Catad_pgroup Combined hypotensive

Lozap plus - instructions for use

LOZAP ® PLUS

Registration number:

LSR-000084

Trade name of the drug: LOZAP PLUS

Dosage form:

film-coated tablets

COMPOSITION
1 film-coated tablet contains active ingredients:
Losartan potassium 50 mg and hydrochlorothiazide 12.5 mg

Excipients
Mannitol, microcrystalline cellulose, croscarmellose sodium, povidone, magnesium stearate, hypromellose 2910/5, macrogol 6000, talc, simethicone emulsion, Opaspray yellow M-1-22801 (Opaspray yellow M-1-22801) (which includes: purified water, titanium dioxide, denatured ethanol (methylated alcohol BP) (99% ethanol: 1% methanol), hypromellose, dye Quinolin Yellow (E 104), dye Crimson [Ponso 4R] (Pounceau 4R) ( E 124)).

DESCRIPTION
Oblong tablets of light yellow color, film-coated, with a dividing line on both sides.

PHARMACOTHERAPEUTIC GROUP
HYPOTENSIVE COMBINATION PRODUCT
(angiotensin II receptor blocker + diuretic)

ATX code: С09DА01

PHARMACOLOGICAL PROPERTIES

Pharmacodynamics
The combined drug has a hypotensive effect. Contains losartan potassium - an angiotensin II receptor antagonist (AT1 subtype) and hydrochlorothiazide - a diuretic.
Losartan is a specific antagonist of angiotensin II receptors (AT1 subtype). Does not inhibit kinase II, an enzyme that degrades bradykinin. Reduces total peripheral vascular resistance (OPSS), blood concentration of adrenaline and aldosterone, blood pressure (BP), pressure in the pulmonary circulation; reduces afterload, has a diuretic effect. It prevents the development of myocardial hypertrophy, increases exercise tolerance in patients with chronic heart failure.
Hydrochlorothiazide - thiazide diuretic. Reduces reabsorption of Na +, enhances urinary excretion of K +, bicarbonate and phosphates. Lowers blood pressure by reducing the volume of circulating blood (BCC), changing the reactivity of the vascular wall, reducing the pressor effect of vasoconstrictor substances and increasing the depressor effect on the ganglia.

Pharmacokinetics
Losartan quickly absorbed from the gastrointestinal tract. Bioavailability is about 33%. Has a "first pass" effect through the liver, metabolized by carboxylation to form an active metabolite. Communication with blood plasma proteins - 99%. The time to reach the maximum concentration of losartan is 1 hour, the active metabolite is 3-4 hours after oral administration. The half-life is 1.5 - 2 hours, and its main metabolite is 3 - 4 hours, respectively. About 35% of the dose is excreted in the urine, about 60% through the intestines.
Hydrochlorothiazide quickly absorbed from the gastrointestinal tract. The half-life is 5.8 - 14.8 hours. It is not metabolized by the liver. About 61% is excreted by the kidneys unchanged.

INDICATIONS FOR USE
- Arterial hypertension (in patients for whom combination therapy is optimal);
- Reducing the risk of cardiovascular disease and mortality in patients with arterial hypertension and left ventricular hypertrophy.

CONTRAINDICATIONS
- hypersensitivity to drug components;
- anuria;
- severe arterial hypotension;
- severe impairment of liver and kidney function (creatinine clearance? 30 ml / s);
- hypovolemia (including against the background of high doses of diuretics);
- pregnancy and lactation;
- age up to 18 years (efficacy and safety have not been established).

Carefully patients with bilateral renal stenosis or stenosis of an artery of a solitary kidney.
The drug is prescribed with caution in patients with diabetes mellitus, hypercalcemia, hyperuricemia and / or gout, as well as in patients with a history of allergy and bronchial asthma, as well as in systemic connective tissue diseases (including systemic lupus erythematosus).

METHOD OF APPLICATION AND DOSE
Inside, regardless of food intake.

Arterial hypertension
The usual starting and maintenance dose of LOZAP PLUS is 1 tablet per day. For those patients who cannot achieve adequate blood pressure control at this dosage, the dose of LOZAP PLUS can be increased to 2 tablets 1 time per day.
The maximum dose is 2 tablets once a day. In general, the maximum hypo-tension effect is achieved within 3 weeks after starting treatment. There is no need for a special selection of the initial dose for elderly patients.

Reducing the risk of cardiovascular disease and mortality in patients with arterial hypertension and left ventricular hypertrophy
The standard starting dose of LOZAP (losartan) is 50 mg once a day. Patients who failed to reach target blood pressure levels while taking LOZAP (losartan) 50 mg / day need to select therapy by combining losartan with low doses of hydrochlorothiazide (12.5 mg) - LOZAP PLUS, and, in the case of If necessary, the dose should be increased to 2 tablets of LOZAP PLUS (only 100 mg of losartan and 25 mg of hydrochlorothiazide per day, once).

SIDE EFFECT
Adverse reactions are limited to those previously observed with the use of losartan potassium and / or hydrochlorothiazide. The most common side effects of essential hypertension include dizziness.
Allergic reactions: angioedema, including edema of the larynx and / or tongue, leading to airway obstruction, and / or edema of the face, lips, pharynx and / or tongue, occasionally noted with losartan. Some of these patients have previously experienced angioedema with other drugs, including ACE inhibitors. It is extremely rare when taking losartan manifestations of vasculitis, including Schönlein-Henoch disease, were noted.
On the part of the cardiovascular system:decrease in blood pressure.
From the digestive tract:while taking losartan, rare (< 1%) случаи гепатита, диарея.
From the respiratory system:when taking losartan - cough.
From the side of the skin: hives.
Laboratory indicators: seldom (< 1%) гиперкалиемия (калий сыворотки более 5,5 ммоль/л), повышение активности "печеночных" трансаминаз.

OVERDOSE
Symptoms:losartan - a marked decrease in blood pressure, tachycardia, bradycardia (as a result of vagal stimulation). Hydrochlorothiazide - loss of electrolytes (hypokalemia, hyperchloremia, hyponatremia), as well as dehydration resulting from excessive diuresis.
Treatment: symptomatic and supportive therapy. If the drug has been taken recently, the stomach should be flushed; if necessary, correction of water-electrolyte disturbances is carried out.
Losartan and its active metabolites are not removed by hemodialysis.

