Metolazone side effects: what 11,165 FDA adverse event reports show

Metolazone · 1,127 reaction terms · 55,315 drug–reaction co-reports · data 2026-09-14

Drug class

Thiazide-like Diuretic

FDA label (Established Pharmacologic Class) · compare the class

Who reports

11,165 reports · 79% serious · 2,203 with death outcome · 53% female

openFDA FAERS counts, all years, deduplication not applied

Used for

Metolazone tablets, USP, are indicated for the treatment of salt and water retention including: · edema accompanying congestive heart failure; · edema accompanying renal diseases, including the nephrotic syndrome and states of diminished renal function. Metolazone tablets, USP, are also indicated for the treatment of hypertension, alone or in combination with other antihypertensive drugs of a different class.

FDA label, Indications and Usage

What it is

DESCRIPTION Metolazone tablets, USP, for oral administration contain 2½, 5, or 10 mg of metolazone, USP, a diuretic/saluretic/antihypertensive drug of the quinazoline class. Metolazone has the.

FDA label, Description section

Boxed warning

None in the current label

How to read this page. FAERS is a spontaneous-reporting system: counts are not incidence rates and a signal is not proof of causation. Each reaction below is run through an automated screen — is the term in the FDA label (known), in the indications (the disease being treated), an administrative/coding term, or none of these (unlabeled)? That screen is mechanical text matching, not a causality assessment. The 30 hand-written Bradford Hill assessments are on the causality assessment page. Not medical advice.

Causality screen of the 40 strongest signals

Labeled (related wording) 1Likely indication confounding 5Reporting / coding artifact 3Lab value / disease marker 8Not in label — unassessed 23

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.
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. 1,087 further terms are in the interactive explorer. Reaction links open the term's cross-drug page.

Show: hide coding/lab/outcome terms hide indication terms unlabeled only hide PRR-only

