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Zaroxolyn Side Effects

Generic Name: metolazone

Note: This page contains side effects data for the generic drug metolazone. It is possible that some of the dosage forms included below may not apply to the brand name Zaroxolyn.

For the Consumer

Applies to metolazone: oral tablet

As well as its needed effects, metolazone (the active ingredient contained in Zaroxolyn) may cause unwanted side effects that require medical attention.

Major Side Effects

If any of the following side effects occur while taking metolazone, check with your doctor immediately:

Incidence not known:
  • Black, tarry stools
  • bleeding gums
  • blistering, peeling, or loosening of skin
  • bloating
  • blood in urine or stools
  • blurred vision
  • bone pain
  • chest pain
  • chills
  • clay-colored stools
  • cold sweats
  • coma
  • confusion
  • constipation
  • convulsions
  • cough
  • dark urine
  • decreased urine
  • diarrhea
  • dizziness, faintness, or lightheadedness when getting up from lying or sitting position
  • drowsiness
  • dry mouth
  • fast, irregular, pounding, or racing heartbeat or pulse
  • fever
  • flushed, dry skin
  • fruit-like breath odor
  • general tiredness and weakness
  • headache
  • incoherent speech
  • increased hunger
  • increased thirst
  • increased urination
  • indigestion
  • irritability
  • itching
  • joint or muscle pain
  • light-colored stools
  • loss of appetite
  • lower back or side pain
  • metallic taste
  • mood changes
  • muscle pain or cramps
  • nausea and vomiting
  • numbness or tingling in hands, feet, or lips
  • pain in lower legs
  • painful or difficult urination
  • pinpoint red spots on skin
  • rash
  • red irritated eyes
  • red skin lesions, often with a purple center
  • redness or swelling of lower leg
  • shortness of breath
  • sore throat
  • sores, ulcers, or white spots in mouth or on lips
  • sugar in the urine
  • sweating
  • swelling of face, ankles, or hands
  • swollen or painful glands
  • tightness in chest
  • trembling
  • troubled breathing
  • unexplained weight loss
  • unpleasant breath odor
  • unusual bleeding or bruising
  • unusual tiredness or weakness
  • upper right abdominal pain
  • vomiting of blood
  • weak pulse
  • wheezing
  • yellow eyes and skin

If any of the following symptoms of overdose occur while taking metolazone, get emergency help immediately:

Symptoms of overdose:
  • Fainting
  • irregular, fast or slow, or shallow breathing
  • pale or blue lips, fingernails, or skin
  • unusual drowsiness, dullness, tiredness, weakness, or feeling of sluggishness
  • weakness and heaviness of legs

Minor Side Effects

Some metolazone side effects may not need any medical attention. As your body gets used to the medicine these side effects may disappear. Your health care professional may be able to help you prevent or reduce these side effects, but do check with them if any of the following side effects continue, or if you are concerned about them:

Incidence not known:
  • Blue-green to black skin discoloration
  • burning, tingling, numbness, or pain in the hands, arms, feet, or legs
  • cracked, dry, or scaly skin
  • decreased interest in sexual intercourse
  • feeling of constant movement of self or surroundings
  • hives or welts
  • inability to have or keep an erection
  • loss in sexual ability, desire, drive, or performance
  • pain, redness, or sloughing of skin at place of injection
  • restlessness
  • sensation of pins and needles
  • sensation of spinning
  • stabbing pain

For Healthcare Professionals

Applies to metolazone: oral tablet


A rare case of hyperosmolar nonketotic hyperglycemia is associated with metolazone (the active ingredient contained in Zaroxolyn) [Ref]

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]


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 (the active ingredient contained in Zaroxolyn) 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 (the active ingredient contained in Zaroxolyn) therapy, as with other diuretics, and may be associated with electrolyte disorders and rapid intravascular volume shifts.[Ref]


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

2. "Product Information. Zaroxolyn (metolazone)." Rhone-Poulenc Rorer, Collegeville, PA.

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

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

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

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

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

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

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

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

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

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

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

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

It is possible that some side effects of Zaroxolyn may not have been reported. These can be reported to the FDA here. Always consult a healthcare professional for medical advice.

Disclaimer: Every effort has been made to ensure that the information provided is accurate, up-to-date and complete, but no guarantee is made to that effect. In addition, the drug information contained herein may be time sensitive and should not be utilized as a reference resource beyond the date hereof. This material does not endorse drugs, diagnose patients, or recommend therapy. This information is a reference resource designed as supplement to, and not a substitute for, the expertise, skill , knowledge, and judgement of healthcare practitioners in patient care. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate safety, effectiveness, or appropriateness for any given patient. does not assume any responsibility for any aspect of healthcare administered with the aid of materials provided. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the substances you are taking, check with your doctor, nurse, or pharmacist.