Hydroxyurea side effects: what 21,015 FDA adverse event reports show
Drug class
Antimetabolite
Brand names
Xromi
Who reports
21,015 reports · 75% serious · 3,145 with death outcome · 53% female
Used for
XROMI is indicated to reduce the frequency of painful crises and reduce the need for blood transfusions in pediatric patients aged 6 months of age and older with sickle cell anemia with recurrent moderate to severe painful crises. XROMI is an antimetab.
What it is
XROMI (hydroxyurea) is available for oral use as oral solution containing 100 mg/mL hydroxyurea. Inactive ingredients include methyl parahydroxybenzoate, purified water, sodium hydroxide, strawberry flavor, sucralose and xanthan gum. Hydroxyurea is a white to off-white crystalline powder.
Boxed warning
MYELOSUPPRESSION and MALIGNANCIES Myelosuppression: XROMI may cause severe myelosuppression. Do not give if bone marrow function is markedly depressed. Monitor blood counts at baseline and throughout treatment. Interrupt treatment and reduce dose as necessary [see Warnings and Precautions(5.1) ] . Malignancies: Hydroxyurea is carcinogenic.
Causality screen of the 40 strongest signals
What the badges mean
- 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.
- 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. 1,132 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 |
|---|---|---|---|---|---|---|
| Granulomatous rosacea | 14 | 393.3 211.7–730.9ROR 393.6 · χ² 3,638 / p <1e-300 | 203.5 EB05 128.8 · IC025 +3.8 3/3 methods agree | Not in label — unassessed | serious n=14 | not reported in cached trials |
| Acute chest syndrome | 174 | 248.0 210.1–292.7ROR 250.0 · χ² 33,983 / p <1e-300 | 194.0 EB05 171.0 · IC025 +6.7 3/3 methods agree | Not in label — unassessed | serious n=174 | NCT01966731: 8/635 (1.3%) on Hydroxyurea (serious AE) |
| Angiodermatitis | 15 | 210.7 120.7–368.0ROR 210.9 · χ² 2,408 / p <1e-300 | 142.6 EB05 91.7 · IC025 +3.9 3/3 methods agree | Not in label — unassessed | serious n=15 | not reported in cached trials |
| Differentiation syndrome | 100 | 162.3 131.4–200.4ROR 163.0 · χ² 13,619 / p <1e-300 | 135.8 EB05 114.9 · IC025 +6.0 3/3 methods agree | Not in label — unassessed | serious n=100 | not reported in cached trials |
| Essential thrombocythaemia | 45 | 140.5 102.8–191.9ROR 140.8 · χ² 5,331 / p <1e-300 | 117.0 EB05 91.1 · IC025 +5.2 3/3 methods agree | Not in label — unassessed | serious n=41 | not reported in cached trials |
| Leukostasis syndrome | 15 | 131.7 76.8–225.7ROR 131.8 · χ² 1,602 / p <1e-300 | 101.6 EB05 65.3 · IC025 +3.8 3/3 methods agree | Not in label — unassessed | serious n=15 | not reported in cached trials |
| Primary myelofibrosis | 32 | 112.0 77.7–161.4ROR 112.1 · χ² 3,061 / p <1e-300 | 95.1 EB05 70.5 · IC025 +4.7 3/3 methods agree | Not in label — unassessed | serious n=32 | not reported in cached trials |
| Nail pigmentation | 23 | 104.7 68.1–160.9ROR 104.8 · χ² 2,042 / p <1e-300 | 88.0 EB05 61.8 · IC025 +4.3 3/3 methods agree | Labeled (related wording) related wording | serious n=14 | not reported in cached trials |
