Protopic
Topical Calcineurin Inhibitor for Atopic Dermatitis (Eczema)
Quick Facts About Protopic
Key Takeaways
- Protopic contains tacrolimus, a calcineurin inhibitor that suppresses the overactive immune response causing eczema flare-ups.
- Available in two strengths: 0.03% for children (2+ years) and adults, and 0.1% for adults only.
- Does not cause skin thinning (atrophy), making it safe for use on the face, neck, and skin folds.
- Can be used as maintenance therapy (twice weekly) to prevent recurrent eczema flare-ups.
- Common side effects include a temporary burning sensation and itching at the application site, which usually resolve within the first week.
What Is Protopic and What Is It Used For?
Protopic contains the active ingredient tacrolimus monohydrate, which belongs to a class of medicines known as calcineurin inhibitors. Originally developed for preventing organ transplant rejection (in oral form), tacrolimus was later formulated as a topical ointment for treating inflammatory skin conditions. When applied to the skin, it acts locally to calm the immune system's overreaction that drives atopic dermatitis.
Atopic dermatitis is a chronic inflammatory skin condition characterised by intense itching, redness, dryness, and sometimes cracking or weeping of the skin. It affects approximately 10–20% of children and 1–3% of adults worldwide, according to the World Health Organization. The condition results from a combination of genetic predisposition, immune system dysfunction, and environmental triggers that lead to a disrupted skin barrier and persistent inflammation.
In atopic dermatitis, the skin's immune system becomes overactive, producing excessive amounts of inflammatory mediators such as interleukins (IL-4, IL-5, IL-13) and other cytokines. Protopic works by inhibiting the enzyme calcineurin inside T-cells, which prevents the activation of nuclear factor of activated T-cells (NF-AT). This, in turn, reduces the production of pro-inflammatory cytokines, effectively calming the immune-mediated inflammation and relieving symptoms of itching, redness, and skin dryness.
Protopic 0.03% ointment is indicated for treating moderate to severe atopic dermatitis in both adults and children aged 2 years and older who have not achieved adequate results from, or who cannot tolerate, conventional topical treatments such as corticosteroid creams and ointments. For adults (aged 16 and older), Protopic is also available in a 0.1% strength for initial treatment of flare-ups.
Additionally, once a flare-up has been successfully treated (cleared or nearly cleared after up to 6 weeks of acute treatment), Protopic can be prescribed as a maintenance therapy. When applied twice weekly to areas prone to eczema, it helps prevent recurrent flare-ups and extends the time between episodes. This proactive approach is particularly beneficial for patients who experience frequent recurrences (four or more flare-ups per year).
What Should You Know Before Using Protopic?
Contraindications
Protopic must not be used if you are allergic (hypersensitive) to tacrolimus or to any of the other ingredients in the ointment, including white petrolatum, liquid paraffin, propylene carbonate, white beeswax, hard paraffin, butylhydroxytoluene (E321), or all-rac-alpha-tocopherol. You should also not use Protopic if you have a known allergy to macrolide antibiotics such as azithromycin, clarithromycin, or erythromycin, as tacrolimus shares structural similarities with this class of drugs.
- Known hypersensitivity to tacrolimus or macrolide antibiotics
- Do not apply to actively infected skin areas
- Not approved for children under 2 years of age
- Do not use in patients with severe immunodeficiency
Warnings and Precautions
Before starting Protopic, tell your doctor if you have any of the following conditions, as they may affect whether this medication is suitable for you or require closer monitoring during treatment:
- Liver impairment: Although systemic absorption from topical tacrolimus is very low, patients with significant liver disease should be monitored carefully, as tacrolimus is metabolised hepatically.
- Skin malignancies or pre-malignant conditions: Protopic should not be used in patients with existing skin cancers or a history of skin tumours at the application site.
- Immunodeficiency: Patients with weakened immune systems (regardless of the cause) should not use Protopic, as further immunosuppression could increase the risk of infections or malignancy.
- Hereditary skin barrier disorders: Conditions such as Netherton syndrome, lamellar ichthyosis, or generalised erythroderma can significantly increase systemic absorption of topical tacrolimus and should be considered absolute contraindications.
- Cutaneous graft-versus-host disease (GvHD): Patients who have undergone bone marrow transplantation and have skin-related GvHD should consult their specialist before using Protopic.
