Enasidenib side effects: what 3,293 FDA adverse event reports show
Drug class
Isocitrate dehydrogenase-2 inhibitor
Label matched
Enasidenib Mesylate (Idhifa)
Who reports
3,293 reports · 61% serious · 822 with death outcome · 42% female
Used for
IDHIFA is an isocitrate dehydrogenase-2 inhibitor indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with an isocitrate dehydrogenase-2 (IDH2) mutation as detected by an FDA-approved test ( 1.1 ). 1.1.
What it is
Enasidenib is an inhibitor of isocitrate dehydrogenase-2 (IDH2) enzyme. Enasidenib is available as the mesylate salt with the chemical name: 2-methyl-1-[(4-[6-(trifluoromethyl)pyridin-2-yl]-6-{[2-(trifluoromethyl)pyridin-4-yl]amino}-1,3,5-triazin-2-yl)amino]propan-2-ol methanesulfonate.
Boxed warning
DIFFERENTIATION SYNDROME Patients treated with IDHIFA have experienced symptoms of differentiation syndrome, which can be fatal if not treated. Symptoms may include fever, dyspnea, acute respiratory distress, pulmona.
Causality screen of the 21 strongest signals
What the badges mean
- 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.
- Lab value / disease marker A laboratory result, investigation or disease-activity marker (antibody positive, CRP abnormal, swollen joint count) not described in the label. These usually mirror the monitored disease or testing protocol rather than a drug effect; not screened further.
- Outcome field, not a reaction Death is a report outcome, not a reaction term. It is dominated by the underlying illness; see the seriousness profile and the boxed warning instead.
- 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. 11 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 |
|---|---|---|---|---|---|---|
| Acute myeloid leukaemia | 119 | 49.0 41.0–58.5ROR 50.8 · χ² 5,507 / p <1e-300 | 48.3 EB05 41.4 · IC025 +5.0 3/3 methods agree | Likely indication confounding term in indications | serious PRR 32.0 | no trial data cached |
| Full blood count decreased | 80 | 25.3 20.4–31.5ROR 25.9 · χ² 1,840 / p <1e-300 | 25.1 EB05 20.8 · IC025 +4.1 3/3 methods agree | Lab value / disease marker | serious PRR 25.6 | no trial data cached |
| Leukaemia | 27 | 18.3 12.5–26.6ROR 18.4 · χ² 422 / p 4e-94 | 17.9 EB05 12.8 · IC025 +3.2 3/3 methods agree | Likely indication confounding term in indications | serious PRR 15.3 | no trial data cached |
| Taste disorder | 33 | 10.5 7.5–14.7ROR 10.6 · χ² 274 / p 9e-62 | 9.9 EB05 7.2 · IC025 +2.6 3/3 methods agree | Not in label — unassessed | serious PRR 9.6 | no trial data cached |
| Blood bilirubin increased | 34 | 8.0 5.7–11.2ROR 8.1 · χ² 201 / p 6e-46 | 7.4 EB05 5.5 · IC025 +2.3 3/3 methods agree | Lab value / disease marker | serious PRR 3.5 | no trial data cached |
| Full blood count abnormal | 13 | 7.9 4.6–13.5ROR 7.9 · χ² 71 / p 2e-17 | 6.5 EB05 3.9 · IC025 +1.7 3/3 methods agree | Lab value / disease marker | serious PRR 5.3 | no trial data cached |
| Platelet count decreased | 125 | 7.5 6.3–8.9ROR 7.7 · χ² 697 / p 6e-154 | 7.3 EB05 6.3 · IC025 +2.6 3/3 methods agree | Labeled (related wording) related wording | serious PRR 6.7 | no trial data cached |
| Hospitalisation | 178 | 7.4 6.4–8.6ROR 7.8 · χ² 992 / p 5e-218 | 7.3 EB05 6.5 · IC025 +2.6 3/3 methods agree | Reporting / coding artifact | serious PRR 7.0 · 89% consumer | no trial data cached |
