Ponatinib side effects: what 5,178 FDA adverse event reports show
Drug class
Kinase inhibitor
Label matched
Ponatinib Hydrochloride (Iclusig)
Who reports
5,178 reports · 86% serious · 1,453 with death outcome · 45% female
Used for
ICLUSIG ® is indicated for the treatment of adult patients with: Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph+ ALL) Newly diagnosed Ph+ ALL in combination with chemotherapy. This indication is approved under accelerated approval based on minimal residual disease (MRD)-negative complete remission (CR) at the end of induction .
What it is
Ponatinib is a kinase inhibitor.
Boxed warning
ARTERIAL OCCLUSIVE EVENTS, VENOUS THROMBOEMBOLIC EVENTS, HEART FAILURE, and HEPATOTOXICITY WARNING: ARTERIAL OCCLUSIVE EVENTS, VENOUS THROMBOEMBOLIC EVENTS, HEART FAILURE, and HEPATOTOXICITY See full prescribing information for complete boxed warning. Arterial occlusive events (AOEs), including fatalities, have occurred in ICLUSIG-treated patients.
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.
- 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.
- 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. 157 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 |
|---|---|---|---|---|---|---|
| Cytopenia | 69 | 23.5 18.6–29.7ROR 23.8 · χ² 1,456 / p <1e-300 | 23.2 EB05 19.0 · IC025 +3.9 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 16.2 | no trial data cached |
| Neoplasm progression | 197 | 22.8 19.9–26.2ROR 23.7 · χ² 4,076 / p <1e-300 | 22.7 EB05 20.1 · IC025 +4.2 3/3 methods agree | Not in label — unassessed | serious PRR 20.6 | no trial data cached |
| Blood count abnormal | 55 | 14.5 11.2–18.9ROR 14.7 · χ² 677 / p 1e-149 | 14.3 EB05 11.3 · IC025 +3.2 3/3 methods agree | Lab value / disease marker | serious PRR 12.6 | no trial data cached |
| Haematotoxicity | 25 | 10.9 7.4–16.2ROR 11.0 · χ² 215 / p 4e-49 | 10.2 EB05 6.9 · IC025 +2.5 3/3 methods agree | Not in label — unassessed | serious PRR 7.5 · ♀ 67% (drug 45%) · 92% clinician | no trial data cached |
| Pericardial effusion | 58 | 10.2 7.9–13.2ROR 10.3 · χ² 473 / p 4e-105 | 9.9 EB05 7.8 · IC025 +2.8 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 6.9 | no trial data cached |
| Splenomegaly | 29 | 10.0 7.0–14.5ROR 10.1 · χ² 227 / p 1e-51 | 9.3 EB05 6.6 · IC025 +2.5 3/3 methods agree | Not in label — unassessed | serious PRR 6.8 | no trial data cached |
| Cytokine release syndrome | 43 | 9.2 6.8–12.3ROR 9.2 · χ² 304 / p 2e-68 | 8.6 EB05 6.6 · IC025 +2.6 3/3 methods agree | Not in label — unassessed | serious PRR 6.2 · 95% clinician | no trial data cached |
| Drug resistance | 53 | 8.4 6.4–10.9ROR 8.4 · χ² 336 / p 2e-75 | 8.0 EB05 6.3 · IC025 +2.5 3/3 methods agree | Reporting / coding artifact | serious PRR 5.6 | no trial data cached |
| Cytomegalovirus infection | 34 | 8.3 5.9–11.6ROR 8.3 · χ² 210 / p 6e-48 | 7.7 EB05 5.7 · IC025 +2.3 3/3 methods agree | Not in label — unassessed | serious PRR 5.6 · ♀ 21% (drug 45%) | no trial data cached |
| Pancreatitis (pancreas inflammation) | 108 | 8.3 6.9–10.0ROR 8.4 · χ² 684 / p 5e-151 | 8.1 EB05 6.8 · IC025 +2.7 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 5.7 | no trial data cached |
| Pancytopenia (all blood cells low) | 110 | 8.0 6.7–9.6ROR 8.2 · χ² 668 / p 2e-147 | 7.8 EB05 6.6 · IC025 +2.6 3/3 methods agree | Labeled (related wording) related wording | serious PRR 5.4 | no trial data cached |
