. Rotate injection sites. Do not inject into areas where skin is tender, damaged, bruised, or scarred.

If a weekly dose of dupilumab is missed, administer the dose as soon as possible, and initiate a new weekly schedule from the date of the last administered dose. If an every other week dose is missed, administer the dose within 7 days of the missed dose and then resume the original schedule. If the missed dose is not administered within 7 days, wait until the next dose on the original schedule. If an every 4 week dose is missed, administer the dose within 7 days from the missed dose and then resume the original schedule. If the missed dose is not administered within 7 days, administer the dose, initiating a new schedule based on this date.

Use strict aseptic technique since drug product contains no preservative. Syringes and pens are for single use only.

Consult manufacturer's prescribing information for additional information on preparation and administration.

Dosage

Pediatric Patients

Moderate to Severe Atopic Dermatitis in Pediatric Patients 6 Months to 5 Years of Age

Sub-Q

Dosage is based on body weight (kg) (see Table 1). No initial loading dose is recommended.

Moderate to Severe Atopic Dermatitis in Pediatric Patients 6–17 Years of Age

Sub-Q

Dosage is based on body weight (kg) (see Table 2).

Moderate to Severe Asthma in Pediatric Patients 6–17 Years of Age

Sub-Q

Pediatric patients 6–11 years of age weighing 15 to <30 kg: 100 mg once every other week or 300 mg once every 4 weeks. No initial loading dose is recommended.

Pediatric patients 6–11 years of age weighing ≥30 kg: 200 mg once every other week. No initial loading dose is recommended.

For patients 6–11 years of age with comorbid moderate to severe atopic dermatitis, refer to the recommended dosage for atopic dermatitis in Table 2, which includes an initial loading dose.

For adolescent patients ≥12 years of age, refer to adult dosage for treatment of moderate to severe asthma.

Eosinophilic Esophagitis in Pediatric Patients ≥1 Year of Age

Sub-Q

Dosage is based on body weight (see Table 3).

Adults

Moderate to Severe Atopic Dermatitis

Sub-Q

Initial dose of 600 mg (given as two 300-mg doses administered at different injection sites) followed by 300 mg once every other week.

Moderate to Severe Asthma

Sub-Q

Initial dose of 400 mg (given as two 200-mg doses administered at different injection sites) followed by 200 mg once every 2 weeks, or initial dose of 600 mg (given as two 300-mg doses administered at different injection sites) followed by 300 mg once every 2 weeks.

For patients with oral corticosteroid-dependent asthma or with comorbid moderate to severe atopic dermatitis, or comorbid CRSwNP, start with the higher initial dose of 600 mg followed by 300 mg every 2 weeks.

Chronic Rhinosinusitis with Nasal Polyposis

Sub-Q

300 mg once every other week.

Eosinophilic Esophagitis

Sub-Q

300 mg every week in adults weighing ≥40 kg.

Prurigo Nodularis

Sub-Q

Initial dose of 600 mg (given as two 300-mg doses administered at different injection sites) followed by 300 mg every other week.

Special Populations

Hepatic Impairment

No specific dosage recommendations.

Renal Impairment

No specific dosage recommendations.

Geriatric Patients

No specific dosage recommendations.

Cautions for Dupilumab

Contraindications

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

Warnings/Precautions

Hypersensitivity

Hypersensitivity reactions, including anaphylaxis, generalized urticaria, serum sickness, rash, erythema nodosum, erythema multiforme, or serum sickness-like reactions, reported.

If an allergic reaction occurs, discontinue dupilumab immediately and initiate appropriate therapy.

Conjunctivitis and Keratitis

Conjunctivitis (e.g., allergic conjunctivitis, bacterial conjunctivitis, viral conjunctivitis, giant papillary conjunctivitis, eye irritation, eye inflammation) and keratitis (e.g., ulcerative keratitis, allergic keratitis, atopic keratoconjunctivitis, ophthalmic herpes simplex) reported. Blepharitis, eye pruritus, and dry eye also reported.