INTERACTION WITH OTHER MEDICINAL PRODUCTS
Losartanenhances the effect of other antihypertensive drugs. There was no clinically significant interaction with hydrochlorothiazide, digoxin, indirect anticoagulants, cimetidine, phenobarbital, ketokenazole, erythromycin. Like other drugs that block angiotensin II or its action, the simultaneous administration of potassium-sparing diuretics (for example, spironolactone, triamterene, amiloride), potassium preparations or salt substitutes containing potassium can lead to hyperkalemia.
Hydrochlorothiazide
The following drugs can interact with thiazide diuretics when administered concurrently:
Barbiturates, narcotic analgesics, ethanol - potentiation of orthostatic hypotension may occur.
Hypoglycemic agents (oral agents and insulin) - dose adjustment of hypoglycemic agents may be required.
Other antihypertensive drugs - an additive effect is possible.
Colistiraminereduces the absorption of hydrochlorothiazide.
Corticosteroids, ACTH- increased loss of electrolytes, especially potassium.
Pressor amines- a slight decrease in the effect of pressor amines, which does not prevent their use, is possible.
Non-depolarizing muscle relaxants (eg, tubocurarine) - it is possible to enhance the action of muscle relaxants.
Lithium preparations - diuretics reduce the renal clearance of Li + and increase the risk of lithium intoxication, therefore, simultaneous use is not recommended.
Non-steroidal anti-inflammatory drugs (NSAIDs) - in some patients, the use of NSAIDs can reduce the diuretic, natriuretic and hypotensive effects of diuretics.

Impact on laboratory results
Due to their effect on calcium excretion, thiazides can interfere with the results of the analysis of the function of the parathyroid glands.

SPECIAL INSTRUCTIONS
LOZAP PLUS can be prescribed together with other antihypertensive drugs.
There is no need for a special selection of the initial dose for elderly patients.
The drug can increase the concentration of urea and creatinine in blood plasma in patients with bilateral renal artery stenosis or renal artery stenosis of a single kidney.
Hydrochlorothiazide can increase arterial hypotension and disturbances in water and electrolyte balance (decrease in circulating blood volume, hyponatremia, hypochloremic alkalosis, hypomagnesemia, hypokalemia), impair glucose tolerance, reduce the excretion of Ca2 + in the urine and cause a transient slight increase in Ca2 + concentration in the plasma blood, increase the concentration of cholesterol and triglycerides, provoke the occurrence of hyperuricemia and / or gout.
Taking drugs that directly act on the renin-angiotensin system during the II and III trimesters of pregnancy can lead to fetal death. When pregnancy occurs, drug withdrawal is indicated.
The use of diuretics is usually not recommended for pregnant women due to the risk of jaundice in the fetus and newborn, maternal thrombocytopenia. Diuretic therapy does not prevent the development of pregnancy toxicosis.
There is no information on the effect on the ability to drive a car and other mechanisms.

RELEASE FORM
Film-coated tablets 50 mg / 12.5 mg.14 tablets in a blister made of Al / PVC foil. 2 blisters, together with instructions for use, are placed in a cardboard box.
10 tablets in a blister of Al / PVC foil, 1, 3 or 9 blisters (10, 30 or 90 tablets) together with instructions for use are placed in a cardboard box.

STORAGE CONDITIONS
List B.
Store in a dry place out of the reach of children at temperatures up to 300C.

SHELF LIFE
3 years.
Do not use after the expiration date printed on the package.

TERMS OF RELEASE FROM PHARMACIES
On prescription

MANUFACTURER
ZENTIVA a.s., 102 37 Prague 10,
Czech Republic

Complaints about the quality of the drug should be sent to:
119017, Moscow
st. B. Ordynka, 40, building 4

Lozap Plus from the Slovak pharmaceutical company Zentiva (the third largest European generics company) is a combination antihypertensive drug that includes the angiotensin II receptor blocker (ARB) losartan and the thiazide diuretic hydrochlorothiazide.

The question of which of the many antihypertensive drugs is most effective in the treatment of cardiovascular diseases has been occupying the minds of cardiologists for decades. As shown by numerous clinical trials, the effectiveness of drugs, "oldies" (diuretics, beta-blockers) and representatives of the new pharmacological "wave" (angiotensin-converting enzyme inhibitors, calcium antagonists, BAR), if different, is very insignificant. Another conclusion that was made on the basis of clinical studies is the need to use several (2 or more) drugs to achieve the target blood pressure level. The combination of antihypertensive drugs is superior to monotherapy in many respects. Here it is possible to note an increase in efficiency due to the effect on different mechanisms of the pathogenesis of arterial hypertension, and a decrease in the risk of side effects due to the use of lower dosages, and potentiation of organoprotective action.

The most promising combinations were ACE inhibitors + diuretics and BAR + diuretics (for example, lozap plus), and the latter is endowed with greater versatility, which allows clinicians to prescribe it to the widest range of patients, incl. persons over 45-50 years old. The high hypotensive activity of Lozap Plus is explained by the effect on various pathogenetic mechanisms. This allows you to achieve the desired level of blood pressure in 75-85% of clinical cases and at the same time reduce the frequency of adverse reactions by preventing excessive activation of the renin-angiotensin-aldosterone system (RAAS) and the sympathetic nervous system (SNS), which occurs with diuretic monotherapy.

Losartan inhibits the activity of RAAS and SNS, and hydrochlorothiazide, in turn, facilitating the elimination of sodium from the body, reduces the volume of circulating blood, which enhances the effect of each of the components of the drug. In clinical trials, Lozap Plus has proven itself at its best. Thus, during the pharmacotherapeutic course, patients showed a steady decrease in blood pressure to the target level: a systolic pressure of 140 mm Hg. Art. and lower was achieved in 83% of patients. During treatment, the study participants showed a significant decrease in left ventricular hypertrophy, which is a harbinger of an unfavorable outcome of hypertension (against its background, the risk of myocardial infarction quadruples, and the risk of stroke - 6-12 times). In the process of taking Lozap Plus, biochemical parameters also changed for the better: the level of total cholesterol, triglycerides, glucose, creatinine and uric acid decreased. A pronounced decrease in glycemia due to the intake of Lozap Plus is associated with the positive effect of the drug on insulin resistance. Thus, losartan neutralizes those negative metabolic changes that could develop with hydrochlorothiazide monotherapy. An unconditional positive quality of Lozap Plus, as well as of all BARs, is a better safety profile and tolerability compared to drugs from other pharmacological groups, which, together with high efficacy and organoprotective properties of the drug, determines an improvement in the patient's quality of life (and this is achieved in more than 80% cases) and the forecast of his entire future life, no matter how loud it sounds.

