Tolvaptan side effects: what 14,366 FDA adverse event reports show
Drug class
Vasopressin V2 Receptor Antagonist
Who reports
14,366 reports · 81% serious · 3,190 with death outcome · 50% female
Used for
Tolvaptan tablets are indicated for the treatment of clinically significant hypervolemic and euvolemic hyponatremia (serum sodium <125 mEq/L or less marked hyponatremia that is symptomatic and has resisted correction with fluid restriction), including patients with heart failure and Syndrome of Inappropriate Antidiuretic Hormone (SIADH).
What it is
Tolvaptan, a selective vasopressin V 2 -receptor antagonist in tablets for oral use available in 15 mg or 30 mg strength. Tolvaptan is (±) 4’-[(7-Chloro-2,3,4,5-tetrahydro-5-hydroxy-1H-benzazepin-1-yl) carbonyl]-O-tolu-m-toluidide.
Boxed warning
(A) INITIATE AND RE-INITIATE IN A HOSPITAL AND MONITOR SERUM SODIUM (B) NOT FOR USE FOR AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE (ADPKD) WARNING: (A) INITIATE AND RE-INITIATE IN A HOSPITAL AND MONITOR SERUM SODIU.
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. 975 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 |
|---|---|---|---|---|---|---|
| Rapid correction of hyponatraemia | 204 | 6,212.1 4,525.8–8,526.7ROR 6,301.1 · χ² 236,061 / p <1e-300 | 1,048.5 EB05 933.2 · IC025 +8.0 3/3 methods agree | Labeled — boxed warning exact term | serious n=196 | no trial data cached |
| Renal cyst ruptured | 26 | 361.3 235.0–555.3ROR 361.9 · χ² 7,174 / p <1e-300 | 238.2 EB05 170.8 · IC025 +4.8 3/3 methods agree | Not in label — unassessed | serious n=26 | no trial data cached |
| Urine osmolarity decreased | 17 | 238.5 142.8–398.5ROR 238.8 · χ² 3,246 / p <1e-300 | 166.6 EB05 110.2 · IC025 +4.1 3/3 methods agree | Lab value / disease marker | serious n=14 | no trial data cached |
| Polycystic liver disease | 15 | 235.9 136.7–407.2ROR 236.2 · χ² 2,814 / p <1e-300 | 161.4 EB05 103.8 · IC025 +3.9 3/3 methods agree | Labeled (related wording) related wording | serious n=15 | no trial data cached |
| Renal cyst haemorrhage | 27 | 203.4 136.0–304.3ROR 203.8 · χ² 4,585 / p <1e-300 | 158.4 EB05 114.3 · IC025 +4.8 3/3 methods agree | Labeled (related wording) related wording | serious n=26 | no trial data cached |
| Renal cyst infection | 16 | 161.3 96.2–270.3ROR 161.4 · χ² 2,148 / p <1e-300 | 123.9 EB05 80.9 · IC025 +3.9 3/3 methods agree | Not in label — unassessed | serious n=16 | no trial data cached |
| Low cardiac output syndrome | 30 | 143.1 98.4–208.2ROR 143.4 · χ² 3,721 / p <1e-300 | 120.4 EB05 88.4 · IC025 +4.8 3/3 methods agree | Labeled (related wording) related wording | serious n=30 · ♀ 24% (drug 50%) · 100% clinician | no trial data cached |
| Hypernatraemia | 364 | 114.9 103.4–127.7ROR 117.8 · χ² 37,941 / p <1e-300 | 105.8 EB05 97.0 · IC025 +6.4 3/3 methods agree | Not in label — unassessed | serious n=354 · 97% clinician | no trial data cached |
| Urine osmolarity increased | 10 | 100.1 52.7–190.0ROR 100.2 · χ² 827 / p 5e-182 | 79.8 EB05 46.4 · IC025 +3.0 3/3 methods agree | Lab value / disease marker | serious n=9 | no trial data cached |
| Drug monitoring procedure incorrectly performed | 43 | 99.9 73.4–136.0ROR 100.2 · χ² 3,844 / p <1e-300 | 89.8 EB05 69.5 · IC025 +5.0 3/3 methods agree | Reporting / coding artifact | serious n=36 | no trial data cached |
