Cozaar, pills 50mg, 14pcs

Composition

Active ingredient:

Losartan potassium 50 mg

Pharmacological action

Kozaar is a specific oral angiotensin II (AT1 type) receptor antagonist. Angiotensin II selectively binds to AT1 receptors found in many tissues (vascular smooth muscle, adrenal glands, kidneys, and heart) and performs several important biological functions, including vasoconstriction and aldosterone release. Angiotensin II also stimulates smooth muscle cell proliferation.

Losartan and its pharmacologically active metabolite (E 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 selectively binds to AT1 receptors and does not bind or block the receptors of other hormones and ion channels that play an important role in regulating the function of the cardiovascular system. In addition, losartan does not inhibit ACE, which is responsible for the breakdown of bradykinin. Therefore, effects that are not directly related to AT1-receptor blockade, in particular, increased effects associated with bradykinin exposure or the development of edema (losartan – 1.7%, placebo – 1.9%), are not related to the action of losartan.

Long-term (6-week) treatment of patients with arterial hypertension with losartan at a dose of 100 mg / day showed a 2-3-fold increase in the level of angiotensin II at the time of reaching Cmax of the drug in blood plasma; in some patients, an even greater increase in the concentration of losartan was observed, especially with a short duration of treatment (2 weeks). During treatment, antihypertensive activity and a decrease in plasma aldosterone concentration were observed after 2 and 6 weeks of therapy, which indicates an effective blockade of angiotensin II receptors. However, after losartan was discontinued, plasma renin activity and angiotensin II levels decreased after 3 days to the initial values observed before starting the drug.

Since losartan is a specific angiotensin II AT1 receptor antagonist, it does not inhibit ACE kinase II, an enzyme that inactivates bradykinin. A study comparing the effects of 20 mg and 100 mg losartan with the effects of an ACE inhibitor on the response 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 the specific mechanism of action of losartan. In contrast, ACE inhibitors block the angiotensin I response and increase the severity of the bradykinin response, without affecting the severity of the angiotensin II response, which demonstrates the pharmacodynamic difference between losartan and ACE inhibitors.

The plasma concentrations of losartan and its active metabolite, as well as the antihypertensive effect of losartan, increase with increasing dose. Since losartan and its active metabolite are angiotensin II receptor antagonists, they both cause an antihypertensive effect.

In a study with a single dose of 100 mg of losartan in healthy volunteers (men), the use of the drug in both patients following a diet with a limited amount of table salt and patients consuming a lot of table salt did not affect the glomerular filtration rate, effective renal plasma flow and filtration fraction. Losartan has a natriuretic effect, which was more pronounced with a low-salt diet and, apparently, was not associated with 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 arterial hypertension, proteinuria (more than 2 g/24 h), not suffering from diabetes mellitus 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. during 4 weeks, there was no effect of therapy on renal and systemic prostaglandin levels.

Losartan does not affect autonomic reflexes and does not have a long-term effect on the level of norepinephrine in blood plasma.

In patients with arterial hypertension, losartan in doses up to 150 mg / day. It does not cause clinically significant changes in the level of fasting triglycerides, total cholesterol (Ch) and HDL-C. At the same doses, losartan has no effect on fasting blood glucose levels.

In general, losartan caused a decrease in serum uric acid levels (usually less than 0.4 mg / dl), which persisted during long-term therapy. In controlled clinical trials that included patients with arterial hypertension, there were no cases of drug withdrawal due to an increase in serum creatinine or potassium levels.

Pharmacokinetics

Suction

When taken orally, 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. The systemic bioavailability of losartan is approximately 33%. The average Cmax of losartan and its active metabolite is reached after 1 h and after 3-4 h, respectively. When losartan was taken during a normal meal, no clinically significant effect on the plasma losartan concentration profile was detected.

Distribution

Losartan and its active metabolite bind to plasma proteins (mainly albumin) by more than 99%. The Vd of losartan is 34 l. Studies in rats have shown that losartan practically does not penetrate the BBB.

Metabolism

Approximately 14% of the dose of losartan (when taken orally and administered intravenously) is converted to its active metabolite. After oral or intravenous use of 14C-labeled losartan, radioactivity in the circulating blood plasma is primarily associated with the presence of losartan and its active metabolite. Biologically inactive metabolites are also formed, including two main ones formed as a result of hydroxylation of the butyl side chain, and one minor one-N-2-tetrazole-glucuronide.

