Losartan-Richter film-coated tablets 50 mg 30 pcs. in Moscow

Compound

Losartan-Richter tablet p/pl/o 50 mg N30 (Gedeon)

Losartan Richter is a specific angiotensin II receptor antagonist (type AT1). Angiotensin II selectively binds to AT1 receptors located in many tissues (vascular smooth muscle tissue, adrenal glands, kidneys and heart) and causes important biological effects, including. vasoconstriction and aldosterone release, as well as smooth muscle cell proliferation. In vitro and in vivo studies have shown that losartan and its pharmacologically active metabolite block all physiologically important effects of angiotensin II, regardless of the source or route of its synthesis. Does not inhibit kinase II, an enzyme that destroys bradykinin. Reduces total peripheral vascular resistance (TPVR), blood concentrations of norepinephrine and aldosterone, blood pressure (BP), pressure in the pulmonary circulation; reduces afterload and has a diuretic effect. Prevents the development of myocardial hypertrophy, increases exercise tolerance in patients with chronic heart failure (CHF). After a single oral dose, the hypotensive effect (decrease in systolic and diastolic blood pressure) reaches a maximum after 6 hours, then gradually decreases over 24 hours. Maximum hypotensive effect develops 3-6 weeks after the start of regular use of the drug. Losartan does not inhibit angiotensin-converting enzyme (ACE) and, accordingly, does not prevent the destruction of bradykinin, so losartan is not characterized by side effects indirectly associated with bradykinin (for example, angioedema). in patients with arterial hypertension with proteinuria (more than 2 g/day) without concomitant diabetes mellitus, the use of the drug significantly reduces proteinuria, excretion of albumin and immunoglobulins G. Losartan stabilizes the level of urea in the blood plasma. Does not affect autonomic reflexes. Losartan at a dose of up to 150 mg/day does not affect the level of triglycerides, total cholesterol and high-density lipoprotein (HDL) cholesterol in the blood serum in patients with arterial hypertension. At the same dose, losartan does not affect fasting blood glucose levels. Pharmacokinetics Absorption When taken orally, losartan is well absorbed and is metabolized during the “first pass” through the liver by carboxylation with the participation of the CYP2C9 isoenzyme of cytochrome P450 with the formation of a 10-40 times more active metabolite. Systemic bioavailability of losartan is about 33%. Cmax of losartan in blood plasma after oral administration is achieved after 1-1.5 hours, Cmax of its active metabolite - after 3-4 hours. Food intake does not affect the bioavailability of losartan. Distribution: 92% of losartan and 99% of its active metabolite are bound to blood plasma proteins, in mainly with albumins. Vd of losartan - 34 l. Losartan practically does not penetrate the blood-brain barrier. Metabolism: Approximately 14% of losartan taken orally by the patient is converted into an active metabolite. In a small number of patients (approximately 1%), a minimal amount of active metabolite is formed from losartan. Elimination: Plasma clearance of losartan is 600 ml/min, and of the active metabolite is 50 ml/min. The renal clearance of losartan and its active metabolite is 74 ml/min and 26 ml/min, respectively. Losartan and its active metabolite are characterized by linear pharmacokinetics when taken orally in doses up to 200 mg. After oral administration, plasma concentrations of losartan and its active metabolite decrease polyexponentially with a final T1/2 of losartan of about 2 hours, and of the active metabolite - about 6-9 hours. When taking the drug at a dose of 100 mg/neither losartan nor the active metabolite significantly accumulates in the blood plasma. Losartan and its metabolites are excreted from the body through the intestines and kidneys. 35% is excreted by the kidneys (of which 4% - unchanged and 6% - in the form of an active metabolite), the rest (60%) - through the intestines. In healthy volunteers, after ingestion of 14C isotope labeled losartan, the radioactive label was found in the urine in quantities about 35%, in feces - about 58%. Pharmacokinetics in special groups of patients In patients with mild to moderate alcoholic cirrhosis of the liver, the concentration of losartan was 5 times higher, and the active metabolite was 1.7 times higher than in healthy male volunteers. QC above 10 ml/min, the concentration of losartan in the blood plasma does not differ from that with normal renal function. In patients who require hemodialysis, the AUC value is approximately 2 times higher than in patients with normal renal function. Neither losartan nor its active metabolite is removed from the body by hemodialysis. Plasma concentrations of losartan and its active metabolite in the elderly men with arterial hypertension do not differ significantly from the values ​​of these parameters in young men with arterial hypertension. The values ​​of plasma concentrations of losartan in women with arterial hypertension are 2 times higher than the corresponding value in men with arterial hypertension. This pharmacokinetic difference is not clinically significant. The concentration of the active metabolite does not differ between men and women.

