Carbonic anhydrase inhibitor (acetazolamide)
AMT in HFrEF · Class IIaAMT in HFpEF · Class IIaRemoval by dialysis
What each drug's prescribing information says about removal by (haemo)dialysis. Where the label is silent, this page says so rather than inferring from protein binding.
- AcetazolamidePartly or possibly removed
“Despite its high intraerythrocytic distribution and plasma protein binding properties, acetazolamide may be dialyzable.”
Acetazolamide for Injection USP (500 mg vial), prescribing information, Hikma Pharmaceuticals USA Inc. (2025)· OVERDOSAGE Source
Drugs and doses
| Drug | Brands | Start | Target | Kidney dosing |
|---|---|---|---|---|
| Acetazolamide | Diamox (discontinued brand), generic | 500 mg i.v. once daily, added to i.v. loop diuretic (ESC Figure 15; ADVOR, 3 days). Label CHF: 250-375 mg once daily in the morning, intermittent dosing | No uptitration; label says higher doses do not increase diuresis. ESC Table S13 maximum 500 mg three times daily (oral or i.v.) | No eGFR dose table. Label contraindicates use in 'marked kidney and liver disease or dysfunction', hyperchloraemic acidosis and low serum Na/K. ADVOR excluded eGFR <20 and prior KRT; ESC CVD-CKD supports use at eGFR >=20; ESC HF says it may be preferable in more advanced CKD. May be dialyzable. |
Status by kidney stage
| Stage | Initiate | Continue |
|---|---|---|
| G1 | Recommended Class IIa (B1) short-term i.v. 500 mg add-on to i.v. loop diuretic in DHF with fluid overload in patients previously on loop diuretics; in-hospital only. | Allowed Complete the short course (ADVOR: 3 days); not a chronic therapy. |
| G2 | Recommended As G1. | Allowed Short course only. |
| G3a | Recommended As G1; ESC CVD-CKD IIa B1 for DHF + CKD with eGFR >=20 on chronic loop therapy. | Allowed Short course; transient WRF more common but not linked to worse outcomes (ADVOR renal analysis). |
| G3b | Recommended IIa; greater natriuresis/diuresis at eGFR <40 than at higher eGFR; ESC names acetazolamide as possibly preferable to HCTZ in more advanced CKD. | Allowed Short course; WRF (creatinine rise >=0.3 mg/dL) more frequent (40.5% vs 18.9%) without adverse outcomes and no creatinine difference at 3 months. |
| G4 | Use with caution eGFR 20-29: supported by ESC CVD-CKD (eGFR >=20) and ADVOR inclusion, but the FDA label contraindicates use in 'marked kidney disease or dysfunction' (undefined). eGFR 15-19: outside ADVOR and ESC CVD-CKD criteria, so treat as not recommended. | Use with caution Short course with daily creatinine, electrolytes and acid-base (bicarbonate) checks; stop for hyperchloraemic acidosis, low K/Na or progressive kidney dysfunction. |
| G5 | Not recommended Not recommended: the label lists marked kidney disease as a contraindication (undefined), ADVOR excluded eGFR <20 and renal replacement therapy, and the ESC CVD–CKD recommendation applies at eGFR ≥20. | Not recommended Not recommended: the label lists marked kidney disease as a contraindication (undefined), ADVOR excluded eGFR <20 and renal replacement therapy, and the ESC CVD–CKD recommendation applies at eGFR ≥20. |
| dialysis | Not recommended Not recommended: the label lists marked kidney disease as a contraindication (undefined), ADVOR excluded eGFR <20 and renal replacement therapy, and the ESC CVD–CKD recommendation applies at eGFR ≥20. | Not recommended Not recommended: the label lists marked kidney disease as a contraindication (undefined), ADVOR excluded eGFR <20 and renal replacement therapy, and the ESC CVD–CKD recommendation applies at eGFR ≥20. |
