Instruction for use: Lorista

Dosage form: film coated tablets

Active substance: Losartanum

ATX

C09CA01 Losartan

Pharmacological group

Angiotensin II receptor antagonists (AT1 subtype)

Nosological classification (ICD-10)

I10 Essential (primary) hypertension: hypertension; Arterial hypertension; Arterial hypertension crisis course; Essential Hypertension; Essential hypertension; Essential hypertension; Essential hypertension; Essential hypertension; Primary hypertension; Arterial hypertension, complications of diabetes; The sudden increase in blood pressure; Hypertensive disorders of blood circulation; hypertensive condition; hypertensive crises; arterial Hypertension; malignant Hypertension; Hypertonic disease; hypertensive crises; accelerated hypertension; malignant hypertension; The aggravation of hypertensive disease; Transient hypertension; Isolated systolic hypertension

I15 Secondary hypertension: Arterial hypertension, complications of diabetes; hypertension; The sudden increase in blood pressure; Hypertensive disorders of blood circulation; hypertensive condition; hypertensive crises; hypertension; arterial Hypertension; malignant Hypertension; hypertensive crises; accelerated hypertension; malignant hypertension; The aggravation of hypertensive disease; Transient hypertension; hypertension; Arterial hypertension; Arterial hypertension crisis course; renovascular hypertension; Hypertension symptomatic; Renal hypertension; Renovascular hypertension; renovascular hypertension; Symptomatic hypertension

I50.0 Congestive heart failure: anasarca heart; Decompensated congestive heart failure; Congestive heart failure; Congestive heart failure with high afterload; Congestive chronic heart failure; Cardiomyopathy with severe chronic heart failure; Compensated chronic heart failure; Swelling with circulatory failure; Edema of cardiac origin; Swelling of the heart; Edematous syndrome in diseases of the heart; Edematous syndrome in congestive heart failure; Edematous syndrome in heart failure; Edematous syndrome in heart failure or liver cirrhosis; right ventricular failure; Congestive Heart Failure; Heart failure stagnant; Heart failure with low cardiac output; Heart failure is a chronic; Cardiac edema; Chronic decompensated heart failure; Chronic Congestive Heart Failure; Chronic heart failure; Change of liver function in heart failure

N08.3 Glomerular lesions in diabetes mellitus (E10-14 + with common fourth sign .2): Nephropathy diabetic; Diabetic Nephropathy; Diabetic nephropathy in the background of type 1 diabetes mellitus; Diabetic nephropathy in patients with type I diabetes; Proteinuria in patients with type 2 diabetes mellitus

N39.1 Persistent proteinuria, unspecified: Severe proteinuria; Proteinuria; Nephrotic-proteinuric syndrome

Composition

Tablets covered with a film coating.

active substance: Losartan potassium 12.5 mg; 25 mg; 100 mg

Auxiliary substances: cellactose (a mixture of lactose monohydrate and cellulose); Pregelatinized starch; corn starch; MCC; Silicon dioxide colloidal anhydrous; Magnesium stearate

Membrane film: hypromellose; talc; Propylene glycol; Dye quinoline yellow (E104) - only for tablets of 12.5 and 25 mg; Titanium dioxide (E171)

Description of dosage form

Tablets 12,5 mg: oval, slightly biconcave tablets, covered with a film membrane, from light yellow to yellow, with a bevel.

Tablets 25 mg: oval, slightly biconvex tablets, film-coated, yellow, with a risk on one side and bevel.

Tablets of 50 mg: round, slightly biconvex tablets, film-coated, white, with a risk on one side, with a bevel.

Tablets of 100 mg: oval, slightly biconvex tablets, film-coated, white.

Pharmachologic effect

Mode of action - hypotensive.

Pharmacodynamics

Losartan is a selective antagonist of angiotensin II receptor (type AT1) for oral administration, non-protein nature.