| Arteriosclerosis | 18 | 7.7 4.9–12.3ROR 7.8 · χ² 99 / p 1e-23 | 6.7 EB05 4.4 · IC025 +1.9 3/3 methods agree | Not in label — unassessed | serious PRR 4.8 | no trial data cached |
| Bone marrow failure | 36 | 7.1 5.1–9.9ROR 7.2 · χ² 184 / p 4e-42 | 6.6 EB05 5.0 · IC025 +2.2 3/3 methods agree | Not in label — unassessed | serious PRR 4.8 | no trial data cached |
| Red blood cell count decreased | 47 | 6.7 5.0–8.8ROR 6.7 · χ² 220 / p 4e-50 | 6.3 EB05 4.9 · IC025 +2.2 3/3 methods agree | Lab value / disease marker | serious PRR 5.1 | no trial data cached |
| White blood cell count increased | 63 | 6.6 5.2–8.5ROR 6.7 · χ² 296 / p 1e-66 | 6.3 EB05 5.1 · IC025 +2.2 3/3 methods agree | Lab value / disease marker | serious PRR 4.9 | no trial data cached |
| Ischaemic stroke | 29 | 6.6 4.6–9.5ROR 6.6 · χ² 132 / p 1e-30 | 6.0 EB05 4.4 · IC025 +2.0 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 4.4 · ♀ 75% (drug 45%) | no trial data cached |
| Transaminases increased | 36 | 6.6 4.7–9.1ROR 6.6 · χ² 164 / p 6e-38 | 6.1 EB05 4.6 · IC025 +2.1 3/3 methods agree | Not in label — unassessed | serious PRR 4.6 | no trial data cached |
| Transfusion | 17 | 6.6 4.1–10.5ROR 6.6 · χ² 74 / p 3e-18 | 5.7 EB05 3.7 · IC025 +1.7 3/3 methods agree | Not in label — unassessed | serious PRR 4.6 | no trial data cached |
| Platelet count decreased | 166 | 6.3 5.4–7.3ROR 6.5 · χ² 740 / p 3e-163 | 6.2 EB05 5.5 · IC025 +2.4 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 4.8 | no trial data cached |
| Hepatotoxicity (liver damage) | 33 | 6.0 4.3–8.5ROR 6.1 · χ² 134 / p 3e-31 | 5.6 EB05 4.2 · IC025 +1.9 3/3 methods agree | Labeled — boxed warning exact term | serious PRR 3.9 | no trial data cached |
| Bone pain | 86 | 5.9 4.8–7.3ROR 6.0 · χ² 349 / p 3e-78 | 5.8 EB05 4.8 · IC025 +2.2 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 5.3 | no trial data cached |
| Febrile neutropenia | 96 | 5.9 4.8–7.2ROR 6.0 · χ² 384 / p 8e-86 | 5.7 EB05 4.8 · IC025 +2.2 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 3.9 | no trial data cached |
| Septic shock | 58 | 5.4 4.2–7.0ROR 5.5 · χ² 206 / p 6e-47 | 5.2 EB05 4.2 · IC025 +2.0 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 3.7 | no trial data cached |
| Hepatocellular injury | 19 | 5.4 3.5–8.5ROR 5.4 · χ² 64 / p 6e-16 | 4.8 EB05 3.3 · IC025 +1.5 3/3 methods agree | Not in label — unassessed | serious PRR 3.6 | no trial data cached |
| Hospice care | 13 | 5.3 3.1–9.2ROR 5.4 · χ² 42 / p 5e-11 | 4.6 EB05 2.8 · IC025 +1.3 3/3 methods agree | Not in label — unassessed | serious PRR 4.8 | no trial data cached |
| Blood lactate dehydrogenase increased | 21 | 5.3 3.5–8.2ROR 5.4 · χ² 70 / p 3e-17 | 4.8 EB05 3.3 · IC025 +1.5 3/3 methods agree | Lab value / disease marker | serious PRR 3.8 · ♀ 19% (drug 45%) · 90% clinician | no trial data cached |
| Thrombocytopenia (low platelets) | 146 | 5.3 4.5–6.2ROR 5.4 · χ² 508 / p 9e-113 | 5.2 EB05 4.5 · IC025 +2.1 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 3.6 | no trial data cached |
| Lymphocyte count decreased | 23 | 5.3 3.5–7.9ROR 5.3 · χ² 75 / p 2e-18 | 4.8 EB05 3.4 · IC025 +1.6 3/3 methods agree | Lab value / disease marker | serious PRR 4.3 · ♀ 0% (drug 45%) · 100% clinician | no trial data cached |