Pharmacology

The combined drug has a hypotensive effect. Contains losartan potassium - an angiotensin II receptor antagonist (AT 1 subtype) and hydrochlorothiazide - a diuretic.

Losartan is a specific angiotensin II receptor antagonist (AT subtype 1). Does not inhibit kinase II, an enzyme that degrades bradykinin. Reduces OPSS, blood concentration of adrenaline and aldosterone, blood pressure, pressure in the pulmonary circulation; reduces afterload, has a diuretic effect. It prevents the development of myocardial hypertrophy, increases exercise tolerance in patients with chronic heart failure.

Hydrochlorothiazide is a thiazide diuretic. Reduces the reabsorption of sodium ions, increases the urinary excretion of potassium, bicarbonate and phosphate ions. Lowers blood pressure by reducing the BCC, changing the reactivity of the vascular wall, reducing the pressor effect of vasoconstrictor substances and increasing the depressor effect on the ganglia.

Pharmacokinetics

Suction

After oral administration, losartan and hydrochlorothiazide are rapidly absorbed from the gastrointestinal tract. The bioavailability of losartan is about 33%. The time to reach the C max of losartan is 1 hour, its active metabolite is 3-4 hours.

Distribution

The binding of losartan to blood plasma proteins is 99%.

Metabolism

Losartan undergoes a "first pass" effect through the liver, metabolized by carboxylation to form an active metabolite.

Hydrochlorothiazide is not metabolized in the liver.

Withdrawal

T 1/2 of losartan is 1.5-2 hours, and its main metabolite is 3-4 hours. About 35% of the dose is excreted in the urine, about 60% in the feces.

T 1/2 of hydrochlorothiazide is 5.8-14.8 hours. About 61% is excreted in the urine unchanged.

Release form

Tablets, film-coated, light yellow, oblong, with a dividing line on both sides.

Excipients: mannitol - 89 mg, microcrystalline cellulose - 210 mg, croscarmellose sodium - 18 mg, povidone - 7 mg, magnesium stearate - 8 mg, hypromellose 2910/5 - 6.5 mg, macrogol 6000 - 0.8 mg, talc - 1.9 mg, simethicone emulsion - 0.3 mg, Opaspray yellow M-1-22801 dye - 0.5 mg (purified water, titanium dioxide, denatured ethanol (methylated alcohol BP: 99% ethanol and 1% methanol), hypromellose, Quinolin Yellow (E104) dye, dye Pounceau 4R (E124)).

10 pieces. - blisters (1) - cardboard packs.
10 pieces. - blisters (3) - cardboard packs.
10 pieces. - blisters (9) - cardboard packs.
14 pcs. - blisters (2) - cardboard packs.

Dosage

The drug is taken orally, regardless of food intake.

With arterial hypertension, the usual initial and maintenance dose is 1 tablet / day. If, when using the drug at a given dose, it is not possible to achieve adequate blood pressure control, the dose of Lozap Plus can be increased to 2 tab. 1 time / day

The maximum dose is 2 tab. 1 time / day In general, the maximum antihypertensive effect is achieved within 3 weeks after starting treatment.

There is no need for a special selection of the initial dose in elderly patients.

In order to reduce the risk of cardiovascular diseases and mortality in patients with arterial hypertension and left ventricular hypertrophy, losartan (Lozap ®) is prescribed at a standard initial dose of 50 mg / day. Patients who failed to achieve the target blood pressure level while using losartan at a dose of 50 mg / day need to select therapy by combining losartan with hydrochlorothiazide at a low dose (12.5 mg), which is ensured by the appointment of Lozap ® Plus. If necessary, the dose of Lozap ® Plus can be increased to 2 tab. (Losartan 100 mg and hydrochlorothiazide 25 mg) 1 time / day.

Overdose

There is no data on the specific treatment of an overdose with Lozap ® Plus. Taking Lozap ® Plus should be discontinued and the patient should be monitored. In case of an overdose, symptomatic therapy is indicated: gastric lavage if the drug has been taken recently, as well as elimination of dehydration, electrolyte disturbances and lowering blood pressure by standard methods (restoration of the BCC and water-electrolyte balance).

Losartan

The most common symptoms of overdose are a marked decrease in blood pressure and tachycardia; bradycardia can be a consequence of parasympathetic (vagal) stimulation.

In case of symptomatic arterial hypotension, maintenance infusion therapy is indicated. Losartan and its active metabolite are not excreted by hemodialysis.

Hydrochlorothiazide

The most common symptoms of overdose are the result of electrolyte deficiency (hypokalemia, hypochloremia, hyponatremia) and dehydration due to excessive diuresis. With the simultaneous administration of cardiac glycosides, hypokalemia can aggravate the course of arrhythmias.

There is no specific antidote for hydrochlorothiazide overdose. It has not been established to what extent hydrochlorothiazide can be removed from the body by hemodialysis.

Interaction

Losartan

Cases of a decrease in the concentration of the active metabolite have been described with the combined use of rifampicin and fluconazole. The clinical evidence of such interactions has not been evaluated.

As with the treatment of other drugs that block angiotensin II or its effects, the simultaneous use of potassium-sparing diuretics (for example, spironolactone, triamterene, amiloride), potassium preparations or potassium-containing salt substitutes can lead to an increase in serum potassium levels. The combined use of these drugs is not recommended. As with other drugs that affect sodium excretion, the drug may slow down the excretion of lithium. Therefore, with the simultaneous appointment of lithium salts and ARA II, it is necessary to carefully monitor the level of lithium salts in the blood serum.

With the simultaneous use of ARA II and NSAIDs, for example, selective inhibitors of COX-2, acetylsalicylic acid in doses used for anti-inflammatory effect, and non-selective NSAIDs, there may be a weakening of the antihypertensive effect of Lozap ® Plus. The simultaneous use of ARA II or diuretics and NSAIDs may cause an increased risk of deteriorating renal function, incl. acute renal failure and increased serum potassium levels, especially in patients with underlying renal impairment. Combined treatment should be prescribed with caution, especially in elderly patients. Patients should be adequately hydrated and renal function monitored after starting combination treatment and periodically during treatment.