- Swollen lymph nodes: If you notice swollen lymph nodes at the start of, or during, treatment, inform your doctor. While lymphadenopathy is usually related to the underlying eczema, it requires evaluation to rule out other causes.
Sun protection is essential during Protopic treatment. Avoid prolonged exposure to natural sunlight and do not use tanning beds or sunlamps. When spending time outdoors, apply a broad-spectrum sunscreen and wear loose-fitting protective clothing. If you are receiving phototherapy (light therapy) for another condition, inform your doctor, as concurrent use of Protopic and phototherapy is not recommended.
Based on results from long-term clinical studies and post-marketing experience, no confirmed causal relationship between Protopic ointment treatment and the development of malignancies has been established. However, definitive conclusions cannot be drawn, and current guidelines recommend using the lowest effective strength at the lowest frequency for the shortest possible duration. If your doctor prescribes Protopic for maintenance therapy (twice weekly), your condition should be reviewed at least once per year. For children, a break in maintenance treatment should be made after 12 months to assess whether continued therapy is needed.
During Protopic treatment, minimise sun exposure and UV light. Use broad-spectrum sunscreen (SPF 30+), wear protective clothing, and avoid tanning beds. If you are prescribed phototherapy, inform your doctor that you are using Protopic.
Pregnancy and Breastfeeding
If you are pregnant, breastfeeding, think you may be pregnant, or are planning to have a baby, consult your doctor or pharmacist before using Protopic. The safety of topical tacrolimus during pregnancy has not been fully established in human studies. Animal studies with systemic tacrolimus have shown reproductive toxicity at high doses, though relevance to topical application at therapeutic doses is uncertain.
It is known that tacrolimus can pass into breast milk when taken orally. Although systemic absorption from topical Protopic is minimal, the decision to breastfeed while using this medication should be made in consultation with your healthcare provider, weighing the benefits of treatment against any potential risks to the infant.
Use in Children
Protopic 0.03% ointment is approved for use in children aged 2 years and older with moderate to severe atopic dermatitis who have not responded adequately to conventional treatments. The 0.1% strength is not approved for children and should only be used in adults aged 16 years and over. Protopic must not be used in children under the age of 2 years, as the effects on the developing immune system in very young children have not been adequately studied.
Other Medicines, Cosmetics, and Protopic
Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines. You may use emollient creams and moisturising lotions during Protopic treatment, but these products should not be applied within two hours before or after using Protopic, as they may interfere with absorption.
The concurrent use of Protopic with other topical medications applied to the same skin area, oral corticosteroids (such as prednisolone), or systemic immunosuppressive agents has not been studied in clinical trials and is generally not recommended without medical supervision.
Drinking alcohol while using Protopic may cause flushing (redness and a sensation of warmth) in the skin or face. This effect is not harmful but can be uncomfortable. You may wish to limit alcohol intake during treatment.
How Does Protopic Interact with Other Drugs?
Unlike oral tacrolimus (used in transplant medicine), topical Protopic is absorbed into the bloodstream in very small amounts. In most patients, blood levels of tacrolimus remain below the limit of quantification (less than 1 ng/mL). This means that systemic drug interactions are unlikely under normal conditions of use. However, certain situations may warrant caution.
In patients with extensive skin barrier damage (such as those with generalised erythroderma or Netherton syndrome), systemic absorption may be higher than normal. In these patients, the use of CYP3A4 inhibitors could theoretically increase tacrolimus blood levels. CYP3A4 is the primary enzyme responsible for metabolising tacrolimus in the liver, and drugs that inhibit this enzyme can slow the breakdown of tacrolimus.
The table below summarises the key drug interactions to be aware of when using Protopic. Note that these interactions are primarily relevant if significant systemic absorption occurs, which is uncommon with topical application on intact or mildly damaged skin.
