Enalapril and Hydrochlorothiazide side effects: what 911 FDA adverse event reports show
Drug class
Angiotensin-converting enzyme inhibitor
Label matched
Enalapril (Enalapril Maleate)
Who reports
911 reports · 86% serious · 61 with death outcome · 59% female
Used for
Enalapril maleate oral solution is an angiotensin-converting enzyme inhibitor indicated for: treatment of hypertension in adults and children older than one month, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. ( 1.1 ) treatment of symptomatic heart failure.
What it is
Enalapril maleate (enalapril maleate) oral solution is the maleate salt of enalapril, the ethyl ester prodrug of a long-acting angiotensin-converting enzyme inhibitor, enalaprilat. Enalapril m.
Boxed warning
FETAL TOXICITY When pregnancy is detected, discontinue enalapril maleate as soon as possible [see Warnings and Precautions (5.1) ]. Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus [see Warnings and Precautions (5.1) ].
Causality screen of the 21 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. 9 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 |
|---|---|---|---|---|---|---|
| Renal failure acute | 44 | 23.5 17.6–31.4ROR 24.7 · χ² 928 / p 5e-204 | 23.3 EB05 18.1 · IC025 +3.7 3/3 methods agree | Labeled (related wording) related wording | serious PRR 15.8 · 92% clinician | no trial data cached |
| Hypertensive crisis | 8 | 16.5 8.3–32.9ROR 16.6 · χ² 101 / p 4e-24 | 14.3 EB05 6.3 · IC025 +1.9 3/3 methods agree | Likely indication confounding shares a disease stem with the indications wording | serious PRR 11.0 | no trial data cached |
| Hyponatraemia (low sodium) | 34 | 13.9 10.0–19.4ROR 14.4 · χ² 396 / p 3e-88 | 13.6 EB05 10.0 · IC025 +3.0 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 9.5 · 100% clinician | no trial data cached |
| Hypotonia | 6 | 13.8 6.2–30.6ROR 13.8 · χ² 59 / p 9e-15 | 10.1 EB05 4.0 · IC025 +1.4 3/3 methods agree | Not in label — unassessed | serious PRR 10.5 | no trial data cached |
| Inappropriate antidiuretic hormone secretion | 6 | 13.6 6.1–30.1ROR 13.6 · χ² 58 / p 1e-14 | 9.9 EB05 3.9 · IC025 +1.4 3/3 methods agree | Not in label — unassessed | serious PRR 9.1 | no trial data cached |
| Anorexia | 7 | 12.3 5.9–25.8ROR 12.4 · χ² 62 / p 2e-15 | 9.3 EB05 4.1 · IC025 +1.5 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 9.3 | no trial data cached |
| Arteriosclerosis | 5 | 12.2 5.1–29.2ROR 12.3 · χ² 41 / p 8e-11 | 8.0 EB05 3.1 · IC025 +1.0 3/3 methods agree | Not in label — unassessed | serious PRR 8.4 | no trial data cached |
| Lactic acidosis | 17 | 12.2 7.6–19.5ROR 12.4 · χ² 164 / p 9e-38 | 11.1 EB05 6.8 · IC025 +2.4 3/3 methods agree | Not in label — unassessed | serious PRR 8.1 | no trial data cached |
| Economic problem | 8 | 11.9 6.0–23.8ROR 12.0 · χ² 70 / p 4e-17 | 9.3 EB05 4.4 · IC025 +1.6 3/3 methods agree | Reporting / coding artifact | serious PRR 8.7 | no trial data cached |
| Coronary artery disease | 15 | 11.3 6.8–18.7ROR 11.5 · χ² 131 / p 1e-30 | 10.0 EB05 5.9 · IC025 +2.2 3/3 methods agree | Not in label — unassessed | serious PRR 7.7 | no trial data cached |
| Face oedema | 8 | 10.9 5.4–21.7ROR 10.9 · χ² 62 / p 2e-15 | 8.2 EB05 4.0 · IC025 +1.6 3/3 methods agree | Labeled (related wording) related wording | serious PRR 8.1 | no trial data cached |