Some patients with impaired renal function receiving NSAID treatment, incl. selective inhibitors of COX-2, the simultaneous use of angiotensin II receptor antagonists can aggravate renal dysfunction. These effects are usually reversible.

Other drugs that cause hypotension, such as tricyclic antidepressants, antipsychotics, baclofen, amifostine: the simultaneous use of Lozap ® Plus with these drugs that lower blood pressure may increase the risk of arterial hypotension.

Hydrochlorothiazide

When taken simultaneously with thiazide diuretics, interaction with the following substances can be observed:

Alcohol, barbiturates, opioid analgesics or antidepressants: the risk of orthostatic hypotension may increase.

Antidiabetic drugs (insulin and oral drugs): Treatment with thiazide diuretics may affect glucose tolerance. Dose adjustment of antidiabetic drugs may be required. Metformin should be used with caution due to the risk of lactic acidosis caused by possible functional renal failure associated with the use of hydrochlorothiazide.

Other antihypertensive drugs: additive effect.

Cholestyramine and colestipol: in the presence of ion exchange resins, the absorption of hydrochlorothiazide is impaired. Taking a single dose of colestyramine or colestipol leads to the binding of hydrochlorothiazide and a decrease in its absorption from the gastrointestinal tract by 85% and 43%, respectively.

Corticosteroids, ACTH: possible aggravation of electrolyte deficiency, especially hypokalemia.

Pressor amines (eg epinephrine): the effect of pressor amines may be reduced, but not preclude their use.

Non-depolarizing muscle relaxants (for example, tubocurarine chloride): the effect of muscle relaxants may be enhanced.

Lithium preparations: Diuretics decrease renal clearance of lithium and significantly increase the risk of toxic effects. It is recommended to avoid the simultaneous use of hydrochlorothiazide with lithium preparations.

Drugs for the treatment of gout (probenecid, sulfinpyrazone, and allopurinol): Dose adjustment of anti-gout drugs may be required because hydrochlorothiazide may increase serum uric acid levels. Concomitant use with thiazides may increase the incidence of hypersensitivity reactions to allopurinol.

Anticholinergic drugs (for example, atropine, biperidine): it is possible to increase the bioavailability of thiazide diuretics by reducing gastrointestinal motility and gastric emptying rate.

Cytotoxic drugs (for example, cyclophosphamide, methotrexate): thiazide diuretics can inhibit the excretion of cytotoxic drugs through the kidneys and enhance their myelosuppressive effect.

Salicylates: in the case of high doses of salicylates, hydrochlorothiazide can increase their toxic effects on the central nervous system.

Methyldopa: isolated cases of hemolytic anemia have been described in patients simultaneously receiving hydrochlorothiazide and methyldopa.

Cyclosporine: Concomitant treatment with cyclosporine may increase the risk of hyperuricemia and complications of gout.

Cardiac glycosides: Hypokalemia or hypomagnesemia caused by thiazide diuretics may contribute to the development of digitalis-induced arrhythmias.

Medicines whose effect is influenced by changes in serum potassium levels: with the simultaneous administration of Lozap® Plus with medications whose effect is influenced by changes in potassium levels (for example, digitalis glycosides and antiarrhythmic drugs), it is recommended to regularly monitor the serum potassium level and ECG monitoring. These measures are also recommended to be carried out with the simultaneous use of Lozap ® Plus with the following drugs that can cause ventricular tachycardia of the "pirouette" type (including antiarrhythmic ones), since hypokalemia is a factor that predisposes to the development of pirouette tachycardia: antiarrhythmic drugs of class IA (for example , quinidine, hydroquinidine, disopyramide), class III antiarrhythmics (for example, amiodarone, sotalol, dofetilide, ibutilide), some antipsychotics (for example, thioridazine, chlorpromazine, levomepromazine, trifluoperazine, cyamemazine, sulpridis, sultopride, thiamemazine, pulpridis, sultopride haloperidol, droperidol), others (for example, bepridil, cisapride, diphemanil, erythromycin i.v., halofantrine, mizolastine, pentamidine, terfenadine, vincamycin i.v.).

Calcium salts: Thiazide diuretics can increase serum calcium levels by reducing calcium excretion. If the patient is taking calcium supplements, it is necessary to monitor the serum calcium level and, accordingly, adjust the dosage of calcium supplements.

Impact on laboratory results: due to the effect on calcium metabolism, thiazides can distort the results of tests to assess the function of the parathyroid glands.

Carbamazepine: There is a risk of symptomatic hyponatremia. It is necessary to conduct clinical observation and laboratory monitoring of the sodium content in the blood in patients taking carbamazepine.

Amphotericin B (for parenteral administration), GCS, ACTH, stimulant laxatives or glycyrrhizin (found in licorice): hydrochlorothiazide can cause electrolyte deficiencies, especially hypokalemia.

Side effects

Adverse reactions are distributed according to the frequency of development as follows: very frequent (≥ 1/10); frequent (≥ 1/100 and up to<1/10); нечастые (≥ 1/1000 и до <1/100); редкие (≥ 1/10 000 и до <1/1000); очень редкие (<1/10 000), частота неизвестна (не может быть подсчитана на основании имеющихся данных).

In clinical studies with losartan - hydrochlorothiazide, there were no adverse reactions associated with a combination of drugs.

Adverse reactions are limited to those previously observed with the use of losartan and / or hydrochlorothiazide alone.

In controlled clinical trials of the treatment of essential hypertension in patients treated with losartan and hydrochlorothiazide, the only adverse reaction that manifested itself with a frequency of 1% or more compared with placebo was dizziness. In addition, there are other adverse reactions reported with the losartan / hydrochlorothiazide combination:

From the liver and biliary tract: rare - hepatitis.

From laboratory and instrumental studies: rare - hyperglycemia, increased activity of hepatic transaminases.

In addition, with the use of losartan / hydrochlorothiazide, the following adverse reactions may be observed when using each of the components:

Losartan

On the part of the blood and lymphatic system: infrequent - anemia, Shenlein-Henoch disease, ecchymosis, hemolysis.

From the immune system: rare - anaphylactic reactions, angioedema (swelling of the larynx and / or tongue, swelling of the face, lips, pharynx), urticaria.

From the side of metabolism and nutrition: infrequent - anorexia, gout.

From the side of the psyche: frequent - insomnia; infrequent - anxiety, anxiety, panic attacks, confusion, depression, unusual dreams, sleep disturbances, drowsiness, memory impairment.