| Blood sodium increased | 162 | 92.3 78.8–108.1ROR 93.3 · χ² 13,655 / p <1e-300 | 85.9 EB05 75.3 · IC025 +5.8 3/3 methods agree | Likely indication confounding term in indications; also in warnings | serious n=151 | no trial data cached |
| Polyuria | 448 | 83.9 76.4–92.2ROR 86.6 · χ² 34,618 / p <1e-300 | 79.1 EB05 73.1 · IC025 +6.0 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 56.6 | no trial data cached |
| Thirst | 954 | 82.0 77.0–87.4ROR 87.8 · χ² 72,222 / p <1e-300 | 77.5 EB05 73.5 · IC025 +6.1 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 64.8 | no trial data cached |
| Osmotic demyelination syndrome | 39 | 80.8 58.5–111.5ROR 81.0 · χ² 2,834 / p <1e-300 | 73.9 EB05 56.4 · IC025 +4.8 3/3 methods agree | Labeled — boxed warning exact term | serious n=39 · ♀ 28% (drug 50%) | no trial data cached |
| Polydipsia | 208 | 80.5 70.0–92.4ROR 81.6 · χ² 15,381 / p <1e-300 | 75.7 EB05 67.5 · IC025 +5.8 3/3 methods agree | Labeled adverse reaction exact term | serious n=173 | no trial data cached |
| Defect conduction intraventricular | 14 | 65.3 38.2–111.5ROR 65.3 · χ² 787 / p 2e-173 | 57.8 EB05 36.6 · IC025 +3.4 3/3 methods agree | Not in label — unassessed | serious n=14 | no trial data cached |
| Cyst rupture | 26 | 58.0 39.2–85.8ROR 58.1 · χ² 1,345 / p 1e-294 | 53.7 EB05 38.5 · IC025 +4.1 3/3 methods agree | Not in label — unassessed | serious n=25 | no trial data cached |
| Cardiac failure chronic | 158 | 55.9 47.8–65.5ROR 56.6 · χ² 8,154 / p <1e-300 | 53.5 EB05 46.9 · IC025 +5.3 3/3 methods agree | Labeled (related wording) related wording | serious n=158 · 94% clinician | no trial data cached |
| Haemorrhagic cyst | 12 | 46.2 26.0–82.0ROR 46.2 · χ² 471 / p 1e-104 | 42.0 EB05 25.6 · IC025 +3.0 3/3 methods agree | Not in label — unassessed | serious n=12 | no trial data cached |
| Renal transplant | 107 | 44.3 36.6–53.7ROR 44.6 · χ² 4,353 / p <1e-300 | 42.7 EB05 36.3 · IC025 +4.8 3/3 methods agree | Labeled (related wording) related wording | serious n=107 | no trial data cached |
| Blood sodium abnormal | 28 | 39.3 27.0–57.2ROR 39.4 · χ² 981 / p 1e-215 | 37.4 EB05 27.2 · IC025 +3.9 3/3 methods agree | Likely indication confounding term in indications; also in warnings | serious n=25 · ♀ 71% (drug 50%) | no trial data cached |
| Glomerular filtration rate decreased | 284 | 34.8 31.0–39.1ROR 35.5 · χ² 9,081 / p <1e-300 | 34.0 EB05 30.8 · IC025 +4.8 3/3 methods agree | Lab value / disease marker | serious PRR 27.8 | no trial data cached |
| Nocturia (night-time urination) | 281 | 34.5 30.6–38.7ROR 35.1 · χ² 8,887 / p <1e-300 | 33.6 EB05 30.4 · IC025 +4.8 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 26.3 | no trial data cached |
| Aspartate aminotransferase decreased | 12 | 33.9 19.1–60.0ROR 33.9 · χ² 343 / p 9e-77 | 31.6 EB05 19.2 · IC025 +2.9 3/3 methods agree | Lab value / disease marker | serious n=11 | no trial data cached |
| Congestive hepatopathy | 10 | 33.4 17.8–62.4ROR 33.4 · χ² 276 / p 3e-62 | 30.8 EB05 17.8 · IC025 +2.6 3/3 methods agree | Not in label — unassessed | serious n=10 | no trial data cached |
| Protein-losing gastroenteropathy | 11 | 33.3 18.3–60.5ROR 33.3 · χ² 306 / p 9e-69 | 30.9 EB05 18.4 · IC025 +2.8 3/3 methods agree | Not in label — unassessed | serious n=11 | no trial data cached |
| Alanine aminotransferase decreased | 16 | 32.9 20.1–54.1ROR 33.0 · χ² 454 / p 5e-101 | 31.2 EB05 20.3 · IC025 +3.2 3/3 methods agree | Lab value / disease marker | serious n=16 | no trial data cached |
