Dupilumab

You should not use dupilumab if you are allergic to it.

To make sure dupilumab is safe for you, tell your doctor if you have:

• asthma;

• eye problems; or

• a parasite infection (such as roundworms or tapeworms).

It is not known whether this medicine will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

It is not known whether dupilumab passes into breast milk or if it could affect the nursing baby. Tell your doctor if you are breast-feeding.

Dupilumab is not approved for use by anyone younger than 18 years old.

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• new or worsening eye pain or discomfort;

• vision changes;

• feeling like something is in your eye; or

• watery eyes (your eyes may be more sensitive to light).

Common side effects may include:

• pain, swelling, burning, or irritation where an injection was given;

• eye redness or itching;

• puffy eyelids; or

• cold sores or fever blisters on your lips or in your mouth.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Usual Adult Dose for Dermatitis:

Initial dose: 600 mg subcutaneously (two 300 mg injections) initially
Maintenance dose: 300 mg subcutaneously every other week

Comments:
-This drug can be used with or without topical corticosteroids.
-Topical calcineurin inhibitors may be used, but should be reserved for problem areas only (i.e., face, neck, intertriginous and genital areas).
-If a dose is missed, it should be administered within 7 days from the missed dose and then resume the original schedule. If the missed dose is not administered within 7 days, it should be skipped until the next dose on the original schedule.

Use: For the treatment of adult patients with moderate-to-severe atopic dermatitis whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable

Contraindications

Known hypersensitivity to dupilumab or any of its excipients.1

Warnings/Precautions

Hypersensitivity

Hypersensitivity reactions, including generalized urticaria and serum sickness or serum sickness-like reactions, were reported in less than 1% of subjects who received dupilumab in clinical trials. Two subjects experienced serum sickness or serum sickness-like reactions that were associated with high titers of antibodies to dupilumab. If a clinically significant hypersensitivity reaction occurs, institute appropriate therapy and discontinue dupilumab.1

Conjunctivitis and Keratitis

Conjunctivitis and keratitis occurred more frequently in subjects who received dupilumab. Conjunctivitis was the most frequently reported eye disorder. Most subjects with conjunctivitis recovered or were recovering during the treatment period.1

Keratitis was reported in <1% of the dupilumab group (1 per 100 subject-years) and in 0% of the placebo group (0 per 100 subject-years) in the 16-week monotherapy trials. In the 52-week dupilumab + topical corticosteroids (TCS) trial, keratitis was reported in 4% of the dupilumab + TCS group (12 per 100 subject-years) and in 0% of the placebo + TCS group (0 per 100 subject-years). Most subjects with keratitis recovered or were recovering during the treatment period.1

Advise patients to report new onset or worsening eye symptoms to their healthcare provider.1

Comorbid Asthma

Safety and efficacy of dupilumab have not been established in the treatment of asthma. Advise patients with comorbid asthma not to adjust or stop their asthma treatments without consultation with their physicians.1

Parasitic (Helminth) Infections

Patients with known helminth infections were excluded from participation in clinical studies. It is unknown if dupilumab will influence the immune response against helminth infections.1

Specific Populations

There are no available data on dupilumab use in pregnant women to inform any drug associated risk. Human IgG antibodies are known to cross the placental barrier; therefore, dupilumab may be transmitted from the mother to the developing fetus. In an enhanced pre- and post-natal developmental study, no adverse developmental effects were observed in offspring born to pregnant monkeys after subcutaneous administration of a homologous antibody against interleukin-4-receptor alpha (IL-4Rα) during organogenesis through parturition at doses up to 10-times the maximum recommended human dose (MRHD). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.1

In an enhanced pre- and post-natal development toxicity study, pregnant cynomolgus monkeys were administered weekly subcutaneous doses of homologous antibody against IL-4Rα up to 10 times the MRHD (on a mg/kg basis of 100 mg/kg/week) from the beginning of organogenesis to parturition. No treatment-related adverse effects on embryofetal toxicity or malformations, or on morphological, functional, or immunological development were observed in the infants from birth through 6 months of age.1

There are no data on the presence of dupilumab in human milk, the effects on the breastfed infant, or the effects on milk production. Human IgG is known to be present in human milk. The effects of local gastrointestinal and limited systemic exposure to dupilumab on the breastfed infant are unknown. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for dupilumab and any potential adverse effects on the breastfed child from dupilumab or from the underlying maternal condition.1

Safety and efficacy in pediatric patients (<18 years of age) have not been established.1

Of the 1472 subjects with atopic dermatitis exposed to dupilumab in a dose-ranging study and placebo-controlled trials, 67 subjects were 65 years or older. Although no differences in safety or efficacy were observed between older and younger subjects, the number of subjects aged 65 and over is not sufficient to determine whether they respond differently from younger subjects.1

Common Adverse Effects

Most common adverse reactions (incidence ≥1%) are injection site reactions, conjunctivitis, blepharitis, oral herpes, keratitis, eye pruritus, other herpes simplex virus infection, and dry eye.1

AHFS First Release. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about dupilumab, please talk with your doctor, nurse, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

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 dupilumab. 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 dupilumab.

Review Date: October 4, 2017

Atopic dermatitis: Treatment of moderate to severe atopic dermatitis in adults whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable.

Applies to dupilumab: subcutaneous solution

Along with its needed effects, dupilumab may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur while taking dupilumab:

• Blistering or crusting of the skin
• itchiness, redness of the eyes
• excessive tearing
• painful cold sores or blisters on the lips, nose, eyes, or genitals
• reddening of the skin
• scaly patches on the skin
• sores or white patches on the lips, mouth, or throat

• Burning or dry eyes
• fever
• pain, swelling of the eye or eyelid

Some side effects of dupilumab may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Bleeding, blistering, burning, coldness, discoloration of the skin, feeling of pressure, hives, infection, inflammation, itching, lumps, numbness, pain, rash, redness, scarring, soreness, stinging, swelling, tenderness, tingling, ulceration, or warmth at the injection site

Data not available