Lozartan-Richter - instructions for use, dose, side effects, contraindications

Excipients: silicon dioxide colloid - 0.75 mg, magnesium stearate - 1.50 mg, croscarmellose sodium - 3.00 mg, pregelatinized starch 20.20 mg, microcrystalline cellulose 74.55 mg

Composition of the film shell: DIARE 33G28523 white (triacetin - 0.30 mg, macrogol - 0.40 mg, lactose monohydrate - 1.05 mg, titanium dioxide E171, C.I. 77891 - 1.25 mg, hypromellose - 2.00 mg)

Tablets coated with a film coating, 100 mg:

Active substance: Losartan potassium 100 mg;

Excipients: silicon dioxide colloid - 1,50 mg, magnesium stearate - 3,00 mg, croscarmellose sodium - 6,00 mg, pregelatinized starch - 40,40 mg, microcrystalline cellulose - 149.10 mg

Composition of the film shell: DIARE 33G28523 white (triacetin 0.60 mg, macrogol 0.80 mg, lactose monohydrate 2.10 mg, titanium dioxide E171, C L. 77891 2.50 mg, hypromellose 4.00 mg)

Description:

Tablets 50 mg:

Round, biconvex tablets covered with a film shell, white or almost white, on one side - risk, on the other - engraving "50".

Tablets 100 mg:

Oval, biconvex tablets covered with a film shell, white or almost white, on one side - engraving "100", the other side - smooth.

Pharmacotherapeutic group:Angiotensin II receptor antagonist

ATX: & nbsp

C.09.C.A.01 Losartan

C.09.C.A Angiotensin II antagonists

Pharmacodynamics:

Losartan is a specific angiotensin II antagonist (type AT₁) receptors. Angiotensin II selectively binds to AT₁ receptors found in many tissues (in smooth muscle tissues of blood vessels, in the adrenal gland, kidneys and heart) and causes important biological effects, including vasoconstriction and aldosterone release. proliferation of smooth muscles.

Research in vitro and in vivo proved that losartan and its pharmacologically active metabolite block all physiologically important effects of angiotensin II, regardless of the source or the route of its synthesis.

Does not inhibit kinase II - an enzyme that destroys bradykinin. Reduces the overall peripheral vascular resistance (OPSS). concentration in the blood of norepinephrine and aldosterone. arterial pressure (BP), pressure in the "small" circle of blood circulation: reduces afterload, has a diuretic effect, prevents the development of myocardial hypertrophy, increases exercise tolerance in patients with chronic heart failure (CHF).

After a single oral intake, the hypotensive effect (systolic and diastolic blood pressure decreases) reaches a maximum after 6 hours, then gradually decreases within 24 hours.

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

Losartan does not inhibit angiotensin-converting enzyme (ACE) and. accordingly, does not prevent the destruction of bradykinin, therefore, Losartan has no side effects, indirectly associated with bradykinin (eg, angioedema).

In patients with arterial hypertension without concomitant diabetes mellitus with proteinuria (more than 2 g / day), the use of the drug significantly reduces proteinuria,excretion of albumin and immunoglobulins G.

Lozartan stabilizes the level of urea in the blood plasma. Does not affect vegetative reflexes. Losartan in a dose up to 150 mg once a day does not affect the level of triglycerides, total cholesterol and high-density lipoprotein cholesterol (HDL) in the blood serum in patients with hypertension. At the same dose losartan does not affect the fasting blood glucose level.

Pharmacokinetics:

Suction

Ingestion losartan it is well absorbed, and at the same time is metabolized at the "first passage" through the liver by carboxylation with the participation of the isoenzyme CYP2C9 cytochrome P450 with the formation of an active (10-40 times) metabolite. Systemic bioavailability of losartan is about 33%. The maximum concentration of losartan after ingestion in the blood serum is reached after 1-1.5 hours, its active metabolite - after 3-4 hours. Eating does not affect the bioavailability of losartan.

Distribution

92% losartan and 99% of its active metabolite binds to blood plasma proteins, mainly with albumins. The volume of distribution of losartan is 34 liters. Losartan practically does not penetrate the blood-brain barrier.

Metabolism

Approximately 14% of losartan administered to the patient inside is converted to an active metabolite. A small amount (about 1%) of losartan forms the minimum amount of active metabolite.

Excretion

The plasma clearance of losartan is 600 ml / min, and the active metabolite is 50 ml / min. The renal clearance of losartan and its active metabolite is 74 md / min and 26 ml / min, respectively. Losartan and its active metabolite is characterized by linear pharmacokinetics when administered in doses up to 200 mg.