| Sickle cell anaemia with crisis | 1,485 | 103.5 98.3–109.0ROR 111.3 · χ² 136,405 / p <1e-300 | 93.6 EB05 89.7 · IC025 +6.4 3/3 methods agree | Not in label — unassessed | serious PRR 87.0 | not reported in cached trials |
| Sickle cell disease | 41 | 97.6 70.8–134.5ROR 97.8 · χ² 3,479 / p <1e-300 | 85.5 EB05 65.7 · IC025 +4.9 3/3 methods agree | Labeled (related wording) related wording | serious n=37 | not reported in cached trials |
| Myelofibrosis | 269 | 97.2 85.9–110.1ROR 98.5 · χ² 23,233 / p <1e-300 | 88.0 EB05 79.6 · IC025 +6.1 3/3 methods agree | Not in label — unassessed | serious n=267 | not reported in cached trials |
| Myeloproliferative neoplasm | 50 | 82.5 61.8–110.1ROR 82.7 · χ² 3,639 / p <1e-300 | 74.1 EB05 58.4 · IC025 +5.0 3/3 methods agree | Labeled adverse reaction exact term | serious n=49 | not reported in cached trials |
| Polycythaemia vera | 56 | 73.8 56.3–96.8ROR 74.0 · χ² 3,674 / p <1e-300 | 67.2 EB05 53.7 · IC025 +5.0 3/3 methods agree | Not in label — unassessed | serious n=56 | not reported in cached trials |
| Hyperleukocytosis | 58 | 70.8 54.3–92.4ROR 71.0 · χ² 3,661 / p <1e-300 | 64.8 EB05 52.0 · IC025 +5.0 3/3 methods agree | Not in label — unassessed | serious n=58 · ♀ 15% (drug 53%) · 100% clinician | not reported in cached trials |
| Sickle cell anaemia | 39 | 63.5 45.9–87.7ROR 63.6 · χ² 2,195 / p <1e-300 | 58.1 EB05 44.3 · IC025 +4.6 3/3 methods agree | Likely indication confounding term in indications; also in warnings | serious n=38 · ♀ 76% (drug 53%) | not reported in cached trials |
| Blast crisis in myelogenous leukaemia | 74 | 63.4 50.2–80.2ROR 63.7 · χ² 4,214 / p <1e-300 | 58.8 EB05 48.4 · IC025 +5.0 3/3 methods agree | Not in label — unassessed | serious n=74 | not reported in cached trials |
| Erythromelalgia | 20 | 57.0 36.3–89.5ROR 57.1 · χ² 988 / p 4e-217 | 51.4 EB05 35.2 · IC025 +3.8 3/3 methods agree | Not in label — unassessed | serious n=18 | not reported in cached trials |
| Blast cell count increased | 56 | 56.1 42.9–73.5ROR 56.3 · χ² 2,817 / p <1e-300 | 52.3 EB05 41.8 · IC025 +4.7 3/3 methods agree | Lab value / disease marker | serious n=56 · ♀ 25% (drug 53%) | not reported in cached trials |
| Platelet count increased | 647 | 51.9 48.1–56.2ROR 53.6 · χ² 30,676 / p <1e-300 | 49.3 EB05 46.2 · IC025 +5.4 3/3 methods agree | Lab value / disease marker | serious PRR 34.1 | NCT01966731: 68/635 (10.7%) on Hydroxyurea |
| Cytogenetic analysis abnormal | 52 | 51.8 39.2–68.4ROR 51.9 · χ² 2,411 / p <1e-300 | 48.4 EB05 38.3 · IC025 +4.6 3/3 methods agree | Reporting / coding artifact | serious n=51 | not reported in cached trials |
| Philadelphia chromosome positive | 33 | 48.1 34.0–68.3ROR 48.2 · χ² 1,408 / p <1e-300 | 44.8 EB05 33.4 · IC025 +4.2 3/3 methods agree | Lab value / disease marker | serious n=33 · 100% clinician | not reported in cached trials |
| Bone marrow reticulin fibrosis | 12 | 47.6 26.7–84.9ROR 47.6 · χ² 478 / p 2e-106 | 42.6 EB05 26.0 · IC025 +3.1 3/3 methods agree | Not in label — unassessed | serious n=12 | not reported in cached trials |
| Chronic myeloid leukaemia transformation | 20 | 46.8 29.9–73.3ROR 46.9 · χ² 813 / p 4e-179 | 43.0 EB05 29.4 · IC025 +3.7 3/3 methods agree | Likely indication confounding shares a disease stem with the indications wording | serious n=20 | not reported in cached trials |
