Pimecrolimus side effects: what 1,703 FDA adverse event reports show
Drug class
Calcineurin Inhibitor Immunosuppressant
Who reports
1,703 reports · 32% serious · 22 with death outcome · 65% female
Used for
Pimecrolimus cream, 1% is indicated as second-line therapy for the short-term and non-continuous chronic treatment of mild to moderate atopic dermatitis in non-immunocompromised adults and children 2 years of age and older, who have failed to respond adequately to other topical prescription treatments, or when those treatments are not advisable.
What it is
Pimecrolimus cream, 1%, for topical use, contains the compound pimecrolimus, the immunosuppressant 33-epi-chloro-derivative of the macrolactam ascomycin.
Boxed warning
LONG-TERM SAFETY OF TOPICAL CALCINEURIN INHIBITORS HAS NOT BEEN ESTABLISHED Although a causal relationship has not been established, rare cases of malignancy (e.g., skin and lymphoma) have been reported in patients treated with topical calcineurin inhibitors, including pimecrolimus cream, 1% [see Warnings and Precautions (5.1) ].
Causality screen of the 40 strongest signals
What the badges mean
- Labeled — boxed warning The term (or its clinical synonym) appears in the FDA boxed warning: causality is regulator-recognised and considered serious.
- Labeled adverse reaction The exact term appears in the label's warnings or adverse-reactions sections: a known, expected effect. The FAERS signal confirms the label rather than discovering anything.
- Labeled (related wording) The label describes this effect under different wording (e.g. 'neutropenia' for 'neutrophil count decreased'). Treated as known.
- Likely indication confounding The term appears in the label's indications: reports probably describe the disease being treated (or its progression), not a drug effect. Classic confounding by indication.
- Reporting / coding artifact An administrative, monitoring or exposure term (product issue, off-label use, 'test normal', overdose...). Not a biological reaction; a high PRR here reflects how reports are coded.
- Not in label — unassessed Not found in the label text, not an artifact pattern. This is a genuine candidate for a formal causality assessment (Bradford Hill / WHO-UMC); it has NOT had one here.
Strongest disproportionality signals
Flagged terms (PRR ≥ 2, χ² ≥ 4, n ≥ 10), ranked by PRR; infinite PRRs (no comparator reports) excluded. The EBGM column is a second, shrinkage-based estimate (MGPS) with its 5th percentile EB05 and the BCPNN IC025; a pair flagged by PRR alone is marked PRR-only and should be read as fragile. The strata column recomputes the PRR on serious reports only and flags pairs whose reports are unusually skewed by sex or come mostly from consumers rather than clinicians. 25 further terms are in the interactive explorer. Reaction links open the term's cross-drug page.
| Reaction | Reports | PRR 95% CI · ROR · χ²/p | EBGM EB05 · IC025 | Label screen | Serious-only & strata | Trial cross-check |
|---|---|---|---|---|---|---|
| Sleep disorder due to a general medical condition | 66 | 50.4 39.8–63.9ROR 52.4 · χ² 3,137 / p <1e-300 | 49.5 EB05 40.3 · IC025 +4.8 3/3 methods agree | Not in label — unassessed | serious PRR 18.7 | no trial data cached |
| Dermatitis atopic | 200 | 49.5 43.4–56.4ROR 55.9 · χ² 9,432 / p <1e-300 | 49.0 EB05 43.6 · IC025 +5.2 3/3 methods agree | Likely indication confounding term in indications; also in warnings | serious n=22 | no trial data cached |
| Skin fissures | 41 | 26.8 19.8–36.2ROR 27.4 · χ² 990 / p 1e-217 | 26.4 EB05 20.3 · IC025 +3.8 3/3 methods agree | Not in label — unassessed | serious n=6 | no trial data cached |