After ingestion, the plasma concentrations of losartan and its active metabolite decrease polyexponentially with a terminal half-life of losartan about 2 hours, and the active metabolite - about 6-9 hours. When taking the drug at a dose of 100 mg per day, nor losartan, nor an active metabolite significantly cumulate in blood plasma.

Losartan and its metabolites are excreted through the intestine and the kidneys. The kidneys excrete 35% (of which 4% are unchanged and 6% in the form of an active metabolite), the rest (60%) through the intestine.

In healthy volunteers, after oral administration ¹⁴With the isotope of labeled losartan, about 35% of the radioactive label is found in urine and 58% in feces.

Pharmacokinetics in specific patient groups

Patients with alcoholic liver cirrhosis mild and moderate severity, the concentration of losartan was 5 times, and the active metabolite was 1.7 times higher than in healthy male volunteers.

When creatinine clearance (CK) is above 10 ml / min the concentration of losartan in the blood plasma does not differ from that in normal kidney function. In patients who need hemodialysis, the value of the area under the "concentration-time" curve (AUC) 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.

Concentrations of losartan and its active metabolite in blood plasma in older men with arterial hypertension do not differ significantly from the values of these parameters in young men with arterial hypertension.

Values of plasma concentrations of losartan among women with arterial hypertension are 2 times higher than the corresponding values in men suffering from hypertension. The concentrations of the active metabolite in men and women do not differ. This pharmacokinetic difference is not clinically relevant.

Indications:

Arterial hypertension.

Chronic heart failure (with ineffective therapy with ACE inhibitors).

Diabetes mellitus type 2 with proteinuria (reduced risk of hypercreatininemia and proteinuria).

Reducing the risk of developing cardiovascular disease and mortality in patients with hypertension and left ventricular hypertrophy.

Contraindications:

Hypersensitivity to the active ingredient or to any of the auxiliary components of the drug, pregnancy, lactation, age under 18 (efficacy and safety not established); lactose intolerance, galactosemia or the syndrome of impaired glucose / galactose absorption.

Carefully:Arterial hypotension, disturbance of water-electrolyte balance, decrease in the volume of circulating blood, hepatic and / or renal failure (including bilateral stenosis of the renal arteries or stenosis of the artery of a single kidney).

Pregnancy and lactation:

Data on the use of losartan during pregnancy no. Renal perfusion of the fetus, which depends on the development of the renin-angiotensin system, begins to function in the third trimester of pregnancy.The risk to the fetus increases with the use of losartan in the second and third trimesters. When pregnancy is established, losartan should be discontinued immediately.

Lactation period

There is no data on the isolation of losartan in breast milk. Therefore, the question of stopping breastfeeding or abolishing losartan therapy should be addressed, given its importance to the mother.

Dosing and Administration:

Inside, 1 time per day, regardless of food intake.

Arterial hypertension

In most cases, the initial and maintenance dose is 50 mg I once a 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 per day (in two or one at a time).

Against the background of taking large doses of diuretics, it is recommended to start Lozartan-Richter with 25 mg (1/2 tablets 50 mg) per day in one session.

It is not necessary to adjust the dose to 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 (with ineffective therapy with ACE inhibitors)

The initial dose of the drug Lozartan-Richter is 50 mg once a day in a single dose. In the future, you can add hydrochlorothiazide in low doses and / or increased dose of the drug Lozartan-Richter to 100 mg per day.

Kidney protection in patients with type 2 diabetes mellitus with proteinuria

The initial dose of the drug Lozartan-Richter is 50 mg once a day in a single dose. In the course of treatment, depending on the indices of blood pressure, it is possible to increase the daily dose of the drug to 100 mg in one or two doses.

Chronic heart failure

For the treatment of chronic heart failure, the initial dose of the drug is 12.5 mg (you can use losartan in another dosage form: tablets of 12.5 mg) at one time.

To achieve the usual maintenance dose of 50 mg per day, the dose of Lozartan-Richter should be increased gradually, at intervals of one week (for example, 12.5 mg, 25 mg, 50 mg once daily). Lozartan-Richter is usually prescribed in combination with diuretics and cardiac glycosides.

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

1 a week: from 1 to 7 days - 1 tablet 12.5 mg once a day.

2 a week: from 8 to 14 days - 1/2 tablet 50 mg once a day.

3 a week: from 15 to 21 days - 1 tablet 50 mg once a day.

