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Indications/Uses
Indicated in the treatment of mild to moderate hypertension in case of inadequate control of monotherapy.
Dosage/Direction for Use
One tablet once a day or as directed by the physician. It may be administered with or without food.
Direction For Use: Swallow whole tablet do not crush or chew.
Direction For Use: Swallow whole tablet do not crush or chew.
Overdosage
Losartan Potassium: Symptoms: The most likely manifestation of over-dosage would be hypotension and tachycardia. Bradycardia could occur from parasympathetic (vagal) stimulation. Treatment: If symptomatic hypotension occurs, supportive treatment should be instituted. Neither Losartan Potassium nor E-3174 can be removed by hemodialysis.
Amlodipine Besilate: Symptoms: Available data suggests that the gross over dosage could result in excessive peripheral vasodilation with marked and probably prolonged hypotension and possibly a reflex tachycardia. Treatment: Since absorption of amlodipine is slow, gastric lavage should be performed. Active cardiovascular support including monitoring of cardiac and respiratory function, elevation of extremities, and attention of circulating fluid volume and urine output should be given. Intravenous calcium gluconate may help to reverse the effects of calcium entry blockade. A vasoconstrictor agent may be helpful in restoring vascular and blood pressure provided that there is no contraindication to its use. Since amlodipine is highly protein bound, dialysis is unlikely to be of benefit.
Amlodipine Besilate: Symptoms: Available data suggests that the gross over dosage could result in excessive peripheral vasodilation with marked and probably prolonged hypotension and possibly a reflex tachycardia. Treatment: Since absorption of amlodipine is slow, gastric lavage should be performed. Active cardiovascular support including monitoring of cardiac and respiratory function, elevation of extremities, and attention of circulating fluid volume and urine output should be given. Intravenous calcium gluconate may help to reverse the effects of calcium entry blockade. A vasoconstrictor agent may be helpful in restoring vascular and blood pressure provided that there is no contraindication to its use. Since amlodipine is highly protein bound, dialysis is unlikely to be of benefit.
Administration
May be taken with or without food: Swallow whole, do not chew/crush.
Contraindications
It is contraindicated in patients allergic to angiotensin receptor blocker or dihydropyridine calcium channel antagonist. Patients with a history of angioedema or any other adverse effect related to previous treatment with an angiotensin receptor blocker or calcium channel antagonist.
Warnings
Hypotension: Losartan potassium can cause symptomatic hypotension. Symptomatic hypotension is most likely to occur in patients who have been volume and/or salt-depleted as a result of prolonged diuretic therapy, dietary salt restriction, dialysis, diarrhea, or vomiting. Volume and/or salt depletion should be corrected before initiating therapy with Losartan potassium and Amlodipine besilate combination.
Hepatic failure: Rarely, angiotensin receptor inhibitors have been associated with a syndrome that starts with cholestatic jaundice and progresses to fulminant hepatic necrosis and (sometimes) death. The mechanism of this syndrome is not understood. Patients receiving this combination who developed jaundice or marked elevations of hepatic enzymes should discontinue the therapy and receive appropriate medical follow-up.
Hepatic failure: Rarely, angiotensin receptor inhibitors have been associated with a syndrome that starts with cholestatic jaundice and progresses to fulminant hepatic necrosis and (sometimes) death. The mechanism of this syndrome is not understood. Patients receiving this combination who developed jaundice or marked elevations of hepatic enzymes should discontinue the therapy and receive appropriate medical follow-up.
Special Precautions
Impaired Liver Function: Losartan potassium and Amlodipine besilate combination should be given with caution in patients with impaired hepatic function since the half-life of amlodipine is prolonged in patients with impaired liver function.
Impaired Renal Patients: As a consequence of inhibiting the renin-angiotensin-aldosterone system, changes in renal function may be anticipated in susceptible individuals. In patients with severe congestive heart failure whose renal function may depend on the activity of the renin-angiotensin-aldosterone system, treatment with angiotensin receptor blocker may be associated with oliguria and/or progressive azotemia and (rarely) with acute renal/failure and/or death.