| aki | Not recommended Do not start during true AKI (label: marked kidney dysfunction; KDIGO: no diuretics for AKI except volume overload). A creatinine rise during effective decongestion is not by itself a reason to withhold. | Use with caution In ADVOR, WRF on acetazolamide was more frequent but transient and not linked to worse outcomes; stop for progressive kidney dysfunction, metabolic acidosis or low K/Na. |
| transplant | No data No transplant-specific statement found. | No data No transplant-specific statement found. |
Cutoffs recorded from the sources
- egfr < 20 mL/min/1.73m2 → not-recommended (outside ESC CVD-CKD recommendation and ADVOR inclusion) (initiate; acetazolamide)“Upfront treatment with acetazolamide in addition to adequately dosed intravenous loop diuretic therapy should be considered in patients with DHF and CKD with an eGFR ≥20 mL/min/1.73 m2 on chronic loop diuretic therapy to improve decongestion.” — esc2026-ckd, p. 42
- egfr < 20 mL/min/1.73m2 → excluded from trial (initiate; acetazolamide)“Estimated glomerular filtration rate <20 mL/min/1.73m² at screening” — advor-ctgov, Exclusion Criteria
- egfr < 40 mL/min/1.73m2 → informational: larger natriuresis/diuresis effect (initiate; acetazolamide)“In patients with a lower eGFR (<40 mL/min/1.73 m2), acetazolamide resulted in greater natriuresis and diuresis than in patients with a higher eGFR.” — esc2026-ckd, p. 42
- other = 500 mg i.v. once daily → standard dose (ADVOR; ESC Figure 15) (initiate; acetazolamide)“Acetazolamide (500 mg i.v. once daily) or hydrochlorothiazide (if eGFR >50 mL/min/1.73 m2: 25 mg daily; eGFR 20–50 mL/min/1.73 m2: 50 mg daily; and eGFR <20 mL/min/1.73 m2: 100 mg daily).” — esc2026, p. 49
- other >= 27 mmol/L → acetazolamide is the add-on of choice (ESC Table S13 additional notes) (initiate; acetazolamide)“(bicarbonate levels ≥27 mmol/L)” — esc2026-supp, p. 25
- other >= 40 mg/day oral furosemide-equivalent for >=1 month → population studied (initiate; acetazolamide)“Maintenance therapy with oral loop diuretics at a dose of at least 1 mg bumetanide” — advor-ctgov, Inclusion Criteria
Trial evidence (informational)
- ADVOR · DHF with volume overload on chronic loop diuretics, eGFR >=20 (n=519)Successful decongestion within 3 days: 42.2% vs 30.5%; RR 1.46 (95% CI 1.17-1.82)“Successful decongestion occurred in 108 of 256 patients (42.2%) in the acetazolamide group and in 79 of 259 (30.5%) in the placebo group (risk ratio, 1.46; 95% confidence interval [CI], 1.17 to 1.82; P<0.001).” — advor2022, Abstract, Results
- ADVOR · As aboveDeath or HF rehospitalization at 3 months: 29.7% vs 27.8%; HR 1.07 (95% CI 0.78-1.48)“Death from any cause or rehospitalization for heart failure occurred in 76 of 256 patients (29.7%) in the acetazolamide group and in 72 of 259 patients (27.8%) in the placebo group (hazard ratio, 1.07; 95% CI, 0.78 to 1.48).” — advor2022, Abstract, Results
- ADVOR renal analysis · ADVOR, median eGFR 40 (30-52)Decongestion across eGFR: Consistent benefit across eGFR (P-interaction 0.977); larger natriuresis at low eGFR“On admission, median estimated glomerular filtration rate (eGFR) was 40 (30-52) mL/min/1.73 m².” — meekers2023, Abstract, Results
Acute kidney injury
No AKI-specific acetazolamide guidance. Label contraindication for marked kidney dysfunction; KDIGO AKI general advice against diuretics except for volume overload. ADVOR renal analysis: more transient WRF without adverse outcomes; decongestion at discharge was associated with better outcomes regardless of WRF.
“However, decongestion at discharge was associated with a lower incidence of adverse clinical outcomes irrespective of the onset of WRF (P-interaction = .805).”