4 a week: from 22 to 28 days - 1 tablet 50 mg once a day.

Side effects:

The side effects of losartan are usually transient and do not require withdrawal of the drug.

When using losartan for the treatment of essential hypertension in controlled studies, among all the side effects, only the incidence of dizziness differed from placebo by more than 1% (4.1% against 2.4%).

The dose-dependent orthostatic effect characteristic of antihypertensive agents when using losartan was noted in less than 1% patients.

Side effects observed with the use of the drug are classified into categories according to the frequency of their occurrence: very often ≥ 1/10: often> 1/100, ≤ 1/10: sometimes ≥ 1/1000, ≤ 1/100; rarely ≥ 1/10000, ≤ 1/1000; very rarely ≤ 1/10000, including individual messages.

Side effects, occurring with a frequency of more than 1%:

	Losartan (n=2085)	Placebo (n=535)
General symptoms
Asthenia / fatigue	3,8	3,9
Chest pain	1,1	2,6
Peripheral edema	1,7	1,9
The cardiovascular system
Palpitation	1,0	0,4
Tachycardia	1,0	1,7
Digestive system
Abdominal pain	1,7	1,7
Diarrhea	1,9	1,9
Dyspeptic phenomena	1,1	1,5
Nausea	1,8	2,8
Musculoskeletal system
Backache	1,6	1,1
Muscle Cramps	1,0	1,1
Neurology/psychiatry
Dizziness	4,1	2,4
Headache	14,1	17,2
Insomnia	1,1	0,7
Respiratory system
Cough	3,1	2,6
Nasal congestion	1,3	1,1
Pharyngitis	1,5	2,6
Sinusitis	1,0	1,3
Upper respiratory tract infections	6,5	5,6

Side effects, occurring with a frequency of less than 1%:

From the side of the cardiovascular system: Orthostatic hypotension (dose-dependent), epistaxis, palpitations, tachy- and bradycardia, arrhythmias, angina pectoris, vasculitis.

From the digestive system: 1% and more - nausea, diarrhea, dyspeptic phenomena, abdominal pain; less than 1% - decreased appetite, dry mouth. toothache, vomiting, flatulence, gastritis, constipation, hepatitis, a violation of liver function.

From the skin: less than 1% - dry skin, erythema, photosensitivity, increased sweating, alopecia.

Allergic reactions: less than 1% - urticaria, rash, itching, angioedema, (including swelling of the larynx and tongue, causing airway obstruction and / or swelling of the face, lips, pharynx). In some patients, there was an indication in the anamnesis of the transferred angioedema, when taking other medications, including ACE inhibitors.

On the part of the blood system: infrequently, anemia (a slight decrease in the concentration of hemoglobin and hematocrit, an average of 0.11% and 0.09% volume, respectively, rarely having clinical significance), thrombocytopenia. eosinophilia, purpura Shenlaine-Genocha.

From the side of the musculoskeletal system: 1% or more - cramps, myalgia, back pain, chest, legs; less than 1% - arthralgia, arthritis, pain in the shoulder, knee, fibromyalgia.

From the central nervous system and sense organs: 1% and more - dizziness, asthenia, headache, fatigue, insomnia; less 1% - anxiety, sleep disturbance, drowsiness, memory disorders, peripheral neuropathy, paresthesia, hypesthesia, tremor, ataxia, depression, syncope, ringing in the ears, taste disorder, visual impairment, conjunctivitis, migraine

From the respiratory system: 1% and more - nasal congestion, cough, upper respiratory tract infections, pharyngitis, dyspnoea, bronchitis, edema of the nasal mucosa.

From the genitourinary system: less than 1% - mandatory urination, urinary tract infections, impaired renal function, weakening of libido, decreased potency.

Laboratory indicators: often: hyperkalemia (the level of potassium in the blood plasma is more than 5.5 mmol / l); infrequently: increased levels of urea and residual nitrogen or creatinine in serum; very rarely: a moderate increase in the activity of "liver" transaminases: aspartate aminotransferase (ACT) and alanine aminotransferase (ALT), hyperbilirubinemia.

Other: gout.

Overdose:

Symptoms: marked decrease in blood pressure, tachycardia; As a result of parasympathetic (vagal) stimulation, a bradycardia can develop.

Treatment: forced diuresis, symptomatic therapy. Hemodialysis is ineffective.

Interaction:

There were no pharmacokinetic interactions of losartan with hydrochlorothiazide, digoxin, warfarin, cimetidine, phenobarbital, ketoconazole and erythromycin.