Deduction

The plasma clearance of losartan and its active metabolite is approximately 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 with oral use of losartan potassium in doses up to 200 mg.

After oral use, plasma concentrations of losartan and its active metabolite decrease polyexponentially with a final T1/2 of approximately 2 and 6-9 hours, respectively. When taking the drug at a dose of 100 mg 1 time/day. there is no significant accumulation in the blood plasma of either losartan or its active metabolite.

The elimination of losartan and its metabolites occurs in the bile and urine. After oral use of losartan labeled with 14C, about 35% of the radioactive label is detected in the urine and 58% in the feces. After intravenous use of 14C-labeled losartan, approximately 43% of the radioactive label is detected in the urine and 50% in the feces.

Pharmacokinetics in special patient groups

The plasma concentrations of losartan and its active metabolite in elderly patients with arterial hypertension do not significantly differ from those in younger patients with arterial hypertension.

Plasma concentrations of losartan were 2 times higher in women with arterial hypertension compared to men with arterial hypertension. Concentrations of the active metabolite did not differ between men and women. This apparent pharmacokinetic difference is not clinically relevant.

When taking losartan orally in patients with alcoholic cirrhosis of mild and moderate severity, the concentrations of losartan and its active metabolite in blood plasma were 5 and 1.7 times higher (respectively) than in young healthy male volunteers.

Plasma concentrations of losartan in patients with creatinine clearance above 10 ml/min did not differ from those in patients with normal renal function. When compared, the AUC value in patients undergoing hemodialysis was approximately 2 times higher 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 undergoing hemodialysis. Losartan and its active metabolite cannot be removed by hemodialysis.

Indications

• Arterial hypertension;

• Heart failure.

Contraindications

Hypersensitivity to the drug Kozaar.

Side effects

From the cardiovascular system: in controlled clinical trials, dizziness was observed more often than with placebo; orthostatic reactions were also observed, depending on the dose of the drug. Laboratory parameters: in controlled clinical trials, significant changes in standard laboratory parameters were rarely associated with the use of Kozaar. Hyperkalemia (serum potassium greater than 5.5 meq/l) was observed in 1.5% of patients, with elevated ALT levels. Allergic reactions: angioedema (including swelling of the face, lips, pharynx and / or tongue), urticaria. From the digestive system: diarrhea. From the central nervous system: migraine. Dermatological reactions: pruritus. Other: impaired renal function, myalgia. In most cases, Kozaar is well tolerated, side effects are mild and transient and do not require discontinuation of the drug. The overall frequency of side effects of Kozaar is comparable to placebo.

Interaction

There was no clinically significant interaction of Kozaar with other drugs. Pharmacokinetic clinical trials have used hydrochlorothiazide, digoxin, warfarin, cimetidine, phenobarbital, and ketoconazole.

How to take, course of use and dosage

With arterial hypertension, the average daily dose is 50 mg.

The frequency of reception is 1 time/day.

The maximum hypotensive effect develops in 3-6 weeks after the start of taking the drug.

If necessary, the daily dose of the drug can be increased to 100 mg.

Overdose

Information about overdose is limited.

The most likely symptoms of overdose are a marked decrease 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.

Special instructions

Patients with dehydration (for example, those treated with high-dose diuretics) may experience symptomatic hypotension at the beginning of treatment with Kozaar. It is necessary to correct dehydration before prescribing Kozaar or start treatment with a lower dose of the drug. Pharmacological data indicate that the plasma concentration of losartan in patients with cirrhosis of the liver is significantly increased, so patients with a history of liver disease should use the drug at a lower dose. Some drugs that affect the renin-angiotensin system may increase blood urea and serum creatinine levels in patients with bilateral renal stenosis or stenosis of the artery of a single kidney. Angiotensin II receptor antagonists may potentially have a similar effect, although such data are not currently available. Clinical studies have not revealed any differences in the safety and efficacy of Kozaar in elderly patients.

Form of production

Pills.

Storage conditions

The drug should be stored in a tightly closed package, protected from light at a temperature not exceeding 30°C.

Active ingredient

Losartan

Conditions of release from pharmacies

By prescription

Dosage form

Tablets