Amlotitan

Amlotitan

Manufacturer:

GXI

Distributor:

Metro Drug
Full Prescribing Info
Contents
Losartan potassium, amlodipine besilate.
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.
Indications/Uses
Treatment of mild to moderate hypertension in case of inadequate control with monotherapy.
Dosage/Direction for Use
Usual initial dose is one (1) tablet daily. Increase if necessary to two (2) tablets daily or as prescribed by the physician. Similar doses are given in the treatment of stable angina and Prinzmetal's angina or as prescribed by the physician.
Overdosage
Losartan: Hypotension and tachycardia; Bradycardia could occur from parasympathetic (vagal) stimulation, LD50=1000 mg/kg (orally in rat).
Amlodipine: Gross overdosage could result in excessive peripheral vasodilation and possibly reflex tachycardia. Marked and probably prolonged systemic hypotension up to and including shock with fatal outcome have been reported.
Contraindications
Losartan plus Amlodipine is contraindicated in patients who are hypersensitive to any component of this product.
Warnings
Hypersensitivity to any component of this product.
Special Precautions
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 therefore be required with renal impairment and should be considered in patients with 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 hyperkalemia 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.
Amlodipine should be used with caution in patients with hypotension, in patients whose cardiac reserve is poor, and in those with heart failure has been noted. It should not be used in cardiogenic shock, in patient who have recently suffered a myocardial infarction, or in acute unstable angina. It should not be used to treat an angina attack in chronic stable angina. In patients with severe aortic stenosis it may increase the risk of developing heart failure. Sudden withdrawal might be associated with an exacerbation of angina. The dose may need to be reduced in patients with hepatic impairment. It should be discontinued in patients who experience ischaemic pain following its administration.
Use In Pregnancy & Lactation
Pregnancy: Drugs that act directly on the RAAS can cause fetal and neonatal morbidity and death when administered to pregnant women. When pregnancy is detected, this combination of Losartan and Amlodipine should be discontinued as soon as possible. Oligohydramnios has also been reported, presumably reporting from decreased fetal renal function.
Lactation: It is not known whether Losartan or Amlodipine is excreted in human milk. In the absence of this information, it is recommended that nursing may be discontinued while combination is administered.
Adverse Reactions
Adverse effect of Losartan have been reported to be usually mild and transient, and include dizziness, headache 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, myalgia and arthralgia have been reported. Losartan appears less likely than ACE inhibitors to cause cough. Other adverse effects that have been reported with angiotensin II receptor antagonist include respiratory-tract disorder, back pain, gastrointestinal disturbances, fatigue and neutropenia. The most common adverse effects of Amlodipine are associated with its vasodilator action and often diminish on continued therapy. They include dizziness, flushing headache, hypotension peripheral edema, tachycardia and palpitations. Nausea and other gastrointestinal disturbances, increased micturition frequency, lethargy, eye pain, and mental depression have also occurred. A paradoxical increase in ischaemic chest pain may occur at the start of treatment and in a few patients excessive fall in blood pressure has led to cerebral or myocardial ischaemia or transient blindness. There have been reports of rashes (including erythema multiforme) fever, and abnormalities in liver function, including cholestasis, due to hypersensitivity reactions, Gingival hyperplasia, myalgia, tremor and impotence have been reported.
Overdose may be associated with bradycardia and hypotension.
Drug Interactions
Rifampicin: Rifampicin, an inducer of drug metabolism, decreased the concentrations of Losartan and its active metabolite.
Fluconazole: Fluconazole, an inhibitor of cytochrome P4502C9, decreased active metabolite concentration and increased Losartan concentration.
Agents that increases Serum Potassium: As with other drugs that block angiotensin II or its effects, concomitant use of potassium-sparing diuretics, potassium supplements or salt substitutes containing potassium may lead to increase in serum potassium.
Lithium: Losartan reduces lithium excretion; hence, serum lithium levels should be monitored carefully if lithium salts are to be co-administered with this combination.
Non-Steroidal Anti-Inflammatory Agents (NSAIDs) including Selective Cyclooxygenase-2 inhibitors: In some patients with compromised renal function who are being treated with NSAIDs, including those that selectively inhibit cyclooxygenase-2 inhibitors (COX-2 inhibitors), the co-administration of Losartan may result in a further deterioration of renal function. These effects are reversible. Reports suggest that NSAIDs, including selective COX-2 inhibitors may diminish the antihypertensive effect of Losartan. This interaction should be given consideration in patients taking NSAIDs, including selective COX-2 inhibitors, concomitantly with this combination of Losartan and Amlodipine.
Storage
Store at temperatures not exceeding 30°C. Protect from light.
ATC Classification
C09DB06 - losartan and amlodipine ; Belongs to the class of angiotensin II receptor blockers (ARBs) and calcium channel blockers. Used in the treatment of cardiovascular disease.
Presentation/Packing
FC tab (peach to light-orange, biconvex, oval shaped, plain on one side and bisected on the other side) 30's.
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