Reportedly rifampicin and fluconazole reduce the level of active metabolite in the blood plasma. The clinical significance of these interactions is still unknown.

As with the use of other agents that inhibit the enzyme angiotensin II or its effect, the combined use of losartan with potassium-sparing diuretics (for example, spironolactone, triamterene, amiloride), preparations of potassium and salts containing potassium, increases the risk of hyperkalemia.

Non-steroidal anti-inflammatory drugs (NSAIDs), including selective inhibitors of cyclooxygenase-2 (COX-2), acetylsalicylic acid in a dose above 3 g per day can reduce the effectiveness of angiotensin II receptor antagonists. The combined use of angiotensin II receptor antagonists with NSAIDs, including selective COX-2 inhibitors, especially in the presence of reduced renal function, can lead to impaired renal function, including acute renal failure and increased potassium levels in the blood plasma. This effect is usually reversible.

With the combined use of angiotensin II receptor antagonists and lithium, an increase in the concentration of lithium in blood plasma is possible. Considering this, it is necessary to weigh the benefit and risk of joint use of losartan with lithium salts. In case you need to use drugs together, you should regularly monitor the level of lithium in the blood plasma.

The combined use of losartan with diuretics has an additive effect.

Strengthens (mutually) the effect of other antihypertensive drugs (diuretics, beta-blockers,pathology).

Special instructions:

Hypersensitivity reactions

There may be an angioedema.

Arterial hypotension and disturbance of water-electrolyte balance

In the presence of hypovolemia (for example, when therapy with large doses of diuretics), symptomatic arterial hypotension may develop. This condition must be corrected before starting a course of therapy with Lozartan-Richter or starting therapy with a lower dose.

With kidney disease with or without diabetes mellitus, violations of the water-electrolyte balance are often encountered, which must be corrected. In clinical studies conducted with patients with type 2 diabetes mellitus with proteinuria, the frequency of occurrence of hyperkalemia increased with losartan therapy, compared with placebo. However, the level of hyperkalemia only in a small number of cases required the discontinuation of the drug.

Impaired liver function

With cirrhosis of the liver, according to pharmacokinetic studies, the concentration of losartan in the blood plasma is significantly increased, so those patients who have a history of liver abnormality should be prescribed a drug in a lower dose.

Impaired renal function

The drug, due to the suppression of the renin-angiotensin system, can worsen the function of the kidneys, especially in those patients in whom the kidney functional status depends heavily on the renin-angiotensin-aldosterone system, for example, in the presence of severe CHF or previously present renal dysfunction.

Drugs that affect the renin-angiotensin-aldosterone system can increase the level of residual nitrogen or creatinine in the blood plasma in patients with bilateral renal artery stenosis or stenosis of the artery of a single kidney.

These changes in kidney function may disappear after discontinuation of therapy.

During treatment with the drug LOZARTAN-RICHTER, special attention should be paid to patients who have severe renal insufficiency and patients after kidney transplantation, as these patients noted the development of anemia.

Hyperkalemia and violation of water-salt balance. During treatment with losartan should monitor the level of potassium in the blood serum, especially in elderly patients.

Lactose intolerance

When lactose intolerance should be taken into account that the 50 mg tablet of the drug Lozartan-Richter contains 1,050 mg of lactose, 100 mg tablet - 2.10 mg of lactose.

Effect on the ability to drive transp. cf. and fur:Data on the effect of losartan on the ability to control transport or other technical means are not available.

Form release / dosage:

Tablets, film-coated, 50 mg and 100 mg.

Packaging:

10 tablets, film-coated, in a blister made of PVC / PE / PVDC and aluminum foil.

1 or 3 blisters in a cardboard box with instructions for use.

Storage conditions:

At a temperature of no higher than 25 ° C.

Keep out of the reach of children!

Shelf life:

5 years.

Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LSR-007394/09

Date of registration:18.09.2009 / 23.03.2016

Expiration Date:Unlimited

The owner of the registration certificate:GEDEON RICHTER, OJSC GEDEON RICHTER, OJSC Hungary

Manufacturer: & nbsp

GEDEON RICHTER POLAND, Co. Ltd. Poland

GEDEON RICHTER-RUS, CJSC Russia

Representation: & nbspGEDEON RICHTER OJSC GEDEON RICHTER OJSC Hungary

Information update date: & nbsp04.04.2018

Illustrated instructions

Instructions

Losartan-Richter (Losartan-Richter)