Indication

Hypertension, Stroke, risk reduction of hypertensive or LVH patients

Adult dose

Hypertension Initial: 50 mg/12.5 mg PO qDay If dose titrated upward, do not to exceed final titration of 100 mg/25 mg PO qDay or 50 mg/12.5 mg PO q12hr Decrease losartan to 25 mg PO qDay initially if volume depleted

Child dose

Safety and efficacy not established

Renal dose

Renal impairment CrCl <30 mL/min: Do not use thiazide-containing products; loop diuretic preferred CrCl >30 mL/min: No dosage adjustment required

Contraindication

Pregnancy, lactation; intravascular volume depletion.

Mode of action

Hydrochlorothiazide increases renal excretion of sodium and chloride and reduces cardiac load. Losartan is an angiotensin II receptor (type AT1) antagonist antihypertensive which acts by blocking the actions of angiotensin II of renin-angiotensin-aldosterone system. The drug and its active metabolite selectively block the vasoconstrictor and aldosterone secreting effects of angiotensin II. The two drugs exert additive effects in hypertension.

Precaution

Existing electrolyte disturbances; hepatic cirrhosis; severe hepatic failure; oedema; elderly (>75 yr); renal impairment; hepatic impairment; diabetes, gout, hyperlipidaemia; hyperuricaemia; ECG: LVH and/or ventricular ectopics extrasystoles); volume depleted patients; patients on diuretics and salt restriction; renal artery stenosis; aortic and mitral stenosis. Monitor potassium concentration. Discontinue before performing tests for parathyroid function. Lactation: Discontinue drug or do not nurse

Side effect

>10% Losartan Fatigue (14%),Hypoglycemia (14%),Chest pain (12%),Cough, incidence higher in previous cough related to ACE therapy (3-11%) 1-10% Losartan Diarrhea (2-10%),URI (8%),Hypotension (7%),Dizziness (4%),Nausea (2%) Hydrochlorothiazide Hypotension,Anorexia,Epigastric distress,Hypokalemia,Phototoxicity,Thrombocytopenia Potentially Fatal: Hypersensitivity reactions; hemolytic anaemia; toxic epidermal necrolysis.

Interaction

Reduced excretion of lithium; effect of diuretic, natriuretic & other antihypertensive w/ NSAIDs including selective COX-2 inhibitors. Do not co-administer w/ aliskiren in patients w/ diabetes & renal impairment. Losartan: Rifampin & fluconazole. Increased serum potassium w/ K-sparing diuretics (eg spironolactone, triamterene, amiloride), K supplements or salt substitutes containing K. Hydrochlorothiazide: Potentiate orthostatic hypotension w/ alcohol, barbiturates or narcotics. Antidiabetic drugs (oral agents, insulin), other antihypertensive drugs. Impaired absorption w/ cholestyramine & colestipol resins. Intensified electrolyte depletion w/ corticosteroids, ACTH, glycyrrhizin (liquorice). Possible decreased response to pressor amines (eg adrenaline); increased response to nondepolarizing skeletal muscle relaxants (eg tubocurarine). May interfere w/ parathyroid function test.