dupilumab

Dupilumab is a medication used in the treatment of allergic and inflammatory conditions such as asthma and eczema.

Dupilumab is a lab-made human monoclonal immunoglobulin G4 (IgG4) antibody that blocks the activity of certain chemicals in the body responsible for promoting inflammation. Dupilumab blocks the signaling of pro-inflammatory proteins (cytokines) interleukin-4 (IL-4) and IL-13 which an  induce immune response and inflammatory reaction in allergic diseases.

Dupilumab binds to and blocks IL-4 receptor-alpha (IL-4-RA) subunit, protein molecules that are expressed on immune cells including mast cells, eosinophils, macrophages, lymphocytes, epithelial cells and goblet cells. This prevents IL-4 and IL-13 cytokines from signaling and inducing inflammatory responses from these immune cells. Blockage of IL-4-RA results in inhibition of cytokine-induced inflammatory responses including the release of proinflammatory cytokines, chemokines, nitric oxide and immunoglobulin E (IgE).

The 6 uses of dupilumab include:

FDA-approved

Adult and children:

• Moderate-to-severe eczema (atopic dermatitis) not adequately controlled with topical prescription therapies or when those therapies are not advisable
• Add-on maintenance treatment for patients with eosinophilic phenotype or oral corticosteroid dependent asthma
• Add-on maintenance treatment in patients with inadequately controlled chronic rhinosinusitis with nasal polyposis (CRSwNP), a nasal inflammatory condition
• Eosinophilic esophagitis, an allergic inflammation of the esophagus

Adult:

• Prurigo nodularis, a chronic skin disorder with itchy nodules

Orphan designation

• Bullous pemphigoid, a skin disorder that causes rashes with blisters

• Do not administer to patients hypersensitive to any of the components in dupilumab.
• Hypersensitivity skin reactions including rash, (hives) urticaria, erythema nodosum and serum sickness have been reported, and in one case, severe allergic reaction (anaphylaxis) occurred. Discontinue dupilumab and institute appropriate therapy if patient develops clinically significant hypersensitivity reactions.
• Some patients developed eye inflammations such as conjunctivitis and keratitis after dupilumab therapy. Advise patients to report new onset or worsening of eye symptoms.
• Rarely, asthma patients treated with dupilumab may develop serious systemic eosinophilia including eosinophilic pneumonia or vasculitis consistent with eosinophilic granulomatosis with polyangiitis. Monitor patients for symptoms.
• Do not use dupilumab to treat acute asthma episodes or exacerbations, including acute bronchospasm and status asthmaticus.
• Do not discontinue corticosteroids abruptly when initiating dupilumab, reduce gradually, under medical supervision.
• It is not known if dupilumab influences the immune response against parasitic (helminth) infections. Treat patients for pre-existing parasitic infections before starting dupilumab therapy, and if infection develops during therapy, interrupt dupilumab until parasitic infection resolves.
• Advise patients with atopic dermatitis or CRSwNP who have co-morbid asthma not to adjust or stop their asthma treatments without consulting with their physicians.
• In case of home-administration of pre-filled syringes, provide proper training to the patients and/or caregivers on proper subcutaneous injection technique, including aseptic technique, and the preparation and administration of dupilumab, as well as disposal of the used syringes.

Common side effects of dupilumab include:

• Injection site reactions including:
  • Pain
  • Itching (pruritus)
  • Redness (erythema)
  • Swelling (edema)
  • Inflammation
• Inflammation of the conjunctiva, the membrane over the eye whites and inner eyelid surfaces (conjunctivitis)
• Eyelid inflammation (blepharitis)
• Inflammation of the cornea (keratitis)
• Dry eyes
• Itchy eyes
• Upper respiratory tract infection
• Oral herpes
• Other herpes simplex virus infections including:
  • Genital herpes
  • Herpes simplex in the external ear
• Herpes zoster
• Eczema herpeticum
• Parasitic infection (helminthiasis) in children treated for asthma
• Pain in the mouth and throat (oropharyngeal)
• Nose and throat inflammation (nasopharyngitis)
• Toothache
• High count of eosinophil immune cells (eosinophilia)
• Gastritis
• Diarrhea
• Muscle pain (myalgia)
• Joint pain (arthralgia)
• Insomnia
• Dizziness
• Antibody development, including neutralizing antibodies