From the nervous system: frequent - headache, dizziness; infrequent - increased excitability, paresthesia, peripheral neuropathy, tremor, migraine, fainting.

From the side of the organ of vision: infrequent - blurred vision, burning sensation in the eyes, conjunctivitis, decreased visual acuity.

On the part of the organ of hearing and labyrinth disorders: infrequent - vertigo, ringing in the ears.

From the heart: infrequent - arterial hypotension, orthostatic hypotension, pain in the sternum, angina pectoris, AV block II degree, cerebrovascular disorders, myocardial infarction, palpitations, arrhythmias (atrial fibrillation, sinus bradycardia, tachycardia, ventricular tachycardia).

From the side of the vessels: infrequent - vasculitis.

On the part of the respiratory system: frequent - cough, upper respiratory tract infections, nasal congestion, sinusitis; infrequent - pharyngitis, laryngitis, dyspnea, bronchitis, nosebleeds, rhinitis.

From the side of the digestive tract: frequent - abdominal pain, nausea, diarrhea, dyspepsia; infrequent - constipation, toothache, dry mouth, flatulence, gastritis, vomiting.

From the liver and biliary tract: frequency unknown - abnormal liver function.

Skin and subcutaneous tissue disorders: infrequent - alopecia, dermatitis, dry skin, erythema, hyperemia, photosensitivity, itching, rash, sweating.

From the musculoskeletal system and connective tissue: frequent - muscle cramps, back pain, leg pain, sciatica; infrequent - joint swelling, muscle and bone pain, joint stiffness, arthralgia, arthritis, fibromyalgia, muscle weakness; frequency unknown - rhabdomyolysis.

On the part of the kidneys and urinary tract: infrequent - nocturia, urge to urinate, urinary tract infections.

On the part of the reproductive system: infrequent - decreased libido, decreased potency.

From the side of the body as a whole: frequent - asthenia, fatigue, chest pain; infrequent - facial swelling, fever.

On the part of laboratory and instrumental studies: frequent - hyperglycemia, a slight decrease in hematocrit and hemoglobin; infrequent - slightly increased serum urea and creatinine levels; very rare - an increase in the level of hepatic transaminases and bilirubin.

Hydrochlorothiazide

From the hematopoietic system: infrequent - agranulocytosis, aplastic anemia, hemolytic anemia, leukopenia, purpura, thrombocytopenia.

From the immune system: rare - anaphylactic reactions up to shock.

From the side of metabolism: infrequent - anorexia, hyperglycemia, hyperuricemia, hypokalemia, hypomagnesemia, hyponatremia, hypercalcemia, hypochloremic alkalosis.

From the side of the psyche: infrequent - insomnia.

From the nervous system: infrequent - headache.

From the side of the organ of vision: infrequent - a temporary decrease in visual acuity, xanthopsia.

From the side of the vessels: infrequent - necrotizing vasculitis, cutaneous vasculitis.

From the respiratory system: infrequent - respiratory distress syndrome, including pneumonitis and noncardiogenic pulmonary edema.

From the gastrointestinal tract: infrequent - sialadenitis, spasms, gastritis, nausea, vomiting, diarrhea, constipation.

From the liver and biliary tract: infrequent - cholestatic jaundice, cholecystitis, pancreatitis.

Skin and subcutaneous tissue disorders: infrequent - photosensitivity, urticaria, toxic epidermal necrolysis.

From the musculoskeletal system and connective tissue: infrequent - muscle cramps.

From the side of the kidneys and urinary tract: infrequent - glycosuria, interstitial nephritis, impaired renal function, renal failure.

From the side of the body as a whole: infrequent - fever, dizziness.

Indications

• arterial hypertension (in patients for whom combination therapy is optimal);
• reducing the risk of cardiovascular disease and mortality in patients with arterial hypertension and left ventricular hypertrophy.

Contraindications

• therapy-resistant hypokalemia or hypercalcemia;
• severe liver dysfunction;
• obstructive diseases of the biliary tract;
• refractory hyponatremia;
• hyperuricemia and / or gout;
• severe renal dysfunction (CC≤30 ml / min);
• anuria;
• pregnancy;
• period of breastfeeding;
• age up to 18 years (efficacy and safety have not been established);
• hypersensitivity to any of the components of the drug or to other drugs that are derivatives of sulfonylamide.

It is prescribed with caution in patients with bilateral renal artery stenosis or stenosis of an artery of a single kidney, hypovolemic conditions (including diarrhea, vomiting), hyponatremia (increased risk of arterial hypotension in patients on a low-salt or salt-free diet), hypochloremic alkalosis, hypomagnesemia , with diseases of the connective tissue (including SLE), patients with impaired liver function or with progressive liver diseases, diabetes mellitus, bronchial asthma (including in history), aggravated allergic history, simultaneously with NSAIDs, in incl. inhibitors of COX-2, as well as representatives of the black race.

Application features

Application during pregnancy and lactation

Application during pregnancy

Angiotensin II receptor antagonists (ARA II)

The use of angiotensin II receptor antagonists during pregnancy is contraindicated.

Patients planning a pregnancy should switch to alternative antihypertensive therapy with an established safety profile. If pregnancy is diagnosed during treatment with Lozap ® Plus, therapy should be stopped immediately and alternative treatment should be started.

It is known that treatment with angiotensin II receptor antagonists in the II and III trimesters leads to fetotoxic effects (decreased renal function, oligohydramnios, delayed ossification of the skull), as well as toxicity to the newborn (renal failure, arterial hypotension, hyperkalemia).

In the case of using Lozap ® Plus in the II and III trimesters of pregnancy, it is recommended to conduct an ultrasound of the kidneys and fetal skull.

Children whose mothers took Lozap ® Plus during pregnancy should be carefully monitored for the development of arterial hypotension.

Hydrochlorothiazide

The experience of using hydrochlorothiazide during pregnancy, especially during the first trimester, is limited. Animal studies are insufficient. Hydrochlorothiazide crosses the placental barrier and is detected in the blood of the umbilical cord. Based on the pharmacological mechanism of action of hydrochlorothiazide, its use during pregnancy can impair feto-placental blood flow and lead to fetal and newborn disorders, such as jaundice, electrolyte imbalance and thrombocytopenia.

The use of Lozap ® Plus is contraindicated during pregnancy.

