Zarnat Plus

Losartan is an angiotensin II receptor antagonist with antihypertensive activity due mainly to selective blockade of AT₁, receptors and the consequent reduced pressor effect of angiotensin II. It is used in management of hypertension and may have a role in patients who develop cough with ACE inhibitors. It has also been tried in heart failure and in myocardial infarction and is under investigation in diabetic neuropathy.
Hydrochlorothiazide is a thiazide diuretic which is used in the treatment of edema associated with heart failure and with renal and hepatic disorders. It is used for hypertension.
Each film-coated tablet contains: Losartan potassium 50 mg, Hydrochlorothiazide 12.5 mg.

Pharmacology: Pharmacokinetics: Losartan is readily absorbed from the gastrointestinal tract following oral administration, with an oral bioavailability of about 33%. It undergoes first-pass metabolism to form an active carboxylic acid metabolite E-3174 (EXP-3174), which has greater pharmacological activity than losartan and some inactive metabolites. Metabolism is primarily by cytochrome P450 isoenzymes CYP2C9 and CYP3A4. Peak plasma concentrations of losartan and E-3174 occur about 1 hour and 3 to 4 hours, respectively, after an oral dose. Both losartan and E-3174 are more than 98% bound to plasma proteins. Losartan is excreted in the urine and in the feces via bile, as unchanged drug and metabolites. Following oral dosing about 35% of the dose is excreted in the urine and about 60% in the feces. The terminal elimination half-lives of losartan and E-3174 are about 1.5 to 2.5 hours and 3 to 9 hours respectively.
Hydrochlorothiazide is fairly rapidly absorbed from the gastrointestinal tract. It is reported to have a bioavailability of about 65 to 70%. It has been estimated to have a plasma half-life of between about 5 and 15 hours and appears to be preferentially bound to red blood cells. It is excreted mainly unchanged in the urine. Hydrochlorothiazide crosses the placental barrier and is distributed into breast milk.

Losartan + Hydrochlorothiazide is indicated for the treatment of hypertension not adequately controlled by individual components.

Losartan + Hydrochlorothiazide 50 mg/12.5 mg film-coated tablet.
Usual dose is 1 to 2 tablets daily or as prescribed by the physician.

Losartan is contraindicated in pregnancy and should be used with care, if at all, during breast feeding. It should be used with caution in patients with renal artery stenosis. Reduced doses may be required in patients with renal impairment and should be considered in patients hepatic impairment. Patients with volume depletion (for example those who have received high-dose diuretic therapy) may experience hypotension, which may be minimized by initiating treatment with a low dose of losartan. Since hyperkalaemia may occur, serum-potassium concentrations should be monitored, especially in the elderly and patients with renal impairment and the concomitant use of potassium-sparing diuretics should generally be avoided.
Hydrochlorothiazide produces changes in fluid and electrolyte balance. It should be used with caution in patients with existing fluid and electrolyte balance, such as the elderly. It should be avoided in patients with severe hepatic impairment.
An increased risk of non-melanoma skin cancer (NMSC) [basal cell carcinoma (BCC) and squamous cell carcinoma (SCC)] with increasing cumulative dose of hydrochlorothiazide (HCTZ) exposure has been observed in two epidemiological studies based on the Danish National Cancer Registry. Photosensitizing actions of HCTZ could act as a possible mechanism for NMSC.
Patients taking HCTZ should be informed of the risk of NMSC and advised to regularly check their skin for any new lesions and promptly report any suspicious skin lesions. Possible preventive measures such as limited exposure to sunlight and UV rays and, in case of exposure, adequate protection should be advised to the patients in order to minimize the risk of skin cancer. Suspicious skin lesions should be promptly examined potentially including histological examinations of biopsies. The use of HCTZ may also need to be reconsidered in patients who have experienced previous NMSC.

Adverse effects of losartan have been reported to be usually transient, and include dizziness and dose related orthostatic hypotension. Hypotension may occur particularly in patients with volume depletion (for example those who have received high-dose diuretics). Impaired renal function and rarely, rash, angioedema and raised liver enzyme values may occur. Hypokalaemia and myalgia have been reported. Losartan appears less likely than ACE inhibitors to cause cough. Other adverse effects that have been reported with angiotensin II receptor antagonists include respiratory tract disorders, back pain, gastrointestinal disturbances, fatigue and neutropenia.
Hydrochlorothiazide may cause a number of metabolic disturbances especially at high doses. They may provoke hyperglycemia and glycosuria in diabetic and other susceptible patients. They may cause hyperuricemia and precipitate attacks of gout in some patients.

Store at temperatures not exceeding 30°C.

Angiotensin II Antagonists / Diuretics

C09DA01 - losartan and diuretics ; Belongs to the class of angiotensin II receptor blockers (ARBs) in combination with diuretics. Used in the treatment of cardiovascular disease.

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