| Red blood cell count decreased | 32 | 7.1 5.0–10.0ROR 7.2 · χ² 162 / p 2e-37 | 6.5 EB05 4.8 · IC025 +2.1 3/3 methods agree | Lab value / disease marker | serious PRR 6.6 | no trial data cached |
| White blood cell count increased | 31 | 5.1 3.6–7.3ROR 5.2 · χ² 99 / p 1e-23 | 4.8 EB05 3.5 · IC025 +1.7 3/3 methods agree | Lab value / disease marker | serious PRR 3.5 | no trial data cached |
| Death | 666 | 4.9 4.6–5.3ROR 5.9 · χ² 2,165 / p <1e-300 | 4.9 EB05 4.6 · IC025 +2.2 3/3 methods agree | Outcome field, not a reaction boxed warning mentions mortality | serious PRR 4.6 | no trial data cached |
| Blood count abnormal | 11 | 4.6 2.5–8.2ROR 4.6 · χ² 27 / p 1e-7 | 3.9 EB05 2.3 · IC025 +1.0 3/3 methods agree | Lab value / disease marker | serious PRR 3.8 | no trial data cached |
| Blood test abnormal | 10 | 4.5 2.4–8.4ROR 4.5 · χ² 24 / p 5e-7 | 3.8 EB05 2.3 · IC025 +0.9 3/3 methods agree | Reporting / coding artifact | serious PRR 3.3 | no trial data cached |
| White blood cell count decreased | 73 | 4.3 3.4–5.4ROR 4.4 · χ² 181 / p 1e-41 | 4.2 EB05 3.4 · IC025 +1.7 3/3 methods agree | Labeled (related wording) related wording | serious PRR 3.9 | no trial data cached |
| Haemoglobin decreased | 54 | 3.3 2.6–4.4ROR 3.4 · χ² 87 / p 7e-21 | 3.3 EB05 2.6 · IC025 +1.3 3/3 methods agree | Labeled (related wording) related wording | serious PRR 2.9 | no trial data cached |
| Neutrophil count decreased | 20 | 3.1 2.0–4.9ROR 3.2 · χ² 27 / p 9e-8 | 3.0 EB05 2.0 · IC025 +0.8 3/3 methods agree | Labeled (related wording) related wording | serious PRR 2.7 | no trial data cached |
| Adverse event | 45 | 3.1 2.3–4.2ROR 3.1 · χ² 62 / p 1e-15 | 3.0 EB05 2.4 · IC025 +1.1 3/3 methods agree | Reporting / coding artifact | serious PRR 3.4 · 80% consumer | no trial data cached |
| Laboratory test abnormal | 13 | 2.8 1.6–4.8ROR 2.8 · χ² 13 / p 1e-4 | 2.6 EB05 1.7 · IC025 +0.5 | Reporting / coding artifact | serious PRR 1.9 | no trial data cached |
| Ageusia (loss of taste) | 11 | 2.8 1.6–5.0ROR 2.8 · χ² 11 / p 5e-4 | 2.6 EB05 1.6 · IC025 +0.4 | Not in label — unassessed | serious PRR 2.1 | no trial data cached |
| Adverse drug reaction | 34 | 2.4 1.7–3.4ROR 2.4 · χ² 27 / p 1e-7 | 2.4 EB05 1.8 · IC025 +0.7 | Reporting / coding artifact | serious PRR 2.5 | no trial data cached |
| Jaundice (yellowing of skin/eyes) | 10 | 2.4 1.3–4.4ROR 2.4 · χ² 7 / p 0.005 | 2.2 EB05 1.3 · IC025 +0.1 | Not in label — unassessed | serious PRR 1.4 | 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 |
|---|---|---|---|---|---|---|
| Death | 666 | 4.9 4.6–5.3ROR 5.9 · χ² 2,165 / p <1e-300 | 4.9 EB05 4.6 · IC025 +2.2 3/3 methods agree | Outcome field, not a reaction boxed warning mentions mortality | serious PRR 4.6 | no trial data cached |
| Hospitalisation | 178 | 7.4 6.4–8.6ROR 7.8 · χ² 992 / p 5e-218 | 7.3 EB05 6.5 · IC025 +2.6 3/3 methods agree | Reporting / coding artifact | serious PRR 7.0 · 89% consumer | no trial data cached |
| Platelet count decreased | 125 | 7.5 6.3–8.9ROR 7.7 · χ² 697 / p 6e-154 | 7.3 EB05 6.3 · IC025 +2.6 3/3 methods agree | Labeled (related wording) related wording | serious PRR 6.7 | no trial data cached |
| Acute myeloid leukaemia | 119 | 49.0 41.0–58.5ROR 50.8 · χ² 5,507 / p <1e-300 | 48.3 EB05 41.4 · IC025 +5.0 3/3 methods agree | Likely indication confounding term in indications | serious PRR 32.0 | no trial data cached |