In clinical studies, conjunctivitis generally resolved or improved in most patients despite continued dupilumab treatment.

Advise patients to report any new onset or worsening eye symptoms to their clinician. Consider ophthalmological examination for patients with conjunctivitis that does not resolve with treatment or those with signs and symptoms of keratitis.

Eosinophilic Conditions

Eosinophilic pneumonia and cases of vasculitis consistent with eosinophilic granulomatosis with polyangiitis reported in adults in asthma clinical trials and CRSwNP clinical trials (patients had comorbid asthma). May be associated with reduction of oral corticosteroid therapy.

Monitor patients treated for asthma for vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy presenting in patients with eosinophilia.

Acute Asthma Symptoms or Deteriorating Disease

Do not use dupilumab to treat acute asthma symptoms, acute exacerbations, acute bronchospasm, or status asthmaticus. If asthma remains uncontrolled or worsens after initiation of dupilumab, patients should seek medical attention.

Risk Associated with Abrupt Reduction of Corticosteroid Dosage

Do not abruptly discontinue systemic, topical, or inhaled corticosteroids upon initiation of dupilumab. If indicated, reductions in corticosteroid doses should be gradual and performed under supervision of a clinician. Systemic withdrawal symptoms or unmasking of conditions previously suppressed by systemic corticosteroid therapy may occur with reduction in corticosteroid doses.

Patients with Comorbid Asthma

Patients with comorbid asthma who are receiving dupilumab for treatment of atopic dermatitis or CRSwNP should not discontinue or adjust their asthma therapy without consulting a clinician.

Arthralgia

Patients have reported arthralgia (gait disturbances or decreased mobility associated with joint symptoms) while receiving dupilumab. Some cases have resulted in hospitalization. Patients should inform their healthcare provider of new or worsening joint symptoms. A rheumatological evaluation and/or discontinuation of dupilumab may be required if symptoms persist or worsen.

Parasitic (Helminth) Infections

Patients with helminth infections were excluded from dupilumab clinical trials; manufacturer states that it is not known whether the drug affects immune responses to such infections. There is some evidence that cytokines IL-4 and IL-13 may be involved in type 2 immune responses to parasitic helminth infections.

Helminth infections (enterobiasis and ascariasis) reported in pediatric patients 6–11 years of age in asthma clinical trials.

Treat patients with pre-existing helminth infections prior to initiation of dupilumab. If patients become infected during treatment with dupilumab and do not respond to anti-helminth therapy, discontinue the drug until infection resolves.

Immunogenicity

Like other therapeutic proteins, potential for immunogenicity exists.

Approximately 5% of patients with atopic dermatitis, asthma, or CRSwNP who received dupilumab in clinical trials developed antibodies to the drug; 2% of these individuals had antibodies that were classified as neutralizing. Similar results were seen in pediatric patients ages 6–11 years of age with atopic dermatitis asthma.

Approximately 16% of adolescent patients with atopic dermatitis who received dupilumab in clinical trials developed antibodies to the drug; approximately 5% of these individuals had antibodies that were classified as neutralizing. Approximately 9% of patients with asthma who received dupilumab developed antibodies to the drug; approximately 4% of these individuals had antibodies that were classified as neutralizing.

Approximately 1% of patients with eosinophilic esophagitis and 8% of patients with prurigo nodularis who received dupilumab 300 mg every week or every 2 weeks, respectively, for 24 weeks in clinical trials developed antibodies to the drug.

Although antibody titers generally are low, high antibody titers reported in 2 patients who developed serum sickness or serum sickness-like reactions to the drug.

Decreased serum concentrations of dupilumab reported in patients with antibodies to the drug; serum concentrations of the drug undetectable in a few patients with high antibody titers.

Specific Populations

Pregnancy

No risk of birth defects, miscarriage, or adverse maternal or fetal outcomes identified in data from case reports. Potential for fetal exposure since human IgG crosses the placenta.

