Cozaar coated pills 50mg N14
Condition: New product
1000 Items
Rating:
Be the first to write a review!
More info
Active ingredients
Losartan
Release form
Pills
Composition
Active ingredient: Losartan (Losartan) Active ingredient concentration (mg): 50
Pharmacological effect
Specific antagonist of angiotensin II receptors (type AT1) for oral administration. Angiotensin II binds selectively to AT1 receptors found in many tissues (in smooth muscle tissue of the vessels, in the adrenal glands, kidneys, and heart) and performs several important biological functions, including vasoconstriction and the release of aldosterone. Angiotensin II also stimulates the growth of smooth muscle cells. Losartan and its pharmacologically active metabolite (Е 3174), both in vitro and in vivo, block all physiological effects of angiotensin II, regardless of the source or route of synthesis. Unlike some angiotensin II peptide antagonists, losartan does not have agonist effects. Losartan binds selectively to AT1 receptors and does not bind or block the receptors of other hormones and ion channels, which play an important role in regulating the function of the cardiovascular system. In addition, losartan does not inhibit the ACE responsible for the destruction of bradykinin. Consequently, effects that are not directly related to the blockade of AT1 receptors, in particular, increased effects associated with the effects of bradykinin or the development of edema (losartan - 1.7%, placebo - 1.9%) are not related to the action of losartan. For long-term (6 weeks ) treatment of patients with arterial hypertension with losartan at a dose of 100 mg / day was observed a 2-3-fold increase in the level of angiotensin II at the time of reaching Cmax of the drug in plasma; some patients showed an even greater increase in the concentration of losartan, especially with a short duration of treatment (2 weeks). In the course of treatment, antihypertensive activity and a decrease in plasma aldosterone concentration were manifested after 2 and 6 weeks of therapy, which indicates an effective blockade of angiotensin II receptors. However, after withdrawal of losartan, plasma renin activity and angiotensin II level decreased after 3 days to baseline values observed before the drug was taken.A study comparing the effects of 20 mg and 100 mg of losartan with the effects of an ACE inhibitor on the reaction to angiotensin I, angiotensin II and bradykinin, showed that losartan blocks the effects of angiotensin I and angiotensin II without affecting the effects of bradykinin due to specific mechanism of action of losartan. In contrast, ACE inhibitors block the response of angiotensin I and increase the severity of the response to bradykinin, without affecting the intensity of the response to angiotensin II, which demonstrates the pharmacodynamic difference between losartan and ACE inhibitors. with increasing doses of the drug. Since losartan and its active metabolite are antagonists of angiotensin II receptors, they both cause an antihypertensive effect. In a study with a single dose of 100 mg of losartan, healthy volunteers (men) use the drug as patients who follow a diet with a limited content of table salt, and patients who consume a lot of boiled salt, did not affect the glomerular filtration rate, effective renal plasma flow and filtration fraction. Losartan has a natriuretic effect, which was more pronounced on a low-salt diet and, apparently, was not associated with the suppression of early sodium reabsorption in the proximal renal tubules. Losartan also caused a transient increase in uric acid excretion by the kidneys. In patients with hypertension, proteinuria (more than 2 g / 24 h) who are not suffering from diabetes and taking losartan for 8 weeks at a dose of 50 mg to 100 mg, there was a significant decrease in proteinuria by 42%, fractional excretion of albumin and IgG. In these patients, losartan stabilized the glomerular filtration rate and reduced the filtration fraction. In postmenopausal women with arterial hypertension who took losartan potassium at a dose of 50 mg / day for 4 weeks, no effect of the therapy on the renal and systemic levels of prostaglandins was found. It affects the autonomic reflexes and does not have a long-lasting effect on the level of norepinephrine in the blood plasma. In patients with arterial hypertension, losartan in doses up to 150 mg / day does not cause clinically significant Changes in the level of triglycerides on an empty stomach, total cholesterol (Hc) and HD-HDL.In the same doses, losartan has no effect on fasting blood glucose. In general, losartan caused a decrease in the serum uric acid level (usually less than 0.4 mg / dL), which was maintained during long-term therapy. In controlled clinical trials in which patients with arterial hypertension were included, there were no cases of drug withdrawal due to an increase in serum creatinine or potassium levels.
