Raloxifene Hydrochloride side effects: what 14,516 FDA adverse event reports show
Drug class
Estrogen agonist/ antagonist
Brand names
Raloxifene Hydrochloride
Who reports
14,516 reports · 57% serious · 560 with death outcome · 100% female
Used for
Raloxifene hydrochloride tablet, USP is an estrogen agonist/ antagonist indicated for: Treatment and prevention of osteoporosis in postmenopausal women. ( 1.1 ) Reduction in risk of invasive breast cancer in postmenopausal women with osteoporosis. ( 1.2 ). Reduction in risk of invasive breast cancer in postmenopausal women at high risk for invasive breast cancer.
What it is
Raloxifene hydrochloride, USP is an estrogen agonist/antagonist, commonly referred to as a selective estrogen receptor modulator (SERM) that belongs to the benzothiophene class of compounds.
Boxed warning
INCREASED RISK OF VENOUS THROMBOEMBOLISM AND DEATH FROM STROKE WARNING: INCREASED RISK OF VENOUS THROMBOEMBOLISM AND DEATH FROM STROKE Increased risk of deep vein thrombosis and pulmonary embolism have been reported with raloxifene hydrochloride tablets [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.
- 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. 1,056 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 |
|---|---|---|---|---|---|---|
| Breast microcalcification | 10 | 129.5 67.8–247.4ROR 129.6 · χ² 1,054 / p 2e-231 | 97.3 EB05 56.5 · IC025 +3.1 3/3 methods agree | Not in label — unassessed | serious n=9 | not reported in cached trials |
| Retinal vein thrombosis | 54 | 119.6 90.7–157.9ROR 120.1 · χ² 5,752 / p <1e-300 | 106.4 EB05 84.6 · IC025 +5.3 3/3 methods agree | Labeled — boxed warning exact term | serious n=52 | NCT00205777: 1/1,849 (0.1%) on Raloxifene; 2/1,885 (0.1%) control (serious AE) |
| Endometrial cancer stage i | 11 | 101.1 54.9–186.3ROR 101.2 · χ² 927 / p 8e-204 | 81.6 EB05 48.6 · IC025 +3.2 3/3 methods agree | Not in label — unassessed | serious n=11 | not reported in cached trials |
| Carbuncle | 15 | 80.9 48.1–136.2ROR 81.0 · χ² 1,046 / p 8e-230 | 70.1 EB05 45.1 · IC025 +3.6 3/3 methods agree | Not in label — unassessed | serious n=15 | not reported in cached trials |
| Body height decreased | 532 | 74.8 68.6–81.4ROR 77.6 · χ² 36,735 / p <1e-300 | 70.9 EB05 66.0 · IC025 +5.9 3/3 methods agree | Not in label — unassessed | serious n=119 · 90% consumer | not reported in cached trials |
| Muscle cramp | 86 | 72.5 58.4–89.9ROR 72.9 · χ² 5,700 / p <1e-300 | 68.0 EB05 56.8 · IC025 +5.3 3/3 methods agree | Labeled (related wording) related wording | serious n=36 | not reported in cached trials |
| Wrist deformity | 27 | 65.8 44.7–96.7ROR 65.9 · χ² 1,585 / p <1e-300 | 60.3 EB05 43.6 · IC025 +4.2 3/3 methods agree | Not in label — unassessed | serious n=26 | not reported in cached trials |
| Endometrial cancer | 94 | 64.3 52.3–79.0ROR 64.7 · χ² 5,544 / p <1e-300 | 60.8 EB05 51.2 · IC025 +5.2 3/3 methods agree | Labeled adverse reaction exact term | serious n=93 | not reported in cached trials |
| Bone scan abnormal | 15 | 52.5 31.4–87.9ROR 52.6 · χ² 682 / p 1e-150 | 47.8 EB05 30.7 · IC025 +3.4 3/3 methods agree | Reporting / coding artifact | serious n=8 | not reported in cached trials |
| Retinal vascular thrombosis | 18 | 51.4 32.1–82.2ROR 51.5 · χ² 810 / p 1e-178 | 47.3 EB05 31.7 · IC025 +3.6 3/3 methods agree | Labeled (related wording) related wording | serious n=18 | not reported in cached trials |
