MYKROX

Clinical safety rating: caution

Comprehensive clinical and safety monograph for MYKROX (MYKROX).

How it works

MYKROX (metolazone) is a thiazide-like diuretic that inhibits sodium reabsorption in the distal convoluted tubule by blocking the Na+-Cl- cotransporter, leading to increased excretion of sodium, chloride, and water.

What the body does with it

Metabolism	Metabolized partially in the liver; primarily excreted unchanged in urine.
Excretion	Primarily hepatic metabolism (CYP3A4) to inactive metabolites; renal excretion accounts for <10% as unchanged drug; biliary/fecal excretion of metabolites ~75%.
Half-life	Terminal elimination half-life: 50–70 hours; achieves steady-state after ~2 weeks of once-daily dosing; prolonged in hepatic impairment but not significantly altered in renal impairment.
Protein binding	99.5% bound to plasma proteins, primarily albumin and α₁-acid glycoprotein.
Volume of Distribution	Volume of distribution: approximately 4.8 L/kg (range 4.0–5.6 L/kg); extensive extravascular distribution.
Bioavailability	Oral bioavailability: ~100% (not subject to first-pass metabolism); delayed absorption with high-fat meal (Tmax increased) but total AUC unchanged.
Onset of Action	Oral: onset of antihypertensive effect within 1–2 hours; maximal effect within 3–6 hours.
Duration of Action	Duration of antihypertensive effect: approximately 24 hours; supports once-daily dosing; clinical effect may persist for >48 hours after last dose.

Classification & Brands

Dosing & administration

Adults: 1 mg orally once daily, preferably in the morning.

Dosage form	TABLET
Renal impairment	GFR 30-60 mL/min: 0.5 mg once daily; GFR <30 mL/min: not recommended.
Liver impairment	Child-Pugh A: no adjustment; Child-Pugh B or C: contraindicated.
Pediatric use	Not established; safety and efficacy not determined in pediatric patients.
Geriatric use	Start at 0.5 mg orally once daily; monitor for electrolyte imbalance and hypotension.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for MYKROX (MYKROX).

Breastfeeding	Metolazone is excreted in human milk. M/P ratio is unknown. Potential for serious adverse reactions in nursing infants. Caution advised; manufacturer recommends discontinue nursing or drug due to importance to mother.
Teratogenic Risk	MYKROX (metolazone) is a thiazide-like diuretic. Pregnancy Category B. No adequate studies in pregnant women. Animal studies have not shown teratogenicity. Use only if clearly needed, especially in first trimester. Fetal/neonatal adverse effects include jaundice, thrombocytopenia, electrolyte imbalance.

Warnings & precautions

■ FDA Black Box Warning

None

Side Effect Profile

Serious Effects

Absolute Contraindications

["Anuria","Hepatic coma or pre-coma","Hypersensitivity to metolazone or other sulfonamide-derived drugs"]

Clinical Precautions

Precautions

["Hypokalemia","Hypomagnesemia","Hyperuricemia","Orthostatic hypotension","Azotemia","Electrolyte imbalance"]

Clinical Tips & Counseling

Drug interactions

Loading safety data…

MYKROX

Clinical safety rating: caution

Comprehensive clinical and safety monograph for MYKROX (MYKROX).

How it works

What the body does with it

Metabolism	Metabolized partially in the liver; primarily excreted unchanged in urine.
Excretion	Primarily hepatic metabolism (CYP3A4) to inactive metabolites; renal excretion accounts for <10% as unchanged drug; biliary/fecal excretion of metabolites ~75%.
Half-life	Terminal elimination half-life: 50–70 hours; achieves steady-state after ~2 weeks of once-daily dosing; prolonged in hepatic impairment but not significantly altered in renal impairment.
Protein binding	99.5% bound to plasma proteins, primarily albumin and α₁-acid glycoprotein.
Volume of Distribution	Volume of distribution: approximately 4.8 L/kg (range 4.0–5.6 L/kg); extensive extravascular distribution.
Bioavailability	Oral bioavailability: ~100% (not subject to first-pass metabolism); delayed absorption with high-fat meal (Tmax increased) but total AUC unchanged.
Onset of Action	Oral: onset of antihypertensive effect within 1–2 hours; maximal effect within 3–6 hours.
Duration of Action	Duration of antihypertensive effect: approximately 24 hours; supports once-daily dosing; clinical effect may persist for >48 hours after last dose.

Classification & Brands

Dosing & administration

Adults: 1 mg orally once daily, preferably in the morning.

Dosage form	TABLET
Renal impairment	GFR 30-60 mL/min: 0.5 mg once daily; GFR <30 mL/min: not recommended.
Liver impairment	Child-Pugh A: no adjustment; Child-Pugh B or C: contraindicated.
Pediatric use	Not established; safety and efficacy not determined in pediatric patients.
Geriatric use	Start at 0.5 mg orally once daily; monitor for electrolyte imbalance and hypotension.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for MYKROX (MYKROX).

Breastfeeding	Metolazone is excreted in human milk. M/P ratio is unknown. Potential for serious adverse reactions in nursing infants. Caution advised; manufacturer recommends discontinue nursing or drug due to importance to mother.
Teratogenic Risk	MYKROX (metolazone) is a thiazide-like diuretic. Pregnancy Category B. No adequate studies in pregnant women. Animal studies have not shown teratogenicity. Use only if clearly needed, especially in first trimester. Fetal/neonatal adverse effects include jaundice, thrombocytopenia, electrolyte imbalance.

Warnings & precautions

■ FDA Black Box Warning

None

Side Effect Profile

Serious Effects

Absolute Contraindications

["Anuria","Hepatic coma or pre-coma","Hypersensitivity to metolazone or other sulfonamide-derived drugs"]

Clinical Precautions

Precautions

["Hypokalemia","Hypomagnesemia","Hyperuricemia","Orthostatic hypotension","Azotemia","Electrolyte imbalance"]

Clinical Tips & Counseling

Drug interactions

Loading safety data…