Meekers E et al. Renal function and decongestion with acetazolamide in acute decompensated heart failure: the ADVOR trial. Eur Heart J 2023;44:3672-3682 (PubMed 37623428 abstract) (2023)· Abstract, Results Source“The incidence of worsening kidney function, hypokalemia, hypotension, and adverse events was similar in the two groups.”
Mullens W et al. Acetazolamide in acute decompensated heart failure with volume overload (ADVOR). N Engl J Med 2022;387:1185-1195 (PubMed 36027559 abstract; no PMC full text; NEJM site bot-blocked) (2022)· Abstract, Results Source
Dialysis
Contraindicated (label: marked kidney disease); ADVOR excluded patients with any prior KRT/ultrafiltration; ESC CVD-CKD recommendation requires eGFR >=20.
Trials: ADVOR (excluded KRT)
“Use of renal replacement therapy or ultrafiltration at any time before study”
ADVOR (NCT03505788) eligibility criteria, ClinicalTrials.gov API v2 (legacy markup) (2026)· Exclusion Criteria Source
Kidney transplant
No kidney-transplant-specific statement found.
No verbatim statement found for this cell.
Albuminuria
No albuminuria-dependent statement found.
No verbatim statement found for this cell.
Monitoring
Daily creatinine and electrolytes during DHF treatment (ESC Figure 15); periodic electrolytes and baseline/periodic CBC per label (sulfonamide); watch for metabolic acidosis, hypokalaemia/hyponatraemia; caution in COPD/impaired ventilation.
“Periodic monitoring of serum electrolytes is recommended.”
Acetazolamide for Injection USP (500 mg vial), prescribing information, Hikma Pharmaceuticals USA Inc. (2025)· PRECAUTIONS, Laboratory Tests Source“Check frequently for hypotension/hypoperfusion. Check serum creatinine and electrolytese at least every 24 h”
“In patients with pulmonary obstruction or emphysema where alveolar ventilation may be impaired, acetazolamide which may precipitate or aggravate acidosis, should be used with caution.”
Acetazolamide for Injection USP (500 mg vial), prescribing information, Hikma Pharmaceuticals USA Inc. (2025)· PRECAUTIONS, Information for Patients Source
In-hospital initiation
i.v. 500 mg once daily for up to 3 days added to i.v. loop diuretic (twice the oral maintenance dose in ADVOR) in DHF with volume overload on chronic loop therapy (ESC IIa B1; ESC CVD-CKD IIa B1 if eGFR >=20).
“In the ADVOR trial, patients were randomized to i.v. acetazolamide (500 mg) or placebo added to i.v. loop diuretics.”
“to receive either intravenous acetazolamide (500 mg once daily) or placebo added to standardized intravenous loop diuretics (at a dose equivalent to twice the oral maintenance dose).”
Mullens W et al. Acetazolamide in acute decompensated heart failure with volume overload (ADVOR). N Engl J Med 2022;387:1185-1195 (PubMed 36027559 abstract; no PMC full text; NEJM site bot-blocked) (2022)· Abstract, Methods Source
Outpatient
No guideline recommendation for outpatient/chronic HF use. Label CHF regimen is oral 250-375 mg once daily on alternate days or 2 days on/1 off; ESC Table S7 lists acetazolamide as an option for volume-overloaded hyponatraemia.
“Acetazolamide yields best diuretic results when given on alternate days, or for two days alternating with a day of rest.”
Acetazolamide for Injection USP (500 mg vial), prescribing information, Hikma Pharmaceuticals USA Inc. (2025)· DOSAGE AND ADMINISTRATION, Congestive Heart Failure Source“Consider increasing dose of loop diuretic or consider adding acetazolamide or eGFR-based hydrochlorothiazide.”
2026 ESC Guidelines for the management of heart failure: Supplementary data (Tables S1-S26) (2026)· p. 17 Source
Where sources disagree
Use in advanced CKD (label contraindication vs guideline preference)
“Acetazolamide therapy is contraindicated in situations in which sodium and/or potassium blood serum levels are depressed, in cases of marked kidney and liver disease or dysfunction, in suprarenal gland failure, and in hyperchloremic acidosis.”
