Metolazone

# metolazone ## Overview - **Classification**: Thiazide-like diuretic - **Mechanism**: Inhibits sodium reabsorption in the cortical diluting segment and proximal part of the distal convoluted tubule. Increases excretion of sodium, chloride, and water. ## Primary Indications 1. **Edema** - Associated with congestive heart failure (CHF), renal disease. 2. **Hypertension** - Alone or in combination with other antihypertensives. 3. **Refractory Edema** - Often used in combination with loop diuretics (e.g., furosemide) for enhanced diuresis. ## Adult Dosing ### Standard Dosing **Edema (CHF, Renal Disease)** - **Dose**: **5-20 mg** - **Frequency**: Once daily (QD) - **Route**: Oral (PO) - **Maximum dose**: Typically **20 mg/day**, but higher doses may be used cautiously under specialist supervision for refractory cases. **Hypertension** - **Dose**: **2.5-5 mg** - **Frequency**: Once daily (QD) - **Route**: Oral (PO) - **Maximum dose**: **10 mg/day** (most patients achieve effect with **5 mg/day**). ### Dose Adjustments - **Renal Impairment**: Can be effective in patients with CrCl < 30 mL/min where thiazide diuretics are less effective. - Initiate with **lower doses** (e.g., **2.5 mg** for hypertension, **5 mg** for edema). - **Avoid in anuria**. - **Hepatic Impairment**: Use with **extreme caution**. - Risk of precipitating hepatic encephalopathy and coma. - **Elderly Patients**: Start with **lowest effective dose** and titrate slowly. - Increased susceptibility to electrolyte disturbances and orthostatic hypotension. ## Pediatric Dosing *Note: Pediatric use is often off-label and requires specialist supervision. Dosing is highly individualized.* ### Neonates (0-28 days) - **Dose**: **0.05-0.1 mg/kg/dose** - **Frequency**: Once daily (QD) - **Maximum**: **Not well-established**, closely monitor response and electrolytes. - **Special Notes**: Use only when benefits outweigh risks. Strict electrolyte monitoring is crucial. ### Infants (1-12 months) - **Dose**: **0.05-0.1 mg/kg/dose** - **Frequency**: Once daily (QD) - **Maximum**: **Not well-established**, consider up to **0.2 mg/kg/day** in divided doses for severe edema, under close supervision. ### Children (1-12 years) - **Dose**: **0.05-0.1 mg/kg/dose** - **Frequency**: Once daily (QD) or every other day (QOD). May be divided BID for refractory edema. - **Maximum**: Generally up to **5 mg/day**. For severe, refractory edema, up to **20 mg/day** may be used short-term under strict medical supervision. ### Adolescents (13-18 years) - **Dose**: Start with **adult lower doses** (e.g., **2.5-5 mg** QD). - **Maximum**: Adult maximum of **20 mg/day**. ## Safety Information ### Contraindications - **Absolute**: Anuria - **Absolute**: Hepatic coma or pre-coma - **Absolute**: Hypersensitivity to metolazone or sulfonamide-derived drugs - **Absolute**: Progressive renal failure with oliguria ### Common Adverse Effects - **Very Common (>10%)**: Dizziness, lightheadedness, headache, orthostatic hypotension. - **Common (1-10%)**: Electrolyte imbalances (hypokalemia, hyponatremia, hypomagnesemia), hyperglycemia, hyperuricemia, nausea, vomiting. - **Serious but Rare**: Stevens-Johnson syndrome, toxic epidermal necrolysis, aplastic anemia, pancreatitis, acute angle-closure glaucoma. ### Key Drug Interactions - **Lithium**: Metolazone reduces renal clearance of lithium, leading to increased lithium levels and toxicity. **Monitor lithium levels closely.** - **Digoxin**: Hypokalemia induced by metolazone increases the risk of digoxin toxicity. **Monitor potassium and digoxin levels.** - **NSAIDs**: May reduce the diuretic and antihypertensive effects of metolazone. **Monitor BP and edema.** - **Corticosteroids/Amphotericin B**: Increased risk of hypokalemia. **Monitor potassium levels.** - **Insulin/Oral Hypoglycemics**: May decrease hypoglycemic effect due to metolazone-induced hyperglycemia. **Monitor blood glucose.** ## Monitoring & Follow-up - **Before Treatment**: Blood pressure (BP), serum electrolytes (Na, K, Mg, Ca), renal function (Cr, BUN), serum uric acid, blood glucose. - **During Treatment**: BP, weight, intake/output, signs of edema. - Serum electrolytes, renal function: Regularly, especially during first few weeks and with dose changes or in high-risk patients. - Serum uric acid, blood glucose: Periodically. - **Clinical Signs**: Monitor for signs of electrolyte imbalance (muscle weakness, cramps, fatigue, confusion), dizziness, or worsening renal/hepatic function. ## Clinical Pearls - 💡 **Potent Diuretic**: More potent than hydrochlorothiazide and effective in patients with reduced renal function (CrCl < 30 mL/min). - 💡 **Sequential Nephron Blockade**: Often used with loop diuretics (e.g., furosemide) for enhanced, synergistic diuresis in refractory edema. - 💡 **Timing**: Administer in the morning to prevent nocturia and sleep disturbance. - 💡 **Electrolyte Supplementation**: Hypokalemia is common; consider potassium supplementation or co-administration with potassium-sparing diuretics. - 💡 **Food**: Can be taken with food to minimize gastrointestinal upset. > **⚠️ Important**: This information is for educational purposes only. Always consult current prescribing information, local guidelines, and clinical judgment before prescribing.