Dupilumab: uses, appearance and warnings

DUPIXENT is an interleukin-4 receptor alpha antagonist indicated: Atopic Dermatitis for the treatment of adult and pediatric patients aged 6 months and older with moderate-to-severe AD whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable. DUPIXENT can be used with or without topical corticosteroids. ( 1.1 ) Asthma as an add-on maintenance treatment of adult and pediatric patients aged 6 years and older with moderate-to-severe asthma characterized by an eosinophilic phenotype or with oral corticosteroid dependent asthma. ( 1.2 ) Limitations of Use: Not for the relief of acute bronchospasm or status asthmaticus. ( 1.2 ) Chronic Rhinosinusitis with Nasal Polyps as an add-on maintenance treatment in adult and pediatric patients aged 12 years and older with inadequately controlled chronic rhinosinusitis with nasal polyps (CRSwNP). ( 1.3 ) Eosinophilic Esophagitis for the treatment of adult and pediatric patients aged 1 year and older, weighing at least 15 kg, with eosinophilic esophagitis (EoE). ( 1.4 ) Prurigo Nodularis for the treatment of adult patients with prurigo nodularis (PN). ( 1.5 ) Chronic Obstructive Pulmonary Disease as an add-on maintenance treatment of adult patients with inadequately controlled chronic obstructive pulmonary disease (COPD) and an eosinophilic phenotype. ( 1.6 ) Limitations of Use: Not for the relief of acute bronchospasm. ( 1.6 ) Chronic Spontaneous Urticaria for the treatment of adult and pediatric patients aged 2 years and older with chronic spontaneous urticaria (CSU) who remain symptomatic despite H1 antihistamine treatment. ( 1.7 ) Limitations of Use: Not indicated for other forms of urticaria. ( 1.7 ) Bullous Pemphigoid for the treatment of adult patients with bullous pemphigoid (BP). ( 1.8 ) Allergic Fungal Rhinosinusitis for the treatment of adult and pediatric patients aged 6 years and older with allergic fungal rhinosinusitis (AFRS) who have a history of sino-nasal surgery. ( 1.9 ) 1.1 Atopic Dermatitis DUPIXENT is indicated for the treatment of adult and pediatric patients aged 6 months and older with moderate-to-severe atopic dermatitis (AD) whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable. DUPIXENT can be used with or without topical corticosteroids. 1.2 Asthma DUPIXENT is indicated as an add-on maintenance treatment of adult and pediatric patients aged 6 years and older with moderate-to-severe asthma characterized by an eosinophilic phenotype or with oral corticosteroid dependent asthma. Limitations of Use DUPIXENT is not indicated for the relief of acute bronchospasm or status asthmaticus. 1.3 Chronic Rhinosinusitis with Nasal Polyps DUPIXENT is indicated as an add-on maintenance treatment in adult and pediatric patients aged 12 years and older with inadequately controlled chronic rhinosinusitis with nasal polyps (CRSwNP). 1.4 Eosinophilic Esophagitis DUPIXENT is indicated for the treatment of adult and pediatric patients aged 1 year and older, weighing at least 15 kg, with eosinophilic esophagitis (EoE). 1.5 Prurigo Nodularis DUPIXENT is indicated for the treatment of adult patients with prurigo nodularis (PN). 1.6 Chronic Obstructive Pulmonary Disease DUPIXENT is indicated as an add-on maintenance treatment of adult patients with inadequately controlled chronic obstructive pulmonary disease (COPD) and an eosinophilic phenotype. Limitations of Use DUPIXENT is not indicated for the relief of acute bronchospasm. 1.7 Chronic Spontaneous Urticaria DUPIXENT is indicated for the treatment of adult and pediatric patients aged 2 years and older with chronic spontaneous urticaria (CSU) who remain symptomatic despite H1 antihistamine treatment. Limitations of Use: DUPIXENT is not indicated for treatment of other forms of urticaria. 1.8 Bullous Pemphigoid DUPIXENT is indicated for the treatment of adult patients with bullous pemphigoid (BP). …

DUPIXENT is a clear to slightly opalescent, colorless to pale yellow solution in a: Single-dose pre-filled syringe with needle shield as: Injection: 300 mg/2 mL (150 mg/mL) Injection: 200 mg/1.14 mL (175 mg/mL) Single-dose pre-filled pen as: Injection: 300 mg/2 mL (150 mg/mL) Injection: 200 mg/1.14 mL (175 mg/mL) Single-Dose Pre-Filled Syringe with Needle Shield ( 3 ): Injection: 300 mg/2 mL (150 mg/mL) Injection: 200 mg/1.14 mL (175 mg/mL) Single-Dose Pre-Filled Pen ( 3 ): Injection: 300 mg/2 mL (150 mg/mL) Injection: 200 mg/1.14 mL (175 mg/mL)