Acetazolamide for Injection USP (500 mg vial), prescribing information, Hikma Pharmaceuticals USA Inc. (2025)· CONTRAINDICATIONS Source“Acetazolamide might be preferable in more advanced CKD.”
“Upfront treatment with acetazolamide in addition to adequately dosed intravenous loop diuretic therapy should be considered in patients with DHF and CKD with an eGFR ≥20 mL/min/1.73 m2 on chronic loop diuretic therapy to improve decongestion.”
2026 ESC Guidelines for the management of cardiovascular disease and chronic kidney disease, in collaboration with the ERA (2026)· p. 42 Source“Estimated glomerular filtration rate <20 mL/min/1.73m² at screening”
ADVOR (NCT03505788) eligibility criteria, ClinicalTrials.gov API v2 (legacy markup) (2026)· Exclusion Criteria Source
Tool uses fda-acetazolamide: Label > guideline, but the label's 'marked kidney disease' is undefined. Proposed mapping: eGFR >=30 recommended (IIa); 20-29 caution; <20 not recommended for initiation (no trial data, outside ESC CVD-CKD); G5 and dialysis contraindicated (label).
Dose and schedule
“For diuresis in congestive heart failure, the starting dose is usually 250 to 375 mg once daily in the morning (5 mg per kg).”
Acetazolamide for Injection USP (500 mg vial), prescribing information, Hikma Pharmaceuticals USA Inc. (2025)· DOSAGE AND ADMINISTRATION, Congestive Heart Failure Source“Increasing the dose does not increase the diuresis and may increase the incidence of drowsiness and/or paresthesia.”
Acetazolamide for Injection USP (500 mg vial), prescribing information, Hikma Pharmaceuticals USA Inc. (2025)· PRECAUTIONS, General Source“Acetazolamide (500 mg i.v. once daily) or hydrochlorothiazide (if eGFR >50 mL/min/1.73 m2: 25 mg daily; eGFR 20–50 mL/min/1.73 m2: 50 mg daily; and eGFR <20 mL/min/1.73 m2: 100 mg daily).”
Tool uses esc2026: In DHF, use the RCT-tested ESC/ADVOR regimen (500 mg i.v. once daily, 3 days). The label CHF regimen is an older intermittent oral schedule; no conflict on contraindications.
Acetazolamide vs HCTZ as the preferred non-loop add-on in CKD
“Therefore, acetazolamide might be preferable in severe CKD.”
2026 ESC Guidelines for the management of cardiovascular disease and chronic kidney disease, in collaboration with the ERA (2026)· p. 42 Source“The addition of short-term intravenous acetazolamide or oral hydrochlorothiazide should be considered in patients with fluid overload previously treated with loop diuretics, to reduce congestion.”
“Thiazide-like diuretics—particularly oral metolazone (2.5–5 mg)—can be used in patients with advanced HF who exhibit diuretic resistance, as part of a sequential nephron blockade approach, or in those with an eGFR <30 mL/min/1.73 m2.”
Tool uses esc2026-ckd: Both are IIa in ESC HF. ESC CVD-CKD grades acetazolamide IIa vs thiazide IIb in DHF + CKD, and ESC HF/CVD-CKD both say acetazolamide may be preferable in more advanced CKD; but the label limits acetazolamide when kidney disease is 'marked'. Show both, ranking acetazolamide first for eGFR 20-44 and noting metolazone for eGFR <30 outpatients.
Open questions
- Numeric interpretation of the label's 'marked kidney ... disease or dysfunction' contraindication: proposed eGFR <15/dialysis = contraindicated, 15-19 = not recommended, 20-29 = caution. Owner to confirm.
- Is the ESC Table S13 note (acetazolamide the add-on of choice when bicarbonate >=27 mmol/L) usable as a threshold? The extracted table text is fragmented, and the quote spans the page break between S13 and its continuation; consider citing ADVOR/ESC narrative instead.
- Continue status 'allowed' at G1-G3b reflects completing a 3-day course; the engine may need a 'short-course only' flag rather than a continuation status.