In vivo and in vitro, losartan and its biologically active carboxylic metabolite (EXP-3174) block all physiologically significant effects of angiotensin II on AT1 receptors, regardless of the route of its synthesis: leads to an increase in renin plasma activity, reduces the concentration of aldosterone in blood plasma, etc. .

Losartan indirectly causes the activation of AT2 receptors by increasing the level of angiotensin II.

Losartan does not inhibit the activity of kininase II, an enzyme that participates in the metabolism of bradykinin.

Reduces OPSS, pressure in a small circle of blood circulation; Reduces afterload, has a diuretic effect. Prevents development of myocardial hypertrophy, increases exercise tolerance in patients with chronic heart failure (CHF). The administration of losartan 1 time per day leads to a statistically significant decrease in SAD and DAD. Lozartan evenly monitors the pressure throughout the day, while the antihypertensive effect corresponds to a natural circadian rhythm. Decrease in blood pressure at the end of the dose was about 70-80% of the effect at the peak of the drug, 5-6 hours after admission. The withdrawal syndrome is not observed; Also losartan does not have a clinically significant effect on heart rate.

Losartan is effective in men and women, as well as in the elderly (over 65 years) and younger patients (under 65 years of age).

Pharmacokinetics

Losartan is well absorbed from the digestive tract. It is subject to significant metabolism during the first passage through the liver, forming an active metabolite (EXP-3174) with carboxylic acid and other inactive metabolites. Bioavailability is approximately 33%. The intake of the drug with food does not have a clinically significant effect on its serum concentrations. Tmax - 1 h after ingestion, and its active metabolite (EXP-3174) - 3-4 h.

More than 99% of losartan and EXP-3174 bind to plasma proteins, mainly albumin. Vd of losartan is 34 liters. Very poorly penetrates the BBB.

Losartan is metabolized with the formation of active (EXP-3174) metabolite (14%) and inactive, including 2 main metabolites formed by hydroxylation of the butyl group of the chain, and a less significant metabolite, N-2-tetrazole glucuronide.

The plasma clearance of losartan and its active metabolite is approximately 10 ml / s (600 ml / min) and 0.83 ml / s (50 ml / min), respectively. The renal clearance of losartan and its active metabolite is about 1.23 ml / s (74 ml / min) and 0.43 ml / s (26 ml / min). T1 / 2 losartan and the active metabolite is 2 hours and 6-9 hours, respectively. It is excreted mainly with bile - 58%, kidneys - 35%.

Indications of the drug Lorista

arterial hypertension;

A reduction in the risk of stroke in patients with hypertension and left ventricular hypertrophy;

Chronic heart failure (as part of combination therapy, with intolerance or ineffective therapy with ACE inhibitors);

Protection of kidney function in patients with type 2 diabetes mellitus with proteinuria in order to reduce proteinuria, reduce the progression of kidney damage, reduce the risk of terminal stage (prevention of dialysis, the probability of increasing serum creatinine levels) or death.

Contraindications

Increased sensitivity to losartan or other components of the drug;

Arterial hypotension;

Hyperkalemia;

dehydration;

pregnancy;

Lactation period;

Lactose intolerance, galactosemia, or disturbed glucose / galactose absorption syndrome;

Age to 18 years (effectiveness and safety not established).

With caution: hepatic and / or renal insufficiency, reduced bcc, abnormal water-electrolyte balance, bilateral stenosis of the renal arteries, or stenosis of the artery of a single kidney.

Application in pregnancy and breastfeeding

There are no data on the use of losartan in pregnancy. Renal perfusion in 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 II and III trimesters. When pregnancy is established, losartan should be discontinued immediately.

There is no data on the isolation of losartan in breast milk. Therefore, the question of stopping breastfeeding or abolishing losartan therapy should be resolved, taking into account its importance for the mother.

Side effects

In most cases, Lorista® is well tolerated, the side effects are mild and transient and do not require withdrawal of the drug.