Encourage participation and enrollment in pregnancy exposure registry. The registry can be accessed by calling 1-877-311-8972 or visiting [Web].

Lactation

Not known whether dupilumab is distributed into human milk, affects human milk production, or affects breast-fed infants. Human IgG is known to be distributed into human milk.

Consider benefits of breast-feeding and importance of the drug to the woman; also consider potential adverse effects on the breast-fed infant from the drug or underlying maternal condition.

Pediatric Use

Safety and efficacy of dupilumab established in pediatric patients ≥6 months of age with atopic dermatitis; not established in pediatric patients <6 months of age with atopic dermatitis.

Safety and efficacy of dupilumab as an add-on maintenance therapy in patients with moderate to severe asthma characterized by an eosinophilic phenotype or with oral corticosteroid dependent asthma established in pediatric patients ≥6 years of age. Safety and efficacy in pediatric patients <6 years of age with asthma not established.

Safety and efficacy of dupilumab in pediatric patients with CRSwNP not established.

Safety and efficacy established in children ≥12 years of age, weighing at least 40 kg, for treatment of eosinophilic esophagitis. Safety and efficacy in pediatric patients <12 years of age and weighing <40 kg not established.

Safety and efficacy in pediatric patients <18 years of age with prurigo nodularis not established.

Geriatric Use

No overall differences in safety and efficacy relative to younger adults across all indications; however, insufficient experience in patients ≥65 years of age in atopic dermatitis trials to determine whether they respond differently than younger adults.

Clinical studies in patients with eosinophilic esophagitis or prurigo nodularis did not include sufficient numbers of individuals ≥65 years of age to assess whether these patients respond differently from younger adults.

Hepatic Impairment

No formal pharmacokinetic studies to date.

Renal Impairment

No formal pharmacokinetic studies to date.

Common Adverse Effects

Adverse effects (≥1%) with dupilumab in clinical studies for atopic dermatitis: injection site reactions, ocular effects (conjunctivitis, blepharitis, keratitis, pruritus, dry eye), eosinophilia, herpes simplex virus infection.

Adverse effects (≥1%) with dupilumab in clinical studies for asthma: injection site reactions, oropharyngeal pain, eosinophilia.

Adverse effects (≥1%) with dupilumab in clinical studies for CRSwNP: injection site reactions, eosinophilia, insomnia, toothache, gastritis, arthralgia, conjunctivitis.

Adverse effects (≥2%) with dupilumab in clinical studies for eosinophilic esophagitis: injection site reactions, upper respiratory tract infections, arthralgia, herpes viral infections.

Adverse effects (≥2%) with dupilumab in clinical studies for prurigo nodularis: nasopharyngitis, conjunctivitis, herpes infection, dizziness, myalgia, diarrhea.

Drug Interactions

Pharmacokinetic drug interactions not expected with coadministered drugs.

Drugs Metabolized by Hepatic Microsomal Enzymes

Because elevated levels of certain cytokines during chronic inflammation may alter formation of CYP isoenzymes, antagonism of IL-4- and IL-13 activity by dupilumab could affect formation of CYP enzymes.

No clinically significant changes in plasma concentrations observed in drug interaction studies with drugs metabolized via CYP enzymes, including midazolam (CYP3A4 substrate), warfarin (CYP2C9 substrate), omeprazole (CYP2C19 substrate), metoprolol (CYP2D6 substrate), and caffeine (CYP1A2 substrate).

Specific Drugs

Dupilumab Pharmacokinetics

Absorption

Bioavailability

Estimated bioavailability is 61–64% following sub-Q administration.

Nonlinear pharmacokinetics over sub-Q dose range of 75–600 mg; systemic exposure increases in a greater than dose-proportional manner.

Plasma Concentrations

Following single 600-mg, 400-mg, or 300-mg sub-Q dose, peak plasma concentrations attained by approximately 7 days.