| Atrophic vulvovaginitis | 25 | 51.3 34.4–76.5ROR 51.4 · χ² 1,143 / p 9e-251 | 47.9 EB05 34.1 · IC025 +4.0 3/3 methods agree | Not in label — unassessed | serious n=21 | not reported in cached trials |
| Endometrial hypertrophy | 13 | 48.0 27.6–83.4ROR 48.0 · χ² 534 / p 2e-118 | 43.7 EB05 27.2 · IC025 +3.2 3/3 methods agree | Not in label — unassessed | serious n=12 | not reported in cached trials |
| Osteoporotic fracture | 58 | 44.8 34.5–58.2ROR 45.0 · χ² 2,368 / p <1e-300 | 42.9 EB05 34.4 · IC025 +4.6 3/3 methods agree | Likely indication confounding shares a disease stem with the indications wording | serious n=17 · 82% consumer | not reported in cached trials |
| Breast hyperplasia | 10 | 42.0 22.4–78.8ROR 42.1 · χ² 350 / p 2e-78 | 38.1 EB05 22.1 · IC025 +2.7 3/3 methods agree | Likely indication confounding term in indications | serious n=10 | not reported in cached trials |
| Breast cancer in situ | 34 | 39.2 27.9–55.0ROR 39.2 · χ² 1,194 / p 7e-262 | 37.4 EB05 28.0 · IC025 +4.1 3/3 methods agree | Likely indication confounding term in indications | serious n=34 | not reported in cached trials |
| Fibrocystic breast disease | 19 | 37.8 23.9–59.5ROR 37.8 · χ² 627 / p 1e-138 | 35.6 EB05 24.1 · IC025 +3.5 3/3 methods agree | Not in label — unassessed | serious n=19 | not reported in cached trials |
| Endometrial hyperplasia | 20 | 36.4 23.4–56.7ROR 36.4 · χ² 637 / p 7e-141 | 34.5 EB05 23.5 · IC025 +3.5 3/3 methods agree | Likely indication confounding shares a disease stem with the indications wording | serious n=16 | NCT00205777: 1/1,849 (0.1%) on Raloxifene (serious AE) |
| Monoclonal immunoglobulin present | 15 | 28.9 17.3–48.1ROR 28.9 · χ² 369 / p 2e-82 | 27.4 EB05 17.6 · IC025 +3.0 3/3 methods agree | Lab value / disease marker | serious n=15 | not reported in cached trials |
| Fractured sacrum | 24 | 28.6 19.1–42.8ROR 28.6 · χ² 599 / p 1e-132 | 27.5 EB05 19.4 · IC025 +3.5 3/3 methods agree | Not in label — unassessed | serious n=22 | not reported in cached trials |
| Bunion | 14 | 28.3 16.7–48.0ROR 28.3 · χ² 335 / p 4e-75 | 26.8 EB05 16.9 · IC025 +2.9 3/3 methods agree | Not in label — unassessed | serious n=12 | not reported in cached trials |
| Oestrogen receptor assay positive | 20 | 25.6 16.5–39.9ROR 25.7 · χ² 441 / p 3e-98 | 24.7 EB05 16.8 · IC025 +3.2 3/3 methods agree | Lab value / disease marker | serious n=20 | not reported in cached trials |
| Fracture delayed union | 14 | 24.1 14.2–40.8ROR 24.1 · χ² 282 / p 1e-63 | 23.0 EB05 14.4 · IC025 +2.8 3/3 methods agree | Not in label — unassessed | serious n=13 | not reported in cached trials |
| Breast calcifications | 13 | 23.8 13.7–41.1ROR 23.8 · χ² 257 / p 4e-58 | 22.6 EB05 13.8 · IC025 +2.7 3/3 methods agree | Not in label — unassessed | serious n=11 | not reported in cached trials |
| Embolism venous | 49 | 23.7 17.9–31.4ROR 23.8 · χ² 1,025 / p 3e-225 | 23.1 EB05 18.2 · IC025 +3.8 3/3 methods agree | Labeled (related wording) related wording | serious n=49 · 73% consumer | not reported in cached trials |
| Resorption bone increased | 13 | 23.3 13.5–40.2ROR 23.3 · χ² 251 / p 7e-57 | 22.1 EB05 13.5 · IC025 +2.7 3/3 methods agree | Not in label — unassessed | serious n=12 | not reported in cached trials |
