Arbloc

Arbloc

losartan

Manufacturer:

Cathay YSS

Distributor:

Cathay YSS
Full Prescribing Info
Contents
Losartan potassium.
Description
Each film coated tablet contains 50 mg and 100 mg of the active ingredient, Losartan Potassium.
Losartan Potassium is a white to off-white free-flowing crystalline powder with a molecular weight of 461.01. It is freely soluble in water, soluble in alcohols, and slightly soluble in common organic solvents, such as acetonitrile and methyl ethyl ketone. Oxidation of the 5-hydroxy-methyl group on the imidazole ring results in the active metabolite of Losartan.
Action
Pharmacology: Losartan Potassium is an angiotensin II receptor (type AT1) antagonist. Angiotensin II [formed from angiotensin I in a reaction catalyzed by angiotensin-converting enzyme (ACE; kininase II)] is a potent vasoconstrictor, the primary vasoactive hormone of the renin-angiotensin system, and an important component in the pathophysiology of hypertension. Its effects are vasoconstriction, stimulation of synthesis and release of aldosterone, cardiac stimulation and renal re-absorption of sodium. Losartan and its principal active metabolite block the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT1 receptor in many tissues (e.g. vascular smooth muscle, adrenal gland). There is also an AT2 receptor in many tissues but it is not known to be associated with cardiovascular homeostasis. Both Losartan and its principal active metabolite have much greater affinity (about 1,000 fold) for the AT1 than for the AT2 receptor and do not exhibit any agonist activity.
In vitro binding studies indicate that Losartan is a reversible, competitive inhibitor of the AT1 receptor. The active metabolite is 10 to 40 times more potent by the weight than Losartan and appears to be a reversible, non-competitive inhibitor of the AT1 receptor.
Losartan do not inhibit ACE (kininase II, the enzyme that converts angiotensin I to angiotensin II and degrades bradykinin) nor do they bind to or block other hormone receptor or ion channels known to be important in cardiovascular regulation. It inhibits the pressor effect of angiotensin II (as well as angiotensin I) infusions. Removal of the negative feedback of angiotensin II causes 2- to 3-fold rise in plasma renin activity and a consequent rise in angiotensin II plasma concentration in hypertensive patients. The resulting increased plasma renin activity and angiotensin II circulating levels are insufficient to alter the effects of Losartan and its principal active metabolite on blood pressure. There was a small uricosuric effects with Losartan leading to a minimal decrease in serum uric acid (mean decrease less than 0.4 mg/dL) during chronic oral administration.
Pharmacokinetics: Losartan Potassium 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, which has a greater pharmacological activity than Losartan Potassium, and some inactive metabolites. Metabolism is primarily by cytochrome P450 isoenzymes CYP2C9 and CYP3A4. Peak plasma concentrations of Losartan Potassium and its active metabolite occur about 1 hour and 3 to 4 hours, respectively, after an oral dose. Both Losartan Potassium and its active metabolite are more than 98% bound to plasma proteins. Losartan Potassium 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 Potassium and its metabolite are about 1.5 to 2.5 hours and 3 to 9 hours, respectively.
Indications/Uses
Losartan Potassium is an angiotensin II receptor antagonist with an antihypertensive activity due mainly to selective blockade of AT1 receptors and the consequent reduced pressor effect of angiotensin II.
Hypertension: Losartan Potassium is used in the management of hypertension alone or in combination with other antihypertensive agents and may have a role in patients who develop cough with ACE inhibitors.
Hypertensive patients with left ventricular hypertrophy: Losartan Potassium is indicated to reduce the risk of stroke, heart failure and myocardial infarction in patients with hypertension and left ventricular hypertrophy, but there is evidence that this benefit does not apply to black patients.
Nephropathy in type 2 diabetic patients: Losartan Potassium is also indicated in the treatment of diabetic nephropathy with an elevated serum creatinine and proteinuria (urinary albumin to creatinine ratio greater than or equal to 300 mg/g) in patients with type 2 diabetes and a history of hypertension. In this population, Losartan reduces the rate of progression of nephropathy as measured by the occurrence of doubling of serum creatinine or end renal disease (need for dialysis or renal transplantation).
Dosage/Direction for Use
Losartan Potassium may be administered with or without food. It may also be administered with other antihypertensive agents.
Losartan is given by mouth as the potassium salt. The maximum hypotensive effect is achieved in about 3 to 6 weeks after initiating treatment.
Hypertension: The usual starting and maintenance dose is 50 mg once daily for most patients. The dose may be increased, if necessary, to 100 mg daily as a single dose or in two divided doses.