On the part of the blood system: infrequently - anemia, Shenlaine-Henoch disease.

Allergic reactions: less than 1% - urticaria, skin rash, itching, angioedema (including swelling of the larynx and tongue, causing airway obstruction and / or swelling of the face, lips, pharynx).

From the side of the central nervous system and sensory organs: with a frequency of 1% or more - dizziness, asthenia, headache, fatigue, insomnia; Less than 1% - anxiety, sleep disturbance, drowsiness, memory disorders, peripheral neuropathy, paresthesia, hypoesthesia, migraine, tremor, ataxia, depression, syncope, ringing in the ears, impaired taste, visual impairment, conjunctivitis.

On the part of the CAS: orthostatic hypotension (dose-dependent), palpitations, tachy- or bradycardia, arrhythmias, angina pectoris, vasculitis.

On the part of the genitourinary system: with a frequency of less than 1% - mandatory urination, urinary tract infections, impaired renal function, decreased libido, impotence.

On the part of the respiratory system: with a frequency of 1% or more - nasal congestion, cough *, upper respiratory tract infections, pharyngitis, dyspnoea, bronchitis, edema of the nasal mucosa.

From the digestive tract: with a frequency of 1% or more - nausea, diarrhea *, dyspeptic phenomena *, abdominal pain; Less than 1% - anorexia, dry mouth, toothache, vomiting, flatulence, gastritis, constipation, hepatitis, a violation of liver function.

From the skin: with a frequency of less than 1% - dry skin, erythema, photosensitization, increased sweating, alopecia.

On the part of the musculoskeletal system: with a frequency of 1% or more - convulsions, myalgia *, pain in the back, chest, legs; Less than 1% - arthralgia, arthritis, pain in the shoulder, knee, fibromyalgia.

Laboratory indicators: hyperkalemia; Infrequently - moderate increase in the level of urea and creatinine in the blood serum; Very rarely - increased activity of liver enzymes, hyperbilirubinemia.

Other: gout.

The "*" symbol indicates side effects, the incidence of which is comparable to placebo.

Interaction

There were no clinically significant drug interactions with hydrochlorothiazide, digoxin, indirect anticoagulants, cimetidine, phenobarbital, ketoconazole, and erythromycin. During simultaneous administration with rifampicin and fluconazole, a decrease in the level of the active metabolite of potassium losartan was noted. The clinical consequences of this phenomenon are not known.

Simultaneous reception with potassium-sparing diuretics (eg spironolactone, triamterene, amiloride) and potassium preparations increases the risk of hyperkalemia.

When combined with non-steroidal anti-inflammatory drugs (NSAIDs), including selective inhibitors of COX-2, the effect of antihypertensive drugs may be reduced.

If losartan is administered concomitantly with thiazide diuretics, a decrease in blood pressure is additive.

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

Dosing and Administration

Inside, regardless of food intake.

Multiplicity of admission - 1 time per day.

Arterial hypertension: the average daily dose is 50 mg. The maximum antihypertensive effect is achieved within 3-6 weeks of therapy. In some patients, a more pronounced effect can be achieved by increasing the dose of the drug to 100 mg / day in 2 or 1 administration.

Against the background of taking large doses of diuretics, it is recommended to start LORIST® therapy with 25 mg / day in 1 dose.

In elderly patients, as well as in patients with impaired renal function, including patients on hemodialysis, correction of the initial dose is not required.

Do not 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: the initial dose is 12.5 mg / day in 1 dose. In order to reach the usual maintenance dose of 50 mg / day, the dose should be increased gradually, at intervals of one week (for example, 12.5, 25 or 50 mg with a single dose per day). Lorist® 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 (1st-7th day) - 1 table. 12.5 mg / day.

2 nd week (8-14th day) - 1 table. 25 mg / day.

3rd week (15-21th day) - 1 table. 50 mg / day.

4 nd week (22-28th day) - 1 table. 50 mg / day.

