Contents

Losartan K 50 mg, amlodipine besilate 5 mg

Indication

Mild to moderate HTN in case of inadequate control w/ monotherapy.

Dosage / Direction For Use

1 tab daily, may increase to 2 tab daily.

Overdosage

Losartan: Hypotension and tachycardia; Bradycardia could occur from parasympathetic (vagal) stimulation, LD50=1000 mg/kg (orally in rat).

Administration

May be taken with or without food.

Contraindication

Hypersensitivity. Pregnancy.

Special Precaution

Losartan: Renal artery stenosis. Hypotension in patients w/ vol depletion. Monitor serum K conc. Renal & hepatic impairment. Lactation. Amlodipine: Hypotension, poor cardiac reserve, history of heart failure. Should not be used in cardiogenic shock, MI, or in acute unstable angina; angina attack in chronic stable angina. Risk of developing heart failure in patients w/ severe aortic stenosis. Avoid abrupt w/drawal. Discontinue if ischaemic pain occurred.

Adverse Reactions

Dizziness, headache, & dose-related orthostatic hypotension.

Drug Interaction

Decreased conc w/ rifampicin. Decreased active metabolite conc & increased losartan conc w/ fluconazole. Increase in serum K w/ K-sparing diuretics, K supplements, or salt substitutes containing K. Reduced excretion of lithium. Further deterioration of renal function & may diminish the antihypertensive effect of losartan w/ NSAIDs including selective COX-2 inhibitors.

Storage

Store at temperatures not exceeding 30°C. Protect from light.

Description

Each film-coated tablet contains: Losartan potassium 50 mg.Amlodipine (as besilate) 5 mg.

Action

Pharmacology: Pharmacodynamics: Losartan: 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 found in many tissues, (eg., vascular smooth muscle, adrenal gland). Both Losartan and its principal active metabolite do not exhibit any partial agonist activity at the AT1 receptor and have much greater affinity (about 1000-fold) for the AT1 receptor than for the AT2 receptor.Amlodipine: Amlodipine inhibits the transmembrane influx of calcium ions into vascular smooth muscle and cardiac muscle. Experimental data suggest that Amlodipine binds to both dihydropyridine and non-dihydropyridine binding sites. The contractile processes of cardiac muscle and vascular smooth muscle are dependent upon the movement of extracellular calcium ions into these cells through specific ion channels. Amlodipine inhibits calcium ion influx across cell membranes selectively, with a greater effect on vascular smooth muscle cells than on cardiac muscle cells. Amlodipine is a peripheral arterial vasodilator that acts directly on vascular smooth muscle to cause a reduction in peripheral vascular resistance and reduction in blood pressure.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 faeces via bile, as unchanged drug and metabolites. Following oral dosing about 35% of the dose if excreted in the urine and about 60% in the faeces. The terminal elimination half-lives of Losartan and E-3174 are about 1.5 to 2.5 hours and 3 to 9 hours, respectively.Amlodipine is well absorbed following oral administration with peak blood concentrations occurring after 6 to 12 hours. The bioavailability is about 60 to 65%. Amlodipine is reported to be about 97.5% bound to plasma proteins. It has a prolonged terminal elimination half-life of 35 to 50 hours and steady-state plasma concentrations are not achieved until 7 to 8 days of administration. Amlodipine is extensively metabolized in the liver; metabolites are mostly excreted in urine together with less than 10% of dose as unchanged drug.