Application during breastfeeding

Angiotensin II receptor antagonists

Due to the lack of information on the use of Lozap ® Plus during breastfeeding, the administration of the drug during this period is contraindicated. During breastfeeding, preference is given to alternative treatments with a better known safety profile.

Hydrochlorothiazide

Hydrochlorothiazide is excreted in breast milk. Thiazides can induce intense diuresis and can inhibit milk production. Therefore, the use of the drug Lozap ® Plus during breastfeeding is contraindicated.

Application for violations of liver function

Pharmacokinetic data indicate a pronounced increase in plasma concentrations of losartan in patients with liver cirrhosis. Based on these data, Lozap ® Plus should be used with caution in patients with a history of mild or moderate hepatic impairment. There is no experience with losartan in patients with severe hepatic dysfunction.

Application for impaired renal function

Contraindicated in severe renal impairment (CC≤30 ml / min).

It was reported about impaired renal function due to inhibition of the RAAS, incl. about renal failure (in particular, in patients whose renal function depends on the RAAS, for example, with severe heart failure or existing renal dysfunction). As in the case of the use of other drugs that affect the RAAS, cases of increased levels of urea and creatinine in serum have been described in patients with bilateral renal artery stenosis or with renal artery stenosis of a single kidney. These changes in renal function may be reversible and decrease after discontinuation of treatment. Lozap Plus should be used with caution in patients with bilateral renal artery stenosis or renal artery stenosis of a single kidney.

Application in children

The drug is contraindicated in children and adolescents under 18 years of age (efficacy and safety have not been established).

special instructions

Losartan

Angioedema

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

Hypotension and decreased blood volume

In patients with hypovolemia and / or low sodium levels resulting from intensive use of diuretics, restriction of salt intake with food, diarrhea or vomiting, symptomatic hypotension may develop (especially after taking the first dose). It is necessary to correct such conditions before taking Lozap Plus.

Electrolyte imbalance

Electrolyte imbalance often occurs in patients with impaired renal function, therefore, the content of potassium in the blood plasma and CC should be carefully monitored, especially carefully monitor the condition of patients with heart failure and CC 30-50 ml / min. Combined use of Lozap ® Plus with potassium-sparing diuretics, potassium preparations and potassium-containing salt substitutes is not recommended.

Liver dysfunction

Pharmacokinetic data indicate a pronounced increase in plasma concentrations of losartan in patients with liver cirrhosis. Based on these data, Lozap ® Plus should be used with caution in patients with a history of mild or moderate hepatic impairment. There is no experience with losartan in patients with severe hepatic dysfunction. Therefore, Lozap ® Plus is contraindicated in patients with severe liver dysfunction.

Impaired renal function

It was reported about impaired renal function due to inhibition of the RAAS, incl. about renal failure (in particular, in patients whose renal function depends on the RAAS, for example, with severe heart failure or existing renal dysfunction). As in the case of the use of other drugs that affect the RAAS, cases of increased levels of urea and creatinine in the blood serum have been described in patients with bilateral renal artery stenosis or with renal artery stenosis of a solitary kidney. These changes in renal function may be reversible and decrease after discontinuation of treatment. Lozap Plus should be used with caution in patients with bilateral renal artery stenosis or renal artery stenosis of a single kidney.

Kidney transplant

There is no experience of using the drug in patients who have recently undergone kidney transplantation.

Primary hyperaldosteronism

In patients with primary hyperaldosteronism, as a rule, there is no response to treatment with antihypertensive drugs that inhibit the renin-angiotensin system. For this reason, the use of Lozap Plus is not recommended.

IHD and cerebrovascular disease

As with any other antihypertensive drug, an excessive decrease in blood pressure in patients with coronary artery disease or cerebrovascular disease can lead to the development of myocardial infarction or stroke.

Heart failure

As with other drugs that affect the RAAS, patients with heart failure (with or without impaired renal function) are at risk of developing severe arterial hypotension, as well as impaired renal function (often acute).

Aortic and mitral valve stenosis, obstructive hypertrophic cardiomyopathy

As with other vasodilators, special care should be taken when treating patients with aortic or mitral stenosis or obstructive hypertrophic cardiomyopathy.

Differences related to ethnicity

By analogy with other ACE inhibitors, losartan and other angiotensin antagonists are noticeably less effective in lowering blood pressure in blacks compared to patients of other races. Perhaps this is due to more frequent cases of low renin content in the population of representatives of the Negroid race with arterial hypertension.

Hydrochlorothiazide

Arterial hypotension and disturbances in water and electrolyte balance

As with any other antihypertensive drug, some patients may develop symptomatic hypotension. Patients should be monitored for clinical signs of fluid and electrolyte imbalance, such as hypovolemia, hyponatremia, hypochloremic alkalosis, hypomagnesemia or hypokalemia, which may develop against the background of concomitant diarrhea or vomiting. In such patients, it is necessary to periodically (at appropriate intervals) monitor serum electrolyte levels. Patients with edema in hot weather may develop hypervolemic hyponatremia.

Endocrine and metabolic effects

Treatment with thiazides can lead to impaired glucose tolerance. Dose adjustment of antidiabetic drugs may be required, incl. insulin. During treatment with thiazides in patients with impaired glucose tolerance, the manifestation of diabetes mellitus is possible.

Thiazides can reduce urinary calcium excretion and cause a slight periodic increase in serum calcium levels. Severe hypercalcemia may be a sign of latent hyperparathyroidism. Before examining the function of the parathyroid glands, treatment with thiazides should be discontinued.

Treatment with thiazide diuretics may be accompanied by an increase in blood cholesterol and triglyceride levels.

In some patients, treatment with thiazides can cause hyperuricemia and / or gout. Since losartan lowers uric acid levels, the use of losartan in combination with hydrochlorothiazide may slow down the development of diuretic-induced hyperuricemia.

Liver dysfunction

Thiazides should be used with caution in patients with impaired liver function or progressive liver disease due to the risk of developing intrahepatic cholestasis, and also due to the fact that minor disturbances in water and electrolyte balance can be a prerequisite for the development of hepatic coma.

Lozap Plus is contraindicated in patients with severe hepatic impairment.

While taking thiazides, hypersensitivity reactions may develop in patients with a history of bronchial asthma, as well as in patients with a burdened allergic history. Cases of the occurrence or exacerbation of systemic lupus erythematosus have been described during treatment with thiazides.

The preparation contains Crimson dye [Ponso 4R], which may cause allergic reactions.