| Transformation to acute myeloid leukaemia | 29 | 46.0 31.7–66.7ROR 46.1 · χ² 1,177 / p 3e-258 | 42.8 EB05 31.3 · IC025 +4.0 3/3 methods agree | Likely indication confounding shares a disease stem with the indications wording | serious n=29 · 100% clinician | not reported in cached trials |
| Erythropoiesis abnormal | 12 | 40.8 22.9–72.7ROR 40.9 · χ² 410 / p 2e-91 | 37.1 EB05 22.6 · IC025 +3.0 3/3 methods agree | Not in label — unassessed | serious n=12 | not reported in cached trials |
| Hypersplenism | 19 | 39.9 25.2–63.1ROR 40.0 · χ² 656 / p 6e-145 | 37.1 EB05 25.1 · IC025 +3.5 3/3 methods agree | Not in label — unassessed | serious n=17 | not reported in cached trials |
| Splenomegaly | 430 | 38.0 34.5–41.8ROR 38.8 · χ² 14,890 / p <1e-300 | 36.6 EB05 33.8 · IC025 +5.0 3/3 methods agree | Not in label — unassessed | serious PRR 26.2 | not reported in cached trials |
| Chronic myelomonocytic leukaemia | 24 | 37.3 24.8–56.0ROR 37.3 · χ² 782 / p 2e-172 | 35.0 EB05 24.8 · IC025 +3.7 3/3 methods agree | Not in label — unassessed | serious n=24 · 100% clinician | not reported in cached trials |
| Myeloid leukaemia | 18 | 36.8 23.0–58.9ROR 36.8 · χ² 570 / p 3e-126 | 34.3 EB05 23.0 · IC025 +3.4 3/3 methods agree | Not in label — unassessed | serious n=18 | not reported in cached trials |
| Chronic myeloid leukaemia | 162 | 36.2 30.9–42.3ROR 36.4 · χ² 5,308 / p <1e-300 | 34.8 EB05 30.5 · IC025 +4.7 3/3 methods agree | Not in label — unassessed | serious n=161 | not reported in cached trials |
| Chronic myeloid leukaemia recurrent | 19 | 35.8 22.6–56.6ROR 35.8 · χ² 587 / p 6e-130 | 33.5 EB05 22.7 · IC025 +3.4 3/3 methods agree | Not in label — unassessed | serious n=19 | not reported in cached trials |
| Thrombocytosis | 125 | 35.3 29.6–42.2ROR 35.5 · χ² 3,993 / p <1e-300 | 34.0 EB05 29.3 · IC025 +4.6 3/3 methods agree | Not in label — unassessed | serious n=114 | not reported in cached trials |
| Marrow hyperplasia | 22 | 32.9 21.5–50.3ROR 33.0 · χ² 628 / p 5e-139 | 31.1 EB05 21.7 · IC025 +3.5 3/3 methods agree | Not in label — unassessed | serious n=21 | not reported in cached trials |
| Antineutrophil cytoplasmic antibody positive | 23 | 32.5 21.5–49.2ROR 32.5 · χ² 649 / p 1e-143 | 30.8 EB05 21.6 · IC025 +3.6 3/3 methods agree | Lab value / disease marker | serious n=23 · ♀ 0% (drug 53%) | not reported in cached trials |
| Haematocrit increased | 69 | 31.1 24.4–39.4ROR 31.2 · χ² 1,916 / p <1e-300 | 29.9 EB05 24.4 · IC025 +4.2 3/3 methods agree | Lab value / disease marker | serious n=49 | not reported in cached trials |
| Thrombocythaemia | 16 | 29.4 17.9–48.3ROR 29.4 · χ² 398 / p 6e-89 | 27.7 EB05 18.0 · IC025 +3.1 3/3 methods agree | Not in label — unassessed | serious n=16 | not reported in cached trials |
| Blast cells present | 13 | 27.8 16.0–48.2ROR 27.8 · χ² 301 / p 1e-67 | 26.1 EB05 16.1 · IC025 +2.8 3/3 methods agree | Lab value / disease marker | serious n=13 | not reported in cached trials |
| Reticulocyte count increased | 22 | 27.8 18.2–42.4ROR 27.8 · χ² 526 / p 9e-117 | 26.5 EB05 18.4 · IC025 +3.4 3/3 methods agree | Lab value / disease marker | serious n=20 | NCT01966731: 63/635 (9.9%) on Hydroxyurea |