Less common side effects of dupilumab include:

• Hypersensitivity reactions including:
  • Swelling of tissue under the skin and mucous membranes (angioedema)
  • Serum sickness
  • Serum sickness-like reaction
  • Severe allergic reaction (anaphylaxis)
• Swelling (edema)
• Heart attack (myocardial infarction)
• Cerebrovascular accident
• Eosinophilic granulomatosis with polyangiitis, a rare condition with blood vessel inflammation (vasculitis) caused by clusters of inflammatory cells (granulomas)
• Eosinophilic lung inflammation (pneumonitis)
• Skin reactions including:
  • Skin rash
  • Hives (urticaria)
  • Burning sensation and pain
  • Skin peeling
  • Bumps in the skin (papules)
  • Redness (erythema)
  • Facial rash and erythema
  • Erythema nodosum
  • Erythema multiforme
  • Psoriasis
• Hair loss (alopecia)
• Immune-mediated low platelet count (immune thrombocytopenia)

Call your doctor immediately if you experience any of the following symptoms or serious side effects while using this drug:

• Serious heart symptoms include fast or pounding heartbeats, fluttering in your chest, shortness of breath, and sudden dizziness;
• Severe headache, confusion, slurred speech, severe weakness, vomiting, loss of coordination, feeling unsteady;
• Severe nervous system reaction with very stiff muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, and feeling like you might pass out; or
• Serious eye symptoms include blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

Injectable Solution

• 300 mg/2 mL (single-dose prefilled syringe or pen)
• 200 mg/1.14 mL (single-dose prefilled syringe or pen)
• 100 mg/0.67 mL (single-dose prefilled syringe)

Adult:

Atopic Dermatitis

• 600 mg (i.e., two 300-mg injections) subcutaneous (SC) once, and then 300 mg SC every other week
• Can be used with or without topical corticosteroids

Moderate-to-Severe Asthma

• 400 mg SC once, then 200 mg every 2 weeks, OR
• 600 mg SC once, then 300 mg every 2 weeks
• 600 mg initial, then 300 mg every 2 weeks for patients with oral corticosteroid-dependent asthma or comorbid moderate-to-severe atopic dermatitis (for which dupilumab is indicated)

Severe Chronic Rhinosinusitis with Nasal Polyps (CRSwNP)

• 300 mg SC every 2 weeks

Eosinophilic Esophagitis

• 300 mg SC every week

Prurigo Nodularis

• 600 mg SC once, followed by 300 mg every 2 weeks

Dosing Considerations

• Topical calcineurin inhibitors may be used, for topical dermatitis, but should be reserved for problem areas only (e.g., face, neck, intertriginous, and genital areas)
• Not indicated for acute bronchospasm or status asthmaticus

Vaccinations

• Consider completing all age-appropriate vaccinations as recommended by current immunization guidelines before initiating treatment

Pediatric:

Atopic Dermatitis

Children below 6 months:

• Safety and efficacy not established

Children 6 months through 5 years

• No initial loading dose recommended
• 5 to below 15 kg: 200 mg SC every 4 weeks
• 15 to 30 kg: 300 mg SC every 4 weeks

Children 6-17 years

• 60 kg or above: 600 mg (i.e., two 300-mg injections) SC once, and then 300 mg SC every other week
• 30 kg to 60 kg: 400 mg (i.e., two 200-mg injections) SC once, and then 200 mg SC every other week
• 15 kg to below 30 kg: 600 mg (i.e., two 300-mg injections) SC once, and then 300 mg SC every 4 weeks
• May be used with or without topical corticosteroids

Moderate-to-Severe Asthma

Children below 6 years

• Safety and efficacy not established

Children 6-11 years

• No initial loading dose recommended
• 15 to 30 kg: 100 mg SC every 2 weeks OR 300 mg SC every 4 weeks
• 30 kg and above: 200 mg SC every 2 weeks
• Patients with asthma and comorbid moderate-to-severe atopic dermatitis, follow the recommended dosage for atopic dermatitis, including initial loading dose