Reaction	Reports	PRR 95% CI · ROR · χ²/p	EBGM EB05 · IC025	Label screen	Serious-only & strata	Trial cross-check
Burkholderia test positive	10	163.8 85.8–312.6ROR 163.9 · χ² 1,341 / p 9e-294	117.4 EB05 68.2 · IC025 +3.1 3/3 methods agree	Lab value / disease marker	serious n=10	not reported in cached trials
Urine sodium decreased	10	156.9 82.3–299.0ROR 157.0 · χ² 1,287 / p 3e-282	113.9 EB05 66.1 · IC025 +3.1 3/3 methods agree	Lab value / disease marker	serious n=10	not reported in cached trials
Chronic left ventricular failure	22	124.5 80.9–191.7ROR 124.8 · χ² 2,411 / p <1e-300	106.2 EB05 73.9 · IC025 +4.3 3/3 methods agree	Not in label — unassessed	serious n=21	not reported in cached trials
Venous pressure jugular increased	17	90.9 55.9–147.9ROR 91.1 · χ² 1,357 / p 3e-297	79.3 EB05 52.4 · IC025 +3.8 3/3 methods agree	Not in label — unassessed	serious n=17	not reported in cached trials
Jugular vein distension	19	64.3 40.7–101.5ROR 64.4 · χ² 1,084 / p 6e-238	58.7 EB05 39.7 · IC025 +3.8 3/3 methods agree	Not in label — unassessed	serious n=18	not reported in cached trials
Necrotising oesophagitis	16	63.1 38.4–103.9ROR 63.2 · χ² 887 / p 3e-195	57.2 EB05 37.3 · IC025 +3.6 3/3 methods agree	Not in label — unassessed	serious n=16	not reported in cached trials
Nephrogenic anaemia	152	63.1 53.7–74.0ROR 63.9 · χ² 8,918 / p <1e-300	60.6 EB05 52.9 · IC025 +5.4 3/3 methods agree	Likely indication confounding shares a disease stem with the indications wording	serious n=152	not reported in cached trials
Hyperparathyroidism secondary	79	60.4 48.3–75.5ROR 60.8 · χ² 4,414 / p <1e-300	57.8 EB05 47.8 · IC025 +5.1 3/3 methods agree	Not in label — unassessed	serious n=79	not reported in cached trials
Chronic kidney disease-mineral and bone disorder	32	57.5 40.5–81.7ROR 57.7 · χ² 1,669 / p <1e-300	54.1 EB05 40.1 · IC025 +4.3 3/3 methods agree	Not in label — unassessed	serious n=32	not reported in cached trials
Cor pulmonale	24	47.9 31.9–71.8ROR 48.0 · χ² 1,028 / p 6e-226	45.1 EB05 31.9 · IC025 +3.9 3/3 methods agree	Not in label — unassessed	serious n=24 · ♀ 79% (drug 53%)	not reported in cached trials
Device maintenance issue	12	40.8 23.0–72.2ROR 40.8 · χ² 417 / p 5e-93	37.7 EB05 23.0 · IC025 +3.0 3/3 methods agree	Reporting / coding artifact	–	not reported in cached trials
Cardiorenal syndrome	12	40.3 22.8–71.4ROR 40.4 · χ² 413 / p 5e-92	37.3 EB05 22.7 · IC025 +3.0 3/3 methods agree	Likely indication confounding shares a disease stem with the indications wording	serious n=12	not reported in cached trials
Right ventricular failure	147	39.9 33.9–46.9ROR 40.4 · χ² 5,416 / p <1e-300	38.9 EB05 33.9 · IC025 +4.8 3/3 methods agree	Not in label — unassessed	serious PRR 28.3	not reported in cached trials
Hypervolaemia	99	39.5 32.4–48.2ROR 39.9 · χ² 3,602 / p <1e-300	38.4 EB05 32.5 · IC025 +4.7 3/3 methods agree	Likely indication confounding shares a disease stem with the indications wording	serious n=95	not reported in cached trials
Orthopnoea	65	39.0 30.5–49.8ROR 39.2 · χ² 2,320 / p <1e-300	37.8 EB05 30.7 · IC025 +4.5 3/3 methods agree	Not in label — unassessed	serious n=63	not reported in cached trials
Metabolic alkalosis	32	38.4 27.1–54.5ROR 38.5 · χ² 1,106 / p 8e-243	36.9 EB05 27.4 · IC025 +4.0 3/3 methods agree	Labeled (related wording) related wording	serious n=32 · ♀ 74% (drug 53%) · 90% clinician	not reported in cached trials
Paracentesis	12	37.1 21.0–65.8ROR 37.2 · χ² 379 / p 1e-84	34.6 EB05 21.1 · IC025 +2.9 3/3 methods agree	Not in label — unassessed	serious n=12	not reported in cached trials
Dyspnoea paroxysmal nocturnal	14	36.3 21.4–61.6ROR 36.3 · χ² 437 / p 2e-97	34.1 EB05 21.6 · IC025 +3.1 3/3 methods agree	Not in label — unassessed	serious n=14	not reported in cached trials
End stage renal disease	315	32.6 29.2–36.4ROR 33.6 · χ² 9,471 / p <1e-300	32.0 EB05 29.2 · IC025 +4.7 3/3 methods agree	Not in label — unassessed	serious PRR 23.3	not reported in cached trials
Cardioactive drug level increased	22	31.6 20.7–48.1ROR 31.6 · χ² 611 / p 3e-135	30.3 EB05 21.1 · IC025 +3.5 3/3 methods agree	Lab value / disease marker	serious n=22	not reported in cached trials