| Myelodysplastic syndrome transformation | 14 | 27.3 16.0–46.4ROR 27.3 · χ² 319 / p 9e-72 | 25.7 EB05 16.2 · IC025 +2.9 3/3 methods agree | Likely indication confounding shares a disease stem with the indications wording | serious n=14 | not reported in cached trials |
| Blood iron increased | 49 | 26.6 20.1–35.4ROR 26.7 · χ² 1,153 / p 5e-253 | 25.7 EB05 20.2 · IC025 +3.9 3/3 methods agree | Lab value / disease marker | serious n=45 | not reported in cached trials |
Trial evidence (ClinicalTrials.gov)
✓ Trial adverse-event data found on ClinicalTrials.gov
Largest completed trials with posted results that list Hydroxyurea as a study intervention. The right-hand column of the signal table shows whether each FAERS term was also recorded in these trials, with a real denominator (3 of 40 signal terms matched).
- NCT01966731 — Realizing Effectiveness Across Continents With Hydroxyurea (REACH) (N=635, PHASE1, PHASE2; 27 AE terms posted; arms: Hydroxyurea)
- NCT02516579 — European Sickle Cell Disease Cohort - Hydroxyurea (N=1906, phase n/a; 7 AE terms posted; arms: Patients With Sickle Cell Disease Treate)
Caveats: trial populations, doses and follow-up differ from the reporting population; AE terms are sponsor-coded and matched here by wording; absence from a trial list means the term was not reported above the sponsor's frequency threshold, not that it cannot occur.
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 |
|---|---|---|---|---|---|---|
| Off label use (used outside approved label) | 2,188 | 2.5 2.4–2.6ROR 2.7 · χ² 2,083 / p <1e-300 | 2.5 EB05 2.4 · IC025 +1.3 3/3 methods agree | Reporting / coding artifact | serious PRR 2.2 | not reported in cached trials |
| Fatigue (tiredness) | 1,547 | 2.0 1.9–2.1ROR 2.1 · χ² 787 / p 2e-173 | 2.0 EB05 1.9 · IC025 +0.9 | Labeled (related wording) related wording | serious PRR 1.8 | not reported in cached trials |
| Sickle cell anaemia with crisis | 1,485 | 103.5 98.3–109.0ROR 111.3 · χ² 136,405 / p <1e-300 | 93.6 EB05 89.7 · IC025 +6.4 3/3 methods agree | Not in label — unassessed | serious PRR 87.0 | not reported in cached trials |
| Diarrhoea (diarrhea) | 1,408 | 2.2 2.1–2.3ROR 2.3 · χ² 931 / p 7e-205 | 2.2 EB05 2.1 · IC025 +1.0 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 1.7 | not reported in cached trials |
| Nausea | 1,305 | 1.7 1.6–1.7ROR 1.7 · χ² 347 / p 1e-77 | 1.6 EB05 1.6 · IC025 +0.6 | Labeled adverse reaction exact term | serious PRR 1.5 | not reported in cached trials |
| Headache | 1,067 | 1.7 1.6–1.8ROR 1.7 · χ² 316 / p 4e-71 | 1.7 EB05 1.6 · IC025 +0.7 | Labeled adverse reaction exact term | serious PRR 1.6 | not reported in cached trials |
| Anaemia (low red blood cells) | 1,045 | 5.5 5.2–5.8ROR 5.7 · χ² 3,843 / p <1e-300 | 5.4 EB05 5.2 · IC025 +2.3 3/3 methods agree | Labeled — boxed warning exact term | serious PRR 4.2 | NCT01966731: 7/635 (1.1%) on Hydroxyurea (serious AE) |
| Death | 1,041 | 1.2 1.1–1.3ROR 1.2 · χ² 38 / p 4e-10 | 1.2 EB05 1.1 · IC025 +0.2 | Outcome field, not a reaction | serious PRR 0.9 | NCT01966731: 2/635 (0.3%) on Hydroxyurea (serious AE) |