| Retinal vein occlusion | 45 | 23.2 17.3–31.1ROR 23.2 · χ² 917 / p 1e-201 | 22.6 EB05 17.6 · IC025 +3.7 3/3 methods agree | Labeled adverse reaction exact term | serious n=41 | not reported in cached trials |
| Thoracic vertebral fracture | 46 | 22.9 17.1–30.6ROR 23.0 · χ² 927 / p 5e-204 | 22.4 EB05 17.5 · IC025 +3.7 3/3 methods agree | Not in label — unassessed | serious n=42 | not reported in cached trials |
| Cystocele | 13 | 22.0 12.8–38.1ROR 22.1 · χ² 237 / p 9e-54 | 21.0 EB05 12.7 · IC025 +2.7 3/3 methods agree | Not in label — unassessed | serious n=12 | not reported in cached trials |
| Kyphosis | 26 | 21.5 14.6–31.6ROR 21.5 · χ² 480 / p 1e-106 | 20.9 EB05 14.9 · IC025 +3.3 3/3 methods agree | Not in label — unassessed | serious n=23 | not reported in cached trials |
| No adverse drug effect | 10 | 21.2 11.4–39.6ROR 21.2 · χ² 171 / p 3e-39 | 19.7 EB05 10.7 · IC025 +2.3 3/3 methods agree | Labeled (related wording) related wording | – | not reported in cached trials |
| Uterine polyp | 26 | 21.2 14.4–31.2ROR 21.2 · χ² 473 / p 4e-105 | 20.6 EB05 14.7 · IC025 +3.3 3/3 methods agree | Not in label — unassessed | serious n=21 | not reported in cached trials |
| Bone density decreased | 456 | 21.1 19.3–23.1ROR 21.7 · χ² 8,592 / p <1e-300 | 20.8 EB05 19.2 · IC025 +4.2 3/3 methods agree | Lab value / disease marker | serious PRR 10.4 · 77% consumer | not reported in cached trials |
| Compression fracture | 74 | 20.8 16.6–26.2ROR 20.9 · χ² 1,357 / p 2e-297 | 20.4 EB05 16.8 · IC025 +3.8 3/3 methods agree | Not in label — unassessed | serious n=64 | not reported in cached trials |
| Fracture nonunion | 19 | 20.2 12.9–31.8ROR 20.2 · χ² 324 / p 1e-72 | 19.5 EB05 13.0 · IC025 +3.0 3/3 methods agree | Not in label — unassessed | serious n=19 | not reported in cached trials |
| Intramedullary rod insertion | 28 | 19.7 13.6–28.6ROR 19.7 · χ² 472 / p 6e-105 | 19.2 EB05 13.9 · IC025 +3.2 3/3 methods agree | Not in label — unassessed | serious n=28 | not reported in cached trials |
| Cerumen impaction | 12 | 19.0 10.8–33.6ROR 19.1 · χ² 185 / p 2e-42 | 17.9 EB05 10.2 · IC025 +2.5 3/3 methods agree | Not in label — unassessed | serious n=11 | not reported in cached trials |
| Limb asymmetry | 10 | 19.0 10.2–35.4ROR 19.0 · χ² 151 / p 5e-35 | 17.5 EB05 9.1 · IC025 +2.3 3/3 methods agree | Not in label — unassessed | serious n=9 | not reported in cached trials |
| Low turnover osteopathy | 52 | 18.8 14.3–24.7ROR 18.8 · χ² 846 / p 3e-186 | 18.4 EB05 14.6 · IC025 +3.5 3/3 methods agree | Likely indication confounding shares a disease stem with the indications wording | serious n=52 | not reported in cached trials |
| Spinal compression fracture | 107 | 18.6 15.4–22.5ROR 18.8 · χ² 1,746 / p <1e-300 | 18.4 EB05 15.6 · IC025 +3.8 3/3 methods agree | Not in label — unassessed | serious PRR 18.1 | not reported in cached trials |
| Meniscus lesion | 17 | 17.6 10.9–28.4ROR 17.6 · χ² 247 / p 6e-56 | 16.8 EB05 10.7 · IC025 +2.8 3/3 methods agree | Not in label — unassessed | serious n=17 | NCT00205777: 1/1,886 (0.1%) on Raloxifene; 1/1,885 (0.1%) control (serious AE) |
Trial evidence (ClinicalTrials.gov)
✓ Trial adverse-event data found on ClinicalTrials.gov
Largest completed trials with posted results that list Raloxifene 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).
