Metolazone

CLINICAL USE

Thiazide diuretic, acts synergistically with loop diuretics:Oedema Hypertension

DOSE IN NORMAL RENAL FUNCTION

Oedema: 5–10 mg, increased to 20 mg daily; maximum 80 mg dailyHypertension: 5 mg initially; maintenance: 5 mg on alternate days

PHARMACOKINETICS

Molecular weight :365.8

%Protein binding :95

%Excreted unchanged in urine : 80–95

Volume of distribution (L/kg) :1.6

half-life – normal/ESRD (hrs) :8–10/–

DOSE IN RENAL IMPAIRMENT

GFR (mL/MIN)

20 to 50 : Dose as in normal renal function

10 to 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

IMPORTANT DRUG INTERACTIONS

Potentially hazardous interactions with other drugs

Analgesics: increased risk of nephrotoxicity with NSAIDs; antagonism of diuretic effect

Anti-arrhythmics: hypokalaemia leads to increased cardiac toxicity; effects of lidocaine and mexiletine antagonised

Antibacterials: avoid administration with lymecycline

Antidepressants: increased risk of hypokalaemia with reboxetine; enhanced hypotensive effect with MAOIs; increased risk of postural hypotension with tricyclics

Anti-epileptics: increased risk of hyponatraemia with carbamazepine

Antifungals: increased risk of hypokalaemia with amphotericinAntihypertensives: enhanced hypotensive effect; increased risk of first dose hypotension with post-synaptic alpha-blockers like prazosin; hypokalaemia increases risk of ventricular arrhythmias with sotalol

Antipsychotics: hypokalaemia increases risk of ventricular arrhythmias with amisulpride or sertindole; enhanced hypotensive effect with phenothiazines; hypokalaemia increases risk of ventricular arrhythmias with pimozide – avoid concomitant use

Atomoxetine: hypokalaemia increases risk of ventricular arrhythmiasCardiac glycosides: increased toxicity if hypokalaemia occurs

Ciclosporin: increased risk of nephrotoxicity and possibly hypomagnesaemiaLithium excretion reduced, increased toxicity

ADMINISTRATION

Reconstition

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Route

Oral

Rate of Administration

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Comments

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OTHER INFORMATION

May result in profound diuresis. Monitor patient’s fluid balance carefullyMonitor for hypokalaemia In patients with creatinine clearance less than 50 mL/minute there is no clinical evidence of accumulation.

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