Directions for use and doses

Orally, 1 time per day, regardless of meals.

Arterial hypertension

In most cases, the initial and maintenance dose is 50 mg 1 time per day. The maximum antihypertensive effect is achieved after 3–6 weeks of taking the drug. If necessary, the dose of the drug can be increased to 100 mg/day (in 1–2 doses).

While taking large doses of diuretics, it is recommended to start therapy with Losartan-Richter with 25 mg (1/2 tablet of 50 mg each) per day in one dose.

No dose adjustment is required for elderly patients or patients with impaired renal function, including patients on hemodialysis.

Patients with impaired liver function should be prescribed lower doses of the drug.

Chronic heart failure (if therapy with ACE inhibitors is ineffective)

The initial dose of Losartan-Richter is 50 mg 1 time per day in one dose. In the future, hydrochlorothiazide may be added in low doses and/or the dose of Losartan-Richter may be increased to 100 mg per day.

Kidney protection in patients with type 2 diabetes mellitus with proteinuria

The initial dose of Losartan-Richter is 50 mg 1 time per day in one dose. During treatment, depending on blood pressure levels, the daily dose of the drug can be increased to 100 mg in 1–2 doses.

Chronic heart failure

For the treatment of chronic heart failure, the initial dose of the drug is 12.5 mg (losartan can be used in another dosage form - 12.5 mg tablets) in one dose.

In order to achieve the usual maintenance dose of 50 mg/day, the dose of Losartan-Richter must be increased gradually, at intervals of 1 week (for example, 12.5, 25, 50 mg once daily). Losartan-Richter is usually prescribed in combination with diuretics and cardiac glycosides.

The dose of the drug should be increased according to the following scheme:

- 1st week - from 1st to 7th day - 1 tablet. 12.5 mg 1 time per day;

- 2nd week - from the 8th to the 14th day - 1/2 tablet. 50 mg 1 time per day;

— 3rd week — from the 15th to the 21st day — 1 tablet. 50 mg 1 time per day;

— 4th week — from the 22nd to the 28th day — 1 tablet. 50 mg 1 time per day.

Losartan-Richter film-coated tablets 50 mg 30 pcs. in Moscow

The use of the drug in patients with acute myocardial infarction is not recommended due to insufficient experience in clinical use. It should also not be used to relieve a hypertensive crisis.

Hydrochlorothiazide

Renal dysfunction

In patients with impaired renal function, hydrochlorothiazide may cause azotemia. In case of renal failure, accumulation of hydrochlorothiazide is possible.

In patients with reduced renal function, periodic monitoring of CK is necessary. If renal dysfunction progresses and/or oliguria (anuria) occurs, hydrochlorothiazide should be discontinued.

Liver dysfunction

When using thiazide diuretics in patients with impaired liver function, hepatic encephalopathy may develop. In patients with severe liver failure or hepatic encephalopathy, the use of thiazides is contraindicated. In patients with mild to moderate hepatic impairment and/or progressive liver disease, hydrochlorothiazide should be used with caution, since even slight changes in fluid and electrolyte balance and serum ammonium accumulation can cause hepatic coma. If symptoms of encephalopathy occur, diuretics should be discontinued immediately.

Water-electrolyte balance and metabolic disorders

Thiazide diuretics (including hydrochlorothiazide) can cause a decrease in blood volume (hypovolemia) and disturbances in water and electrolyte balance (including hypokalemia, hyponatremia, hypochloremic alkalosis). Clinical symptoms of water-electrolyte balance disorders are dryness of the oral mucosa, thirst, weakness, lethargy, fatigue, drowsiness, anxiety, muscle pain or cramps, muscle weakness, marked decrease in blood pressure, oliguria, tachycardia, arrhythmia and gastrointestinal disorders (such such as nausea and vomiting). In patients receiving hydrochlorothiazide therapy (especially with long-term course treatment), clinical symptoms of water-electrolyte imbalance should be identified and the content of electrolytes in the blood plasma should be regularly monitored.

Sodium

All diuretics can cause hyponatremia, sometimes leading to severe complications. Hyponatremia and hypovolemia can lead to dehydration and orthostatic hypotension. A concomitant decrease in chlorine ions can lead to secondary compensatory metabolic alkalosis, but the frequency and severity of this effect are insignificant. It is recommended to determine the content of sodium ions in the blood plasma before starting treatment and regularly monitor this indicator while taking hydrochlorothiazide.