In patients who received either initial 600-mg sub-Q dose followed by 300-mg sub-Q doses once every other week, initial 400-mg sub-Q dose followed by 200-mg sub-Q dose every other week, or 300-mg sub-Q dose every other week without a loading dose, steady-state concentrations attained by week 16.

Following the last steady-state dose of 300 mg every 2 weeks, 300 mg weekly, or 200 mg every 2 weeks, the median time to undetectable serum concentrations of dupilumab (<78 ng/mL) was 10–12 weeks, 13 weeks, and 9 weeks, respectively.

Following last 300-mg steady-state dose given 2 weeks after previous dose, median time to undetectable serum concentrations (<78 ng/mL) is 10 weeks.

Special Populations

Steady-state trough concentrations decrease as body weight increases.

Age does not substantially alter steady-state trough concentrations in adults with atopic dermatitis.

Distribution

Extent

Not known whether distributed into human milk.

Elimination

Metabolism

Metabolic pathway not characterized.

Expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous IgG.

Special Populations

Pharmacokinetics not formally studied in renal or hepatic impairment.

Stability

Storage

Parenteral

Pre-filled Syringes and Injection Pens

2–8°C; keep in original carton to protect from light.

If necessary, may be kept at room temperature (≤25°C) for maximum of 14 days; after removal from refrigerator, must be used within 14 days or discarded.

Do not expose to heat or sunlight; do not freeze.

Actions

• Recombinant fully human IgG monoclonal antibody that binds specifically to IL-4Rα, a shared cell-surface subunit of IL-4 and IL-13.

• Disrupts signaling through IL-4- and IL-13 receptors, thereby inhibiting release of proinflammatory cytokines, chemokines, and IgE.

• IL-4 and IL-13 are key cytokines involved in inflammatory skin response in patients with atopic dermatitis, asthma, and CRSwNP.

Advice to Patients

• Instruct patients to read the medication guide prior to initiating therapy and each time the prescription is refilled.

• Advise women to inform their clinician if they are or plan to become pregnant or plan to breastfeed. Encourage participation in the pregnancy exposure registry and instruct patients on how to enroll if a patient becomes pregnant while receiving dupilumab.

• Instruct patients and/or caregiver regarding proper storage, dosage, and administration of dupilumab, including use of aseptic technique and safe disposal of needles and syringes, if it is determined that the patient and/or caregiver is competent to safely administer the drug. Provide the patient with a copy of the manufacturer’s instructions for use.

• Advise patients to immediately discontinue dupilumab and contact a clinician if symptoms of hypersensitivity (e.g., hives, itching, fever, swollen lymph nodes, joint pain, rash) occur.

• Inform patients that dupilumab may cause eye problems (e.g., conjunctivitis, keratitis) and to promptly contact a clinician if new-onset or worsening eye symptoms occur, including eye pain or changes in vision.

• Advise patients to contact their clinician if they experience clinical features of eosinophilic pneumonia or vasculitis consistent with eosinophilic granulomatosis with polyangiitis.

• Advise patients to contact their clinician if new or worsening joint symptoms occur.

• Inform patients that dupilumab should not be used for acute asthma symptoms or acute exacerbations, and to contact their clinician if their asthma remains uncontrolled or worsens after initiation of dupilumab.

• Advise patients to not discontinue systemic or inhaled corticosteroids unless directed by their clinician. Inform patients that a reduction in corticosteroid doses may be associated with systemic withdrawal symptoms and/or unmask conditions previously suppressed by systemic corticosteroid therapy.

• Advise patients with atopic dermatitis or chronic rhinosinusitis with nasal polyposis (CRSwNP) who have comorbid asthma that they should not discontinue or adjust their asthma therapy during dupilumab treatment without consulting a clinician.

• Advise patients to contact their clinician if they experience clinical features consistent with helminthic infection.

• Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary and herbal supplements, as well as any concomitant illnesses.

• Inform 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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