- NCT00205777 — Study Evaluating Bazedoxifene Acetate In Osteoporosis In Postmenopausal Women (N=7609, PHASE3; 444 AE terms posted; arms: Bazedoxifene 20 mg; Bazedoxifene 40/ 20 mg; Raloxifene 60 mg (Core Study); Placebo)
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 |
|---|---|---|---|---|---|---|
| Nausea | 775 | 1.4 1.3–1.5ROR 1.4 · χ² 99 / p 1e-23 | 1.4 EB05 1.3 · IC025 +0.4 | Labeled adverse reaction exact term | serious PRR 1.4 | NCT00205777: 2/1,849 (0.1%) on Raloxifene; 3/1,885 (0.2%) control (serious AE) |
| Fall | 771 | 3.4 3.1–3.6ROR 3.5 · χ² 1,290 / p 7e-283 | 3.3 EB05 3.2 · IC025 +1.6 3/3 methods agree | Not in label — unassessed | serious PRR 3.4 | not reported in cached trials |
| Drug ineffective (drug did not work) | 750 | 0.8 0.8–0.9ROR 0.8 · χ² 30 / p 2e-8 | 0.8 EB05 0.8 · IC025 -0.4 PRR-only: not supported by EBGM or IC | Reporting / coding artifact | serious PRR 0.8 · 77% consumer | not reported in cached trials |
| Pain in extremity | 717 | 3.5 3.3–3.8ROR 3.6 · χ² 1,303 / p 1e-285 | 3.5 EB05 3.3 · IC025 +1.7 3/3 methods agree | Not in label — unassessed | serious PRR 2.9 · 77% consumer | not reported in cached trials |
| Pain | 687 | 1.6 1.5–1.7ROR 1.6 · χ² 164 / p 6e-38 | 1.6 EB05 1.5 · IC025 +0.6 | Labeled adverse reaction exact term | serious PRR 1.2 · 78% consumer | NCT00205777: 8/1,849 (0.4%) on Raloxifene; 8/1,885 (0.4%) control (serious AE) |
| Arthralgia (joint pain) | 636 | 2.2 2.1–2.4ROR 2.3 · χ² 433 / p 2e-96 | 2.2 EB05 2.1 · IC025 +1.0 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 2.0 | NCT00205777: 7/1,849 (0.4%) on Raloxifene; 9/1,885 (0.5%) control (serious AE) |
| Dizziness | 614 | 1.8 1.6–1.9ROR 1.8 · χ² 215 / p 5e-49 | 1.8 EB05 1.7 · IC025 +0.7 | Not in label — unassessed | serious PRR 1.6 | NCT00205777: 1/1,849 (0.1%) on Raloxifene; 5/1,885 (0.3%) control (serious AE) |
| Muscle spasms | 588 | 4.6 4.3–5.0ROR 4.8 · χ² 1,685 / p <1e-300 | 4.6 EB05 4.3 · IC025 +2.1 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 3.4 · 79% consumer | NCT00205777: 1/1,885 (0.1%) control (serious AE) |
| Fatigue (tiredness) | 562 | 1.0 1.0–1.1ROR 1.0 · χ² 1 / p 0.148 | 1.0 EB05 1.0 · IC025 -0.1 PRR-only: not supported by EBGM or IC | Not in label — unassessed | serious PRR 1.1 | not reported in cached trials |
| Headache | 556 | 1.3 1.2–1.4ROR 1.3 · χ² 36 / p 1e-9 | 1.3 EB05 1.2 · IC025 +0.2 | Labeled adverse reaction exact term | serious PRR 1.3 | NCT00205777: 1/1,849 (0.1%) on Raloxifene; 1/1,885 (0.1%) control (serious AE) |