Cardiac amyloidosis	18	31.6 19.8–50.3ROR 31.6 · χ² 494 / p 8e-110	30.2 EB05 20.2 · IC025 +3.3 3/3 methods agree	Not in label — unassessed	serious n=18	not reported in cached trials
Brash syndrome	22	30.9 20.3–47.1ROR 31.0 · χ² 597 / p 3e-132	29.7 EB05 20.7 · IC025 +3.5 3/3 methods agree	Not in label — unassessed	serious n=22 · 100% clinician	not reported in cached trials
Rebound acid hypersecretion	48	29.8 22.4–39.6ROR 29.9 · χ² 1,288 / p 2e-282	29.1 EB05 22.8 · IC025 +4.0 3/3 methods agree	Not in label — unassessed	serious n=48	not reported in cached trials
Fluid overload	230	29.7 26.1–33.8ROR 30.3 · χ² 6,252 / p <1e-300	29.2 EB05 26.1 · IC025 +4.6 3/3 methods agree	Not in label — unassessed	serious PRR 27.0	not reported in cached trials
Brain natriuretic peptide increased	48	29.7 22.3–39.4ROR 29.8 · χ² 1,281 / p 7e-281	28.9 EB05 22.7 · IC025 +4.0 3/3 methods agree	Lab value / disease marker	serious n=48	not reported in cached trials
Calcium deficiency	20	29.2 18.8–45.5ROR 29.3 · χ² 510 / p 4e-113	28.1 EB05 19.2 · IC025 +3.4 3/3 methods agree	Not in label — unassessed	serious n=20	not reported in cached trials
Device infusion issue	35	27.2 19.5–37.9ROR 27.3 · χ² 844 / p 6e-186	26.5 EB05 19.9 · IC025 +3.7 3/3 methods agree	Reporting / coding artifact	serious n=17 · 80% consumer	not reported in cached trials
Therapeutic agent toxicity	47	26.4 19.8–35.2ROR 26.5 · χ² 1,110 / p 1e-243	25.8 EB05 20.2 · IC025 +3.9 3/3 methods agree	Not in label — unassessed	serious n=46 · ♀ 74% (drug 53%)	not reported in cached trials
Ischaemic cardiomyopathy	43	26.4 19.6–35.7ROR 26.5 · χ² 1,012 / p 3e-222	25.8 EB05 19.9 · IC025 +3.8 3/3 methods agree	Likely indication confounding shares a disease stem with the indications wording	serious n=43 · ♀ 31% (drug 53%)	not reported in cached trials
Pulmonary arterial hypertension	202	26.4 23.0–30.3ROR 26.8 · χ² 4,841 / p <1e-300	26.0 EB05 23.1 · IC025 +4.4 3/3 methods agree	Likely indication confounding shares a disease stem with the indications wording	serious PRR 18.8 · ♀ 73% (drug 53%)	not reported in cached trials
Acute prerenal failure	16	26.0 15.9–42.5ROR 26.0 · χ² 355 / p 2e-79	24.9 EB05 16.2 · IC025 +3.0 3/3 methods agree	Not in label — unassessed	serious n=16	not reported in cached trials
Pulmonary arterial pressure increased	22	25.6 16.8–38.9ROR 25.6 · χ² 489 / p 1e-108	24.8 EB05 17.2 · IC025 +3.3 3/3 methods agree	Lab value / disease marker	serious n=21	not reported in cached trials
Catheter management	12	25.3 14.3–44.7ROR 25.3 · χ² 252 / p 4e-57	24.0 EB05 14.4 · IC025 +2.7 3/3 methods agree	Reporting / coding artifact	serious n=12	not reported in cached trials
Waist circumference increased	13	23.6 13.7–40.8ROR 23.7 · χ² 256 / p 5e-58	22.5 EB05 13.8 · IC025 +2.7 3/3 methods agree	Not in label — unassessed	serious n=13	not reported in cached trials
Anaemia of chronic disease	11	23.1 12.8–41.9ROR 23.1 · χ² 208 / p 1e-47	21.8 EB05 12.6 · IC025 +2.5 3/3 methods agree	Not in label — unassessed	serious n=11	not reported in cached trials
Packed red blood cell transfusion	16	22.6 13.8–37.1ROR 22.7 · χ² 306 / p 8e-69	21.8 EB05 14.1 · IC025 +2.9 3/3 methods agree	Not in label — unassessed	serious n=16	not reported in cached trials
Dilatation atrial	14	22.5 13.3–38.1ROR 22.5 · χ² 263 / p 1e-59	21.6 EB05 13.4 · IC025 +2.8 3/3 methods agree	Not in label — unassessed	serious n=14	not reported in cached trials
Oxygen consumption increased	27	21.7 14.9–31.7ROR 21.7 · χ² 507 / p 2e-112	21.2 EB05 15.2 · IC025 +3.3 3/3 methods agree	Lab value / disease marker	serious n=19 · ♀ 73% (drug 53%)	not reported in cached trials
Urine protein/creatinine ratio increased	10	21.3 11.4–39.7ROR 21.3 · χ² 172 / p 2e-39	19.9 EB05 10.8 · IC025 +2.4 3/3 methods agree	Lab value / disease marker	–	not reported in cached trials
Blood chloride decreased	29	21.2 14.7–30.5ROR 21.2 · χ² 531 / p 9e-118	20.7 EB05 15.0 · IC025 +3.3 3/3 methods agree	Lab value / disease marker	serious n=28	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 Metolazone 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 (0 of 40 signal terms matched).