Use in Children: The use of this product is not currently recommended for children and adolescents of less than 18 years of age.
Impaired Renal Patients: As a consequence of inhibiting the renin-angiotensin-aldosterone system, changes in renal function may be anticipated in susceptible individuals. In patients with severe congestive heart failure whose renal function may depend on the activity of the renin-angiotensin-aldosterone system, treatment with angiotensin receptor blocker may be associated with oliguria and/or progressive azotemia and (rarely) with acute renal/failure and/or death.
Use in Children: The use of this product is not currently recommended for children and adolescents of less than 18 years of age.
Use In Pregnancy & Lactation
Pregnancy: It should not be administered during pregnancy and lactation or to women of childbearing potential unless effective contraception is ensured.
Nursing Mothers: Women receiving the product should not breast-feed.
Nursing Mothers: Women receiving the product should not breast-feed.
Adverse Reactions
Losartan K: Diarrhea, dyspepsia; muscle cramp, myalgia, back & leg pain; dizziness, insomnia; nasal congestion, cough, upper resp tract infection, sinus disorder, sinusitis. Amlodipine besilate: Edema, flushing, palpitation, fatigue, headache, somnolence, abdominal pain, dizziness.
Drug Interactions
Losartan Potassium: Losartan potassium administered for 12 days, did not affect the pharmacokinetics or pharmacodynamics of a single dose of warfarin. Losartan potassium did not affect the pharmacokinetics of oral or intravenous digoxin. Co-administration of Losartan and Cimetidine led to an increase of about 18% in AUC of Losartan Potassium but did not affect the pharmacokinetics of E-3174. Co-administration of Losartan potassium and phenobarbital led to reduction of about 20% in the AUC of Losartan potassium and E-3174. There is no pharmacokinetic interaction between Losartan potassium and hydrochlorothiazide.
Inhibitors of Cytochrome P3A4 are unlikely to have significant drug interactions while potent inducers of Cytochrome P3A4 might cause a significant interaction.
As with other drugs that block angiotensin II or its side effects, concomitant use of potassium-sparing diuretics (e.g. Spironolactone, triamterene, amiloride), potassium supplements, or salt substitutes containing potassium may lead to an increase in serum potassium.
Amlodipine Besilate: Amlodipine besilate has been safely administered with thiazide diuretics, beta adrenoreceptor blocking drugs, angiotensin converting enzyme inhibitors, long acting nitrates, sublingual glyceryl trinitrate, nonsteroidal anti-inflammatory drugs, antibiotics and oral hypoglycemic agents.
Co-administration of amlodipine besilate with digoxin did not change serum digoxin levels or digoxin renal clearance in normal volunteers. Co-administration of cimetidine did not alter the pharmacokinetics of amlodipine.
In healthy volunteers, co-administration of amlodipine besilate did not significantly alter the effect of warfarin on prothrombin time. The introduction of amlodipine besilate is not likely to result in the need for modification of an established warfarin regimen.
Inhibitors of Cytochrome P3A4 are unlikely to have significant drug interactions while potent inducers of Cytochrome P3A4 might cause a significant interaction.
As with other drugs that block angiotensin II or its side effects, concomitant use of potassium-sparing diuretics (e.g. Spironolactone, triamterene, amiloride), potassium supplements, or salt substitutes containing potassium may lead to an increase in serum potassium.
Amlodipine Besilate: Amlodipine besilate has been safely administered with thiazide diuretics, beta adrenoreceptor blocking drugs, angiotensin converting enzyme inhibitors, long acting nitrates, sublingual glyceryl trinitrate, nonsteroidal anti-inflammatory drugs, antibiotics and oral hypoglycemic agents.
Co-administration of amlodipine besilate with digoxin did not change serum digoxin levels or digoxin renal clearance in normal volunteers. Co-administration of cimetidine did not alter the pharmacokinetics of amlodipine.