Pharmacokinetics
Absorption When ingested, losartan is well absorbed from the gastrointestinal tract and undergoes a first pass effect through the liver, resulting in the formation of an active carboxylated metabolite and inactive metabolites. Systemic bioavailability of losartan is approximately 33%. The average Cmax of losartan and its active metabolite are reached after 1 h and after 3-4 h, respectively. When taking losartan during normal eating, there was no clinically significant effect on the plasma concentration profile of losartan. DistributionLosartan and its active metabolite bind to plasma proteins (mainly albumin) by more than 99%. Vd losartan is 34 liters. Studies in rats have shown that losartan hardly penetrates through the BBB. Metabolism Approximately 14% of the dose of losartan (when ingested and / or injected) turns into its active metabolite. After ingestion or in / in the introduction of losartan, labeled 14C, the radioactivity of circulating blood plasma is primarily associated with the presence of losartan and its active metabolite. Biologically inactive metabolites are also formed, incl. two primary hydroxylation of the butyl side chain, and one minor, N-2-tetrazole-glucuronide. Withdrawal The plasma clearance of losartan and its active metabolite is about 600 ml / min and 50 ml / min, respectively. The renal clearance of losartan and its active metabolite is approximately 74 ml / min and 26 ml / min, respectively. When losartan is taken orally, about 4% of the dose is excreted unchanged in the urine and about 6% of the dose is excreted in the urine as an active metabolite. Losartan and its active metabolite have linear pharmacokinetics when taken orally with potassium losartan in doses up to 200 mg. After ingestion, plasma concentrations of losartan and its active metabolite are reduced polyexponentially with a final T1 / 2 of approximately 2 and 6-9 hours, respectively.When taking the drug in a dose of 100 mg 1 time / day, neither losartan nor its active metabolite accumulates significantly in blood plasma. Excretion of losartan and its metabolites occurs with bile and urine. After ingestion of losartan, labeled with 14C, about 35% of the radioactive label is found in the urine and 58% in the feces. After iv administration of losartan labeled with 14C, approximately 43% of the radioactive label is detected in the urine and 50% in the feces. Pharmacokinetics in special patient groups in younger patients with arterial hypertension. Plasma concentrations of losartan were 2 times higher in women with arterial hypertension compared with men suffering from arterial hypertension. The concentrations of the active metabolite in men and women did not differ. This clear pharmacokinetic difference has no clinical significance. When losartan was taken orally, patients with cirrhosis of alcoholic origin had mild and moderate severity of losartan and its active metabolite in plasma were 5 and 1.7 times (respectively) higher than in young healthy volunteers male. The concentration of losartan in the blood plasma of patients with creatinine clearance above 10 ml / min did not differ from those in patients with normal renal function. When comparing the value of AUC in patients on hemodialysis, was about 2 times greater than in patients with normal renal function. Plasma concentrations of the active metabolite do not change in patients with impaired renal function or in patients on hemodialysis. Losartan and its active metabolite cannot be removed by hemodialysis.
Indications
Arterial hypertension - reducing the risk of associated cardiovascular morbidity and mortality in patients with arterial hypertension and left ventricular hypertrophy, manifested by a decrease in the cumulative incidence of cardiovascular mortality, stroke and myocardial infarction; protection of the kidneys in patients with type 2 diabetes mellitus with proteinuria - slowing the progression of renal failure, manifested by a decrease in the frequency of hypercreatininemia, the incidence of end-stage CRF requiring hemodes analysis or kidney transplantation, mortality rates, as well as reduction of proteinuria; - chronic heart failure with the failure of treatment with ACE inhibitors.
Contraindications
Pregnancy, hypersensitivity to the drug.
Precautionary measures
Do not exceed the recommended dose. With caution, the drug should be prescribed to patients with reduced BCC, for example, receiving treatment with diuretics in high doses (symptomatic hypotension may occur), as well as patients with a history of liver and kidney diseases.
Use during pregnancy and lactation
The use of Cozaar during pregnancy is contraindicated. The use of drugs acting on the renin-angiotensive system in the second and third trimesters of pregnancy can cause serious damage or even death of the developing fetus, therefore, when establishing pregnancy, Cozaar should be stopped immediately. In the fetus, renal perfusion, depending on the development of the renin-angiotensin system, appears in the second trimester; the risk to the fetus increases if Cozaar is prescribed in the II or III trimester of pregnancy. It is not recommended to take Cozaar during lactation. Experience of losartan use during breastfeeding is not, and it is not known whether losartan is excreted in breast milk. Since many drugs are excreted in breast milk and may have an adverse effect on infants, taking into account the need for a mother's drug, a decision should be made to discontinue breastfeeding or to discontinue the drug.
Dosage and administration
Cozaar is taken orally, regardless of the meal, it can be used both as monotherapy and in combination with other antihypertensive agents. In hypertension, the standard initial and maintenance dose for most patients is 50 mg 1 time / day. The maximum antihypertensive effect is achieved 3-6 weeks after the start of therapy. In some patients, to achieve a greater effect, the dose may be increased to 100 mg 1 time / day. In patients with reduced BCC (for example, when taking diuretics in high doses), the initial dose of the drug should be reduced to 25 mg 1 time / day. There is no need for selection of the initial dose in elderly people and patients with renal insufficiency, including patients on dialysis. Patients with a history of liver disease are recommended to prescribe the drug in lower doses. To reduce the risk of associated cardiovascular morbidity and in patients with arterial hypertension and left ventricular hypertrophy, the standard initial dose of the drug is 50 mg 1 time / day.In the future, it is recommended to add hydrochlorothiazide in low doses or increase the dose of Cozaar to 100 mg 1 time / day, taking into account the degree of reduction in blood pressure. To protect kidney function in patients with type 2 diabetes and proteinuria, the standard initial dose of the drug is 50 mg 1 time / day. In the future, it is recommended to increase the dose of Cozaar to 100 mg 1 time / day, taking into account the degree of decrease in blood pressure. Cozaar can be prescribed together with other antihypertensive drugs (diuretics, calcium channel blockers, alpha and beta blockers, centrally acting drugs), insulin and other hypoglycemic agents (sulfonylurea derivatives, glitazones and glucosidase inhibitors). In chronic heart failure, initial dosage is 12.5 mg 1 time / day. Typically, the dose is titrated at weekly intervals (ie, 12.5 mg / day, 25 mg / day, 50 mg / day) to the usual maintenance dose of 50 mg 1 time / day, depending on the individual tolerance.
