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Metolazone Side Effects

Medically reviewed by Last updated on Mar 26, 2024.

Applies to metolazone: oral tablet.

Serious side effects of Metolazone

Along with its needed effects, metolazone may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking metolazone:

Incidence not known

Get emergency help immediately if any of the following symptoms of overdose occur while taking metolazone:

Symptoms of overdose

Other side effects of Metolazone

Some side effects of metolazone may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects.

Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

Incidence not known

For Healthcare Professionals

Applies to metolazone: oral tablet.


Metabolic side effects are the most common and profound. The rapid onset of hyponatremia or hypokalemia is often sudden and may be profound, particularly if metolazone is given with a loop diuretic. Hypokalemia may be important in patients with underlying cardiac arrhythmias. Metolazone may increase serum calcium and uric acid levels and lower serum magnesium and phosphate levels. Glucose intolerance is reported in rare cases.[Ref]

A rare case of hyperosmolar nonketotic hyperglycemia is associated with metolazone.[Ref]


Cardiovascular side effects are uncommon. Postural hypotension is reported in less than 5% of patients. Rare cases of venous thrombosis are reported, thought to be due to metolazone-induced hypovolemia and increased serum concentrations of clotting factors. Rare cardiovascular side effects also include palpitations, hypovolemia, and chest pain.[Ref]


Renal insufficiency, manifest as a rise in serum creatinine and BUN, may occur, although, in most cases, creatinine clearance increases as a result of metolazone therapy.[Ref]

Nervous system

Nervous system side effects include headache, dizziness, and fatigue. Two cases of syncope and seizures are reported. Metolazone-induced hypovolemia and electrolyte changes may induce hepatic encephalopathy in some patients.[Ref]

It is not clear whether the patients who developed syncope and seizure activity were hypotensive or hypovolemic at the time of the seizures or that metolazone can definitively be implicated. In one case the patient was also taking theophylline and had hypomagnesemia, which may be a complication of metolazone therapy.[Ref]


Hypersensitivity reactions include rare case reports of necrotizing vasculitis, angiitis, and pruritic rashes.[Ref]

A case of cutaneous hypersensitivity angiitis has been reported in a patient who had previously tolerated thiazide diuretics, indicating that, despite the chemical similarity between thiazides and metolazone, there is not necessarily cross-reactivity.[Ref]


Hematologic abnormalities are rare. Cases of reversible hypoplastic anemia, aplastic anemia, agranulocytosis, and mild leukopenia are reported.[Ref]


Gastrointestinal side effects are rare, and include a case of acute pancreatitis. Nausea, vomiting, anorexia, and abdominal bloating are also rare.[Ref]


Hepatic side effects include a rare case of cholestatic jaundice.[Ref]


Musculoskeletal cramps are associated with metolazone therapy, as with other diuretics, and may be associated with electrolyte disorders and rapid intravascular volume shifts.[Ref]


1. Anderson PE, Ellis GG, Austin SM (1991) "Case report: metolazone-associated hypercalcemia and acute pancreatitis." Am J Med Sci, 302, p. 235-7

2. Bennett WM, Porter GA (1973) "Efficacy and safety of metolazone in renal failure and the nephrotic syndrome." J Clin Pharmacol, 13, p. 357-64

3. Craswell PW, Ezzat E, Kopstein J, Varghese Z, Moorhead JF (1974) "Use of metolazone, a new diuretic, in patients with renal disease." Nephron, 12, p. 63-73

4. (2001) "Product Information. Zaroxolyn (metolazone)." Rhone Poulenc Rorer

5. Fitzgerald M, Brennan N (1976) "Muscle cramps, collapse, and seizures in two patients taking metolazone." Br Med J, 1, p. 1381-2

6. Stern A (1976) "Metolazone, a diuretic agent." Am Heart J, 91, p. 262-3

7. Black W, Shiner P, Roman J (1978) "Severe electrolyte disturbances associated with metolazone and furosemide." South Med J, 71, p. 381

8. Rowe P, Mather H (1985) "Hyperosmolar non-ketotic diabetes mellitus associated with metolazone." Br Med J, 291, p. 25-6

9. Pickkers P, Schachter M, Hughes AD, Feher MD, Sever PS (1996) "Thiazide-induced hyperglycaemia: a role for calcium-activated potassium channels?" Diabetologia, 39, p. 861-4

10. Nichols T (1977) "Initial experience with metolazone." Minn Med, 60, p. 549-53

11. Weinrauch L, Belok S, Gauvin G, D'Elia J (1982) "Palpable acute necrotizing arteritis secondary to metolazone." Cutis, 30, p. 83-4

12. Cox N, Hodkin P (1991) "Vasculitis due to metolazone." Postgrad Med J, 67, p. 860

13. Suh K (1979) "Hypoplastic anemia associated with metolazone." JAMA, 242, p. 139-40

14. Donovan K (1989) "Neutropenia and metolazone." Br Med J, 299, p. 981

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Some side effects may not be reported. You may report them to the FDA.