| Eczema | 97 | 23.8 19.6–28.8ROR 25.1 · χ² 2,094 / p <1e-300 | 23.6 EB05 19.9 · IC025 +4.1 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 21.6 | no trial data cached |
| Impaired quality of life | 23 | 19.7 13.1–29.6ROR 20.0 · χ² 389 / p 6e-87 | 19.3 EB05 13.5 · IC025 +3.1 3/3 methods agree | Not in label — unassessed | serious PRR 2.3 · 100% clinician | no trial data cached |
| Skin haemorrhage | 20 | 17.1 11.0–26.4ROR 17.3 · χ² 287 / p 1e-64 | 16.6 EB05 11.0 · IC025 +2.9 3/3 methods agree | Not in label — unassessed | serious n=2 | no trial data cached |
| Dermatitis | 25 | 14.9 10.1–21.9ROR 15.1 · χ² 309 / p 1e-69 | 14.4 EB05 10.0 · IC025 +2.9 3/3 methods agree | Labeled — boxed warning exact term | serious PRR 10.7 | no trial data cached |
| Dermatitis contact | 13 | 14.1 8.2–24.2ROR 14.2 · χ² 145 / p 9e-34 | 12.9 EB05 7.2 · IC025 +2.3 3/3 methods agree | Labeled (related wording) related wording | serious n=7 | no trial data cached |
| Scratch | 10 | 11.9 6.4–22.1ROR 12.0 · χ² 89 / p 2e-21 | 9.8 EB05 5.0 · IC025 +1.9 3/3 methods agree | Not in label — unassessed | serious n=1 | no trial data cached |
| Skin exfoliation | 76 | 11.3 9.0–14.0ROR 11.7 · χ² 703 / p 4e-155 | 11.1 EB05 9.0 · IC025 +3.0 3/3 methods agree | Not in label — unassessed | serious PRR 9.3 | no trial data cached |
| Skin infection | 10 | 11.0 5.9–20.5ROR 11.1 · χ² 81 / p 9e-20 | 8.9 EB05 4.7 · IC025 +1.8 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 21.6 | no trial data cached |
| Discomfort | 53 | 10.8 8.3–14.0ROR 11.1 · χ² 461 / p 2e-102 | 10.4 EB05 8.2 · IC025 +2.8 3/3 methods agree | Not in label — unassessed | serious PRR 7.6 | no trial data cached |
| Oral herpes | 17 | 10.8 6.7–17.3ROR 10.9 · χ² 141 / p 8e-33 | 9.6 EB05 5.9 · IC025 +2.3 3/3 methods agree | Not in label — unassessed | serious PRR 7.9 | no trial data cached |
| Conjunctivitis | 16 | 10.7 6.6–17.5ROR 10.8 · χ² 132 / p 1e-30 | 9.4 EB05 5.8 · IC025 +2.2 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 6.6 | no trial data cached |
| Eye pruritus | 28 | 10.5 7.2–15.1ROR 10.6 · χ² 230 / p 3e-52 | 9.8 EB05 6.8 · IC025 +2.5 3/3 methods agree | Labeled (related wording) related wording | serious PRR 4.9 | no trial data cached |
| Therapeutic response shortened | 26 | 10.1 6.9–14.7ROR 10.2 · χ² 203 / p 2e-46 | 9.3 EB05 6.4 · IC025 +2.4 3/3 methods agree | Reporting / coding artifact | serious PRR 8.1 · 92% clinician | no trial data cached |
| Dry skin | 101 | 9.5 7.8–11.4ROR 10.0 · χ² 759 / p 2e-167 | 9.2 EB05 7.8 · IC025 +2.9 3/3 methods agree | Labeled (related wording) related wording | serious PRR 7.9 | no trial data cached |
| Sleep disorder | 52 | 9.2 7.0–12.0ROR 9.4 · χ² 370 / p 8e-83 | 8.7 EB05 6.8 · IC025 +2.6 3/3 methods agree | Not in label — unassessed | serious PRR 1.5 | no trial data cached |
| Application site pain | 16 | 8.9 5.5–14.6ROR 9.0 · χ² 105 / p 6e-25 | 7.7 EB05 4.8 · IC025 +2.0 3/3 methods agree | Labeled (related wording) related wording | – | no trial data cached |
| Dry eye | 34 | 8.6 6.2–12.1ROR 8.8 · χ² 222 / p 1e-50 | 8.0 EB05 5.9 · IC025 +2.4 3/3 methods agree | Not in label — unassessed | serious PRR 3.7 | no trial data cached |
| Drug ineffective for unapproved indication | 38 | 8.4 6.1–11.5ROR 8.6 · χ² 241 / p 1e-54 | 7.8 EB05 5.9 · IC025 +2.4 3/3 methods agree | Reporting / coding artifact | serious PRR 9.6 | no trial data cached |
| Eye irritation | 38 | 8.4 6.1–11.5ROR 8.6 · χ² 241 / p 1e-54 | 7.8 EB05 5.9 · IC025 +2.4 3/3 methods agree | Labeled (related wording) related wording | serious PRR 3.9 | no trial data cached |
