Metolazone
Mechanism :
The actions of metolazone result from interference with the renal tubular mechanism of electrolyte reabsorption. Metolazone acts primarily to inhibit sodium reabsorption at the cortical diluting site and to a lesser extent in the proximal convoluted tubule. Sodium and chloride ions are excreted in approximately equivalent amounts. The increased delivery of sodium to the distal tubular exchange site results in increased potassium excretion. Metolazone does not inhibit carbonic anhydrase. The antihypertensive mechanism of action of metolazone is not fully understood but is presumed to be related to its saluretic and diuretic properties.
Indication :
- Treatment of hypertension and edema
Contraindications :
Hypersensitivity, Hepatic coma, Anuria.
Dosing :
Edema:
0.2-0.4 mg/kg/day orally in 1-2 divided doses.
Hypertension:
2.5-5 mg orally, once daily. May be increased to 20 mg once daily as and when needed.
Adverse Effect :
Serious Reactions: Arrhythmias, cholestatic jaundice, pancreatitis, anaphylaxis, necrotizing angiitis, erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis, exfoliative dermatitis, photosensitivity, renal failure, aplastic anemia, agranulocytosis, leukopenia, thrombocytopenia, SLE exacerbation.
Common Reactions: Hypokalemia, hyponatremia, hypochloremia, hyperuricemia, hypomagnesemia, hypercalcemia, orthostatic hypotension, palpitations, syncope, nausea, dizziness, headache, fatigue/weakness, constipation, anorexia, diarrhea, muscle cramps, pruritus/rash, photosensitivity, urticaria, elevated creatinine.
Interaction :
Deslanoside: Possible electrolyte variations and arrhythmias.
Digitoxin: Possible electrolyte variations and arrhythmias.
Digoxin: Possible electrolyte variations and arrhythmias.
Dofetilide: Increased risk of cardiotoxicity and arrhythmias.
Lithium: The thiazide diuretic, metolazone, may increase serum levels of lithium.
Tenoxicam: Tenoxicam may antagonize the blood pressure lowering effect of Metolazone. Monitor for changes in the therapeutic effect of Metolazone if Tenoxicam is initiated, discontinued or dose changed.
Trandolapril: The thiazide diuretic, Metolazone, may increase the hypotensive effect of Trandolapril. Metolazone may also increase the nephrotoxicity of Trandolapril. Monitor for postural hypotension at initiation of concomitant therapy and renal dysfunction during chronic therapy.
Treprostinil: Additive hypotensive effect. Monitor antihypertensive therapy during concomitant use.
Renal Dose :
Dose in Renal Impairment GFR (mL/min)
| 20-50 | Dose as in normal renal function |
| 10-20 | Dose as in normal renal function |
| <10 | Dose as in normal renal function |
Dose in Patients undergoing Renal Replacement Therapies
| CAPD | Unlikely to be dialysed. Dose as in normal renal function |
| HD | Not dialysed. Dose as in normal renal function |
| HDF/High flux | Unknown dialysability. Dose as in normal renal function |
| CAV/VVHD | Not Dialysed. Dose as in normal renal function |
Hepatic Dose :
No dose adjustments are recommended.
Use with caution in hepatic disease since minor alterations of fluid and electrolyte balance may precipitate hepatic coma.