Chlortalidone

CLINICAL USE

Thiazide-like diuretic:Hypertension Ascites Oedema Diabetes insipidus Mild to moderate heart failure

DOSE IN NORMAL RENAL FUNCTION

Hypertension: 25–50 mg daily Oedema: 50 mg daily initially Diabetes insipidus: 100 mg every 12 hours initially, reducing to 50 mg daily where possibleHeart failure: 25–50 mg daily increasing to 100–200 mg daily

PHARMACOKINETICS

Molecular weight &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp :338.8

%Protein binding &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp :76

%Excreted unchanged in urine &nbsp &nbsp : 50

Volume of distribution (L/kg) &nbsp &nbsp &nbsp :3.9

half-life – normal/ESRD (hrs)&nbsp &nbsp &nbsp :40–60/Unchanged

DOSE IN RENAL IMPAIRMENT

GFR (mL/MIN)

30–50 Dose as in normal renal function <30 Avoid. See ‘Other Information’

DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

CAPD &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp:Unlikely to be dialysed. Avoid

HD &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp :Not dialysed. Avoid

HDF/high flux &nbsp :Unknown dialysability. Avoid

CAV/VVHD &nbsp &nbsp &nbsp:Unknown dialysability. Dose as in normal renal function

IMPORTANT DRUG INTERACTIONS

Potentially hazardous interactions with other drugsAnalgesics: increased risk of nephrotoxicity with NSAIDs; antagonism of diuretic effectAnti-arrhythmics: hypokalaemia leads to increased cardiac toxicity; effects of lidocaine and mexiletine antagonisedAntibacterials: avoid administration with lymecyclineAntidepressants: increased risk of hypokalaemia with reboxetine; enhanced hypotensive effect with MAOIs; increased risk of postural hypotension with tricyclicsAnti-epileptics: increased risk of hyponatraemia with carbamazepineAntifungals: 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 sotalolAntipsychotics: hypokalaemia increases risk of ventricular arrhythmias with amisulpiride 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 occursCiclosporin: increased risk of nephrotoxicity and hypomagnesaemiaLithium excretion reduced, increased toxicity

ADMINISTRATION

Reconstition

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Route

Oral

Rate of Administration

–

Comments

A single dose at breakfast time is preferable

OTHER INFORMATION

Can precipitate diabetes mellitus and gout, and cause severe electrolyte disturbances and an increase in serum lipidsThiazide diuretics are unlikely to be of use once GFR<30 mL/min

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