Asthma (moderate to severe), maintenance treatment:
Children 6 to <12 years: Prefilled syringe:
Note: In children 6 to <12 years, an initial loading dose is not necessary. If patient has atopic dermatitis comorbidity, the dosing for atopic dermatitis (including the initial loading dose) should be used to determine dupilumab therapy.
15 to <30 kg: SUBQ: 100 mg every other week or 300 mg every 4 weeks.
≥30 kg: SUBQ: 200 mg every other week.
Children ≥12 years and Adolescents: Prefilled pen, prefilled syringe: 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 moderate to severe atopic dermatitis: 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 ≥6 years and Adolescents ≤17 years: Note: Prefilled syringe may be used in ages ≥6 years; prefilled pen is only for use in ages ≥12 years.
15 to <30 kg: SUBQ: Initial: 600 mg once (administered as two 300 mg injections), followed by a maintenance dose of 300 mg every 4 weeks.
30 to <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).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
(For additional information see "Dupilumab: Drug information")
Asthma, moderate to severe eosinophilic or oral glucocorticoid dependent: Note: May consider as add-on therapy in patients inadequately controlled on standard therapies (eg, an inhaled glucocorticoid with a long-acting beta agonist, oral glucocorticoids) (GINA 2021). Some experts reserve use for patients with peripheral blood eosinophils ≥150 cells/mcL. The eosinophil threshold required for patients on systemic glucocorticoids is less clear (GINA 2021; Wenzel 2021). A minimum of 4 months of treatment is suggested to determine efficacy (GINA 2021).
SUBQ: 400 mg once (given as two 200 mg injections), followed by 200 mg every other week.
OR
SUBQ: 600 mg once (given as two 300 mg injections), followed by 300 mg every other week. Note: Preferred dosing for patients with severe asthma (eg, oral glucocorticoid dependent).
Asthma with comorbid moderate to severe atopic dermatitis: SUBQ: 600 mg once (given as two 300 mg injections), followed by 300 mg 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.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Pen-injector, Subcutaneous [preservative free]:
Dupixent: 300 mg/2 mL (2 mL); 200 mg/1.14 mL (1.14 mL) [contains polysorbate 80]
Solution Prefilled Syringe, Subcutaneous [preservative free]:
Dupixent: 100 mg/0.67 mL (0.67 mL) [latex free; contains polysorbate 80]
Dupixent: 300 mg/2 mL (2 mL); 200 mg/1.14 mL (1.14 mL) [contains polysorbate 80]
No
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Pen-injector, Subcutaneous:
Dupixent: 300 mg/2 mL (2 mL) [contains polysorbate 80]
Solution Prefilled Syringe, Subcutaneous:
Dupixent: 300 mg/2 mL (2 mL); 200 mg/1.14 mL (1.14 mL) [contains polysorbate 80]
SUBQ: Allow prefilled syringe/pen to reach room temperature for 45 minutes (300 mg prefilled syringe/pen) or 30 minutes (200 mg prefilled syringe/pen or 100 mg prefilled syringe) prior to use; do not remove needle cap while allowing product to reach room temperature; do not heat prefilled pen in microwave, hot water, or direct sunlight. Do not shake. Do not use if solution is discolored or contains particulate matter. Do not administer if window on prefilled pen is yellow (indicates pen has been used). Administer as a subcutaneous injection into the thigh or lower abdomen (avoiding areas within 2 inches of navel); caregiver may administer in patient's upper arm. Rotate injection sites, including initial doses (administer 600 mg initial dose as two 300 mg injections at different injection sites; administer 400 mg initial dose as two 200 mg injections at different injection sites). Do not administer into skin that is tender, damaged, bruised, or scarred. Prefilled syringes and pens do not contain a preservative; discard unused portion.
Note: Prefilled syringe may be used in ages ≥6 years; prefilled pen is only for use in ages ≥12 years. Patients ≥12 years of age may self-administer injection under adult supervision after proper training; doses in patients <12 years of age should be administered by a properly trained caregiver.
Missed dose:
For every-other-week dosing: 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.
For every-4-weeks dosing: 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, a new schedule should be started based on the date next dose given.
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 at different sites; administer 400 mg initial dose as two 200 mg injections at different sites). 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 prefilled pen) or 30 minutes (200 mg prefilled syringe or prefilled pen; 100 mg prefilled syringe) prior to use; do not heat prefilled pen in microwave, hot water, or direct sunlight; 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. Do not administer if window on prefilled pen is yellow (indicates pen has been used). Prefilled syringes and pens do not contain a preservative; discard unused portion. Refer to manufacturer's labeling for additional information.
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. May store up to 25°C (77°F) for a maximum of 14 days; after removal from refrigerator, use within 14 days or discard.
Treatment of moderate to severe atopic dermatitis (AD) in patients whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable (Prefilled syringe: FDA approved in ages ≥6 years and adults; Prefilled pen: FDA approved in ages ≥12 years and adults); treatment of moderate to severe asthma as add-on maintenance therapy in patients with an eosinophilic phenotype or with oral corticosteroid-dependent asthma (Prefilled syringe: FDA approved in ages ≥6 years and adults; Prefilled pen: FDA approved in ages ≥12 years and adults); add-on maintenance treatment of inadequately controlled chronic rhinosinusitis with nasal polyposis (Prefilled pen; prefilled syringe: FDA approved in adults). Note: For asthma, not indicated for the relief of acute bronchospasm or status asthmaticus.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for adolescents and adults unless otherwise specified.