In healthy volunteers, co-administration of amlodipine besilate did not significantly alter the effect of warfarin on prothrombin time. The introduction of amlodipine besilate is not likely to result in the need for modification of an established warfarin regimen.
Storage
Store at temperatures not exceeding 30°C.
Action
Pharmacology: Pharmacodynamics: Losartan Potassium: it is an angiotensin II receptor (type AT1) antagonist. Angiotensin II is a potent vasoconstrictor and an important component in the pathophysiology of hypertension. Losartan potassium blocks 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 (e.g. Vascular smooth muscle, adrenal gland).
Amlodipine Besilate: Amlodipine besilate is a dihydropyridine calcium antagonist (calcium ion antagonist or slow-channel blocker) that inhibits the transmembrane influx of calcium ions into vascular smooth muscle and cardiac muscle. The contractile process of cardiac muscle and vascular smooth muscle are dependent upon movement of extra cellular calcium ions into these cells through specific ion channels. By inhibiting calcium ion influx, it directly dilates vascular smooth muscle, resisting hypertension. The mechanism of relieve angina pectoris with amlodipine is not yet determined completely, but it is clear that this product can bate myocardial ischemia through the following functions: Dilate the peripheral small artery, decreasing peripheral resistance, causing the reduction of energy consumption and oxygen requirement of cardiac muscle.
Dilate the coronary artery and the small coronary artery at normal and ischaemic areas, increasing the oxygen supply of cardiac muscle in patients with coronary spasm.
Pharmacokinetics: Losartan Potassium: The pharmacokinetics of Losartan potassium and its active metabolite (E-3174) are linear with oral doses up to 200 mg and do not change overtime. Neither Losartan potassium, nor its metabolite accumulates in plasma upon repeated once-a-day dosing. Following oral administration, Losartan potassium has a systemic bioavailability of around 33%. Losartan potassium undergoes substantial first pass metabolism by cytochrome P450 enzymes. It is converted, in part, to an active carboxylic acid metabolite that is responsible for most of the angiotensin II receptor antagonism that follows Losartan potassium treatment. About 14% of an orally administered dose is converted to the active metabolite. After oral administration Losartan potassium is rapidly absorbed, reaching peak plasma concentrations within an hour. Losartan potassium and E-3174 have been reported to reach peak plasma concentration of 296 ng/mL and 249 ng/mL in 1.0 and 4.1 hours respectively after single oral dose of 50 mg in healthy volunteers. The area under the plasma concentration time curve (AUC) for E-3174 is approximately 4 fold greater than for Losartan potassium (1915 vs 476 ng*h/mL). Absorption is slowed and Cmax reduced by food. Losartan potassium and E-3174 are highly protein bound (98.7% and 99.8%) with volumes of distribution of 34L and 12L respectively. Approximately 35% of the drug is eliminated in the urine and approximately 60% is excreted in the feces. Losartan potassium and E-3174 have elimination half-lives of 2 and 6-9 hours respectively. The rate of renal clearance of Losartan potassium and E-3174 is 4.3 and 1.6L/h.
AMLODIPINE BESILATE: After oral administration of therapeutic doses of amlodipine besilate, absorption occurs gradually with peak plasma concentration occurring between 6 to 12 hours. Absolute bioavailability has been estimated to be between 64 and 90%. The bioavailability of amlodipine is not altered by the presence of food. Amlodipine has a large volume of distribution (Vd) of 21L/kg and highly plasma protein bound (95%).
Amlodipine undergoes extensive, but slow hepatic metabolism. The dihydropyridine moiety is oxidized to the pyridine analogue during initial biotransformation, with minimal first-pass or presystemic metabolism. Metabolites have no significant activity. Less than 10% of an oral dose is excreted unchanged. Following oral administration 60% of oral dose is recovered in the urine mainly as metabolites and 20 to 25% in the feces. The elimination half-life of Amlodipine is in the range of 30 to 50 hours in healthy subjects.
