Metolazone Side Effects
Metolazone can cause significant electrolyte disturbances, particularly hypokalemia, hyponatremia, and hypochloremia, as well as metabolic abnormalities including hyperuricemia and glucose intolerance. 1
Common Side Effects
Electrolyte and Metabolic Abnormalities
- Hypokalemia (low potassium) - occurs in up to 80% of patients when used alone 2
- Hyponatremia (low sodium)
- Hypochloremia (low chloride) and hypochloremic alkalosis
- Hyperuricemia (elevated uric acid) - may precipitate gout attacks
- Hyperglycemia and glucose intolerance
- Hypercalcemia
- Hypomagnesemia
- Hypophosphatemia
- Increased BUN and creatinine (worsening renal function)
Cardiovascular Effects
- Orthostatic hypotension
- Excessive volume depletion
- Hemoconcentration
- Venous thrombosis
- Palpitations
- Chest pain/discomfort
Neurological Effects
- Dizziness/lightheadedness
- Syncope
- Headache
- Drowsiness
- Fatigue and weakness
- Restlessness (sometimes causing insomnia)
- Paresthesias
- Neuropathy
- Vertigo
Gastrointestinal Effects
- Nausea and vomiting
- Epigastric distress
- Diarrhea or constipation
- Anorexia
- Abdominal bloating and pain
- Hepatitis
- Intrahepatic cholestatic jaundice
- Pancreatitis
Severe Side Effects
Dermatologic/Hypersensitivity Reactions
- Toxic epidermal necrolysis (TEN)
- Stevens-Johnson syndrome
- Necrotizing angiitis (cutaneous vasculitis)
- Skin necrosis
- Purpura and petechiae
- Dermatitis (including photosensitivity)
- Urticaria and pruritus
Hematologic Abnormalities
- Aplastic/hypoplastic anemia
- Agranulocytosis
- Leukopenia
- Thrombocytopenia
Other Side Effects
- Muscle cramps or spasm
- Joint pain
- Acute gouty attacks
- Transient blurred vision
- Dry mouth
Monitoring and Management
Electrolyte Monitoring
- Check electrolytes 1-2 weeks after initiation and after each dose increase 3
- Monitor potassium, sodium, and renal function regularly
- For patients with heart failure, frequent measurement of creatinine and electrolytes is recommended 3
Prevention of Complications
- Hypokalemia prevention: Consider combining with potassium-sparing diuretics like spironolactone or amiloride 4
- Renal function: Use with caution in patients with significant renal dysfunction (creatinine >221 μmol/L or eGFR <30 mL/min) 3
- Hyperuricemia/gout: Consider allopurinol prophylaxis for patients at risk 3
Special Populations
- Liver disease: Use with extreme caution due to high risk of encephalopathy (35%) 2
- Heart failure: When used in severe heart failure, start with low doses (≤5 mg) and monitor closely 5
- Elderly: Higher risk of adverse effects due to age-related physiological changes
Clinical Pearls and Pitfalls
- Metolazone is more potent than most thiazides and can cause more profound electrolyte disturbances
- When combined with loop diuretics, the risk of electrolyte abnormalities and volume depletion increases significantly
- Recent evidence suggests that high-dose loop diuretics may be preferable to adding metolazone in acute heart failure, as metolazone was associated with increased mortality, hypokalemia, hyponatremia, and worsening renal function 6
- Dosage should be reduced or therapy withdrawn if adverse reactions become moderate or severe 1
- The initial recommended dose is 2.5 mg, with a maximum daily dose of 10 mg 3
By understanding these side effects and implementing appropriate monitoring strategies, the risks associated with metolazone therapy can be minimized while maintaining its therapeutic benefits.