Metolazone
Metolazone.JPG

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

    Route

    Oral

    Rate of Administration

    Comments

    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.



    See how to identify renal failure stages according to GFR calculation

    See how to diagnose irreversible renal disease

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