Metolazone

Indications

Metolazone is used for: Oedema, Hypertension

Adult Dose

Oral Hypertension Adult: Initially, 1.25 mg daily, adjusted after 3-4 wk according to response. Usual dose: 2.5-5 mg daily, either alone or with other antihypertensives. Maintenance dose: 5 mg on alternate days. Formulations with enhanced bioavailability: 0.5-1 mg daily. Oedema Adult: 5-10 mg daily, increased if necessary to 20 mg daily. Max: 80 mg in 24 hr. Elderly: Initially, 2.5 mg/day or every other day.

Child Dose

Oedema 0.2-0.4 mg/kg/day PO in single daily dose or divided q12hr

Renal Dose

Renal impairment: Not necessary to supplement dose in hemodialysis or peritoneal dialysis

Administration

Should be taken with food. Take after breakfast.

Contra Indications

Anuria; hepatic coma or pre-coma. Pregnancy.

Precautions

Pre-diabetes or DM; gout; SLE; hepatic and renal impairment; hypercholesterolaemia. Correct electrolyte disturbances prior to therapy. Risk of cross-sensitivity with sulfonamides, sulfonylureas, carbonic anhydrase inhibitors, thiazides and loop diuretics. Lactation: Not recommended

Pregnancy-Lactation

Pregnancy Drug appears in cord blood and crosses placenta; hypokalemia, hypoglycemia, jaundice, thrombocytopenia, and hyponatremia reported in fetus or newborn following maternal use of thiazide diuretics Lactation Drug excreted in breast milk; decision on whether to discontinue nursing or discontinue drug should be based on importance of treatment to mother

Interactions

Hypotensive and nephrotoxic effects of ACE inhibitors may be enhanced. Absorption may be reduced with bile acid sequestrants. Hyperglycaemic effect may be enhanced with diazoxide. May increase serum concentration and QTc-prolonging effect of dofetilide. May reduce lithium excretion. Hypotensive effect may be increased with alcohol. Potentially Fatal: Increased risk of nephrotoxicity with ciclosporin. Severe electrolyte disturbances may occur with furosemide.

Adverse Effects

Side effects of Metolazone : Chest pain, palpitation, necrotising angiitis, orthostatic hypotension, syncope, venous thrombosis, vertigo, volume depletion; depression, dizziness, chills, drowsiness, fatigue, restlessness, headache, lightheadedness; petechiae, photosensitivity, hypersensitivity reactions; gout attacks, electrolyte disturbances; abdominal bloating, diarrhoea, abdominal pain, anorexia, constipation, epigastric distress, nausea, xerostomia, pancreatitis, vomiting; impotence; aplastic anaemia, thrombocytopenia, haemoconcentration, leukopenia; cholestatic jaundice, hepatitis; joint pain, muscle cramps, weakness, neuropathy, paraesthesia; blurred vision; increased BUN, glucosuria. Potentially Fatal: Stevens-Johnson syndrome, toxic epidermal necrolysis.

Mechanism of Action

Metolazone is a thiazide-like diuretic. It inhibits reabsorption of sodium in the distal tubules resulting in increased excretion of sodium and water, as well as potassium and hydrogen ions.