Influence on the ability to drive vehicles and use mechanisms

Studies to study the effect of the drug on the ability to drive vehicles or work with mechanisms have not been conducted. However, it must be borne in mind that against the background of treatment with antihypertensive drugs, dizziness or drowsiness may occur when driving or working with mechanisms, especially during the initiation of treatment or when the dosage of the drug is increased.

thank

The site provides background information for informational purposes only. Diagnosis and treatment of diseases must be carried out under the supervision of a specialist. All drugs have contraindications. A specialist consultation is required!

Lozap represents antihypertensive drugdesigned to reduce, maintain and control blood pressure levels within normal or acceptable values. The drug lowers both blood pressure and pressure in the pulmonary circulation, reduces the load on the heart and causes a moderate diuretic effect. In addition, Lozap prevents myocardial hypertrophy and increases the tolerance of physical or emotional stress. The drug is used in the treatment of arterial hypertension and heart failure.

Composition, varieties and form of release

There are two types of the drug on the pharmaceutical market - Lozap and Lozap plus. These varieties differ in that Lozap contains only one active ingredient, and Lozap Plus - two. Moreover, the main active ingredient in Lozap and Lozap plus is the same, and the second substance in Lozap plus is an additional one that enhances the effect of the first. In this article, we will consider both types of the drug, since they have almost the same effect, are indicated for use in the same conditions, etc.

Both Lozap and Lozap plus are available in a single dosage form - this is oral tablets... Lozap as an active ingredient contains losartan, and Lozap plus is losartan and hydrochlorothiazide... The substance losartan is an angiotensin converting enzyme (ACE) inhibitor, and hydrochlorothiazide is a diuretic. Accordingly, losartan lowers blood pressure and reduces stress on the heart, while hydrochlorothiazide removes excess fluid from the body, enhancing the hypotensive effect of the first substance. Therefore, Lozap plus has a stronger hypotensive effect compared to Lozap, since it contains a combination of active ingredients, and not one substance.

In principle, Lozap Plus was created for ease of use, since diuretics are often used to enhance the effect with ACE inhibitors. Manufacturers simply combined these components in one preparation, which is very convenient for a person who needs to take only one pill, and not two, three, etc.

Lozap is available in three dosages - 12.5 mg, 50 mg and 100 mg losartan per tablet. Lozap Plus is available in a single dosage - 50 mg losartan + 12.5 mg hydrochlorothiazide. Lozap tablets 12.5 mg have an oblong biconvex shape, are white or almost white and are available in packs of 30, 60 and 90 pieces. Lozap tablets 50 mg and 100 mg have an oblong biconvex shape, are painted in white or almost white color, are provided with risks on both sides and are available in packs of 30, 60 and 90 pieces. Lozap Plus tablets have an oblong shape, are colored in light yellow, are provided with risks on both sides and are available in packs of 10, 20, 30 and 90 pieces.

Lozap action

The therapeutic effect of Lozap is to lower blood pressure and reduce the load on the heart. This effect of the drug is due to its ability to suppress the activity of the angiotensin-converting enzyme (ACE), which ensures the conversion of angiotensin I to angiotensin II. It is due to the fact that Lozap suppresses the work of the enzyme that it belongs to the group of ACE inhibitors.

Due to the action of Lozap, angiotensin II is not formed in the human body - a substance that narrows blood vessels and, accordingly, increases blood pressure. If the formation of angiotensin II is blocked, then the vessels do not narrow, and blood pressure decreases or remains within normal limits. Against the background of regular use of Lozap, blood pressure decreases and is kept within normal values. Moreover, the first hypotensive effect is noted within 1 - 1.5 hours after taking the drug and lasts for a day, but for a persistent decrease in pressure, you need to drink the medicine for at least 4 - 5 weeks. Lozap for lowering pressure is very effective in the elderly and young patients suffering from malignant arterial hypertension.

By expanding blood vessels, Lozap reduces the load on the heart, which makes it easier to push blood through them. By facilitating the work of the heart, the drug increases the tolerance of physical and emotional stress in people with chronic heart disease.

Lozap also improves blood supply to the heart and the intensity of renal blood flow, therefore it is successfully used in the treatment of chronic heart failure and diabetic nephropathy.

Lozap is well combined with other antihypertensive drugs and has a moderate diuretic effect, due to which the body does not retain fluid and does not form edema.

Lozap plus has a more pronounced hypotensive effect compared to Lozap, since the diuretic hydrochlorothiazide, which is part of it, enhances the effect of an ACE inhibitor.

Separately, it should be noted that Lozap increases the excretion of uric acid and, accordingly, reduces its concentration in the blood.

When you stop taking Lozap and Lozap plus, "withdrawal" syndrome does not develop.

Indications for use

Lozap - indications for use.

• Arterial hypertension ;
• As part of a combination therapy for chronic heart failure;
• In order to reduce the risk of cardiovascular diseases (stroke, etc.) and reduce mortality in people suffering from hypertension and left ventricular hypertrophy;
• Diabetic nephropathy with hypercreatininemia and proteinuria (the ratio of the concentrations of albumin and creatinine in the urine is more than 300 mg / g) in patients with type 2 diabetes mellitus, combined with arterial hypertension (to protect the kidneys and prevent renal failure).

Lozap plus - indications for use. The drug is indicated for use in the treatment of the following diseases:

• Arterial hypertension;
• In order to reduce the risk of cardiovascular diseases (stroke, etc.) and reduce mortality in people suffering from hypertension and left ventricular hypertrophy.

Instructions for use

Instructions for use Lozap

A Lozap tablet of any dosage can be taken regardless of food, swallowing it whole, without chewing or crushing it in other ways, but with a small amount of still water (half a glass is enough). Since the drug has a long-term effect, then all the necessary daily dosage is taken once, that is, the tablets are drunk 1 time per day. It is optimal to take the drug every day at the same time, preferably in the evening.

Lozap dosages are determined by the disease for which the drug is being taken. The course of therapy is usually long - from several months to several years. The duration of the drug is determined individually, based on the ratio of effectiveness / side effects.

If a person has hypertrophic obstructive cardiomyopathy or stenosis of the aortic or mitral valve, or heart failure is combined with arrhythmias or severe renal failure, then he should take Lozap or Lozap plus with caution and only under the supervision of doctors.

It is not recommended to take Lozap in combination with other ACE inhibitors (for example, Captopril, Enalapril, etc.), as this increases the risk of side effects, renal impairment and hyperkalemia (increased levels of potassium in the blood).

