Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Prefilled Syringe, Subcutaneous [preservative free]:
Dupixent: 300 mg/2 mL (2 mL); 200 mg/1.14 mL (1.14 mL) [contains polysorbate 80]
Pharmacology
Mechanism of Action
Dupilumab is a human monoclonal IgG4 antibody that inhibits interleukin-4 (IL-4) and interleukin-13 (IL-13) signaling by binding to the IL-4Rα subunit. Blocking IL-4Rα with dupilumab inhibits IL-4 and IL-13 cytokine-induced inflammatory responses, including the release of proinflammatory cytokines, chemokines, nitric oxide and IgE; however, the mechanism of dupilumab action in asthma has not been definitively established.
Pharmacokinetics/Pharmacodynamics
Distribution
Vd: ~4.8 ± 1.3 L
Metabolism
Monoclonal antibodies are primarily degraded into small peptides and amino acids by catabolism
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). Age did not affect clearance.
Time to Peak
~1 week
Use in Specific Populations
Special Populations Note
Weight: Dupilumab trough concentrations were lower in subjects with higher body weight.
Use: Labeled Indications
Asthma: Add-on maintenance treatment of moderate to severe asthma in adults and pediatric patients ≥12 years of age with an eosinophilic phenotype or with corticosteroid dependent asthma
Limitations of use: Not indicated for the relief of acute bronchospasm or status asthmaticus.
Atopic dermatitis: Treatment of moderate to severe atopic dermatitis in adults and pediatric patients ≥12 years of age whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable
Rhinosinusitis (chronic) with nasal polyposis: Add-on maintenance treatment in adults with inadequately controlled chronic rhinosinusitis with nasal polyposis
Contraindications
Known hypersensitivity to dupilumab or any component of the formulation
Dosage and Administration
Dosing: Adult
Asthma, moderate to severe: 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.
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.
Atopic dermatitis: SubQ:
Initial: 600 mg (given as two 300 mg injections).
Maintenance: 300 mg once every other week.
Rhinosinusitis (chronic) with nasal polyposis: SubQ: 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. If the missed dose is not administered within 7 days, wait until the next dose on the original schedule.
Dosing: Geriatric
Refer to adult dosing.
Dosing: Pediatric
Asthma (moderate to severe), maintenance treatment:
Children ≥12 years and Adolescents: SubQ: Initial: 400 mg once (administered as two 200 mg injections), 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), followed by a maintenance dose of 300 mg every other week.
Atopic dermatitis (AD), moderate to severe:
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), 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. Once clinical response achieved, continue with maintenance schedule of every-other-week administration; less frequent dosing (every 4 or 8 weeks) has been associated with diminution of efficacy (Worm 2019).
Administration
SubQ: Administer as a subcutaneous injection into the thigh or lower abdomen (avoiding areas within 2 inches of navel); caregiver may administer in upper arm. Rotate injection sites, including initial doses (administer 600 mg initial dose as two 300 mg injections; administer 400 mg initial dose as two 200 mg injections). Do not administer into skin that is tender, damaged, bruised, or scarred. Patients may self-administer injection after proper training. Allow solution to reach room temperature for 45 minutes (300 mg prefilled syringe) or 30 minutes (200 mg prefilled syringe) prior to use; do not remove needle cap while allowing product to reach room temperature. Do not shake. Do not use if solution is discolored or contains particulate matter. Prefilled syringe does not contain a preservative; discard unused portion.
Storage
Store at 2°C to 8°C (36°F to 46°F). Do not freeze. Do not expose to direct heat. Protect from light; do not expose to direct sunlight. Do not shake. Prefilled syringes may be stored up to 25°C (77°F) for a maximum of 14 days; after removal from refrigerator, use within 14 days or discard.