Children 12 years and above

• 400 mg SC once, then 200 mg every 2 weeks, OR
• 600 mg SC once, then 300 mg every 2 weeks
• Patients with oral corticosteroid-dependent asthma or comorbid moderate-to-severe atopic dermatitis: 600 mg SC once, then 300 mg every 2 weeks

Eosinophilic Esophagitis

• Children below 12 years: Safety and efficacy not established
• Children 12 years and above weighing 40 kg or more: 300 mg SC every week

Dosing Considerations

• Topical calcineurin inhibitors may be used, for topical dermatitis, but should be reserved for problem areas only (e.g., face, neck, intertriginous, and genital areas)
• Not indicated for acute bronchospasm or status asthmaticus
• NOTE: Prefilled pen is only for use in adolescents aged 12 years and above

Vaccinations

• Consider completing all age-appropriate vaccinations as recommended by current immunization guidelines before initiating treatment

Overdose

• There is limited data on dupilumab overdose. Overdose may be treated with symptomatic and supportive care as appropriate.

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

• Dupilumab has no known serious interactions with other drugs.
• Serious interactions of dupilumab include:
  • adenovirus types 4 and 7 live, oral
  • axicabtagene ciloleucel
  • BCG vaccine live
  • brexucabtagene autoleucel
  • cholera vaccine
  • ciltacabtagene autoleucel
  • idecabtagene vicleucel
  • influenza virus vaccine quadrivalent, intranasal
  • lisocabtagene maraleucel
  • measles mumps and rubella vaccine, live
  • smallpox (vaccinia) vaccine, live
  • tisagenlecleucel
  • typhoid polysaccharide vaccine
  • typhoid vaccine live
  • yellow fever vaccine
  • zoster vaccine live
• Moderate interactions of dupilumab include:
  • carbamazepine
  • clonidine
  • cyclosporine
  • dengue vaccine
  • disopyramide
  • fosphenytoin
  • phenobarbital
  • phenytoin
  • primidone
  • quinidine
  • quinine
  • sirolimus
  • tacrolimus
  • theophylline
  • valproic acid
• Dupilumab has no known mild interactions with other drugs.

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider of all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or healthcare provider if you have any questions about the medication.

• Available data from case reports with dupilumab use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.
• Poorly or moderately controlled asthma during pregnancy can increase the risk of preeclampsia in the mother and prematurity, low birth weight, and being small for gestational age in the newborn infant.
• Asthma control should be closely monitored in pregnant women and treatment adjusted appropriately to achieve optimum control.
• It is not known whether dupilumab is present in human milk. Its effects on milk production and on the breastfed infant are unknown. Decision to breastfeed should be based on the mother’s clinical need for dupilumab, benefits of breastfeeding to the infant, and potential risk to the infant from drug exposure or underlying maternal condition.
• Data collection to monitor pregnancy and infant outcomes following exposure to dupilumab is ongoing. Health care providers and patients are encouraged to enroll exposed pregnant patients in the MotherToBaby Pregnancy Studies conducted by the Organization of Teratology Information Specialists (877-311-8972 or https://mothertobaby.org).

• Administer dupilumab injection exactly as instructed if you administer them at home, and dispose the used syringes appropriately.
• Contact your physician immediately if you develop:
  • Hypersensitivity symptoms
  • New onset or worsening of eye inflammations
  • Rash, worsening pulmonary symptoms, cardiac complications, and/or nerve damage symptoms
• Dupilumab does not treat acute, severe asthma episodes, contact your physician if your asthma remains uncontrolled or worsens after starting dupilumab therapy.
• While using dupilumab for eczema or chronic rhinosinusitis with nasal polyposis, if you also have asthma, do not adjust or stop your asthma medications without checking with your physician.
• If you are using systemic or inhaled corticosteroid, do not discontinue corticosteroids when you start dupilumab treatment, except under direct supervision of a physician.