| Rash macular | 22 | 7.8 5.1–11.8ROR 7.9 · χ² 123 / p 6e-29 | 6.9 EB05 4.7 · IC025 +2.0 3/3 methods agree | Not in label — unassessed | serious PRR 3.1 | no trial data cached |
| Ocular hyperaemia | 29 | 7.6 5.3–11.0ROR 7.8 · χ² 161 / p 3e-37 | 7.0 EB05 5.0 · IC025 +2.2 3/3 methods agree | Not in label — unassessed | serious PRR 6.9 | no trial data cached |
| Product dose omission in error | 16 | 7.3 4.5–11.9ROR 7.4 · χ² 81 / p 9e-20 | 6.2 EB05 4.0 · IC025 +1.8 3/3 methods agree | Reporting / coding artifact | serious PRR 6.4 | no trial data cached |
| Product prescribing issue | 12 | 7.3 4.1–12.8ROR 7.3 · χ² 59 / p 9e-15 | 5.9 EB05 3.5 · IC025 +1.6 3/3 methods agree | Reporting / coding artifact | serious PRR 5.6 | no trial data cached |
| Skin lesion | 15 | 6.8 4.1–11.2ROR 6.8 · χ² 68 / p 7e-17 | 5.7 EB05 3.7 · IC025 +1.6 3/3 methods agree | Labeled (related wording) related wording | serious PRR 13.5 | no trial data cached |
| Product use in unapproved indication | 126 | 6.3 5.4–7.5ROR 6.8 · χ² 569 / p 5e-126 | 6.2 EB05 5.4 · IC025 +2.3 3/3 methods agree | Reporting / coding artifact | serious PRR 3.2 | no trial data cached |
| Therapeutic response decreased | 31 | 6.3 4.5–9.0ROR 6.4 · χ² 134 / p 3e-31 | 5.8 EB05 4.3 · IC025 +1.9 3/3 methods agree | Reporting / coding artifact | serious PRR 2.8 | no trial data cached |
| Pruritus (itching) | 193 | 6.3 5.5–7.2ROR 7.0 · χ² 868 / p 4e-191 | 6.2 EB05 5.5 · IC025 +2.4 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 4.2 | no trial data cached |
| Treatment failure | 40 | 6.0 4.4–8.1ROR 6.1 · χ² 162 / p 2e-37 | 5.6 EB05 4.3 · IC025 +2.0 3/3 methods agree | Reporting / coding artifact | serious PRR 4.1 | no trial data cached |
| Exposure via skin contact | 10 | 5.4 2.9–10.1ROR 5.5 · χ² 32 / p 8e-9 | 4.4 EB05 2.6 · IC025 +1.1 3/3 methods agree | Reporting / coding artifact | serious n=1 | no trial data cached |
| Skin discolouration | 20 | 5.4 3.5–8.3ROR 5.4 · χ² 67 / p 2e-16 | 4.8 EB05 3.3 · IC025 +1.5 3/3 methods agree | Not in label — unassessed | serious PRR 7.6 | no trial data cached |
| Rash pruritic | 22 | 5.0 3.3–7.6ROR 5.1 · χ² 67 / p 1e-16 | 4.6 EB05 3.2 · IC025 +1.5 3/3 methods agree | Not in label — unassessed | serious PRR 8.7 | no trial data cached |
| Psoriatic arthropathy | 16 | 4.9 3.0–8.0ROR 4.9 · χ² 46 / p 6e-12 | 4.3 EB05 2.8 · IC025 +1.3 3/3 methods agree | Not in label — unassessed | serious PRR 9.6 | no trial data cached |
| Psoriasis | 45 | 4.2 3.2–5.7ROR 4.3 · χ² 109 / p 9e-26 | 4.1 EB05 3.2 · IC025 +1.5 3/3 methods agree | Not in label — unassessed | serious PRR 7.3 | no trial data cached |
| Skin burning sensation | 19 | 3.3 2.1–5.1ROR 3.3 · χ² 28 / p 6e-8 | 3.1 EB05 2.1 · IC025 +0.9 3/3 methods agree | Labeled (related wording) related wording | serious PRR 7.1 | no trial data cached |
| Injection site pain (pain where injected) | 75 | 3.0 2.4–3.8ROR 3.1 · χ² 102 / p 3e-24 | 3.0 EB05 2.5 · IC025 +1.2 3/3 methods agree | Labeled (related wording) related wording | serious PRR 4.2 | no trial data cached |
| Skin irritation | 11 | 2.9 1.6–5.3ROR 3.0 · χ² 12 / p 2e-4 | 2.7 EB05 1.6 · IC025 +0.4 | Labeled (related wording) related wording | serious n=4 | no trial data cached |
| Injection site reaction | 16 | 2.9 1.8–4.7ROR 2.9 · χ² 18 / p 1e-5 | 2.7 EB05 1.8 · IC025 +0.6 | Not in label — unassessed | serious PRR 6.6 | no trial data cached |
Trial evidence (ClinicalTrials.gov)
Most frequently reported reactions
By raw co-report count, regardless of disproportionality. Common terms here are often the illness itself or generic outcomes.
