METOZ 5 TABLETS

Indications

• Hypertension
• Oedema resistant to loop diuretics in heart failure
• Oedema in renal disease
• Oedema in hepatic disease
• Adjunct to loop diuretics to induce diuresis

Dosage

Children: Refer to the BNF for Children for

Adults: For hypertension, the initial dose is 50/25 mg daily, which can be increased up to 200/100 mg daily if necessary. For edema, the dose is 50/25 mg twice daily, taken after breakfast and midday meal, increased if necessary to 150/75 mg daily, with a maximum of 200/100 mg per day.

Mechanism of action

Metolazone acts by interfering with the renal tubular mechanism of electrolyte reabsorption. It primarily inhibits sodium reabsorption at the cortical diluting site and to a lesser extent in the proximal convoluted tubule. This results in the excretion of sodium and chloride ions in approximately equivalent amounts, along with an increased potassium excretion. The exact antihypertensive mechanism is not fully understood but is presumed to be related to its saluretic and diuretic properties.

Pharmacodynamics

As a quinazoline diuretic, metolazone exhibits properties similar to thiazide diuretics. It enhances the excretion of phosphate and magnesium ions, and markedly increases the fractional excretion of sodium in patients with severely compromised glomerular filtration. Its diuretic potency is comparable to that of thiazides.

Pharmacokinetics

Metolazone is well absorbed from the gastrointestinal tract, with peak plasma concentrations occurring within 1 to 2 hours after oral administration. It has a half-life of approximately 14 hours, allowing for once or twice daily dosing. Metolazone is metabolized in the liver and excreted primarily via the kidneys, necessitating dosage adjustments in patients with renal impairment.

Contra-indications

• Acute porphyrias
• Severe hepatic impairment
• Severe renal impairment

Adverse effects

• Gastrointestinal discomfort
• Palpitations
• Peripheral neuropathy
• Psychotic depression
• Hypotensive reactions
• Hyperlipidaemia
• Jaundice
• Acute interstitial nephritis
• Cholecystitis acute
• Hemoconcentration
• Hepatic disorders
• Hypoplastic anaemia
• Fatigue
• Dizziness
• Blurred vision

Interactions

• Methenamine: Unknown (decreases efficacy)
• Other antihypertensives and diuretics may have additive effects

Precautions

• Caution in patients with renal impairment
• Monitor electrolytes, especially potassium levels
• Advise patients regarding increased risk of dizziness affecting driving and skilled tasks
• Caution in patients with a history of gout or hyperuricaemia

Pregnancy

Limited data available, use only if clearly needed. Risk cannot be ruled out.

Breast-feeding

Levels in milk are likely too low to affect the infant, but large doses may suppress lactation.

Storage

Store in a cool, dry place. Keep out of reach of children.

Formulations

• Metolazone 2.5 mg tablets
• Metolazone 5 mg tablets
• Metolazone 10 mg tablets

Mechanism of action

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. IT ACTS PRIMARILY TO INHIBIT SODIUM REABSORPTION AT CORTICAL DILUTING SITE & IN PROXIMAL CONVOLUTED TUBULE. SODIUM & CHLORIDE IONS ARE EXCRETED IN APPROX EQUAL AMT; INCR POTASSIUM EXCRETION MAY ALSO OCCUR. DIURETIC POTENCY APPROXIMATES THAT OF THIAZIDES.

Pharmacodynamics

Metolazone is a quinazoline diuretic, with properties generally similar to the thiazide diuretics. A proximal action of metolazone has been shown in humans by increased excretion of phosphate and magnesium ions and by a markedly increased fractional excretion of sodium in patients with severely compromised glomerular filtration. This action has been demonstrated in animals by micropuncture studies.