| Drug / Drug Class | Interaction Type | Clinical Significance | Recommendation |
|---|---|---|---|
| Erythromycin, Clarithromycin | CYP3A4 inhibitor | May increase tacrolimus levels if significant systemic absorption occurs | Use with caution; monitor for increased side effects |
| Itraconazole, Ketoconazole | Strong CYP3A4 inhibitor | Potentially significant increase in tacrolimus blood levels | Avoid concurrent use on large body surface areas |
| Fluconazole | Moderate CYP3A4 inhibitor | May modestly increase tacrolimus exposure | Monitor if used on extensive skin areas |
| Rifampicin | CYP3A4 inducer | May reduce tacrolimus efficacy | Unlikely clinically relevant for topical use |
| Other topical treatments | Absorption interference | May alter absorption of Protopic | Apply emollients at least 2 hours apart from Protopic |
| Systemic immunosuppressants | Additive immunosuppression | Theoretical risk of increased immunosuppression | Not studied; use under specialist supervision only |
Vaccines and Protopic
There is no specific contraindication for vaccination while using topical Protopic. However, because tacrolimus is an immunomodulator, it is theoretically possible that the effectiveness of vaccines could be affected if Protopic is applied over very large body surface areas. If you are due to receive a vaccine, particularly a live vaccine, discuss the timing with your doctor. In general, routine vaccination schedules should be followed as normal.
What Is the Correct Dosage of Protopic?
Always use Protopic exactly as your doctor has prescribed. Apply a thin layer of the ointment to the affected skin areas. Protopic can be used on most body parts, including the face, neck, and skin folds such as the elbows and behind the knees. However, avoid applying the ointment inside the nose, mouth, or eyes. If the ointment accidentally comes into contact with these areas, wipe it off carefully and rinse with water.
Do not cover treated skin areas with bandages, dressings, or occlusive wraps. Wash your hands after applying Protopic, unless your hands are being treated. Before applying Protopic after a bath or shower, make sure your skin is completely dry first.
Children (2 Years and Older)
Protopic 0.03% – Paediatric Dosage
Acute treatment: Apply Protopic 0.03% ointment twice daily (morning and evening) for up to 3 weeks. After this initial period, reduce to once daily application on affected areas until the eczema clears.
Maintenance therapy: Once the eczema is clear or nearly clear, apply once daily on two days per week (e.g., Monday and Thursday), with 2–3 days between applications. A treatment break should be considered after 12 months to reassess.
Adults (16 Years and Older)
Protopic 0.1% or 0.03% – Adult Dosage
Acute treatment: Treatment usually begins with Protopic 0.1% ointment, applied twice daily (morning and evening) until the eczema clears. Depending on treatment response, your doctor may switch you to the 0.03% strength or reduce application frequency.
Maintenance therapy: Once the eczema is clear or nearly clear, apply Protopic (0.1% for adults) once daily on two days per week, with 2–3 treatment-free days between each application. If symptoms return, resume twice-daily treatment and consult your doctor.
Improvement is usually seen within the first week of treatment. If no improvement is noticed after two weeks, consult your doctor to discuss alternative treatment options. Your doctor will determine the most appropriate strength and duration of treatment based on how your eczema responds.
| Patient Group | Strength | Acute Treatment | Maintenance |
|---|---|---|---|
| Children (2–15 years) | 0.03% | Twice daily for up to 3 weeks, then once daily | Once daily, 2 days/week |
| Adults (16+ years) | 0.1% (initial), may step down to 0.03% | Twice daily until clear | Once daily, 2 days/week |
| Elderly | As per adult dosing | No dose adjustment required | As per adult maintenance |
Missed Dose
If you forget to apply Protopic at your usual time, apply it as soon as you remember, then continue with your normal schedule. Do not apply a double amount to make up for a missed application.
Overdose and Accidental Ingestion
If you accidentally swallow Protopic ointment, contact your doctor or pharmacist as soon as possible. Do not try to induce vomiting. If a large amount of ointment has been applied to the skin or ingested, medical attention should be sought promptly. Although serious systemic toxicity from topical application is extremely unlikely due to the very low absorption rate, accidental oral ingestion of the ointment requires medical evaluation.
What Are the Side Effects of Protopic?
Like all medicines, Protopic can cause side effects, although not everyone experiences them. The side effects associated with Protopic are predominantly localised to the area of application and tend to be most pronounced during the initial days of treatment, decreasing as the skin condition improves.
The burning sensation and itching that many patients experience when first starting Protopic are caused by the drug's interaction with sensory nerve fibres in the skin. This effect is transient and generally mild to moderate in severity. It is important to continue treatment as directed, as these symptoms almost always subside within the first 3 to 7 days of regular use.