Amlodipine Besilate: Amlodipine besilate is a dihydropyridine calcium antagonist (calcium ion antagonist or slow-channel blocker) that inhibits the transmembrane influx of calcium ions into vascular smooth muscle and cardiac muscle. The contractile process of cardiac muscle and vascular smooth muscle are dependent upon movement of extra cellular calcium ions into these cells through specific ion channels. By inhibiting calcium ion influx, it directly dilates vascular smooth muscle, resisting hypertension. The mechanism of relieve angina pectoris with amlodipine is not yet determined completely, but it is clear that this product can bate myocardial ischemia through the following functions: Dilate the peripheral small artery, decreasing peripheral resistance, causing the reduction of energy consumption and oxygen requirement of cardiac muscle.
Dilate the coronary artery and the small coronary artery at normal and ischaemic areas, increasing the oxygen supply of cardiac muscle in patients with coronary spasm.
Pharmacokinetics: Losartan Potassium: The pharmacokinetics of Losartan potassium and its active metabolite (E-3174) are linear with oral doses up to 200 mg and do not change overtime. Neither Losartan potassium, nor its metabolite accumulates in plasma upon repeated once-a-day dosing. Following oral administration, Losartan potassium has a systemic bioavailability of around 33%. Losartan potassium undergoes substantial first pass metabolism by cytochrome P450 enzymes. It is converted, in part, to an active carboxylic acid metabolite that is responsible for most of the angiotensin II receptor antagonism that follows Losartan potassium treatment. About 14% of an orally administered dose is converted to the active metabolite. After oral administration Losartan potassium is rapidly absorbed, reaching peak plasma concentrations within an hour. Losartan potassium and E-3174 have been reported to reach peak plasma concentration of 296 ng/mL and 249 ng/mL in 1.0 and 4.1 hours respectively after single oral dose of 50 mg in healthy volunteers. The area under the plasma concentration time curve (AUC) for E-3174 is approximately 4 fold greater than for Losartan potassium (1915 vs 476 ng*h/mL). Absorption is slowed and Cmax reduced by food. Losartan potassium and E-3174 are highly protein bound (98.7% and 99.8%) with volumes of distribution of 34L and 12L respectively. Approximately 35% of the drug is eliminated in the urine and approximately 60% is excreted in the feces. Losartan potassium and E-3174 have elimination half-lives of 2 and 6-9 hours respectively. The rate of renal clearance of Losartan potassium and E-3174 is 4.3 and 1.6L/h.
AMLODIPINE BESILATE: After oral administration of therapeutic doses of amlodipine besilate, absorption occurs gradually with peak plasma concentration occurring between 6 to 12 hours. Absolute bioavailability has been estimated to be between 64 and 90%. The bioavailability of amlodipine is not altered by the presence of food. Amlodipine has a large volume of distribution (Vd) of 21L/kg and highly plasma protein bound (95%).
Amlodipine undergoes extensive, but slow hepatic metabolism. The dihydropyridine moiety is oxidized to the pyridine analogue during initial biotransformation, with minimal first-pass or presystemic metabolism. Metabolites have no significant activity. Less than 10% of an oral dose is excreted unchanged. Following oral administration 60% of oral dose is recovered in the urine mainly as metabolites and 20 to 25% in the feces. The elimination half-life of Amlodipine is in the range of 30 to 50 hours in healthy subjects.
MedsGo Class
Angiotensin II Antagonists / Calcium Antagonists
Features
Brand
Tozam
Full Details
Dosage Strength
50 mg / 5 mg
Drug Ingredients
- Amlodipine
- Losartan Potassium
Drug Packaging
Film-Coated Tablet 100's
Generic Name
Losartan Potassium / Amlodipine Besilate
Dosage Form
Film-Coated Tablet
Registration Number
DRP-2407
Drug Classification
Prescription Drug (RX)