How Supplied DUPIXENT (dupilumab) Injection is a clear to slightly opalescent, colorless to pale yellow solution, supplied in single-dose pre-filled syringes with needle shield or pre-filled pens. The pre-filled syringe with needle shield is designed to deliver: 300 mg of DUPIXENT in 2 mL solution (NDC 0024-5914-00) 200 mg of DUPIXENT in 1.14 mL solution (NDC 0024-5918-00) The pre-filled pen is designed to deliver: 300 mg of DUPIXENT in 2 mL solution (NDC 0024-5915-00) 200 mg of DUPIXENT in 1.14 mL solution (NDC 0024-5919-00) DUPIXENT is available in cartons containing 2 pre-filled syringes with needle shield or 2 pre-filled pens. Pack Size 300 mg/2 mL (150 mg/mL) Pre-filled Syringe with Needle Shield 200 mg/1.14 mL (175 mg/mL) Pre-filled Syringe with Needle Shield Pack of 2 syringes NDC 0024-5914-01 NDC 0024-5918-01 Pack Size 300 mg/2 mL (150 mg/mL) Pre-filled Pen 200 mg/1.14 mL (175 mg/mL) Pre-filled Pen Pack of 2 pens NDC 0024-5915-02 NDC 0024-5919-02 Storage and Handling DUPIXENT is sterile and preservative-free. Discard any unused portion. Store refrigerated at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light. If necessary, DUPIXENT may be kept at room temperature up to 25°C (77°F) for a maximum of 14 days. Do not store above 25°C (77°F). After removal from the refrigerator, DUPIXENT must be used within 14 days or discarded. Do not expose DUPIXENT to heat or direct sunlight. Do NOT freeze. Do NOT shake.

DUPIXENT is contraindicated in patients who have known hypersensitivity to dupilumab or any excipients of DUPIXENT [see Warnings and Precautions (5.1) ] . Known hypersensitivity to dupilumab or any excipients in DUPIXENT. ( 4 )