| Blood sodium decreased | 367 | 28.9 26.1–32.0ROR 29.6 · χ² 9,661 / p <1e-300 | 28.3 EB05 25.9 · IC025 +4.6 3/3 methods agree | Labeled — boxed warning synonym match | serious PRR 20.7 | no trial data cached |
| Brain natriuretic peptide increased | 60 | 28.8 22.3–37.2ROR 28.9 · χ² 1,551 / p <1e-300 | 28.0 EB05 22.6 · IC025 +4.1 3/3 methods agree | Lab value / disease marker | serious n=59 · ♀ 73% (drug 50%) · 93% clinician | no trial data cached |
| Carbon dioxide decreased | 22 | 28.5 18.7–43.5ROR 28.6 · χ² 547 / p 3e-121 | 27.4 EB05 19.1 · IC025 +3.4 3/3 methods agree | Lab value / disease marker | serious n=22 · 95% clinician | no trial data cached |
| Marasmus | 29 | 28.5 19.7–41.2ROR 28.6 · χ² 728 / p 1e-160 | 27.5 EB05 20.1 · IC025 +3.6 3/3 methods agree | Not in label — unassessed | serious n=29 | no trial data cached |
| Pulmonary veno-occlusive disease | 13 | 27.6 15.9–47.8ROR 27.6 · χ² 301 / p 8e-68 | 26.1 EB05 16.2 · IC025 +2.8 3/3 methods agree | Labeled (related wording) related wording | serious n=13 | no trial data cached |
| N-terminal prohormone brain natriuretic peptide increased | 26 | 27.4 18.6–40.4ROR 27.4 · χ² 623 / p 7e-138 | 26.4 EB05 19.0 · IC025 +3.5 3/3 methods agree | Lab value / disease marker | serious n=25 | no trial data cached |
| Hyperuricaemia | 74 | 26.7 21.2–33.5ROR 26.8 · χ² 1,769 / p <1e-300 | 26.0 EB05 21.4 · IC025 +4.1 3/3 methods agree | Not in label — unassessed | serious n=72 · 92% clinician | no trial data cached |
| Transplant | 42 | 26.1 19.2–35.4ROR 26.2 · χ² 971 / p 2e-213 | 25.4 EB05 19.6 · IC025 +3.8 3/3 methods agree | Labeled adverse reaction exact term | serious n=42 | no trial data cached |
| Urine output increased | 46 | 25.9 19.3–34.6ROR 25.9 · χ² 1,056 / p 7e-232 | 25.2 EB05 19.6 · IC025 +3.8 3/3 methods agree | Labeled adverse reaction exact term | serious n=37 | no trial data cached |
| Blood urea increased | 291 | 25.5 22.7–28.6ROR 26.0 · χ² 6,715 / p <1e-300 | 25.0 EB05 22.7 · IC025 +4.4 3/3 methods agree | Lab value / disease marker | serious PRR 19.6 · 96% clinician | no trial data cached |
| Blood chloride increased | 29 | 24.8 17.2–35.8ROR 24.9 · χ² 629 / p 5e-139 | 24.1 EB05 17.6 · IC025 +3.5 3/3 methods agree | Lab value / disease marker | serious n=29 | no trial data cached |
| Bronchial carcinoma | 13 | 24.2 14.0–41.8ROR 24.2 · χ² 262 / p 4e-59 | 23.0 EB05 14.1 · IC025 +2.8 3/3 methods agree | Not in label — unassessed | serious n=13 | no trial data cached |
| Congenital cystic kidney disease | 13 | 22.4 13.0–38.8ROR 22.4 · χ² 241 / p 1e-54 | 21.3 EB05 13.0 · IC025 +2.7 3/3 methods agree | Not in label — unassessed | serious n=13 | 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 | 1,018 | 1.7 1.6–1.8ROR 1.8 · χ² 316 / p 5e-71 | 1.7 EB05 1.6 · IC025 +0.7 | Outcome field, not a reaction boxed warning mentions mortality | serious PRR 1.2 | no trial data cached |
| Thirst | 954 | 82.0 77.0–87.4ROR 87.8 · χ² 72,222 / p <1e-300 | 77.5 EB05 73.5 · IC025 +6.1 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 64.8 | no trial data cached |
| Off label use (used outside approved label) | 871 | 1.5 1.4–1.6ROR 1.5 · χ² 130 / p 2e-30 | 1.5 EB05 1.4 · IC025 +0.4 | Reporting / coding artifact | serious PRR 0.9 | no trial data cached |
| Renal impairment | 856 | 15.0 14.0–16.0ROR 15.9 · χ² 11,093 / p <1e-300 | 14.8 EB05 14.0 · IC025 +3.8 3/3 methods agree | Labeled (related wording) related wording | serious PRR 10.9 | no trial data cached |
