Allergies Common Treatments What to Know About Elidel and Protopic Despite being effective, an FDA warning raises concerns By Daniel More, MD Daniel More, MD Daniel More, MD, is a board-certified allergist and clinical immunologist with a background in internal medicine. Learn about our editorial process Updated on March 02, 2022 Medically reviewed by Corinne Savides Happel, MD Medically reviewed by Corinne Savides Happel, MD LinkedIn Corinne Savides Happel, MD, is a board-certified allergist and immunologist with a focus on allergic skin disorders, asthma, and other immune disorders. Learn about our Medical Expert Board Print Table of Contents View All Table of Contents Uses Before Taking Dosage Side Effects Warnings Interactions Frequently Asked Questions Elidel (pimecrolimus) and Protopic (tacrolimus) are topical drugs used for the short-term treatment of eczema (atopic dermatitis). The drugs, classified as topical calcineurin inhibitors (TCIs), are the first nonsteroid topical medications developed to treat eczema. Garo / Getty Images Unlike topical steroids, TCIs can be used on the face and eyelids and are not associated with skin injury or the loss of drug action with repeated use. Side effects tend to be mild and may include mild itching and burning sensations. Despite these benefits, Elidel and Protopic have their limitations and risks. Chief among them is a possible link to certain skin and blood cancers, a concern that prompted the Food and Drug Administration (FDA) to issue a black box warning in 2006. Uses Elidel and Protopic are the only topical calcineurin inhibitors currently approved by the FDA. Elidel is recommended for the treatment of mild to moderate atopic dermatitis, while Protopic is labeled for moderate to severe atopic dermatitis. Topical calcineurin inhibitors work by blocking calcineurin, a naturally occurring compound that helps activate the immune system and stimulate pro-inflammatory cytokines. By "switching off" this response, the inflammation that drives eczema can be significantly relieved. Elidel and Protopic are also often prescribed to treat other inflammatory skin conditions such as psoriasis, seborrheic dermatitis, cutaneous lupus erythematosus, oral lichen planus, and vitiligo. Because of their cost, healthcare providers will sometimes reserve Elidel and Protopic for use on thinner/smaller areas of skin (such as the face or hands) and use cheaper topical steroids for larger areas of thicker skin (such as the arms, legs, and trunk). Elidel and Protopic have certain benefits that set them apart from topical steroids: They can be used repeatedly with no loss of drug action. They can be used in children as young as 2. They do not cause skin atrophy (thinning), striae (stretch marks), telangiectasia (spider veins), or skin discoloration. They can be safely used on the face, neck, groin, around the eyes, or in skin folds. When Eczema Affects Your Face Before Taking Elidel and Protopic are recommended for the second-line treatment of eczema when topical steroids and other conservative therapies fail to provide relief. They are reserved for use in adults and children 2 years of age and over. Precautions and Considerations Because Elidel and Protopic work by tempering the immune response, they should not be used in anyone with a compromised immune system. Doing so may lead to further suppression of the immune response and an increased risk of opportunistic infections. This includes people with advanced HIV infection, as well as organ transplant recipients and individuals undergoing cancer therapy (both of whom take immunosuppressant drugs). Elidel and Protopic should also not be used in persons with a known hypersensitivity to pimecrolimus, tacrolimus, or any ingredient in the topical formulation. Because these effects are cross-reactive—meaning hypersensitivity to one drug translates to hypersensitivity to both—you would need to avoid these and any other calcineurin inhibitors, including cyclosporine and oral or injectable Prograf (tacrolimus). Treating Eczema in Children Dosage Elidel is available in a topical cream and contains 1 percent pimecrolimus. Protopic is available as a topical ointment with either 0.03 percent or 0.1 percent tacrolimus. The choice of drug is based on the severity of your symptoms as diagnosed by a qualified dermatologist. How to Take and Store Elidel and Protopic are applied twice daily to the skin in a thin layer. The drugs should not be used as a moisturizer, even in severe cases. If symptoms do not improve after six weeks of use, treatment options should be reviewed. Applying Elidel or Protopic more frequently will not improve results. Elidel and Protopic can be safely stored at room temperature (77 degrees F). Short-term exposure to temperatures ranging from 59 degrees F to 86 degrees F will not compromise the drugs' efficacy, but you should avoid storing the drugs in hot places (e.g., your glove compartment) or in direct sunlight. Never use a drug after its expiration date. Elidel and Protopic are intended for short-term use or the intermittent treatment of chronic eczema. They are not intended for continuous, long-term use. Side Effects As with all drugs, Elidel and Protopic may cause side effects. Most are relatively mild and tend to resolve once the body adapts to treatment. Common The most common side effect is a burning or itching sensation, which is experienced by approximately 25 percent of users. A headache, cough, nasal congestion, sore throat, upset stomach, and muscle aches have also been noted. Elidel is associated with an increased risk of certain infections, including folliculitis, pneumonia, impetigo, sinusitis, otitis media, and influenza. Between 3 percent and 8 percent of users may be affected. Skin reactions are more common with Protopic, including urticaria (hives), erythema (redness), and bacterial skin infections. Oral antihistamines and topical antibiotics can often provide relief. Severe Although the risk of anaphylaxis (a severe, whole-body allergy) is considered low, Protopic has been known to cause the reactivation of the chickenpox virus in some people, leading to an outbreak of shingles. Others may experience a vesiculobullous rash, characterized