Drug Interactions
Vaccines (Live): Dupilumab may enhance the adverse/toxic effect of Vaccines (Live). Avoid combination
Adverse Reactions
>10%:
Immunologic: Antibody development (5% to 16%; neutralizing: 2% to 5%)
Local: Injection site reaction (6% to 18%)
1% to 10%:
Central nervous system: Insomnia (1%)
Gastrointestinal: Oral herpes simplex infection (4%), gastritis (2%), toothache (1%)
Hematologic & oncologic: Eosinophilia (≤2%)
Infection: Herpes simplex infection (2%)
Neuromuscular & skeletal: Arthralgia (3%)
Ophthalmic: Conjunctivitis (2% to 10%), eye pruritus (1%)
Respiratory: Oropharyngeal pain (2%)
<1%, postmarketing, and/or case reports: Anaphylaxis, dry eye syndrome, eosinophilic granulomatosis with polyangiitis, eosinophilic pneumonitis, erythema nodosum, hypersensitivity reaction, keratitis, serum sickness, serum sickness-like reaction, significant cardiovascular event, vasculitis
Warnings/Precautions
Concerns related to adverse effects:
- Hypersensitivity: Hypersensitivity reactions, including urticaria, rash, erythema nodosum, and serum sickness or serum sickness-like reactions, have been reported (rare); if signs/symptoms of a serious hypersensitivity reaction develop discontinue immediately and initiate appropriate treatment.
- Eosinophilia and vasculitis: In rare cases, patients may present with serious systemic eosinophilia, sometimes presenting with clinical features of eosinophilic pneumonia or vasculitis consistent with eosinophilic granulomatosis with polyangiitis, a condition which is often treated with systemic corticosteroid therapy. Monitor for eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy; especially upon reduction of oral corticosteroids. A causal association between dupilumab and these underlying conditions has not been established.
- Ocular effects: Conjunctivitis and keratitis have been reported; report new-onset or worsening eye symptoms to health care provider.
Disease-related concerns:
- Asthma: Discontinuation or adjustment of asthma medications in patients treated for atopic dermatitis or rhinosinusitis with comorbid asthma should not be done without consulting health care provider.
- Helminth infections: It is unknown if administration of dupilumab will influence a patient's response against parasitic infections; patients with known helminth infections were not studied. Therefore, patients with preexisting helminth infections should undergo treatment of the infection prior to initiation of dupilumab therapy. Patients who become infected during treatment and do not respond to anti-helminth therapy should discontinue dupilumab until the infection resolves.
Concurrent drug therapy issues:
- Corticosteroid therapy: Gradually taper systemic, topical, or inhaled corticosteroid therapy; do not discontinue corticosteroids abruptly following initiation of dupilumab therapy.
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
Dosage form specific issues:
- Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.
Other warnings/precautions:
- Appropriate use: Asthma: Therapy has not been shown to alleviate acute asthma exacerbations; do not use to treat acute bronchospasm or status asthmaticus.
- Appropriate use: Atopic dermatitis: Dupilumab may be used in combination with or without topical corticosteroids. Topical calcineurin inhibitors may be used, but should be reserved for problem areas only (eg, face, neck intertriginous and genital areas).
- Immunogenicity: Dupilumab antibodies, including neutralizing antibodies, may develop; may be associated with lower serum dupilumab concentrations.
- Vaccines: Avoid the use of live vaccines in patients treated with dupilumab.
Monitoring Parameters
Monitor for signs/symptoms of hypersensitivity reactions and ocular adverse effects; signs of infection; pulmonary function in patients treated for asthma
Pregnancy
Pregnancy Considerations
Dupilumab is a monoclonal IgG antibody; IgG molecules are known to cross the placenta therefore exposure to the fetus during pregnancy may occur. Uncontrolled asthma is associated with adverse events on pregnancy (increased risk of preeclampsia, preterm birth, low birth weight infants). Asthma should be closely monitored in pregnant women.
Data collection to monitor pregnancy and infant outcomes following exposure to dupilumab is ongoing. For additional information or to enroll pregnancies exposed to dupilumab, contact the registry at 1-877-311-8972 or https://mothertobaby.org/ongoing-study/dupixent/.
Patient Education
What is this drug used for?
- It is used to treat eczema.
- It is used to treat asthma.
- It is used to treat long-term sinus problems with nose polyps.
For asthma:
- Do not use this drug to treat an asthma attack. Use a rescue inhaler. Talk with your doctor.
Frequently reported side effects of this drug
- Injection site irritation
- Sore throat
- Cold sores
Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:
- Severe eye irritation
- Vision changes
- Eye pain
- Swollen glands
- Joint pain
- Dizziness
- Passing out
- Persistent fever
- Trouble breathing
- Chest pain
- Shortness of breath
- Excessive weight gain
- Swelling of arms or legs
- Burning or numbness feeling
- Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.
Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.
Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.