| Eosinophilia | 8 | 10.5 5.3–21.0ROR 10.6 · χ² 60 / p 5e-15 | 7.9 EB05 3.9 · IC025 +1.5 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 7.4 | no trial data cached |
| Gamma-glutamyltransferase increased | 10 | 10.4 5.6–19.2ROR 10.5 · χ² 76 / p 2e-18 | 8.3 EB05 4.4 · IC025 +1.8 3/3 methods agree | Lab value / disease marker | serious PRR 7.2 | no trial data cached |
| Blood creatine phosphokinase increased | 13 | 10.2 6.0–17.5ROR 10.4 · χ² 99 / p 1e-23 | 8.6 EB05 5.0 · IC025 +2.0 3/3 methods agree | Lab value / disease marker | serious PRR 6.4 | no trial data cached |
| International normalised ratio increased | 12 | 9.6 5.5–16.8ROR 9.7 · χ² 84 / p 3e-20 | 7.9 EB05 4.5 · IC025 +1.9 3/3 methods agree | Lab value / disease marker | serious PRR 6.5 | no trial data cached |
| Hypoglycaemia (low blood sugar) | 19 | 9.0 5.8–14.0ROR 9.2 · χ² 128 / p 7e-30 | 7.9 EB05 5.2 · IC025 +2.1 3/3 methods agree | Not in label — unassessed | serious PRR 6.8 | no trial data cached |
| Cholestasis (bile flow blockage) | 7 | 8.4 4.0–17.6ROR 8.5 · χ² 39 / p 2e-10 | 6.0 EB05 3.0 · IC025 +1.2 3/3 methods agree | Not in label — unassessed | serious PRR 5.7 | no trial data cached |
| Pharmaceutical product complaint | 9 | 7.9 4.1–15.1ROR 7.9 · χ² 47 / p 3e-12 | 6.0 EB05 3.3 · IC025 +1.4 3/3 methods agree | Likely indication confounding shares a disease stem with the indications wording | serious PRR 4.7 | no trial data cached |
| Pharyngeal oedema | 5 | 7.4 3.1–17.7ROR 7.4 · χ² 22 / p 2e-6 | 4.8 EB05 2.2 · IC025 +0.7 3/3 methods agree | Not in label — unassessed | serious PRR 6.5 | no trial data cached |
| Extrapyramidal disorder | 6 | 5.5 2.5–12.2ROR 5.5 · χ² 18 / p 1e-5 | 4.1 EB05 2.0 · IC025 +0.6 3/3 methods agree | Not in label — unassessed | serious PRR 4.1 | no trial data cached |
| Intentional overdose | 7 | 2.5 1.2–5.3ROR 2.5 · χ² 5 / p 0.012 | 2.3 EB05 1.2 · IC025 -0.1 PRR-only: not supported by EBGM or IC | Reporting / coding artifact | serious PRR 1.8 | 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 |
|---|---|---|---|---|---|---|
| Renal failure acute | 44 | 23.5 17.6–31.4ROR 24.7 · χ² 928 / p 5e-204 | 23.3 EB05 18.1 · IC025 +3.7 3/3 methods agree | Labeled (related wording) related wording | serious PRR 15.8 · 92% clinician | no trial data cached |
| Hyponatraemia (low sodium) | 34 | 13.9 10.0–19.4ROR 14.4 · χ² 396 / p 3e-88 | 13.6 EB05 10.0 · IC025 +3.0 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 9.5 · 100% clinician | no trial data cached |
| Hypoglycaemia (low blood sugar) | 19 | 9.0 5.8–14.0ROR 9.2 · χ² 128 / p 7e-30 | 7.9 EB05 5.2 · IC025 +2.1 3/3 methods agree | Not in label — unassessed | serious PRR 6.8 | no trial data cached |
| Lactic acidosis | 17 | 12.2 7.6–19.5ROR 12.4 · χ² 164 / p 9e-38 | 11.1 EB05 6.8 · IC025 +2.4 3/3 methods agree | Not in label — unassessed | serious PRR 8.1 | no trial data cached |
| Coronary artery disease | 15 | 11.3 6.8–18.7ROR 11.5 · χ² 131 / p 1e-30 | 10.0 EB05 5.9 · IC025 +2.2 3/3 methods agree | Not in label — unassessed | serious PRR 7.7 | no trial data cached |
| Blood creatine phosphokinase increased | 13 | 10.2 6.0–17.5ROR 10.4 · χ² 99 / p 1e-23 | 8.6 EB05 5.0 · IC025 +2.0 3/3 methods agree | Lab value / disease marker | serious PRR 6.4 | no trial data cached |