by the formation of tiny, chickenpox-like blisters on the application site. When to See a Healthcare Provider Rashes of any sort should be seen by a healthcare provider. If they are accompanied by shortness of breath, rapid heartbeat, dizziness, or the swelling of the face, tongue, or throat, call 911. These may be the signs of an anaphylactic emergency. Warnings Animal research has shown a slight increase in the risk of birth defects when Elidel and Protopic are given at doses far beyond what would be used in humans. Adequate studies in humans are lacking, but the potential benefits of treatment may outweigh the risks. Due to the lack of safety research, it is important to speak with your healthcare provider about the potential benefits and risks of Elidel or Protopic if you are pregnant or breastfeeding (or intend to be). Black Box Warning In 2006, the FDA issued a black box warning advising consumers and healthcare professionals that Elidel and Protopic were linked to an increased risk of skin cancer and lymphoma (in particular, T-cell lymphoma). While recognizing the incidence of cancer was "rare," the FDA decided the advisement was warranted given the overprescribing of the drug among infants and toddlers as well as the drugs' off-label use in treating a variety of other rashes. It was a controversial decision that continues to be criticized by both the American Academy of Dermatology (AAD) and the American Academy of Allergy, Asthma, and Immunology (AAAAI). Research submitted to the FDA in 2013 found no evidence of an increased risk of lymphoma among 625,915 people who used Protopic or Elidel for an average of five and a half years. With respect to skin cancer, the FDA based its conclusions on studies involving organ recipients exposed to intravenous tacrolimus or cyclosporine. Although these users did experience an increased risk of skin cancer and lymphoma, no such increase has ever been seen in users of topical tacrolimus or pimecrolimus. According to research published at the time of the FDA warning, the risk of lymphoma or skin cancer among the 11 million users of Protopic or Elidel has never been greater than that of the general population. Interactions It remains unclear if Elidel or Protopic can interact with other medications. Although little research has been done to investigate potential interactions, both drugs are known to utilize an enzyme known as cytochrome P450 3A4 (CYP3A4) for metabolization. As such, it may be possible for Elidel or Protopic to interact with drugs that inhibit CYP3A4, resulting in an abnormal buildup of Elidel and Protopic in the body. These include: Calcium channel blockers Diflucan (fluconazole) Erythromycin Nizoral (ketoconazole) Sporanox (itraconazole) Tagamet (cimetidine) While it is unclear how significant the interactions may be (if at all), it is important to advise your healthcare provider of any drug you may be taking—whether it is prescription, over-the-counter, nutritional, or recreational. Frequently Asked Questions Is pimecrolimus cream over-the-counter? No, pimecrolimus cream is not over-the-counter and requires a prescription. It can help manage eczema symptoms when other medications are unsuccessful or when they cannot be used for health reasons. Pimecrolimus cream is the generic version of Elidel. Can you use Elidel for perioral dermatitis? Elidel is not usually used to treat perioral dermatitis. Sometimes the rash can go away by itself, but topical antibiotics like tetracycline or erythromycin may be used if it sticks around. Treatment for perioral dermatitis may benefit from gentle face washing using a fragrance-free cleanser, but a healthcare provider can create a treatment plan. Can erythema cause itchy eyelids with bumps? Yes, it is possible for erythema multiforme to cause itchy eyelids along with the formation of red spots or bumps. Other symptoms include cold sores, fatigue, fever, joint pain, and red patches or blisters that can appear on the face, palms of hands, and foot soles. As long as an infection does not form, erythema multiforme minor can go away on its own after a week or two. Erythema multiforme major is potentially serious and may require visiting a healthcare provider. How Eczema Is Treated 12 Sources Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy. U.S. Food and Drug Administration. FDA approves updated labeling with boxed warning and medication guide for two eczema drugs, Elidel and Protopic. U.S. Food and Drug Administration. Elidel (pimecrolimus) cream 1% for topical use. U.S. Food and Drug Administration. Protopic (tacrolimus) ointment 0.03% ointment 0.1% for dermatological use only. Carr WW. Topical calcineurin inhibitors for atopic dermatitis: review and treatment recommendations. Paediatr Drugs. 2013;15(4):303-10. doi:10.1007/s40272-013-0013-9 Heneberg P, Riegerová K, Kučera P. Pimecrolimus is a potent inhibitor of allergic reactions to hymenopteran venom extracts and birch pollen allergen in vitro. PLoS ONE. 2015;10(11):e0142953. doi:10.1371/journal.pone.0142953 Nevers W, Pupco A, Koren G, Bozzo P. Safety of tacrolimus in pregnancy. 2014;60(10):905-906. Siegfried EC Jaworski JC, Hebert AA. Topical calcineurin inhibitors and lymphoma risk: Evidence update with implications for daily practice. Am J Clin Dermatol. 2013;14:163-78. doi:10.1007/s40257-013-0020-1 Lebwohl M, Gower T. A safety assessment of topical calcineurin inhibitors in the treatment of atopic dermatitis. MedGenMed. 2006;8(4):8. Crissinger A, Nguyen NV. The use of topical calcineurin inhibitors in atopic dermatitis. Open Dermatol J. MedlinePlus. Pimecrolimus Topical. American Academy of Dermatology Association (AAD). Red Rash Around Your Mouth Could Be Perioral Dermatitis. Johns Hopkins Medicine. Erythema Multiforme. By Daniel More, MD Daniel More, MD, is a board-certified allergist and clinical immunologist. He is an assistant clinical professor at the University of California, San Francisco School of Medicine and currently practices at Central Coast Allergy and Asthma in Salinas, California. See Our Editorial Process Meet Our Medical Expert Board Share Feedback Was this page helpful? Thanks for your feedback! What is your feedback? Other Helpful Report an Error Submit