Side effects
On the part of the digestive system: hepatitis (rare), abnormal liver function. On the part of the hematopoietic system: anemia, thrombocytopenia. On the part of the musculoskeletal system: myalgia; arthralgia; rarely - rhabdomyolysis. For the central nervous system: migraine, rarely - dysgeusia. For the respiratory system: cough. Dermatological reactions: urticaria, pruritus, skin flushing. For laboratory parameters: during controlled clinical trials in patients with essential arterial hypertension, clinically significant changes standard laboratory parameters have rarely been associated with cozaar administration. Hyperkalemia was observed in 1.5% of patients (serum potassium> 5.5 mEq / l). In a study on patients with type 2 diabetes mellitus with proteinuria, hyperkalemia developed in 9.9% of patients treated with Cozaar and in 3.4% of patients treated with placebo. Increased ALT levels were rarely observed and usually returned to normal after discontinuation of therapy. In general, Cozaar is well tolerated, side effects are mild and transient, and do not require discontinuation of the drug. The cumulative incidence of Kozar's side effects is comparable to that given with placebo.
Overdose
Overdose information is limited. The most likely symptoms of overdose: marked reduction in blood pressure and tachycardia; bradycardia may occur due to parasympathetic stimulation. Treatment: symptomatic therapy. Losartan and its active metabolite are not removed from the bloodstream during hemodialysis.
Interaction with other drugs
No clinically significant drug interactions with drugs such as hydrochlorothiazide, digoxin, warfarin, cimetidine, phenobarbital, ketoconazole and erythromycin were noted. Rifampin and fluconazole reduce the level of the active metabolite. The clinical significance of these interactions has not been studied. As with other agents blocking the formation of angiotensin II and its effects, the concomitant use of potassium-saving diuretics (spironolactone, triamterene, amiloride), potassium supplements and salts containing potassium can lead to an increase in serum potassium blood. As with the use of other agents that affect the excretion of sodium, treatment with losartan may be accompanied by a decrease in excretion and an increase in the serum concentration of lithium; With serum lithium preparations, its serum concentration should be monitored. The NSA, including selective COX-2 inhibitors, can reduce the effect of diuretics and other antihypertensive drugs. Therefore, the hypotensive effect of angiotensin II receptor antagonists may be weakened by simultaneous use of NSAIDs, including selective COX-2 inhibitors. In some patients with impaired renal function who have been treated with NSAIDs, including selective COX-2 inhibitors, simultaneous administration of angiotensin II receptor antagonists further deterioration of renal function. This effect is usually reversible. Fluconazole, an inhibitor of cytochrome P450 isoenzyme 2C9, reduces plasma concentrations of the active metabolite and increases losartan concentrations, however, the pharmacodynamic significance of this phenomenon has not been established. It has been shown that individuals who do not metabolize losartan to the active metabolite have a very rare and specific defect of the isoenzyme 2C9 cytochrome P450.
special instructions
Perhaps the manifestation of this symptom of hypersensitivity as angioedema. Patients with reduced BCC (for example, receiving treatment with large doses of diuretics) may experience symptomatic arterial hypotension. Correction of such conditions should be carried out before prescribing Cozaar or starting treatment with a lower dose. Violation of water and electrolyte balance is typical for patients with renal insufficiency with or without diabetes, therefore, in the appointment of the drug in this category of patients should be especially careful.In clinical trials involving patients with type 2 diabetes mellitus with proteinuria, the number of cases of hyperkalemia was higher in the Cozaar group than in the placebo group. Several patients had to discontinue therapy due to hyperkalemia. Patients should not take potassium or potassium containing salt substitutes during treatment with Cozaar without prior consultation with the physician. Pharmacokinetic studies indicate that plasma levels of losartan in cirrhosis liver significantly increases, so patients with liver disease in the history should prescribe a drug at a lower dose. As a result of inhibition of rhenium n-angiotensin system in some susceptible patients showed changes in renal function, including renal failure; these changes may disappear after cessation of therapy. Some drugs that affect the renin-angiotensin system may increase the level of blood urea and serum creatinine in patients with bilateral renal artery stenosis or single kidney artery stenosis. Reported the occurrence of similar effects when taking Cozaar; Changes in renal function may disappear when therapy is discontinued. Patients with renin-angiotensin-aldosterone system-dependent kidney function (ie, severe chronic heart failure) are treated with ACE inhibitors in some cases with oliguria and acute renal failure (rare), and / or fatal conditions. Similar outcomes were reported in the treatment of this category of patients with Kozaar. Clinical studies did not reveal any particulars regarding the safety and efficacy of losartan in elderly patients. The use of pediatrics The safety and efficacy of the drug in children under 18 have not been established.