Very Common
May affect more than 1 in 10 people
- Burning sensation at the application site
- Itching (pruritus) at the application site
Common
May affect up to 1 in 10 people
- Redness (erythema) at the application site
- Warmth or heat sensation
- Pain or stinging
- Increased skin sensitivity (especially to heat and cold)
- Tingling or paraesthesia
- Rash
- Localised skin reactions (e.g., inflamed or infected hair follicles / folliculitis)
- Herpes virus infections (e.g., cold sores, herpes simplex)
- Facial flushing or skin irritation after drinking alcohol
Uncommon
May affect up to 1 in 100 people
- Acne
Post-Marketing Reports
Reported after market introduction (frequency not precisely determined)
- Rosacea or rosacea-like dermatitis (facial redness)
- Lentigo (flat brown spots on the skin)
- Oedema (swelling) at the application site
- Herpetic eye infection (ocular herpes)
- Impetigo (superficial bacterial skin infection – reported in children during maintenance therapy)
- Application site infections (during twice-weekly maintenance therapy)
If you experience any worsening of your skin condition, new skin infections, or side effects that concern you, contact your doctor. It is particularly important to seek medical advice if you develop signs of a skin infection such as increased pain, swelling, pus, or spreading redness, as infected eczema may require additional treatment with antibiotics or antiviral medication.
Reporting suspected side effects after a medicine has been authorised is important for ongoing monitoring of its safety profile. Healthcare professionals and patients are encouraged to report suspected adverse reactions through their national pharmacovigilance system (e.g., the Yellow Card Scheme in the UK, MedWatch in the USA, or the EMA in the EU).
How Should You Store Protopic?
Proper storage of Protopic helps maintain its effectiveness and safety throughout the treatment period. The ointment should be stored at a temperature not exceeding 25°C (77°F). Do not freeze the ointment. Keep the tube tightly closed when not in use and store it in the original carton to protect it from light.
Keep Protopic out of the sight and reach of children at all times. Do not use the ointment after the expiry date stated on the tube and the outer carton after "EXP". The expiry date refers to the last day of the stated month. After opening the tube, use the ointment within the timeframe recommended by your pharmacist or as indicated in the patient information leaflet.
Do not dispose of Protopic via wastewater or household waste. Return unused or expired medication to your pharmacy for safe disposal. Proper disposal of medicines helps protect the environment and prevents accidental exposure.
What Does Protopic Contain?
Each gram of Protopic 0.03% ointment contains 0.3 mg of tacrolimus (as tacrolimus monohydrate) as the active ingredient. The ointment base consists of several excipients that provide the vehicle for drug delivery and ensure stability of the formulation:
- White petrolatum (white soft paraffin): The primary ointment base, providing an occlusive barrier that helps retain moisture in the skin and enhances drug penetration.
- Liquid paraffin (mineral oil): An emollient that helps soften the skin and improve the spreadability of the ointment.
- Propylene carbonate: A solvent that assists in dissolving tacrolimus within the ointment base for uniform distribution.
- White beeswax: Provides structure and consistency to the ointment.
- Hard paraffin: A thickening agent that contributes to the ointment's semi-solid consistency.
- Butylhydroxytoluene (BHT, E321): An antioxidant preservative. Note that BHT may cause localised skin reactions (such as contact dermatitis) or irritation to the eyes and mucous membranes in some individuals.
- All-rac-alpha-tocopherol (vitamin E): An antioxidant that helps prevent degradation of the active ingredient and other ointment components.
Protopic is a white to slightly yellowish ointment supplied in aluminium tubes containing 10, 30, or 60 grams. Not all pack sizes may be marketed in all countries. Protopic is available in two strengths: 0.03% and 0.1% ointment.
The marketing authorisation holder is LEO Pharma A/S, Industriparken 55, 2750 Ballerup, Denmark. Additional information about Protopic is available from the European Medicines Agency (EMA) website.
Frequently Asked Questions
Protopic (tacrolimus) ointment is used to treat moderate to severe atopic dermatitis (eczema) in adults and children aged 2 years and older who have not responded adequately to, or are intolerant of, conventional treatments such as topical corticosteroids. It can also be used as maintenance therapy twice weekly to prevent eczema flare-ups in patients who experience frequent recurrences (four or more times per year).
The most common side effects are a burning sensation and itching at the application site, occurring in more than 1 in 10 users. These are usually mild to moderate and resolve within the first week of treatment. Other common effects include redness, warmth, tingling, stinging, rash, folliculitis, herpes virus infections (e.g., cold sores), and facial flushing after alcohol consumption.