| Pancreatitis acute | 29 | 5.3 3.7–7.6ROR 5.3 · χ² 96 / p 6e-23 | 4.9 EB05 3.6 · IC025 +1.7 3/3 methods agree | Labeled (related wording) related wording | serious PRR 3.6 · ♀ 18% (drug 45%) | no trial data cached |
| Leukocytosis | 23 | 5.2 3.4–7.8ROR 5.2 · χ² 73 / p 7e-18 | 4.7 EB05 3.3 · IC025 +1.5 3/3 methods agree | Not in label — unassessed | serious PRR 3.5 | no trial data cached |
| Pleural effusion | 77 | 5.1 4.1–6.4ROR 5.2 · χ² 252 / p 5e-57 | 5.0 EB05 4.1 · IC025 +1.9 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 3.0 | no trial data cached |
| Skin exfoliation | 104 | 5.1 4.2–6.1ROR 5.2 · χ² 337 / p 2e-75 | 5.0 EB05 4.2 · IC025 +2.0 3/3 methods agree | Not in label — unassessed | serious PRR 7.7 | no trial data cached |
| Multiple organ dysfunction syndrome | 34 | 4.9 3.5–6.9ROR 5.0 · χ² 103 / p 2e-24 | 4.6 EB05 3.5 · IC025 +1.7 3/3 methods agree | Labeled (related wording) related wording | serious PRR 3.3 | no trial data cached |
| Haematocrit decreased | 24 | 4.9 3.3–7.3ROR 4.9 · χ² 70 / p 3e-17 | 4.5 EB05 3.2 · IC025 +1.5 3/3 methods agree | Lab value / disease marker | serious PRR 3.4 · ♀ 23% (drug 45%) | no trial data cached |
| Full blood count decreased | 24 | 4.8 3.2–7.2ROR 4.8 · χ² 69 / p 5e-17 | 4.4 EB05 3.1 · IC025 +1.5 3/3 methods agree | Lab value / disease marker | serious PRR 3.9 | no trial data cached |
| Dry skin | 148 | 4.6 3.9–5.3ROR 4.7 · χ² 410 / p 2e-91 | 4.5 EB05 3.9 · IC025 +1.9 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 10.2 | no trial data cached |
| Hepatomegaly | 11 | 4.5 2.5–8.1ROR 4.5 · χ² 27 / p 1e-7 | 3.9 EB05 2.3 · IC025 +0.9 3/3 methods agree | Not in label — unassessed | serious PRR 3.0 | no trial data cached |
| Cholestasis (bile flow blockage) | 21 | 4.5 2.9–6.8ROR 4.5 · χ² 53 / p 2e-13 | 4.1 EB05 2.8 · IC025 +1.3 3/3 methods agree | Not in label — unassessed | serious PRR 3.0 · 90% clinician | no trial data cached |
| Ejection fraction decreased | 17 | 4.4 2.8–7.1ROR 4.4 · χ² 42 / p 5e-11 | 4.0 EB05 2.7 · IC025 +1.2 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 3.1 | no trial data cached |
| Cerebral infarction | 26 | 4.3 2.9–6.3ROR 4.3 · χ² 63 / p 1e-15 | 4.0 EB05 2.9 · IC025 +1.4 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 2.9 | 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 | 742 | 3.5 3.3–3.7ROR 3.9 · χ² 1,371 / p 2e-300 | 3.5 EB05 3.3 · IC025 +1.7 3/3 methods agree | Outcome field, not a reaction boxed warning mentions mortality | serious PRR 2.3 | no trial data cached |
| Rash | 271 | 2.5 2.3–2.8ROR 2.6 · χ² 255 / p 1e-57 | 2.5 EB05 2.3 · IC025 +1.1 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 2.9 · ♀ 67% (drug 45%) | no trial data cached |
| Pyrexia (fever) | 254 | 3.0 2.6–3.4ROR 3.1 · χ² 336 / p 3e-75 | 3.0 EB05 2.7 · IC025 +1.4 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 2.3 | no trial data cached |
| Neoplasm progression | 197 | 22.8 19.9–26.2ROR 23.7 · χ² 4,076 / p <1e-300 | 22.7 EB05 20.1 · IC025 +4.2 3/3 methods agree | Not in label — unassessed | serious PRR 20.6 | no trial data cached |
| Hypertension (high blood pressure) | 194 | 3.7 3.2–4.3ROR 3.8 · χ² 384 / p 8e-86 | 3.7 EB05 3.3 · IC025 +1.6 3/3 methods agree | Labeled — boxed warning exact term | serious PRR 2.8 | no trial data cached |
