metolazone
Brand: Zaroxolyn
Prototype: hydrochlorothiazide
Drug Class: thiazide-like diuretic
Drug Family: diuretic
Subclass: quinazoline sulfonamide diuretic
Organ Systems: cardiovascularrenal
Mechanism of Action
Thiazide-like diuretic acting at distal tubule; retains efficacy at low GFR; synergistic with loop diuretics.
NCC cotransporter
Indications
- edema (diuretic-resistant)
- hypertension
- heart failure with diuretic resistance
Contraindications
- anuria
Adverse Effects
Common
- profound hypokalemia
- hypotension
- dehydration
Serious
- severe electrolyte disturbances
- profound diuresis
Pharmacokinetics (ADME)
| Absorption | 65% oral |
| Distribution | large Vd |
| Metabolism | minimal hepatic |
| Excretion | renal |
| Half-life | ~14 hours |
| Onset | 2-4 hours |
| Peak | 8 hours |
| Duration | 12-24 hours |
| Protein Binding | 95% |
| Vd | large |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| furosemide | synergistic — profound diuresis; risk of severe electrolyte depletion | major |
| digoxin | hypokalemia → toxicity | major |
Nursing Considerations
- Start 30 minutes before furosemide when using combination (sequential nephron blockade)
- Combination metolazone + loop diuretic: powerful — monitor K+, Na+, Mg2+ closely every 24-48h
- Effective in CKD where other thiazides fail
Clinical Pearls
- Retains efficacy at GFR as low as 20 mL/min unlike HCTZ
- Sequential nephron blockade: add 30 min before loop diuretic for profound diuresis in refractory HF
Safety Profile
Pregnancy use-with-caution
Lactation avoid
Renal Adjustment Required
Hepatic Adjustment Not required
TDM Not required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.