Tacrolimus

Tacrolimus ointment (Protopic) is the stronger of the two Topical Calcineurin Inhibitors (TCIs). It is used for moderate to severe Atopic Dermatitis. It comes in two strengths, 0.03% and 0.1%, and is a steroid-free anti-inflammatory: it blocks calcineurin, which T-cells need to switch on, and so damps the Th2 Immune Response (National Eczema Society). Unlike Topical Corticosteroids it does not cause Skin Atrophy, so it is mainly used on thin, sensitive skin: face, eyelids, neck and skin folds (PCDS). It can be used twice daily to treat a flare (up to about 6 weeks) or twice a week on non-consecutive days as maintenance (Weekend Therapy).

Tacrolimus [part-of] Topical Calcineurin Inhibitors Tacrolimus [treats] Atopic Dermatitis Tacrolimus [relates] Topical Corticosteroids Tacrolimus [part-of] Weekend Therapy

Licensing ages and toddler off-label use. In the UK the 0.03% strength is licensed from age 2 and the 0.1% strength from age 16 (National Eczema Society; PCDS). The FDA approved it in 2000 for children aged 2 and over, and in South Africa 0.03% is registered from age 2 for moderate to severe AD (South African Eczema Guidance, Kannenberg 2020). So for a toddler under 2 it is off-label everywhere. For a 2–4-year-old only 0.03% is licensed. NICE CG57 (TA82, 2004) recommends it as a second-line option for moderate to severe eczema in children aged 2 and over that TCS have not controlled, or where more TCS risks irreversible skin damage. NICE says to start TCIs only with specialist dermatological advice. In under-2s, where a steroid-free option is wanted, Pimecrolimus is the TCI that is licensed in the UK (from 3 months).

NICE CG57 [regulates] Tacrolimus FDA [regulates] Tacrolimus South African Eczema Guidance [regulates] Tacrolimus

Conflict: [NICE CG57 recommendations, 2004 TA82 wording, page updated 2025] says “start treatment with tacrolimus or pimecrolimus only with specialist dermatological advice”. [PCDS, n.d., post-2023] says GPs experienced in eczema can start TCIs. Unresolved — add to open_questions.

Evidence of benefit. Efficacy is well established. A Cochrane review (2015; 20 RCTs, 5,885 participants, cited by PCDS) supports tacrolimus for AD. For flare prevention, a meta-analysis of vehicle-controlled RCTs found twice-weekly tacrolimus cut the risk of a flare (RR 0.78, 95% CI 0.60–1.00). That is probably a smaller effect than proactive potent fluticasone (RR 0.46) by indirect comparison (Schmitt, Br J Dermatol 2011). TCIs work more slowly than TCS, which is one reason they are second-line. A common pattern is TCS to settle a flare, then tacrolimus to step down on the face.

Tacrolimus [prevents] Atopic Dermatitis Cochrane [supports] Tacrolimus

Side effects, burning and sun advice. The most common side effect is burning or stinging for 15–20 minutes after applying it. It is not an allergy and usually settles within the first week (National Eczema Society), but a toddler may resist the next application, so parents should expect it. Tacrolimus lowers local skin immunity. It should not go on skin with Impetigo, cold sores or suspected Eczema Herpeticum, and it is not used under Wet Wrap Therapy or other occlusion. Sun protection is advised on treated skin, because of the animal and transplant data behind the cancer warning. The manufacturer advises not applying emollient within 2 hours of tacrolimus. On cancer: the 2006 US boxed warning remains, but the APPLES paediatric tacrolimus cohort (n=7,954, 10 years) found no lymphoma signal. The Devasenapathy meta-analysis (2023; 110 studies, 3.4 million patients) found tacrolimus OR 0.99 for any cancer, and a 2026 FAERS analysis found no lymphoma signal. Lam et al. (2021) did find a raised lymphoma relative risk with TCIs; full details and the conflict are in Topical Calcineurin Inhibitors.

Tacrolimus [relates] Eczema Herpeticum FDA [opposes] Tacrolimus

Not on infected skin

Do not apply tacrolimus to skin with impetigo, cold sores, or punched-out sores with fever (possible eczema herpeticum). Seek same-day medical review instead.

Cost and access. Protopic 0.03% 30 g has an NHS indicative price of £23.33 (NHS dm+d). In the US a 60 g tube of generic 0.03% averages about $133 cash (GoodRx), and about half of Medicaid enrollees need prior authorisation (Cost of Eczema Care). In South Africa TCIs have limited availability in public clinics (Kannenberg 2020).

Tacrolimus [relates] Cost of Eczema Care

What parents report (evidence: anecdotal). Several parents say tacrolimus worked “within one or two applications, after trying steroids unsuccessfully for months” (r/ScienceBasedParenting) and was “very effective when steroidal topicals weren’t helping” (Mumsnet). One parent of a child with dark skin chose it partly over worry about steroid-related skin lightening. Parents’ downsides: the boxed warning (“put me off more than the dupixent”) with sun avoidance, and refusals for under-2s (r/eczema). See Parent Experiences.

Tacrolimus [relates] Parent Experiences

Connections

• Topical Calcineurin Inhibitors — one of two TCIs, source: National Eczema Society
• Weekend Therapy — proactive twice-weekly use, source: Schmitt 2011
• South African Eczema Guidance — SA 0.03% ≥2 y for moderate–severe AD, source: Kannenberg 2020
• Pimecrolimus — milder TCI, the licensed option under 2 in the UK, source: PCDS
• NICE CG57 — second-line from age 2; specialist initiation, source: NICE CG57/TA82
• FDA — 2000 approval ≥2 y; 2006 boxed warning, source: Arcuri 2026
• Cost of Eczema Care — £23.33/30 g NHS; ~$133/60 g US, source: NHS dm+d; GoodRx
• Eczema Herpeticum — avoid on infected skin, source: National Eczema Society
• Wet Wrap Therapy — not under occlusion, source: National Eczema Society; NICE CG57
• Skin Atrophy — does not cause it, source: PCDS
• Parent Experiences — parent reports (anecdotal), source: round-10 forum threads