Dupilumab

Dupilumab is used to treat atopic dermatitis (eczema), asthma, chronic rhinosinusitis with nasal polyps, eosinophilic esophagitis, prurigo nodularis, COPD, chronic spontaneous urticaria, bullous pemphigoid, and allergic fungal rhinosinusitis. It is administered subcutaneously every 1 to 4 weeks, depending on the condition or the patient's weight or age. The brand name is Dupixent.

Dupilumab is a subcutaneous injection that can be self-administered using a prefilled syringe or pen every 1 to 4 weeks, depending on the condition.

Dupilumab first gained FDA approval on March 28, 2017, for eczema. Dupilumab, under the brand name Dupixent, is made by Sanofi and Regeneron Pharmaceuticals under a collaborative agreement. There is no generic or biosimilar.

Dupilumab is FDA-approved to treat:

• Moderate-to-severe atopic dermatitis (eczema) in adults and children 6 months and older whose disease is not adequately controlled with topical prescription treatments or who cannot use these treatments. May be used with or without topical corticosteroids
• Moderate-to-severe asthma characterized by an eosinophilic phenotype or that is oral corticosteroid dependent in adults and children 6 years and older. Not for the relief of an acute asthma attack (acute bronchospasm) or status asthmaticus (an extreme form of acute asthma)
• Inadequately controlled chronic rhinosinusitis with nasal polyps (CRSwNP), as an add-on maintenance treatment in adults and children 12 years and older
• COPD with an eosinophilic phenotype that is inadequately controlled, as add-on maintenance treatment in adults. Not for the relief of sudden breathing problems. Does not replace rescue inhalers.
• Eosinophilic esophagitis (EoE) in adults and children 1 year of age and older, who weigh at least 33 pounds (15 kg)
• Chronic spontaneous urticaria in adults and children 2 years and older who remain symptomatic despite H1 antihistamine treatment. Dupixent is not approved for other types of urticaria.
• Prurigo nodularis (PN) in adults
• Bullous pemphigoid (BP) in adults.
• Allergic fungal rhinosinusitis (AFRS) in adults and children 6 years and older who have a history of sino-nasal surgery.

Use dupilumab exactly as prescribed by your doctor. See the detailed “Instructions for Use” that comes with the Package Insert.

• Your healthcare provider will tell you how much dupilumab to inject and how often to inject it. Dupilumab is only available from a specialty pharmacy that will work with you to schedule your shipments.

Dupilumab is usually administered 1 time every 1 to 4 weeks, depending on the condition.

• It is given as an injection under the skin (subcutaneous injection).
• The pre-filled pen is for adults and children 2 years and older.
• The pre-filled syringe is for adults and children 6 months and older.

A caregiver or patient 12 years of age and older may inject dupilumab using the pre-filled syringe or pre-filled pen.

• In children 12 to 17 years of age, administer under the supervision of an adult.
• In children 6 months to less than 12 years of age, administer dupilumab by a caregiver.

Your healthcare provider may prescribe other medicines to use with this medicine. Use them exactly as your healthcare provider tells you to.

How to administer dupilumab

Dupilumab is injected subcutaneously (under the skin), usually 1 time every 1 to 4 weeks. Your first dose may be given in 2 injections.

Take a syringe or pen out of the refrigerator and let it reach room temperature for 30 to 45 minutes before injecting your dose. Leave the needle cap on until you are ready to inject your dose.

• Do not shake the prefilled syringe or injection pen. Prepare your injection only when you are ready to give it.
• Do not use it if the medicine looks cloudy, has changed color, or contains particles. Call your pharmacist for a new medicine.

The prefilled pen or syringe may be injected under the skin of your upper thigh or stomach area (except for the 2 inches [5 cm]) around your belly button (navel). Caregivers may also inject it in the outer area of the upper arm.

• Choose a different site for each injection. Do not inject into skin that is tender, damaged, has bruises or scars, or into areas with visible veins. Do not inject through clothes.
• Each prefilled syringe or injection pen is for one use only. Throw it away after one use, even if medicine is left inside.

