Losartan + Hydrochlorothiazide

Oral
Hypertension

Dialysis patients: Avoid.

CrCl	Dosage
<20	Avoid.

May be taken with or without food.

Pregnancy, lactation; intravascular volume depletion.

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.

Volume depletion and electrolyte imbalance (especially hyperkalaemia); dry mouth, thirst; lethargy, drowsiness; muscle pain and cramps; rashes, photosensitivity, thrombocytopenia, jaundice, pancreatitis; fatigue, weakness; may precipitate an attack of gout; impotence; hyperglycaemia; anorexia, nausea, vomiting, constipation, diarrhoea; sialdenitis; raised urinary calcium concentration; headache, dizziness; back pain, myalgia; first-dose hypotension; angiodema; neutropenia; GI disturbances; transient elevation of liver enzymes; taste disturbances, cough; exacerbation or activation of systemic lupus erythematous; palpitations; xanthopsia; leucopenia, agranulocytosis, aplastic anaemia; necrotising angiitis; glucosuria; renal dysfunction, interstitial nephritis, renal failure; migraine; hyponatraemia; UTI; chest pain; gastritis, wt gain, dyspepsia, abdominal pain; bronchitis, upper respiratory infection, nasal congestion, sinusitis; rise in cholesterol and/or triglycerides.
Potentially Fatal: Hypersensitivity reactions; hemolytic anaemia; toxic epidermal necrolysis.

PO: D

Symptoms: hypotension and tachycardia. Treatment: supportive and symptom specific. Not removed via haemodialysis.

Hydrochlorothiazide increases plasma concentration fluconazole. Increased hypotensive effect with: ACE inhibitors, alcohol, adrenergic neurone blockers, aldesleukin, α-blockers, alprostadil, general anaesthetics, antipsychotics, anxiolytics and hypnotics, baclofen, β-blockers, calcium-channel blockers, clonidine, diazoxide, epoetin, hydralazine, levodopa, MAOIs, methyldopa, minoxidil, monoxidine, nitrates, NSAIDs, oestrogens, sodium nitroprusside, tizanidine, phenothiazines. Increased risk of renal impairment with aspirin (in doses >300 mg daily), NSAIDs. Hypotensive effect antagonised by aspirin, corticosteroids, indomethacin, ketorolac. Increased risk of hyperkalaemia with potassium-sparing and aldosterone antagonists, drospirenone (monitor serum potassium during 1st cycle), epoetin, heparin, ketorolac, potassium salts. Increased risk of hypersensitivity with allopurinol (especially in renal impairment). May antagonise hypoglycaemic effects of antidiabetics. Increased risk of hypercalcaemia with calcium salts and vitamin D. Increased risk of hyponatraemia with chlorpropamide. Increased risk of hypermagnesaemia with ciclosporin. Absorption may be reduced by colestipol and colestyramine (take at least 2 hr apart).
Potentially Fatal: Increased risk of nephrotoxicity and ototoxicity with platinum compounds, aminoglycosides. Hypokalaemia caused by diuretics may cause cardiac toxicity with amiodarone (interaction may occur for several weeks or months due to long half life of amiodarone). Increased risk of nephrotoxicity and hyperkalaemia with ciclosporin. Reduced excretion of lithium (risk of lithium toxicity with diuretics).

Avoid dong quai (if using for hypertension as it has estrogenic activity; ephedra, ginseng, yohimbe (may worsen hypertension), garlic (may have additive effects), St John's wort (may decrease levels).

Description: 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.
Onset: Hydrochlorothiazide: diuresis: approx 2 hr; losartan: 6 hr.
Duration: Hydrochlorothiazide: 6-12 hr.
Pharmacokinetics:
Absorption: Hydrochlorothiazide: oral absorption: Approx 50-80%; time to peak: 1-2.5 hr; peak effect: 4-6 hr; bioavailability: 50-80%. Losartan: time to peak: 1 hr; losartan's active metabolite (E-3174): time to peak 3-4 hr (AUC is 4 times greater than that of losartan); bioavailability: 25-33%.
Distribution: Hydrochlorothiazide: 3.6-7.8 L/kg; protein binding: 68%. Losartan: volume of distribution: 34 L; plasma protein binding: high. Losartan's active metabolite (E-3174): volume of distribution:12 L.
Metabolism: Hydrochlorothiazide: Not metabolised. Losartan: Hepatic (14%) via CYP2CP and CYP3A4 to active metabolite, E-3174 (40 more times potent than losartan), extensive 1st-pass effect.
Excretion: Hydrochlorothiazide: half life elimination: 5.6-14.8 hr; excretion: via urine (as unchanged drug). Losartan: excretion via urine (4% as unchanged drug and 6% as active metabolite); plasma clearance: 600 ml/minute (active metabolite: 50 ml/min).

Protect from light and store at 15-30 °C.

Angiotensin II Antagonists / Diuretics