| Constipation | 192 | 3.6 3.1–4.1ROR 3.7 · χ² 360 / p 1e-80 | 3.6 EB05 3.2 · IC025 +1.6 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 3.6 | no trial data cached |
| Platelet count decreased | 166 | 6.3 5.4–7.3ROR 6.5 · χ² 740 / p 3e-163 | 6.2 EB05 5.5 · IC025 +2.4 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 4.8 | no trial data cached |
| Arthralgia (joint pain) | 165 | 1.6 1.4–1.9ROR 1.6 · χ² 39 / p 3e-10 | 1.6 EB05 1.4 · IC025 +0.4 | Labeled adverse reaction exact term | serious PRR 1.4 | no trial data cached |
| Abdominal pain | 160 | 2.8 2.4–3.2ROR 2.8 · χ² 183 / p 4e-42 | 2.8 EB05 2.4 · IC025 +1.2 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 2.2 | no trial data cached |
| Dry skin | 148 | 4.6 3.9–5.3ROR 4.7 · χ² 410 / p 2e-91 | 4.5 EB05 3.9 · IC025 +1.9 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 10.2 | no trial data cached |
| Thrombocytopenia (low platelets) | 146 | 5.3 4.5–6.2ROR 5.4 · χ² 508 / p 9e-113 | 5.2 EB05 4.5 · IC025 +2.1 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 3.6 | no trial data cached |
| Chest pain | 137 | 3.0 2.5–3.5ROR 3.0 · χ² 181 / p 2e-41 | 3.0 EB05 2.6 · IC025 +1.3 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 2.1 | no trial data cached |
| Hospitalisation | 137 | 3.6 3.1–4.3ROR 3.7 · χ² 262 / p 4e-59 | 3.6 EB05 3.1 · IC025 +1.6 3/3 methods agree | Reporting / coding artifact | serious PRR 2.5 | no trial data cached |
| Neutropenia (low neutrophils (infection-fighting cells)) | 116 | 3.5 2.9–4.2ROR 3.5 · χ² 202 / p 3e-46 | 3.4 EB05 2.9 · IC025 +1.5 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 2.4 · ♀ 23% (drug 45%) | no trial data cached |
| Anaemia (low red blood cells) | 111 | 2.4 2.0–2.8ROR 2.4 · χ² 86 / p 9e-21 | 2.3 EB05 2.0 · IC025 +0.9 | Labeled adverse reaction exact term | serious PRR 1.7 | 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.
- Neoplasm progression — n=197, PRR 22.8
- Haematotoxicity — n=25, PRR 10.9
- Splenomegaly — n=29, PRR 10.0
- Cytokine release syndrome — n=43, PRR 9.2
- Cytomegalovirus infection — n=34, PRR 8.3
- Bone marrow failure — n=36, PRR 7.1
- Transaminases increased — n=36, PRR 6.6
- Leukocytosis — n=23, PRR 5.2
- Skin exfoliation — n=104, PRR 5.1
- Cholestasis — n=21, PRR 4.5
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 Ponatinib?
In FDA FAERS, the most frequently co-reported reaction terms for Ponatinib are rash, pyrexia, neoplasm progression, hypertension, constipation, platelet count decreased. 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 Ponatinib have an FDA boxed warning?
Yes. The current FDA label carries a boxed warning: ARTERIAL OCCLUSIVE EVENTS, VENOUS THROMBOEMBOLIC EVENTS, HEART FAILURE, and HEPATOTOXICITY WARNING: ARTERIAL OCCLUSIVE EVENTS, VENOUS THROMBOEMBOLIC EVENTS, HEART FAILURE, and HEPATOTOXICITY See full prescribing information for complete boxed warning. Arterial occlusive events (AOEs), including fatalities, have occurred in ICLUSIG-treated patients.
Do FAERS signals prove that Ponatinib 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 16d804b6-4957-43ee-b18c-3b36ec37c5ac, effective 20260814; matched on
openfda.generic_name.exact:"PONATINIB HYDROCHLORIDE") - 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, 197 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.