Do not receive dupilumab if you are allergic to dupilumab, Dupixent, or any inactive ingredients in the injection.

Before using dupilumab injection, tell your healthcare provider about all your medical conditions, including if you:

• have eye problems, including significant dry eye disease, or a history of eyelid or tear duct surgery
• have a parasitic (helminth) infection, such as pinworms, roundworms, or tapeworms
• are scheduled to receive any vaccinations. You should not receive a “live vaccine” right before and during treatment with dupilumab
• are taking oral, topical, or inhaled corticosteroid medicines
• have asthma and use an asthma medicine, or have other medical conditions such as AD, chronic rhinosinusitis, EOE, prurigo nodularis, or chronic obstructive pulmonary disease, and also have asthma
• are pregnant or plan to become pregnant
• are breastfeeding or plan to breastfeed.

Do not change or stop your other medicines, including corticosteroid medicine or other asthma medicine, without talking to your healthcare provider first. This may cause other symptoms that were controlled by those medicines to come back.

Pregnancy

It is not known whether dupilumab will harm your unborn baby. Ask your healthcare provider about the risks vs benefits of using dupilumab during pregnancy.

There is a pregnancy exposure registry for women who use dupilumab during pregnancy. The purpose of this registry is to collect information about your health and your baby's health. Your healthcare provider can enroll you in this registry. You may also enroll yourself or get more information about the registry by calling 1-877-311-8972 or going to the Mother To Baby Dupixent study page.

Breastfeeding

It is not known whether dupilumab passes into your breast milk.

The most common side effects of dupilumab are:

• injection site reactions, such as pain, swelling, or burning at the injection site
• upper respiratory tract infections, such as a cold or the flu
• eye-related problems, including eye and eyelid inflammation, redness, swelling, itching, eye infection, dry eye, and blurred vision
• herpes virus infections and cold sores
• elevated white blood cell counts
• musculoskeletal issues (back pain, muscle/joint pain)
• respiratory symptoms (rhinitis, throat pain)
• diarrhea
• stomach problems (gastritis)
• dizziness, sleeplessness, or headache
• other infections, such as parasitic infections or urinary tract infections
• facial rashes or redness.

Serious side effects and warnings

Dupilumab can cause the following serious side effects.

• Allergic reactions. Dupilumab can cause serious hypersensitivity reactions such as anaphylaxis, acute generalized exanthematous pustulosis (AGEP), serum sickness, angioedema, urticaria, rash, erythema nodosum, and erythema multiforme. Do not use dupilumab if you are allergic to dupilumab or any of the ingredients. Seek immediate medical attention for signs of severe allergic reactions, including: breathing difficulties or wheezing rapid heartbeat fever lymph node swelling facial/throat swelling skin reactions (hives, itching, blisters, pustules, or a skin rash, including a rash that looks like a bullseye, painful red or blue bumps under the skin, or red pus-filled spots on the skin) gastrointestinal symptoms (nausea, vomiting, stomach cramps) fainting or dizziness joint pain.
• Eye problems. Promptly tell your healthcare provider if you develop any new or worsening eye problems while taking dupilumab, including eye pain, vision changes (such as blurred vision or blindness), conjunctivitis (red or sticky eyes), blepharitis, or keratitis (inflammation of the cornea). These conditions may sometimes require surgery. Your healthcare provider may send you to an ophthalmologist for an eye exam.
• Blood vessel inflammation. Tell your healthcare provider right away if you have: an unexplained rash worsening breathing difficulties persistent fever chest pain pins and needles sensation or numbness in your limbs.
• Joint aches and pain. Arthralgia (joint aches and pains) has been reported with dupilumab, with some patients reporting gait disturbances or decreased mobility associated with joint symptoms; some cases resulted in hospitalization. In postmarketing reports, the onset of arthralgia was variable, ranging from days to months after the first dose of dupilumab. Cases of new-onset psoriatic arthritis requiring systemic treatment have been reported with the use of dupilumab. Tell your healthcare provider about any new or worsening joint symptoms.
• 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. Tell your doctor if you develop a red or purple rash, shortness of breath, tingling, or nerve pain in your hands or feet.
• Parasitic (helminthic) infections may be more common with dupilumab. Treat existing infections before starting dupilumab. Your healthcare provider may discontinue dupilumab if you develop a new parasitic infection that doesn't respond to treatment.
• Psoriasis. This can happen in people with atopic dermatitis and asthma who receive dupilumab. Tell your healthcare provider about any new skin symptoms. Your healthcare provider may send you to a dermatologist for an examination if needed.