>10%:
Immunologic: Antibody development (5% to 16%; neutralizing: 2% to 5%)
Local: Injection site reaction (6% to 18%)
1% to 10%:
Gastrointestinal: Gastritis (2%), oral herpes simplex infection (4%), toothache (1%)
Hematologic & oncologic: Eosinophilia (<3%)
Infection: Helminthiasis (children: 2%; including enterobiasis and ascariasis), herpes simplex infection (2%)
Nervous system: Insomnia (1%)
Neuromuscular & skeletal: Arthralgia (3%)
Ophthalmic: Conjunctivitis (2% to 10%), eye pruritus (1%)
Respiratory: Oropharyngeal pain (2%)
<1%:
Cardiovascular: Thromboembolic complications (acute myocardial infarction, cerebrovascular accident)
Dermatologic: Erythema multiforme, erythema nodosum, skin rash, urticaria
Hypersensitivity: Anaphylaxis, hypersensitivity reaction, serum sickness
Immunologic: Serum sickness-like reaction
Ophthalmic: Keratitis, xerophthalmia
Postmarketing:
Cardiovascular: Edema, eosinophilic granulomatosis with polyangiitis, vasculitis
Dermatologic: Burning sensation of skin, desquamation, erythema of skin, facial rash, papule of skin, pruritus, skin pain
Hypersensitivity: Angioedema
Respiratory: Eosinophilic pneumonitis
Known hypersensitivity to dupilumab or any component of the formulation
Concerns related to adverse effects:
• Arthralgia: Arthralgia, including gait disturbances or decreased mobility associated with joint symptoms, has been reported, sometimes requiring hospitalization. May occur within days to months following initiation of therapy and has resolved with or without therapy discontinuation; report new-onset or worsening joint symptoms to health care provider.
• Hypersensitivity: Hypersensitivity reactions, including anaphylaxis, angioedema, urticaria, rash, erythema nodosum, erythema multiforme, 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; patients with atopic dermatitis are at increased risk. Visual disturbances may occur; 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. Adverse reactions of helminth infections were reported in pediatric patients 6 to 11 years of age who participated in the pediatric asthma development program. 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: Do not discontinue corticosteroids abruptly following initiation of dupilumab therapy. Reductions in corticosteroid dose should be gradual, if appropriate. Clinicians should note that a reduction in corticosteroid dose may be associated with withdrawal symptoms and/or unmask conditions previously suppressed by systemic corticosteroid therapy.
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: Patients should be up to date with all immunizations before initiating therapy. Avoid the use of live vaccines in patients treated with dupilumab.
None known.
Efgartigimod Alfa: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy
Vaccines (Live): Dupilumab may enhance the adverse/toxic effect of Vaccines (Live). Risk X: Avoid combination
Dupilumab is a humanized monoclonal antibody (IgG4). Placental transfer of human IgG is dependent upon the IgG subclass, maternal serum concentrations, newborn birth weight, and gestational age, generally increasing as pregnancy progresses. The lowest exposure would be expected during the period of organogenesis (Palmeira 2012; Pentsuk 2009).
Uncontrolled asthma is associated with adverse events on pregnancy (increased risk of perinatal mortality, preeclampsia, preterm birth, low birth weight infants, cesarean delivery, and the development of gestational diabetes). Poorly controlled asthma or asthma exacerbations may have a greater fetal/maternal risk than what is associated with appropriately used asthma medications. Maternal treatment improves pregnancy outcomes by reducing the risk of some adverse events (eg, preterm birth, gestational diabetes). Maternal asthma symptoms should be monitored monthly during pregnancy (ERS/TSANZ [Middleton 2020]; GINA 2020).
Use of monoclonal antibodies for the treatment of asthma in pregnancy may be considered when conventional therapies are insufficient; use of an agent other than dupilumab may be preferred (ERS/TSANZ [Middleton 2020]).
Data collection to monitor pregnancy and infant outcomes following exposure to dupilumab is ongoing. Health care providers are encouraged to enroll exposed pregnant females in the MotherToBaby Pregnancy Studies conducted by the Organization of Teratology Information Specialists (877-311-8972 or https://mothertobaby.org). Patients may also enroll themselves.
Monitor for signs/symptoms of hypersensitivity reactions and ocular adverse effects (consider eye exam in patients with signs/symptoms of keratitis or unresolved conjunctivitis); signs of infection (particularly parasitic [helminth] in pediatric patients <12 years); signs/symptoms of arthralgia (consider rheumatological evaluation if occurs); pulmonary function in patients treated for asthma.
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.
Distribution: Vd: ~4.8 ± 1.3 L
Metabolism: Monoclonal antibodies are primarily degraded into small peptides and amino acids by catabolism
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). Age did not affect clearance.
Weight: Dupilumab trough concentrations were lower in subjects with higher body weight.
Solution Pen-injector (Dupixent Subcutaneous)
200MG/1.14ML (per mL): $1,753.44
300 mg/2 mL (per mL): $999.46
Solution Prefilled Syringe (Dupixent Subcutaneous)
100 mg/0.67 mL (per 0.67 mL): $1,998.92
200MG/1.14ML (per mL): $1,753.44
300 mg/2 mL (per mL): $999.46
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