| Body height decreased | 532 | 74.8 68.6–81.4ROR 77.6 · χ² 36,735 / p <1e-300 | 70.9 EB05 66.0 · IC025 +5.9 3/3 methods agree | Not in label — unassessed | serious n=119 · 90% consumer | not reported in cached trials |
| Back pain | 470 | 2.9 2.7–3.2ROR 3.0 · χ² 599 / p 1e-132 | 2.9 EB05 2.7 · IC025 +1.4 3/3 methods agree | Not in label — unassessed | serious PRR 3.0 | NCT00205777: 6/1,849 (0.3%) on Raloxifene; 4/1,885 (0.2%) control (serious AE) |
| Diarrhoea (diarrhea) | 465 | 1.0 1.0–1.1ROR 1.0 · χ² 1 / p 0.176 | 1.0 EB05 1.0 · IC025 -0.1 PRR-only: not supported by EBGM or IC | Labeled adverse reaction exact term | serious PRR 1.2 | NCT00205777: 1/1,886 (0.1%) on Raloxifene; 2/1,885 (0.1%) control (serious AE) |
| Bone density decreased | 456 | 21.1 19.3–23.1ROR 21.7 · χ² 8,592 / p <1e-300 | 20.8 EB05 19.2 · IC025 +4.2 3/3 methods agree | Lab value / disease marker | serious PRR 10.4 · 77% consumer | not reported in cached trials |
| Dyspnoea (shortness of breath) | 453 | 1.2 1.1–1.3ROR 1.2 · χ² 10 / p 9e-4 | 1.2 EB05 1.1 · IC025 +0.1 | Not in label — unassessed | serious PRR 1.1 | NCT00205777: 3/1,849 (0.2%) on Raloxifene; 1/1,885 (0.1%) control (serious AE) |
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.
- Body height decreased — n=532, PRR 74.8
- Wrist deformity — n=27, PRR 65.8
- Atrophic vulvovaginitis — n=25, PRR 51.3
- Fractured sacrum — n=24, PRR 28.6
- Thoracic vertebral fracture — n=46, PRR 22.9
- Kyphosis — n=26, PRR 21.5
- Uterine polyp — n=26, PRR 21.2
- Compression fracture — n=74, PRR 20.8
- Intramedullary rod insertion — n=28, PRR 19.7
- Spinal compression fracture — n=107, PRR 18.6
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 Raloxifene?
In FDA FAERS, the most frequently co-reported reaction terms for Raloxifene are nausea, fall, pain in extremity, pain, arthralgia, dizziness. 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 Raloxifene have an FDA boxed warning?
Yes. The current FDA label carries a boxed warning: INCREASED RISK OF VENOUS THROMBOEMBOLISM AND DEATH FROM STROKE WARNING: INCREASED RISK OF VENOUS THROMBOEMBOLISM AND DEATH FROM STROKE Increased risk of deep vein thrombosis and pulmonary embolism have been reported with raloxifene hydrochloride tablets [see Warnings and Precautions ( 5.1 )].
Do FAERS signals prove that Raloxifene 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 53a2db10-4af8-4032-b598-b7c7a0969801, effective 20210317; matched on
openfda.generic_name.exact:"RALOXIFENE") - 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, 1,096 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
RALOXIFENE, 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.