Corticosteroid Usage. Continue as directed by your healthcare provider. Never stop corticosteroids suddenly without medical guidance.

Vaccinations. Avoid live vaccines during treatment because dupilumab may reduce their effectiveness.

Dupilumab's safety and effectiveness have not been established for children:

• Under 6 months with eczema or AD
• Under 6 years with Asthma or AFRS
• Under 12 years with CRSwNP or under 2 years with chronic urticaria
• Under 1 year or below 33 pounds (15 kg) with EOE
• Under 18 years with COPD with eosinophilic phenotype, Prurigo nodularis, or Bullous pemphigoid.

Tell your healthcare provider if you have any side effect that bothers you or does not go away. These are not all of the possible side effects of dupilumab. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Dupilumab (Dupixent) works by targeting and blocking two inflammatory proteins, interleukin-4 (IL-4) and interleukin-13 (IL-13), in your body. These proteins control inflammatory signalling pathways and substances such as proinflammatory cytokines, nitric oxide, and IgE (immunoglobulin E). By blocking IL-4 and IL-13, dupilumab helps to control inflammation caused by conditions such as eczema, asthma, urticaria, COPD, CRSwNP, eosinophilic esophagitis, bullous pemphigoid, and AFRS

Dupilumab does not fully suppress the immune system but calms it down, relieving inflammation. It belongs to the drug class called interleukin inhibitors.

The dosage depends on the condition being treated and the person's age.

Dose of Dupilumab for Eczema

Adults: An initial dose of 600 mg (two 300 mg injections) subcutaneously, followed by 300 mg subcutaneously given every other week.

Children 6 months to 5 years:

Children 6 years to 17 years:

Dose of Dupilumab for Asthma

Adults and Children 12+

• 400 mg subcutaneously for the first dose, then 200 mg subcutaneously every 2 weeks

Or

• 600 mg subcutaneously for the first dose, then 300 mg subcutaneously every 2 weeks.

Adults and Children 12+ with Corticosteroid-Dependent Asthma Plus AD or CRSwNP

• 600 mg subcutaneously for the first dose, then 300 mg subcutaneously every 2 weeks.

Children 6-11 Years

• 15 to <30 kg: 300 mg subcutaneously every 4 weeks
• ≥30 kg: 200 mg subcutaneously every 2 weeks

See the Dupilumab Prescribing Information (Dupixent) for dosing information for children aged 6 to 11 years with asthma and co-morbid moderate-to-severe atopic dermatitis (includes an initial loading dose).

Dose of Dupilumab for Chronic Rhinosinusitis with Nasal Polyps (CRwNP)

Adults and children aged 12 and older: 300 mg subcutaneously given every other week (Q2W).

Dose of Dupilumab for EoE (eosinophilic esophagitis)

Adults and children aged 1 year and older weighing at least 15kg:

Dose of Dupilumab for Prurigo Nodularis

Adults: an initial dose of 600 mg (two 300 mg injections) subcutaneously, followed by 300 mg subcutaneously given every other week (Q2W).

Dose of Dupilumab for COPD (chronic obstructive pulmonary disease)

Adults: 300 mg subcutaneously given every other week (Q2W).