| Reaction | Reports | PRR 95% CI · ROR · χ²/p | EBGM EB05 · IC025 | Label screen | Serious-only & strata | Trial cross-check |
|---|---|---|---|---|---|---|
| Dermatitis atopic | 200 | 49.5 43.4–56.4ROR 55.9 · χ² 9,432 / p <1e-300 | 49.0 EB05 43.6 · IC025 +5.2 3/3 methods agree | Likely indication confounding term in indications; also in warnings | serious n=22 | no trial data cached |
| Pruritus (itching) | 193 | 6.3 5.5–7.2ROR 7.0 · χ² 868 / p 4e-191 | 6.2 EB05 5.5 · IC025 +2.4 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 4.2 | no trial data cached |
| Product use in unapproved indication | 126 | 6.3 5.4–7.5ROR 6.8 · χ² 569 / p 5e-126 | 6.2 EB05 5.4 · IC025 +2.3 3/3 methods agree | Reporting / coding artifact | serious PRR 3.2 | no trial data cached |
| Dry skin | 101 | 9.5 7.8–11.4ROR 10.0 · χ² 759 / p 2e-167 | 9.2 EB05 7.8 · IC025 +2.9 3/3 methods agree | Labeled (related wording) related wording | serious PRR 7.9 | no trial data cached |
| Eczema | 97 | 23.8 19.6–28.8ROR 25.1 · χ² 2,094 / p <1e-300 | 23.6 EB05 19.9 · IC025 +4.1 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 21.6 | no trial data cached |
| Skin exfoliation | 76 | 11.3 9.0–14.0ROR 11.7 · χ² 703 / p 4e-155 | 11.1 EB05 9.0 · IC025 +3.0 3/3 methods agree | Not in label — unassessed | serious PRR 9.3 | no trial data cached |
| Injection site pain (pain where injected) | 75 | 3.0 2.4–3.8ROR 3.1 · χ² 102 / p 3e-24 | 3.0 EB05 2.5 · IC025 +1.2 3/3 methods agree | Labeled (related wording) related wording | serious PRR 4.2 | no trial data cached |
| Sleep disorder due to a general medical condition | 66 | 50.4 39.8–63.9ROR 52.4 · χ² 3,137 / p <1e-300 | 49.5 EB05 40.3 · IC025 +4.8 3/3 methods agree | Not in label — unassessed | serious PRR 18.7 | no trial data cached |
| Discomfort | 53 | 10.8 8.3–14.0ROR 11.1 · χ² 461 / p 2e-102 | 10.4 EB05 8.2 · IC025 +2.8 3/3 methods agree | Not in label — unassessed | serious PRR 7.6 | no trial data cached |
| Sleep disorder | 52 | 9.2 7.0–12.0ROR 9.4 · χ² 370 / p 8e-83 | 8.7 EB05 6.8 · IC025 +2.6 3/3 methods agree | Not in label — unassessed | serious PRR 1.5 | no trial data cached |
| Psoriasis | 45 | 4.2 3.2–5.7ROR 4.3 · χ² 109 / p 9e-26 | 4.1 EB05 3.2 · IC025 +1.5 3/3 methods agree | Not in label — unassessed | serious PRR 7.3 | no trial data cached |
| Skin fissures | 41 | 26.8 19.8–36.2ROR 27.4 · χ² 990 / p 1e-217 | 26.4 EB05 20.3 · IC025 +3.8 3/3 methods agree | Not in label — unassessed | serious n=6 | no trial data cached |
| Treatment failure | 40 | 6.0 4.4–8.1ROR 6.1 · χ² 162 / p 2e-37 | 5.6 EB05 4.3 · IC025 +2.0 3/3 methods agree | Reporting / coding artifact | serious PRR 4.1 | no trial data cached |
| Eye irritation | 38 | 8.4 6.1–11.5ROR 8.6 · χ² 241 / p 1e-54 | 7.8 EB05 5.9 · IC025 +2.4 3/3 methods agree | Labeled (related wording) related wording | serious PRR 3.9 | no trial data cached |
| Drug ineffective for unapproved indication | 38 | 8.4 6.1–11.5ROR 8.6 · χ² 241 / p 1e-54 | 7.8 EB05 5.9 · IC025 +2.4 3/3 methods agree | Reporting / coding artifact | serious PRR 9.6 | no trial data cached |
Unlabeled candidate signals
These flagged terms were not found in the FDA label text and do not match an artifact pattern. They are the pairs that would merit a structured assessment (temporality, dose-response, biological plausibility, consistency across databases, trial or cohort evidence). The screen has not done that; string-matching misses label wording, and a strong PRR can still be stimulated reporting, co-medication, or the disease itself.