| Haemoglobin decreased | 939 | 9.2 8.6–9.8ROR 9.6 · χ² 6,804 / p <1e-300 | 9.1 EB05 8.6 · IC025 +3.1 3/3 methods agree | Labeled — boxed warning synonym match | serious PRR 6.6 | NCT01966731: 239/635 (37.6%) on Hydroxyurea |
| Pyrexia (fever) | 929 | 2.7 2.5–2.9ROR 2.8 · χ² 991 / p 7e-218 | 2.7 EB05 2.5 · IC025 +1.3 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 2.3 | not reported in cached trials |
| Drug ineffective (drug did not work) | 910 | 0.7 0.6–0.7ROR 0.7 · χ² 136 / p 1e-31 | 0.7 EB05 0.7 · IC025 -0.6 PRR-only: not supported by EBGM or IC | Reporting / coding artifact | serious PRR 1.2 | not reported in cached trials |
| Pain | 862 | 1.4 1.3–1.5ROR 1.4 · χ² 100 / p 7e-24 | 1.4 EB05 1.3 · IC025 +0.4 | Likely indication confounding term in indications | serious PRR 1.3 | NCT01966731: 8/635 (1.3%) on Hydroxyurea (serious AE) |
| Product dose omission issue | 833 | 2.9 2.7–3.1ROR 3.0 · χ² 1,064 / p 1e-233 | 2.9 EB05 2.8 · IC025 +1.4 3/3 methods agree | Reporting / coding artifact | serious PRR 4.7 · 90% consumer | not reported in cached trials |
| Dyspnoea (shortness of breath) | 825 | 1.5 1.4–1.6ROR 1.5 · χ² 120 / p 3e-28 | 1.5 EB05 1.4 · IC025 +0.4 | Labeled adverse reaction exact term | serious PRR 1.3 | not reported in cached trials |
| Pneumonia (lung infection) | 768 | 2.4 2.2–2.5ROR 2.4 · χ² 617 / p 2e-136 | 2.4 EB05 2.2 · IC025 +1.1 3/3 methods agree | Labeled — boxed warning synonym match | serious PRR 1.9 | not reported in cached trials |
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.
- Acute chest syndrome — n=174, PRR 248.0 (also seen in trial arm)
- Differentiation syndrome — n=100, PRR 162.3
- Essential thrombocythaemia — n=45, PRR 140.5
- Primary myelofibrosis — n=32, PRR 112.0
- Sickle cell anaemia with crisis — n=1,485, PRR 103.5
- Myelofibrosis — n=269, PRR 97.2
- Polycythaemia vera — n=56, PRR 73.8
- Hyperleukocytosis — n=58, PRR 70.8
- Blast crisis in myelogenous leukaemia — n=74, PRR 63.4
- Erythromelalgia — n=20, PRR 57.0
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 Hydroxyurea?
In FDA FAERS, the most frequently co-reported reaction terms for Hydroxyurea are fatigue, sickle cell anaemia with crisis, diarrhoea, nausea, headache, anaemia. 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 Hydroxyurea have an FDA boxed warning?
Yes. The current FDA label carries a boxed warning: MYELOSUPPRESSION and MALIGNANCIES Myelosuppression: XROMI may cause severe myelosuppression. Do not give if bone marrow function is markedly depressed. Monitor blood counts at baseline and throughout treatment. Interrupt treatment and reduce dose as necessary [see Warnings and Precautions(5.1) ] . Malignancies: Hydroxyurea is carcinogenic.
Do FAERS signals prove that Hydroxyurea 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 4b37d336-86da-4363-aef1-34a7d3ba973b, effective 20260202; matched on
openfda.generic_name.exact:"HYDROXYUREA") - 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, 1,172 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 - ClinicalTrials.gov API v2 (query
HYDROXYUREA, results-bearing studies sorted by enrollment)
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.