Metolazone Safety in Acute Hepatitis
Metolazone should be used with extreme caution in patients with acute hepatitis due to the high risk of severe electrolyte disturbances, particularly hypokalemia (80% incidence), hypochloraemia (35%), and hepatic encephalopathy (35%), and should only be considered when absolutely necessary with concurrent potassium-sparing diuretics and intensive monitoring. 1
Evidence from Liver Disease Populations
The limited available data specifically addressing metolazone use in hepatic disease reveals concerning safety signals:
In patients with chronic liver disease and ascites, metolazone monotherapy was associated with hypokalemia in 80% of cases, hypochloraemia in 35%, and hepatic encephalopathy in 35% of patients 1
The high incidence of these complications represents a major disadvantage and indicates this drug should be used with caution in patients with liver disease 1
However, the low incidence of azotemia (5%) suggests metolazone may have some utility when renal function is particularly impaired in liver disease 1
Risk Mitigation Strategy
If metolazone must be used in acute hepatitis:
Always co-administer with potassium-sparing diuretics (amiloride or spironolactone) to prevent hypokalemia, as this combination prevented decreases in serum potassium that occurred with metolazone alone 1, 2
Start with the lowest effective dose of 5 mg daily, though higher doses may ultimately be required 1
Perform frequent measurement of serum electrolytes, especially potassium, sodium, and chloride, along with monitoring for signs of hepatic encephalopathy 3, 4
General Metolazone Safety Concerns
Beyond liver-specific risks, metolazone carries substantial risks even in other populations:
Metolazone was independently associated with hypokalemia, hyponatremia, worsening renal function, and increased mortality in acute decompensated heart failure patients (hazard ratio 1.20,95% CI 1.04-1.39) 5
Severe electrolyte disturbances with a pattern of hyponatremia, disproportionate hypochloremia, alkalosis, and hypokalemia occur with metolazone-furosemide combinations 6
The greatest diuretic effect and most significant electrolyte shifts occur within the first 3 days of metolazone administration 4
Contraindications in Hepatic Impairment
Metformin (not metolazone, but relevant context) is not recommended in patients with severe hepatic impairment due to risk of lactic acidosis, establishing precedent for caution with medications in hepatic disease 7
The American College of Cardiology recommends avoiding metolazone in patients with baseline serum potassium ≥5.0 mEq/L or anuria 4
Clinical Bottom Line
Given the 80% incidence of hypokalemia and 35% incidence of hepatic encephalopathy in liver disease patients, metolazone should be reserved for situations where other diuretics have failed and the benefits clearly outweigh risks. When used, mandatory co-administration of potassium-sparing diuretics and daily electrolyte monitoring are essential. 1, 2