Yes, Protopic 0.03% ointment is approved for children aged 2 years and older with moderate to severe atopic dermatitis who have not responded to conventional therapies. The higher 0.1% strength is only approved for adults (16 years and older). Protopic should never be used in children under 2 years of age, as its effects on the developing immune system have not been adequately studied in this age group.
Unlike topical corticosteroids, Protopic does not cause skin thinning (atrophy), stretch marks, or visible blood vessels (telangiectasia), even with long-term use. This makes Protopic especially useful for sensitive areas such as the face, neck, eyelids, and skin folds where steroid-related skin damage is a concern. Protopic works by selectively inhibiting calcineurin in T-cells, while steroids have a broader mechanism that affects multiple cell types and pathways.
Yes, emollients and moisturising products can and should be used as part of your eczema management alongside Protopic. However, to avoid interference with absorption, do not apply moisturisers within two hours before or after applying Protopic. Regular use of emollients helps maintain the skin barrier and can reduce the frequency and severity of eczema flare-ups.
Long-term safety studies and extensive post-marketing surveillance have not confirmed a causal link between topical tacrolimus use and the development of malignancies. However, as a precaution, current guidelines recommend using the lowest effective strength for the shortest duration necessary. Maintenance therapy should be reviewed by your doctor at least once per year, and for children, a treatment break should be considered after 12 months to reassess the need for continued use.
References
- European Medicines Agency (EMA). Protopic – Summary of Product Characteristics. EMA/CHMP. Available at: ema.europa.eu/en/medicines/human/EPAR/protopic. Last updated 2025.
- Wollenberg A, et al. European guideline (EuroGuiDerm) on atopic eczema: part I – systemic therapy. J Eur Acad Dermatol Venereol. 2022;36(9):1409–1431. doi:10.1111/jdv.18345.
- Wollenberg A, et al. European guideline (EuroGuiDerm) on atopic eczema: part II – non-systemic treatments and treatment recommendations for special AE patient populations. J Eur Acad Dermatol Venereol. 2022;36(11):1904–1926. doi:10.1111/jdv.18429.
- Eichenfield LF, et al. Guidelines of care for the management of atopic dermatitis: section 2. Management and treatment with topical therapies. J Am Acad Dermatol. 2014;71(1):116–132. doi:10.1016/j.jaad.2014.03.023.
- Reitamo S, et al. Efficacy and safety of tacrolimus ointment compared with that of hydrocortisone butyrate ointment in adult patients with atopic dermatitis. J Allergy Clin Immunol. 2002;109(3):547–555. doi:10.1067/mai.2002.121832.
- Paller AS, et al. Tacrolimus ointment is more effective than pimecrolimus cream with a similar safety profile in the treatment of atopic dermatitis: results from 3 randomized, comparative studies. J Am Acad Dermatol. 2005;52(5):810–822. doi:10.1016/j.jaad.2004.12.038.
- Thaçi D, et al. Proactive disease management with 0.03% tacrolimus ointment for children with atopic dermatitis: results of a randomized, multicentre, comparative study. Br J Dermatol. 2008;159(6):1348–1356. doi:10.1111/j.1365-2133.2008.08813.x.
- British National Formulary (BNF). Tacrolimus (topical). NICE. Available at: bnf.nice.org.uk. Accessed January 2026.
- World Health Organization (WHO). Model List of Essential Medicines – 23rd List. Geneva: WHO; 2023.
- Arellano FM, et al. Risk of lymphoma following exposure to calcineurin inhibitors and topical steroids in patients with atopic dermatitis. J Invest Dermatol. 2007;127(4):808–816. doi:10.1038/sj.jid.5700622.
Editorial Team
This article has been written and reviewed by the iMedic Medical Editorial Team, comprising licensed specialist physicians in dermatology, clinical pharmacology, and immunology. All content is based on peer-reviewed research and current international guidelines.
iMedic Medical Editorial Team – Specialists in dermatology and clinical pharmacology with documented academic background and clinical experience in the management of atopic dermatitis and topical immunomodulatory therapy.
iMedic Medical Review Board – Independent panel of medical experts who review all content according to international guidelines (EMA, AAD, NICE, WHO) and the GRADE evidence framework.
All medical information on iMedic is evidence-based (Level 1A where available), reviewed by specialist physicians, and updated regularly. We follow the GRADE framework for evidence assessment and adhere to HONcode principles. iMedic receives no commercial funding or pharmaceutical sponsorship. For more details, see our Editorial Standards.