- Sleep disorder due to a general medical condition — n=66, PRR 50.4
- Skin fissures — n=41, PRR 26.8
- Impaired quality of life — n=23, PRR 19.7
- Skin haemorrhage — n=20, PRR 17.1
- Skin exfoliation — n=76, PRR 11.3
- Discomfort — n=53, PRR 10.8
- Sleep disorder — n=52, PRR 9.2
- Dry eye — n=34, PRR 8.6
- Rash macular — n=22, PRR 7.8
- Ocular hyperaemia — n=29, PRR 7.6
Want to assess one of these properly? The runbook describes the Bradford Hill / trial-evidence workflow used on the assessment page, and handoff_top1000_signals.csv lists the strongest unassessed pairs across all drugs.
Common questions
What are the most reported side effects of Pimecrolimus?
In FDA FAERS, the most frequently co-reported reaction terms for Pimecrolimus are dermatitis atopic, pruritus, dry skin, eczema, skin exfoliation, injection site pain. These are report counts, not rates: FAERS has no denominator, reporting is voluntary and uneven, and a term can be reported because of the illness being treated rather than the drug.
Does Pimecrolimus have an FDA boxed warning?
Yes. The current FDA label carries a boxed warning: LONG-TERM SAFETY OF TOPICAL CALCINEURIN INHIBITORS HAS NOT BEEN ESTABLISHED Although a causal relationship has not been established, rare cases of malignancy (e.g., skin and lymphoma) have been reported in patients treated with topical calcineurin inhibitors, including pimecrolimus cream, 1% [see Warnings and Precautions (5.1) ].
Do FAERS signals prove that Pimecrolimus causes these side effects?
No. A disproportionality signal (PRR, ROR) means a reaction is reported more often with this drug than with others in the database. That can reflect a real effect, but also the disease being treated, stimulated reporting after news or litigation, co-medications, or how reports are coded. Causality needs temporality, dose-response, biological plausibility, consistency across data sources and, ideally, trial or cohort evidence. This page screens each term against the FDA label and ClinicalTrials.gov results; it does not establish causation.
Sources & methods
- FDA label via openFDA (set ID d5b0403a-065f-42e3-96d6-7dcb9ab127d3, effective 20180507; matched on
openfda.generic_name.exact:"PIMECROLIMUS") - Bayesian shrinkage measures computed offline over all 1,317,300 cached pairs: BCPNN information component (IC, with Norén closed-form IC025) and MGPS empirical-Bayes geometric mean (EBGM, EB05) with a two-component gamma prior fitted by maximum marginal likelihood (α₁=0.57, β₁=0.02, α₂=1.42, β₂=0.70, w=0.17); unstratified
- FAERS pair statistics from the OpenPV build of 2026-09-14 (openFDA
count=aggregation, fieldpatient.drug.openfda.generic_name.exact, 65 reaction terms, min 3 co-reports); PRR/ROR with 95% CI, chi-square with Yates correction - Serious-only and stratified counts (serious:1, patient.patientsex, primarysource.qualification) from openFDA count queries; serious-only PRR uses the drug serious report total and the term global serious total (N_serious=11,882,979); strata shown only when n ≥ 20
- Seriousness and sex counts from openFDA
count=serious,patient.patientsex,seriousnessdeath
Page generated 2026-10-08. Label and PubChem text are retrieved automatically and may lag the current label; always check the current prescribing information. OpenPV is a beta research tool of the Open Source Medicine Foundation.