Hypersensitivity: Hypersensitivity reactions including anaphylaxis, acute generalized exanthematous pustulosis (AGEP), serum sickness, angioedema, urticaria, rash, erythema nodosum, and erythema multiforme have occurred. Discontinue DUPIXENT in the event of a hypersensitivity reaction. ( 5.1 ) Conjunctivitis, Keratitis, and Blepharitis: Advise patients to promptly report new onset or worsening eye symptoms to their healthcare provider. If symptoms persist or worsen, consider discontinuation of DUPIXENT. Consider ophthalmological examination, as appropriate. ( 5.2 ) Eosinophilic Conditions: Be alert to vasculitic rash, worsening pulmonary symptoms, cardiac complications, kidney injury and/or neuropathy, especially upon reduction of oral corticosteroids. ( 5.3 ) Reduction of Corticosteroid Dosage: Do not discontinue systemic, topical, or inhaled corticosteroids abruptly upon initiation of DUPIXENT. Decrease steroids gradually, if appropriate. ( 5.5 ) Psoriasis: Advise patients to report new-onset psoriasis symptoms to their healthcare provider. If symptoms persist or worsen, consider dermatologic evaluation and/or discontinuation of DUPIXENT. ( 5.7 ) Arthralgia and Psoriatic Arthritis: Advise patients to report new onset joint symptoms to their healthcare provider. If symptoms persist or worsen, consider rheumatological evaluation and/or discontinuation of DUPIXENT. ( 5.8 ) Parasitic (Helminth) Infections: Treat pre-existing helminth infections before initiating DUPIXENT. If patients become infected while receiving DUPIXENT and do not respond to anti-helminth treatment, discontinue DUPIXENT until the infection resolves. ( 5.9) Vaccinations: Avoid use of live vaccines. ( 5.10 ) 5.1 Hypersensitivity Hypersensitivity reactions, including anaphylaxis, acute generalized exanthematous pustulosis (AGEP), serum sickness or serum sickness-like reactions, angioedema, generalized urticaria, rash, erythema nodosum and erythema multiforme have been reported. A case of AGEP was reported in an adult subject who participated in the bullous pemphigoid development program. If a clinically significant hypersensitivity reaction occurs, institute appropriate therapy and discontinue DUPIXENT [see Adverse Reactions (6.1 , 6.2) and Clinical Pharmacology (12.6) ] . 5.2 Conjunctivitis, Keratitis, and Blepharitis Conjunctivitis and keratitis adverse reactions have been reported in clinical trials [see Adverse Reactions (6.1) ] . Conjunctivitis and keratitis occurred more frequently in AD subjects who received DUPIXENT compared to those who received placebo. Conjunctivitis was the most frequently reported eye disorder. Most subjects with conjunctivitis or keratitis recovered or were recovering during the treatment period. Among subjects with asthma, the frequencies of conjunctivitis and keratitis were similar between DUPIXENT and placebo. In adult subjects with CRSwNP, the frequency of conjunctivitis was 2% in the DUPIXENT group compared to 1% in the placebo group in the 24-week safety pool; these subjects recovered. Among subjects with EoE, there were no reports of conjunctivitis and keratitis in the DUPIXENT group in placebo-controlled trials. In subjects with PN, the frequency of conjunctivitis was 4% in the DUPIXENT group compared to 1% in the placebo group; these subjects recovered or were recovering during the treatment period. Among subjects with COPD, the frequency of conjunctivitis and keratitis was 1.4% and 0.1% in the DUPIXENT group and 1% and 0% in the placebo group, respectively. In subjects with CSU, the frequency of conjunctivitis was similar between DUPIXENT and placebo. Among subjects with BP, the frequency of conjunctivitis and keratitis was 7.5% and 3.8% in the DUPIXENT group and 0% and 0% in the placebo group, respectively. Conjunctivitis, keratitis, and blepharitis adverse reactions have also been reported with DUPIXENT in postmarketing settings, predominantly in AD patients. Some patients reported varying degrees of transient or ongoing visual impairment including blindness associated with conjunctivitis, keratitis, or blepharitis leading to discontinuation of DUPIXENT and/or surgical intervention. Advise patients or their caregivers to promptly report new onset or worsening eye symptoms to their healthcare provider. Consider discontinuation of DUPIXENT and prompt ophthalmological examination for patients who develop signs and symptoms suggestive of keratitis, or when conjunctivitis or blepharitis do not resolve following standard treatment, as appropriate. Use with caution in patients with significant dry eye disease, history of significant lid abnormalities/surgeries, or history of nasolacrimal surgery [see Adverse Reactions (6.1 , 6.2) ] . 5.3 Eosinophilic Conditions Patients being treated for asthma may present with clinical features of eosinophilic pneumonia or eosinophilic granulomatosis with polyangiitis (EGPA). These events may be associated with the reduction of oral corticosteroid therapy. Healthcare providers should be alert to vasculitic rash, worsening pulmonary symptoms, cardiac complications, kidney injury, and/or neuropathy presenting in their patients with eosinophilia. Cases of eosinophilic pneumonia were reported in adults who participated in the asthma development program. Cases of EGPA have been reported with DUPIXENT in adults who participated in the asthma development program as well as in adults with co-morbid asthma in the CRSwNP development program. Advise patients to report signs of eosinophilic pneumonia and EGPA to their healthcare provider. Consider withholding DUPIXENT if eosinophilic pneumonia or EGPA are suspected. 5.4 Acute Symptoms of Asthma or Chronic Obstructive Pulmonary Disease or Acute Deteriorating Disease DUPIXENT should not be used to treat acute symptoms or acute exacerbations of asthma or COPD. Do not use DUPIXENT to treat acute bronchospasm or status asthmaticus. …

The following clinically significant adverse reactions are described elsewhere in the labeling: Hypersensitivity [see Warnings and Precautions (5.1) ] Conjunctivitis and Keratitis [see Warnings and Precautions (5.2) ] Psoriasis [see Warnings and Precautions (5.7) ] Arthralgia and Psoriatic Arthritis [see Warnings and Precautions (5.8) ] Parasitic (Helminth) Infections [see Warnings and Precautions (5.9) ] Most common adverse reactions are: Atopic Dermatitis (incidence ≥1%): injection site reactions, conjunctivitis, blepharitis, oral herpes, keratitis, eye pruritus, other herpes simplex virus infection, dry eye, and eosinophilia. ( 6.1 ) Asthma (incidence ≥1%): injection site reactions, oropharyngeal pain, and eosinophilia. …