NCT02620384 — Metolazone As Early Add On Therapy For Acute Decompensated Heart Failure (MELT-HF)--A Single Center Pilot Stud (N=147, PHASE3; 4 AE terms posted; arms: Experimental: Placebo; Experimental: Metolazone)
NCT02606253 — Comparison of Oral or Intravenous Thiazides vs Tolvaptan in Diuretic Resistant Decompensated Heart Failure (N=60, PHASE4; 11 AE terms posted; arms: Metolazone; Chlorothiazide; Tolvaptan)

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
Dyspnoea (shortness of breath)	1,247	4.1 3.9–4.4ROR 4.5 · χ² 3,048 / p <1e-300	4.1 EB05 3.9 · IC025 +2.0 3/3 methods agree	Not in label — unassessed	serious PRR 3.6	not reported in cached trials
Death	879	1.9 1.8–2.0ROR 2.0 · χ² 400 / p 2e-89	1.9 EB05 1.8 · IC025 +0.8	Outcome field, not a reaction	serious PRR 1.4	not reported in cached trials
Acute kidney injury (sudden kidney damage)	799	9.9 9.3–10.6ROR 10.6 · χ² 6,390 / p <1e-300	9.8 EB05 9.3 · IC025 +3.2 3/3 methods agree	Not in label — unassessed	serious PRR 7.1	NCT02620384: 10/72 (13.9%) on Metolazone; 4/70 (5.7%) control
Nausea	762	1.8 1.7–1.9ROR 1.9 · χ² 288 / p 8e-65	1.8 EB05 1.7 · IC025 +0.7	Labeled adverse reaction exact term	serious PRR 1.9	NCT02606253: 1/20 (5.0%) on Metolazone
Renal failure (kidney failure)	716	10.1 9.4–10.8ROR 10.7 · χ² 5,862 / p <1e-300	10.0 EB05 9.4 · IC025 +3.2 3/3 methods agree	Likely indication confounding term in indications	serious PRR 7.3	not reported in cached trials
Cardiac failure congestive	684	16.0 14.8–17.2ROR 16.9 · χ² 9,528 / p <1e-300	15.8 EB05 14.8 · IC025 +3.8 3/3 methods agree	Likely indication confounding shares a disease stem with the indications wording	serious PRR 11.5	not reported in cached trials
Fatigue (tiredness)	662	1.6 1.5–1.7ROR 1.6 · χ² 154 / p 1e-35	1.6 EB05 1.5 · IC025 +0.5	Labeled adverse reaction exact term	serious PRR 1.7	not reported in cached trials
Diarrhoea (diarrhea)	659	1.9 1.8–2.1ROR 2.0 · χ² 300 / p 1e-67	1.9 EB05 1.8 · IC025 +0.8	Labeled adverse reaction exact term	serious PRR 1.8	not reported in cached trials
Dizziness	624	2.4 2.2–2.5ROR 2.4 · χ² 496 / p 4e-110	2.3 EB05 2.2 · IC025 +1.1 3/3 methods agree	Labeled adverse reaction exact term	serious PRR 2.3	not reported in cached trials
Chronic kidney disease	593	14.6 13.5–15.8ROR 15.4 · χ² 7,482 / p <1e-300	14.5 EB05 13.6 · IC025 +3.7 3/3 methods agree	Not in label — unassessed	serious PRR 10.7	not reported in cached trials
Hypotension (low blood pressure)	591	5.6 5.1–6.0ROR 5.8 · χ² 2,215 / p <1e-300	5.5 EB05 5.2 · IC025 +2.3 3/3 methods agree	Labeled adverse reaction exact term	serious PRR 4.3	NCT02620384: 1/72 (1.4%) on Metolazone; 6/70 (8.6%) control
Asthenia (weakness)	582	2.9 2.7–3.1ROR 3.0 · χ² 738 / p 6e-163	2.9 EB05 2.7 · IC025 +1.4 3/3 methods agree	Not in label — unassessed	serious PRR 2.6	not reported in cached trials
Headache	570	1.7 1.6–1.9ROR 1.7 · χ² 172 / p 1e-39	1.7 EB05 1.6 · IC025 +0.6	Labeled adverse reaction exact term	serious PRR 1.7	not reported in cached trials
Oedema peripheral (swelling of legs/feet)	532	8.2 7.5–8.9ROR 8.6 · χ² 3,357 / p <1e-300	8.1 EB05 7.6 · IC025 +2.9 3/3 methods agree	Labeled (related wording) related wording	serious PRR 7.2	not reported in cached trials
Fall	522	2.9 2.7–3.2ROR 3.0 · χ² 680 / p 3e-150	2.9 EB05 2.7 · IC025 +1.4 3/3 methods agree	Not in label — unassessed	serious PRR 2.4	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.

Chronic left ventricular failure — n=22, PRR 124.5
Hyperparathyroidism secondary — n=79, PRR 60.4
Chronic kidney disease-mineral and bone disorder — n=32, PRR 57.5
Cor pulmonale — n=24, PRR 47.9
Right ventricular failure — n=147, PRR 39.9
Orthopnoea — n=65, PRR 39.0
End stage renal disease — n=315, PRR 32.6
Brash syndrome — n=22, PRR 30.9
Rebound acid hypersecretion — n=48, PRR 29.8
Fluid overload — n=230, PRR 29.7

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 Metolazone?

In FDA FAERS, the most frequently co-reported reaction terms for Metolazone are dyspnoea, acute kidney injury, nausea, renal failure, cardiac failure congestive, fatigue. 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 Metolazone have an FDA boxed warning?

No. The FDA label retrieved for Metolazone has no boxed warning; see the label's Warnings and Precautions for the recognised risks.

Do FAERS signals prove that Metolazone 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 1a8c38aa-362e-6bcc-e063-6294a90a1e05, effective 20260211; matched on openfda.generic_name.exact:"METOLAZONE")
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, field patient.drug.openfda.generic_name.exact, 1,127 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 METOLAZONE, 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.