| Cardiac failure (heart failure) | 814 | 14.8 13.9–15.9ROR 15.7 · χ² 10,429 / p <1e-300 | 14.7 EB05 13.9 · IC025 +3.8 3/3 methods agree | Labeled (related wording) related wording | serious PRR 10.5 | no trial data cached |
| Product dose omission issue | 723 | 3.7 3.4–4.0ROR 3.8 · χ² 1,432 / p <1e-300 | 3.7 EB05 3.5 · IC025 +1.8 3/3 methods agree | Reporting / coding artifact | serious PRR 3.8 · 71% consumer | no trial data cached |
| Pollakiuria (frequent urination) | 552 | 19.5 17.9–21.2ROR 20.2 · χ² 9,551 / p <1e-300 | 19.2 EB05 17.9 · IC025 +4.1 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 11.1 | no trial data cached |
| Wrong technique in product usage process | 515 | 3.7 3.4–4.0ROR 3.8 · χ² 1,023 / p 1e-224 | 3.7 EB05 3.4 · IC025 +1.7 3/3 methods agree | Reporting / coding artifact | serious PRR 14.1 · 72% consumer | no trial data cached |
| Product use in unapproved indication | 499 | 3.0 2.7–3.2ROR 3.0 · χ² 656 / p 6e-145 | 3.0 EB05 2.7 · IC025 +1.4 3/3 methods agree | Reporting / coding artifact | serious PRR 4.3 | no trial data cached |
| Underdose | 480 | 9.6 8.8–10.5ROR 9.9 · χ² 3,673 / p <1e-300 | 9.5 EB05 8.8 · IC025 +3.1 3/3 methods agree | Reporting / coding artifact | serious PRR 24.2 | no trial data cached |
| Dehydration | 472 | 5.2 4.7–5.6ROR 5.3 · χ² 1,579 / p <1e-300 | 5.1 EB05 4.7 · IC025 +2.2 3/3 methods agree | Labeled — boxed warning exact term | serious PRR 4.0 | no trial data cached |
| No adverse event | 462 | 3.8 3.5–4.1ROR 3.9 · χ² 951 / p 5e-209 | 3.8 EB05 3.5 · IC025 +1.8 3/3 methods agree | Reporting / coding artifact | – | no trial data cached |
| Polyuria | 448 | 83.9 76.4–92.2ROR 86.6 · χ² 34,618 / p <1e-300 | 79.1 EB05 73.1 · IC025 +6.0 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 56.6 | no trial data cached |
| Blood creatinine increased | 445 | 9.9 9.1–10.9ROR 10.2 · χ² 3,553 / p <1e-300 | 9.8 EB05 9.1 · IC025 +3.1 3/3 methods agree | Lab value / disease marker | serious PRR 7.5 | no trial data cached |
| Inappropriate schedule of product administration | 440 | 3.6 3.3–4.0ROR 3.7 · χ² 836 / p 4e-184 | 3.6 EB05 3.3 · IC025 +1.7 3/3 methods agree | Reporting / coding artifact | serious PRR 5.8 | 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.
- Renal cyst ruptured — n=26, PRR 361.3
- Hypernatraemia — n=364, PRR 114.9
- Cyst rupture — n=26, PRR 58.0
- Marasmus — n=29, PRR 28.5
- Hyperuricaemia — n=74, PRR 26.7
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 Tolvaptan?
In FDA FAERS, the most frequently co-reported reaction terms for Tolvaptan are thirst, renal impairment, cardiac failure, pollakiuria, dehydration, polyuria. 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 Tolvaptan have an FDA boxed warning?
Yes. The current FDA label carries a boxed warning: (A) INITIATE AND RE-INITIATE IN A HOSPITAL AND MONITOR SERUM SODIUM (B) NOT FOR USE FOR AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE (ADPKD) WARNING: (A) INITIATE AND RE-INITIATE IN A HOSPITAL AND MONITOR SERUM SODIU.
Do FAERS signals prove that Tolvaptan 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 6f4c5679-8490-45ec-bd34-1a569e3af850, effective 20220905; matched on
openfda.generic_name.exact:"TOLVAPTAN") - 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, 1,015 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.