Reducing the risk of stroke in patients with hypertension and left ventricular hypertrophy: the standard initial dose of Lorista® is 50 mg / day in a single dose. In the future, hydrochlorothiazide can be added at low doses and / or Lorist® dose increased to 100 mg / day.

Kidney protection in patients with type 2 diabetes mellitus with proteinuria: the standard initial dose of Lorist® is 50 mg / day in a single dose. The dose of the drug can be increased to 100 mg / day, taking into account the decrease in blood pressure.

Application in pediatrics. Safety and efficacy of the drug in children are not established.

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.

Special instructions

In patients with reduced BCC (for example, with therapy with large doses of diuretics) symptomatic arterial hypotension may develop. Before starting losartan, it is necessary to eliminate the existing disorders, or to start therapy with small doses.

In patients with mild and moderate cirrhosis of the liver, the concentrations of losartan and its active metabolite in blood plasma after oral administration are higher than in healthy ones. Therefore, patients with liver disease in a history of therapy recommended lower doses.

In patients with renal dysfunction, with or without diabetes, electrolyte disorders (hyperkalemia) often develop, which should be taken into account. However, only in rare cases do they stop treatment due to hyperkalemia. During the treatment period, the concentration of potassium in the blood should be monitored regularly, especially in elderly patients, with renal dysfunction.

The drugs acting on the renin-angiotensin system can increase urea and creatinine in the blood serum in patients with bilateral or unilateral stenosis of the artery of a single kidney. Changes in kidney function can be reversible after the abolition of therapy. During the treatment period, it is necessary to regularly monitor the serum creatinine concentration at regular intervals.

Influence on the ability to drive a car or perform work that requires an increased speed of physical and mental reactions. Data on the effect of losartan on the ability to control transport or other technical means are not available.

Release form

Tablets, film-coated, 12.5 mg, 25 mg, 50 mg, 100 mg. For 10 tab. In a planar cell package; In a cardboard bundle 3, 6, 9 packs (10 tablets each).

Manufacturer

LLC "KRKA-RUS"

A comment

More than 20,000 patients took part in the research on the effectiveness and safety of Lorista.

The results of the conducted studies demonstrated the following data:

- in the study "Rise" of Lorista® (losartan of KRKA company) significantly reduces the level of uric acid by 32.6% in patients with arterial hypertension (AH) and associated hyperuricemia and / or gout. 100% of the patients who participated in the study achieved the target blood pressure level. Loristoy's therapy has a pronounced positive effect on the elasticity of the vascular wall in patients with AH1;

- During the open multicentre clinical trial LAURA2 (Lorista® and uric acid), the relationship between treatment with Lorista and its fixed combination with hydrochlorothiazide (Lorist® H and Lorista® HD) and hyperuricemia was studied. Based on the results of the study, in patients with hypertension and hyperuricemia Lorist®, Lorist® H and Lorist® ND due to the apparent ability to reduce uric acid levels can be used as a preferred therapy;

- EFFECT3 study proved the efficacy and safety of losartan (Lorista®) in patients with mild to moderate AH. In addition, it is important to emphasize the safety of Lorista (undesirable effects less than 1% of patients), which makes the drug an indispensable assistant in the fight against hypertension;

- as a result of an international study by Hemer4, the efficacy and safety of using Lorist® and a fixed combination with hydrochlorothiazide (Lorist® H) in patients with AH of 1-2 degree was confirmed. 100% of patients reached the CAC.

The results of clinical trials conducted with the preparation of KRKA Lorista (losartan) and its fixed combinations with hydrochlorothiazide additionally show that the drug contributes not only to the effective and well tolerated treatment of hypertension, but also to reducing the cardiovascular risk.

Conditions of supply of pharmacies

On prescription.

Storage conditions of the drug Lorista

At a temperature not higher than 25 ° C.

Keep out of the reach of children.

The shelf life of the drug Lorista

5 years.

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