| Full blood count decreased | 80 | 25.3 20.4–31.5ROR 25.9 · χ² 1,840 / p <1e-300 | 25.1 EB05 20.8 · IC025 +4.1 3/3 methods agree | Lab value / disease marker | serious PRR 25.6 | no trial data cached |
| White blood cell count decreased | 73 | 4.3 3.4–5.4ROR 4.4 · χ² 181 / p 1e-41 | 4.2 EB05 3.4 · IC025 +1.7 3/3 methods agree | Labeled (related wording) related wording | serious PRR 3.9 | no trial data cached |
| Haemoglobin decreased | 54 | 3.3 2.6–4.4ROR 3.4 · χ² 87 / p 7e-21 | 3.3 EB05 2.6 · IC025 +1.3 3/3 methods agree | Labeled (related wording) related wording | serious PRR 2.9 | no trial data cached |
| Adverse event | 45 | 3.1 2.3–4.2ROR 3.1 · χ² 62 / p 1e-15 | 3.0 EB05 2.4 · IC025 +1.1 3/3 methods agree | Reporting / coding artifact | serious PRR 3.4 · 80% consumer | no trial data cached |
| Adverse drug reaction | 34 | 2.4 1.7–3.4ROR 2.4 · χ² 27 / p 1e-7 | 2.4 EB05 1.8 · IC025 +0.7 | Reporting / coding artifact | serious PRR 2.5 | no trial data cached |
| Blood bilirubin increased | 34 | 8.0 5.7–11.2ROR 8.1 · χ² 201 / p 6e-46 | 7.4 EB05 5.5 · IC025 +2.3 3/3 methods agree | Lab value / disease marker | serious PRR 3.5 | no trial data cached |
| Taste disorder | 33 | 10.5 7.5–14.7ROR 10.6 · χ² 274 / p 9e-62 | 9.9 EB05 7.2 · IC025 +2.6 3/3 methods agree | Not in label — unassessed | serious PRR 9.6 | no trial data cached |
| Red blood cell count decreased | 32 | 7.1 5.0–10.0ROR 7.2 · χ² 162 / p 2e-37 | 6.5 EB05 4.8 · IC025 +2.1 3/3 methods agree | Lab value / disease marker | serious PRR 6.6 | no trial data cached |
| White blood cell count increased | 31 | 5.1 3.6–7.3ROR 5.2 · χ² 99 / p 1e-23 | 4.8 EB05 3.5 · IC025 +1.7 3/3 methods agree | Lab value / disease marker | serious PRR 3.5 | no trial data cached |
| Leukaemia | 27 | 18.3 12.5–26.6ROR 18.4 · χ² 422 / p 4e-94 | 17.9 EB05 12.8 · IC025 +3.2 3/3 methods agree | Likely indication confounding term in indications | serious PRR 15.3 | no trial data cached |
| Neutrophil count decreased | 20 | 3.1 2.0–4.9ROR 3.2 · χ² 27 / p 9e-8 | 3.0 EB05 2.0 · IC025 +0.8 3/3 methods agree | Labeled (related wording) related wording | serious PRR 2.7 | 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.
- Taste disorder — n=33, PRR 10.5
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 Enasidenib?
In FDA FAERS, the most frequently co-reported reaction terms for Enasidenib are platelet count decreased, acute myeloid leukaemia, full blood count decreased, white blood cell count decreased, haemoglobin decreased, blood bilirubin increased. 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 Enasidenib have an FDA boxed warning?
Yes. The current FDA label carries a boxed warning: DIFFERENTIATION SYNDROME Patients treated with IDHIFA have experienced symptoms of differentiation syndrome, which can be fatal if not treated. Symptoms may include fever, dyspnea, acute respiratory distress, pulmona.
Do FAERS signals prove that Enasidenib 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 a5b4cdf0-3fa8-4c6c-80f6-8d8a00e3a5b6, effective 20250116; matched on
openfda.generic_name.exact:"ENASIDENIB MESYLATE") - 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, 32 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.