| International normalised ratio increased | 12 | 9.6 5.5–16.8ROR 9.7 · χ² 84 / p 3e-20 | 7.9 EB05 4.5 · IC025 +1.9 3/3 methods agree | Lab value / disease marker | serious PRR 6.5 | no trial data cached |
| Gamma-glutamyltransferase increased | 10 | 10.4 5.6–19.2ROR 10.5 · χ² 76 / p 2e-18 | 8.3 EB05 4.4 · IC025 +1.8 3/3 methods agree | Lab value / disease marker | serious PRR 7.2 | no trial data cached |
| Pharmaceutical product complaint | 9 | 7.9 4.1–15.1ROR 7.9 · χ² 47 / p 3e-12 | 6.0 EB05 3.3 · IC025 +1.4 3/3 methods agree | Likely indication confounding shares a disease stem with the indications wording | serious PRR 4.7 | no trial data cached |
| Eosinophilia | 8 | 10.5 5.3–21.0ROR 10.6 · χ² 60 / p 5e-15 | 7.9 EB05 3.9 · IC025 +1.5 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 7.4 | no trial data cached |
| Face oedema | 8 | 10.9 5.4–21.7ROR 10.9 · χ² 62 / p 2e-15 | 8.2 EB05 4.0 · IC025 +1.6 3/3 methods agree | Labeled (related wording) related wording | serious PRR 8.1 | no trial data cached |
| Economic problem | 8 | 11.9 6.0–23.8ROR 12.0 · χ² 70 / p 4e-17 | 9.3 EB05 4.4 · IC025 +1.6 3/3 methods agree | Reporting / coding artifact | serious PRR 8.7 | no trial data cached |
| Hypertensive crisis | 8 | 16.5 8.3–32.9ROR 16.6 · χ² 101 / p 4e-24 | 14.3 EB05 6.3 · IC025 +1.9 3/3 methods agree | Likely indication confounding shares a disease stem with the indications wording | serious PRR 11.0 | no trial data cached |
| Intentional overdose | 7 | 2.5 1.2–5.3ROR 2.5 · χ² 5 / p 0.012 | 2.3 EB05 1.2 · IC025 -0.1 PRR-only: not supported by EBGM or IC | Reporting / coding artifact | serious PRR 1.8 | no trial data cached |
| Cholestasis (bile flow blockage) | 7 | 8.4 4.0–17.6ROR 8.5 · χ² 39 / p 2e-10 | 6.0 EB05 3.0 · IC025 +1.2 3/3 methods agree | Not in label — unassessed | serious PRR 5.7 | no trial data cached |
Unlabeled candidate signals
Every screened signal with n ≥ 20 was either labeled, an indication term, or an artifact pattern — no unlabeled candidate stood out in the top signals.
✓ A hand-written Bradford Hill causality assessment exists for this drug: Hydrochlorothiazide (thiazides) ↔ Hyponatraemia.
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 Enalapril and Hydrochlorothiazide?
In FDA FAERS, the most frequently co-reported reaction terms for Enalapril and Hydrochlorothiazide are renal failure acute, hyponatraemia, hypoglycaemia, lactic acidosis, coronary artery disease, blood creatine phosphokinase 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 Enalapril and Hydrochlorothiazide have an FDA boxed warning?
Yes. The current FDA label carries a boxed warning: FETAL TOXICITY When pregnancy is detected, discontinue enalapril maleate as soon as possible [see Warnings and Precautions (5.1) ]. Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus [see Warnings and Precautions (5.1) ].
Do FAERS signals prove that Enalapril and Hydrochlorothiazide 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 e81a8aca-0e7c-4a02-b596-09e4ac22c70e, effective 20190329; matched on
openfda.generic_name.exact:"ENALAPRIL") - 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, 30 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.