Potassium

When using thiazide and thiazide-like diuretics, there is a risk of a sharp decrease in the potassium content in the blood plasma and the development of hypokalemia (potassium content in the blood plasma less than 3.4 mmol/l). Hypokalemia increases the risk of developing heart rhythm disturbances (including severe arrhythmias) and enhances the toxic effect of cardiac glycosides. In addition, hypokalemia (as well as bradycardia) is a condition that contributes to the development of polymorphic ventricular tachycardia of the “pirouette” type, which can be fatal.

Hypokalemia poses the greatest danger to the following groups of patients: elderly people, patients simultaneously receiving therapy with antiarrhythmic and non-antiarrhythmic drugs that can cause polymorphic ventricular tachycardia of the “pirouette” type or increase the duration of the QT interval on the ECG, patients with impaired liver function, coronary artery disease, CHF . In addition, patients with an increased QT interval are at increased risk. It does not matter whether this increase is caused by congenital causes or the effect of drugs.

In all the cases described above, it is necessary to avoid the risk of developing hypokalemia and regularly monitor the potassium content in the blood plasma. The first measurement of the content of potassium ions in the blood plasma should be carried out within the first week from the start of treatment. If hypokalemia occurs, appropriate treatment should be prescribed. Hypokalemia can be corrected by using potassium-containing medications or eating foods rich in potassium (dried fruits, fruits, vegetables).

Calcium

Thiazide diuretics may reduce the excretion of calcium ions by the kidneys, leading to a slight and temporary increase in plasma calcium levels. In some patients, with long-term use of thiazide diuretics, pathological changes in the parathyroid glands were observed with hypercalcemia and hyperphosphatemia, but without the typical complications of hyperparathyroidism (nephrolithiasis, decreased bone mineral density, peptic ulcer). Severe hypercalcemia may be a manifestation of previously undiagnosed hyperparathyroidism.

Because of their effect on calcium metabolism, thiazides may interfere with laboratory parameters of parathyroid function. Thiazide diuretics (including hydrochlorothiazide) should be discontinued before testing parathyroid function.

Magnesium

Thiazides have been found to increase renal excretion of magnesium, which can lead to hypomagnesemia. The clinical significance of hypomagnesemia remains unclear.

Glucose

Treatment with thiazide diuretics may impair glucose tolerance. When using hydrochlorothiazide in patients with manifest or latent diabetes mellitus, it is necessary to regularly monitor the concentration of glucose in the blood plasma. Dosage adjustment of hypoglycemic medications may be required.

Uric acid

In patients with gout, the frequency of attacks may increase or the course of gout may worsen. Careful monitoring of patients with gout and impaired uric acid metabolism (hyperuricemia) is necessary.

Lipids

When using hydrochlorothiazide, the concentration of both cholesterol and triglycerides in the blood plasma may increase.

Acute myopia/secondary angle-closure glaucoma

Hydrochlorothiazide can cause an idiosyncratic reaction, leading to the development of acute myopia and an acute attack of secondary angle-closure glaucoma. Symptoms include: sudden loss of visual acuity or eye pain, usually occurring within hours to weeks of starting hydrochlorothiazide therapy. If left untreated, acute angle-closure glaucoma can lead to irreversible vision loss. If symptoms appear, you should stop taking hydrochlorothiazide as soon as possible. If intraocular pressure remains uncontrolled, emergency medical treatment or surgery may be required. Risk factors for the development of acute angle-closure glaucoma include a history of an allergic reaction to sulfonamides or penicillin. Immune system disorders

There are reports that thiazide diuretics (including hydrochlorothiazide) may cause exacerbation or progression of systemic lupus erythematosus, as well as lupus-like reactions.

In patients receiving thiazide diuretics, hypersensitivity reactions may occur even in the absence of a history of allergic reactions or bronchial asthma.

Photosensitivity

There is information about cases of the development of photosensitivity reactions when taking thiazide diuretics. If photosensitivity occurs while taking hydrochlorothiazide, treatment should be discontinued. If continued use of a diuretic is necessary, the skin should be protected from exposure to sunlight or artificial ultraviolet rays (UV rays).

Non-melanoma skin cancer (NMSC)

Two pharmacoepidemiological studies using data from the Danish National Cancer Registry demonstrated an association between hydrochlorothiazide use and an increased risk of NMSC—basal cell carcinoma and squamous cell carcinoma. The risk of developing NMSC increased with increasing total (cumulative) dose of hydrochlorothiazide. A possible mechanism for the development of NMSC is the photosensitizing effect of hydrochlorothiazide. Patients taking hydrochlorothiazide as monotherapy or in combination with other drugs should be aware of the risk of developing NMSC. It is recommended that such patients undergo regular skin examination to identify any new suspicious lesions as well as changes in existing skin lesions.