Dose of Dupilumab for Chronic Spontaneous Urticaria (CSU)

Adults: an initial dose of 600 mg (two 300 mg injections) subcutaneously, followed by 300 mg subcutaneously every other week (Q2W).

Children 6 through 17 years:

Children 2 through 5 years:

No initial loading dose is recommended.

Dose of Dupilumab for Bullous Pemphigoid (Adults):

• An initial dose of 600 mg (two 300 mg injections) subcutaneously, followed by 300 mg subcutaneously every other week (Q2W).

Use in combination with a tapering course of oral corticosteroids.

Dose of Dupilumab for AFRS

Adults

• 300 mg subcutaneously every 2 weeks.

Children 6 to 17 years

• 15 kg to <30 kg: 300 mg subcutaneously every 4 weeks.
• 30 to <60 kg: 200 mg subcutaneously every 2 weeks.
• ≥60 kg: 300 mg subcutaneously every 2 weeks.

If your dose schedule is every week and you miss a dose of dupilumab, give the dupilumab injection as soon as possible and start a new every-week dose schedule from the time you remember to take your dupilumab injection.

If your dose schedule is every 2 weeks and you miss a dose of Dupixent, give the Dupixent injection within 7 days of the missed dose, then continue with your original schedule. If the missed dose is not given within 7 days, start a new every 2-week dose schedule from the time you remember to take your Dupixent injection.

If your dose schedule is every 4 weeks and you miss a dose of dupilumab, give the dupilumab injection within 7 days of the missed dose, then continue with your original schedule. If the missed dose is not given within 7 days, start a new 4-week dose schedule from the time you remember to take your dupilumab injection.

If you inject too much dupilumab, call your healthcare provider or Poison Help line at 1-800-222-1222 or go to the nearest hospital emergency room right away.

Do not receive a "live" vaccine while using dupilumab. The vaccine may not work as well during this time and may not fully protect you from the disease. Live vaccines include measles, mumps, rubella (MMR), rotavirus, typhoid, yellow fever, varicella (chickenpox), zoster (shingles), and the nasal flu (influenza) vaccine.

Tell your healthcare provider about all of the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Especially tell your healthcare provider if you:

• are taking oral, topical, or inhaled corticosteroid medicines, have asthma, and use an asthma medicine
• have atopic dermatitis, chronic rhinosinusitis with nasal polyposis, eosinophilic esophagitis, or prurigo nodularis, and also have asthma.

Do not change or stop your corticosteroid medicine or other asthma medicine without talking to your healthcare provider. This may cause other symptoms that were controlled by the corticosteroid medicine or other asthma medicines to come back.

Dupilumab has not been reported to have a drug interaction with alcohol.

This list is not complete. See the Dupilumab Prescribing Information (Dupixent) for a full list. Other drugs may interact, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible drug interactions are listed here.

Store dupilumab in the refrigerator at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light. You may store a prefilled syringe or injection pen at cool room temperature for up to 14 days. Do not store above 25°C (77°F).

Throw the dupilumab injection away if not used within 14 days. Do not put it back into the refrigerator. Do not expose a dupilumab injection to heat or direct sunlight. Do NOT freeze. Do NOT shake.

Dupilumab is only available as the brand name Dupixent.

Active ingredients: dupilumab.

Inactive ingredients: L-arginine hydrochloride, L-histidine, polysorbate 80, sodium acetate, sucrose, and water for injection.

Available as a single-dose pre-filled syringe with a needle shield or as a pre-filled pen.

• The pre-filled syringe is available in 300 mg/2 mL and 200 mg/1.14 mL.
• The pre-filled pen is available in 300 mg/2 mL and 200 mg/1.14 mL.

Dupilumab is manufactured under the brand name Dupixent by Sanofi and Regeneron Pharmaceuticals through a collaborative agreement. Sanofi is headquartered in Paris, France, and Regeneron Pharmaceuticals is headquartered in Tarrytown, New York, USA.