For elderly over 75 years and for patients with moderate to severe renal impairment (creatinine clearance less than 20 mL per minute), or intravascular fluid depletion, an initial dose of 25 mg once daily may be used. A reduced dose should also be considered for patients with hepatic impairment.
Hypertensive Patients with Left Ventricular Hypertrophy: The usual starting dose is 50 mg of Losartan Potassium once daily. A low dose of hydrochlorothiazide should be added and/or the dose of Losartan Potassium should be increased to 100 mg once daily based on blood pressure response.
Nephropathy in type 2 diabetic patients: The usual starting dose is 50 mg once daily. The dose may be increased to 100 mg once daily based on blood pressure response. Losartan Potassium may be administered with other antihypertensive agents like diuretics, calcium channel blockers, alpha- or beta-blockers, and centrally acting agents. It may be also administered with insulin and other commonly used hypoglycemic agents like sulfonylureas, glitazones and glucosidase inhibitors.
Overdosage
There are limited data available in regard to overdosage in humans. The most common effects would be hypotension and tachycardia; bradycardia could occur from parasympathetic (vagal) stimulation. If symptomatic hypotension should occur, supportive treatment should be instituted.
Neither Losartan Potassium nor its active metabolite can be removed by hemodialysis.
Contraindications
Losartan Potassium is contraindicated in patients who are hypersensitive to any component of this product.
Warnings
When used in pregnancy during the second and third trimesters, drugs that act directly on the renin-angiotensin system can cause injury and even death to the developing fetus. When pregnancy is detected, Losartan Potassium should be discontinued as soon as possible.
Special Precautions
Should be used with care in pregnancy and during breast feeding, since the act on the renin-angiotensin system have been associated with fetal toxicity in humans.
Should be used with caution in patients with renal artery stenosis.
Reduced doses may be required in patients with renal impairment and hepatic impairment.
May experience hypotension in patients with volume depletion (e.g. patients who have received high-dose diuretic therapy) which may be minimized by initiating treatment with a low dose of Losartan Potassium.
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 since hyperkalemia may occur.
Use In Pregnancy & Lactation
When used in pregnancy during the second and third trimesters, drugs that act directly on the renin-angiotensin system can cause injury and even death to the developing fetus. When pregnancy is detected, Losartan Potassium should be discontinued as soon as possible.
Should be used with care in pregnancy and during breast feeding, since the act on the renin-angiotensin system have been associated with fetal toxicity in humans.
Adverse Reactions
Adverse effects of Losartan Potassium have been reported to be usually mild and 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. Hyperkalemia and myalgia have been reported. Other adverse effects that have been reported with angiotensin II receptor antagonist include respiratory-tract disorders, back pain, gastrointestinal disturbances, fatigue and neutropenia.
Symptomatic anemia occurred in a patient with a renal transplant 6 weeks after commencing therapy with Losartan Potassium. Decreased hemoglobin concentrations have also been reported in patients with severe renal impairment undergoing hemodialysis.
Raised liver enzyme values have occurred rarely in patients receiving Losartan Potassium. Severe, acute reversible hepatotoxicity occurred in a patient who had been taking Losartan in a dose of 150 mg daily for 6 weeks.
Atypical cutaneous lymphoid infiltrates, taste disturbances in some cases progressing to complete taste loss, it will return to normal after discontinuing therapy; migraine and acute pancreatitis have also been reported in patients receiving Losartan Potassium.
Drug Interactions
No drug interactions of clinical significance have been identified with hydrochlorothiazide, digoxin, warfarin, cimetidine, phenobarbital, ketoconazole and erythromycin. Rifampin and fluconazole have been reported to reduce levels of active metabolite. The clinical consequences of these interactions have not been evaluated.
As with other drugs that block angiotensin II or its effects, concomitant use of potassium-sparing diuretics (e.g. spironolactone, triamterene, amiloride), potassium supplements or salt substitutes containing potassium may lead to increase in serum potassium.
As with other antihypertensive agents, the antihypertensive effect of Losartan may be attenuated by the non-steroidal anti-inflammatory drug indomethacin.
Storage
Store at temperatures not exceeding 30°C.
ATC Classification
C09CA01 - losartan ; Belongs to the class of angiotensin II receptor blockers (ARBs). Used in the treatment of cardiovascular disease.
Presentation/Packing
FC tab 50 mg x 30's. 100 mg x 30's.
Register or sign in to continue
Asia's one-stop resource for medical news, clinical reference and education
Sign up for free
Already a member? Sign in