Osartil Plus

Angiotensin II is formed from angiotensin I in a reaction catalyzed by angiotensin converting enzyme (ACE). It is a potent vasoconstrictor and the main vasoactive hormone of the renin-angiotensin system, and it plays an important part in how hypertension develops. It also stimulates the adrenal cortex to secrete aldosterone. Losartan Potassium and its principal active metabolite block these vasoconstrictor and aldosterone-secreting effects. They do this by selectively stopping angiotensin II from binding to the AT1 receptor, which is found in many tissues (for example vascular smooth muscle and the adrenal gland). In vitro binding studies show that losartan is a reversible, competitive inhibitor of the AT1 receptor. Neither losartan nor its active metabolite inhibits ACE (kinase II, the enzyme that converts angiotensin I to angiotensin II and breaks down bradykinin). They also don't bind to or block other hormone receptors or ion channels known to be important in cardiovascular regulation.

Hydrochlorothiazide is a thiazide diuretic. Thiazides act on the renal tubular mechanisms of electrolyte reabsorption and directly increase the excretion of Sodium and Chloride in approximately equivalent amounts. Indirectly, the diuretic action of Hydrochlorothiazide reduces plasma volume. This brings increased plasma renin activity, increased Aldosterone secretion, increased urinary Potassium loss and decreased serum Potassium. The renin-aldosterone link is mediated by angiotensin II, so giving an angiotensin II receptor antagonist together with these diuretics tends to reverse the Potassium loss they cause.

Angiotensin-II receptor antagonists, the group that includes Losartan Potassium with Hydrochlorothiazide, should be avoided in pregnancy unless they are essential. They may affect blood pressure control and kidney function in the fetus and the newborn. Skull defects and oligohydramnios have also been reported.

There is only limited information on the use of these medicines during breastfeeding. They are not recommended in breastfeeding, and other treatment options with better-established safety information during breastfeeding are available.

Use in patients with renal impairment: The usual 50/12.5 regimen of Losartan Potassium + Hydrochlorothiazide can be followed as long as the patient's creatinine clearance is above 30 ml/min. In patients with more severe renal impairment, loop diuretics are preferred to thiazides, so hydrochlorothiazide is not recommended.

Use in patients with hepatic impairment: This combination of Losartan and Hydrochlorothiazide is not recommended for titration in patients with hepatic impairment, because the appropriate 25 mg starting dose of Losartan cannot be given.

Use in pediatric patients: Safety and effectiveness in pediatric patients have not been established.

Losartan Potassium: There isn't much information on overdose in humans. The most likely effects are low blood pressure (hypotension) and a fast heartbeat (tachycardia). A slow heartbeat (bradycardia) could also happen because of parasympathetic (vagal) stimulation. If hypotension with symptoms occurs, supportive treatment should be started. Hemodialysis cannot remove losartan or its metabolite.

Hydrochlorothiazide: The signs and symptoms seen most often come from electrolyte depletion, meaning hypokalemia, hypochloremia and dehydration caused by excessive diuresis. If digitalis has also been given, hypokalemia may make cardiac arrhythmias worse. How much hemodialysis removes Hydrochlorothiazide has not been established.

Store below 30°C, and keep it away from children.