Any suspicious skin changes should be reported to your doctor immediately. Suspicious areas of skin should be examined by a specialist. To clarify the diagnosis, histological examination of skin biopsies may be required.

To minimize the risk of developing NMSC, patients should be advised to follow preventive measures, such as limiting exposure to sunlight and UV rays, and using appropriate protective equipment.

In patients with a history of NMSC, it is recommended to reconsider the use of hydrochlorothiazide.

Athletes

Hydrochlorothiazide may give a positive result during doping control in athletes.

Other

In patients with severe atherosclerosis of the cerebral and coronary arteries, hydrochlorothiazide should be used with extreme caution.

Thiazide diuretics can reduce the amount of iodine bound to plasma proteins without causing signs of thyroid dysfunction.

Losartan

Angioedema

Patients with a history of angioedema (of the face, lips, pharynx and/or larynx) should be closely monitored.

Arterial hypotension and hypovolemia (dehydration)

In patients with hypovolemia (dehydration) and/or reduced sodium content in the blood plasma, against the background of diuretic therapy, limited salt intake, diarrhea or vomiting, symptomatic arterial hypotension may develop, especially after taking the first dose of Lorista® N. Before using the drug, you should restore the blood volume and/or sodium content in the blood plasma.

Water-electrolyte imbalance

Fluid and electrolyte imbalances are common in patients with impaired renal function, especially in the setting of diabetes mellitus. In this regard, it is necessary to carefully monitor the potassium content in the blood plasma and CC, especially in patients with heart failure and CC 30-50 ml/min.

Concomitant use of ARA II with aliskiren and drugs containing aliskiren is contraindicated in patients with diabetes mellitus and/or with moderate or severe renal impairment (GFR less than 60 ml/min/1.73 m2 body surface area) and is not recommended in other patients . Concomitant use of ARB II with ACE inhibitors is contraindicated in patients with diabetic nephropathy and is not recommended in other patients.

Concomitant use with potassium-sparing diuretics, potassium supplements, salt substitutes containing potassium, or other drugs that can increase the level of potassium in the blood plasma (for example, heparin) is not recommended.

Liver dysfunction

The concentration of losartan in the blood plasma increases significantly in patients with liver cirrhosis, so Lorista® N should be used with caution in patients with mild or moderate liver dysfunction.

Renal dysfunction

Impaired renal function, including renal failure, may occur due to inhibition of the RAAS (especially in patients whose renal function is dependent on the RAAS, such as those with severe heart failure or a history of renal dysfunction).

Renal artery stenosis

In patients with bilateral renal artery stenosis, as well as stenosis of the artery of the only functioning kidney, drugs affecting the RAAS, including ARA II, can reversibly increase the concentrations of urea and creatinine in the blood plasma.

Losartan should be used with caution in patients with bilateral renal artery stenosis or arterial stenosis of a solitary kidney.

Kidney transplant

There is no experience with the use of Lorista® N in patients who have recently undergone kidney transplantation.

Primary hyperaldosteronism

Patients with primary hyperaldosteronism are resistant to antihypertensive drugs that affect the RAAS, therefore the use of Lorista® N is not recommended for such patients.

IHD and cerebrovascular diseases

As with the treatment of any antihypertensive drugs, a pronounced decrease in blood pressure in patients with coronary artery disease or cerebrovascular diseases can lead to the development of myocardial infarction or stroke.

Heart failure

In patients whose renal function depends on the state of the RAAS (for example, with CHF III-IV functional class according to the NYHA classification, accompanied or not accompanied by impaired renal function), therapy with drugs affecting the RAAS may be accompanied by severe arterial hypotension, oliguria and/or progressive azotemia, in rare cases - acute renal failure. It is impossible to exclude the development of these disorders due to suppression of RAAS activity while taking ARA II.

Stenosis of the aortic and/or mitral valves, HOCM

Lorista® N, like other vasodilators, should be used with caution in patients with hemodynamically significant stenosis of the aortic and/or mitral valves or with HOCM.

Ethnic characteristics

Losartan (like other drugs that affect the RAAS) has a less pronounced antihypertensive effect in patients of the Black race compared to representatives of other races, possibly due to the higher incidence of hyporeninemia in these patients with arterial hypertension.

Special information on excipients

The drug Lorista® N contains lactose, therefore the drug is contraindicated in patients with lactase deficiency, lactose intolerance, and glucose-galactose malabsorption syndrome.

Impact on driving vehicles and machinery

At the beginning of therapy, Lorista® N may cause a decrease in blood pressure, dizziness or drowsiness, thus indirectly affecting the psycho-emotional state. For safety reasons, patients should first assess their response to treatment before engaging in activities requiring increased alertness.