CLINICAL USE

Thiazide diuretic: Hypertension Oedema

DOSE IN NORMAL RENAL FUNCTION

Oedema: 40–80 mg in the morning Maintenance: 20 mg in the morning Hypertension: 20 mg in the morning

PHARMACOKINETICS

  • Molecular weight                           : 354.8
  • %Protein binding                           : 99
  • %Excreted unchanged in urine     : 50
  • Volume of distribution (L/kg)       : 10–21 litres
  • half-life – normal/ESRD (hrs)      : 5–8/9–32

    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                : Unknown dialysability. Dose as in normal renal function
  • HD                     : Dialysed. Dose as in normal renal function
  • HDF/high flux   : Dialysed. Dose as in normal renal function
  • CAV/VVHD      : Unknown dialysability. 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 amphotericin Antihypertensives: 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 arrhythmias Cardiac glycosides: increased toxicity if hypokalaemia occurs
  • Ciclosporin: increased risk of nephrotoxicity and possibly hypomagnesaemia Lithium excretion reduced (increased toxicity)

    ADMINISTRATION

    Reconstition

    Route

    Oral

    Rate of Administration

    Comments

    OTHER INFORMATION

    Monitor for hypokalaemia Diuresis starts within 1–2 hours, peaks at 4–6 hours and lasts for almost 24 hours Manufacturer advises to avoid in severe renal impairment due to reduced clearance

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