If a person is on hemodialysis, then the dosage of Lozap should be halved from the recommended one for the condition for which the drug is being taken.

Lozap plus can provoke exacerbation of systemic lupus erythematosus and visual impairment due to the development of an attack of myopia or angle-closure glaucoma. If such complications develop, you should stop taking the drug and consult a doctor.

Impact on the ability to control mechanisms

Lozap and Lozap plus can cause dizziness, drowsiness and fainting, which negatively affects the ability to control mechanisms, therefore, against the background of the use of these drugs, it is recommended to abandon any activities that require a high concentration of attention and speed of reactions.

Overdose

An overdose of Lozap and Lozap plus is possible and is manifested by the following symptoms:

• Tachycardia (heart rate over 70 beats per minute);
• Hypotension (severe drop in blood pressure);
• Fainting;
• Collapse;
• Violations of water and electrolyte balance (decrease in levels of chlorine, sodium in the blood, etc.);
• Dehydration (only for Lozap plus).

With the development of an overdose, it is necessary to carry out symptomatic treatment aimed at maintaining the normal functioning of vital organs, as well as restoring the water and electrolyte balance. So, with severe hypotension, you should lay the person on his back and raise his legs. If necessary, intravenous saline or sympathomimetics are injected to increase pressure. To accelerate the elimination of the drug from the body, diuretics are taken.

Interaction with other medicinal products

First, we present interactions with medications that are characteristic of both Lozap and Lozap plus. And below we give separately the interactions that are characteristic only for Lozap plus.

Simultaneous reception of Lozap plus with the following drugs can provoke arrhythmias, including the deadly "pirouette" type:

• Class IA antiarrhythmics (Quinidine, Hydroquinidine, Disopyramide, etc.);
• Class III antiarrhythmics (Amiodarone, Sotalol, Dofetilide, etc.);
• Some antipsychotics (Thioridazine, Chlorpromazine, Levomepromazine, Trifluoperazine, Cyamemazine, Sulpiride, Sultopride, Amisulpride, Tiapride, Pimozide, Haloperidol, Droperidol);
• Bepridil;
• Cisapride;
• Diphemanil;
• Halofantin;
• Mizolastine;
• Pentamidine;
• Terfenadine;
• Vincamycin.

Lozap plus increases the concentration of calcium in the blood, therefore, when used simultaneously with calcium preparations, the dosage of the latter should be adjusted.

Lozap plus in combination with carbamazepine can provoke hyponatremia (a decrease in the concentration of sodium in the blood).

Iodine-containing contrast agents used in combination with Lozap plus, against the background of dehydration, increase the risk of developing acute renal failure. Therefore, before using such contrast agents, it is necessary to normalize the water-electrolyte balance and the amount of fluid in the tissues.

Side effects

Lozap and Lozap plus can provoke the development of the following side effects from various organs and systems:

1. Blood system:

• Anemia;
• Thrombocytopenia (the level of platelets in the blood is below normal);
• Eosinophilia (the number of eosinophils in the blood is higher than normal);
• Purpura of Schönlein-Genoch.

2. The immune system:

• Quincke's edema;
• Photosensitization.

3. Nervous system:

• Anxiety;
• Dizziness;
• Drowsiness;
• Sleep disturbance;
• Migraine;
• Paresthesia (feeling of running "goose bumps", numbness of the limbs);
• Memory impairment;
• Ataxia (movement coordination disorder);
• Peripheral neuropathy;
• Hypesthesia (hypersensitivity to various stimuli, such as cold, touch, etc.);
• Confusion of consciousness;
• Unusual dreams;
• Sciatica (pain along the sciatic nerve).

4. Senses:

• Taste disturbance (dysgeusia);
• Visual impairment (decreased visual acuity or double vision);
• Vertigo;
• Blurred vision;
• A burning sensation in the eyes.

5. The cardiovascular system:

• Feeling of heartbeat;
• Angina pectoris;
• Fainting;
• Arrhythmia;
• Acute violation of cerebral circulation;
• Hypotension (lowering blood pressure below 90/60);
• Orthostatic hypotension (drop in blood pressure when moving to a standing position from sitting or lying down);
• Nose bleed ;
• Bradycardia (heart rate below 50 beats per minute);
• Myocardial infarction;
• Atrioventricular block II degree.

6. Respiratory system:

• Nasal congestion;
• Pharyngitis;
• Laryngitis;
• Dyspnoea.

7. Digestive tract:

• Diarrhea or constipation;
• Vomiting;
• Dyspeptic symptoms (belching, bloating, flatulence, etc.);
• Disruption of the liver;

8. Soft tissues:

• Myalgia (muscle pain);
• Arthralgia (joint pain);
• Rhabdomyolysis (muscle breakdown);
• Muscle spasms;
• Fibromylagia.

9. Genitourinary organs:

• Disruption of kidney function;
• Renal failure;
• Decreased libido;
• Urgent urge to urinate;
• Urinary tract infections;
• Nocturia (more frequent urination at night than during the day).

10. Laboratory indicators:

• Hyponatremia (blood sodium levels below normal);
• Hypoglycemia (blood glucose levels below normal);
• Increased activity of AsAT and ALT;
• Increased concentration of urea, creatinine and bilirubin in blood plasma.

11. Others:

• Exacerbation or manifestation of gout;
• Weakness;
• Swelling;
• General malaise;
• Alopecia (baldness);
• Bruises no more than 3 mm in diameter;
• Flu-like symptoms;
• Puffiness of the face;
• Swelling and stiffness of the joints;

Lozap plus, in addition to the above, can provoke the following side effects:

• Exacerbation of systemic lupus erythematosus;
• Agranulocytosis (absence of neutrophils, basophils, eosinophils in the blood);
• Leukopenia (the number of leukocytes in the blood is below normal);
• Purpura;
• Xanthopsia (visual impairment in which a person sees everything in yellow);
• Respiratory distress syndrome;
• Sialadenitis (inflammation of the salivary gland);
• Cholestatic jaundice;
• Toxic epidermal necrolysis;
• Muscle cramps;
• Glucosuria (glucose in the urine);
• Interstitial nephritis;
• Fever.

Contraindications for use

Lozap and Lozap plus are contraindicated for use

• Individual hypersensitivity or allergic reactions to drug components;
• Simultaneous reception with Aliskiren against the background of diabetes mellitus, combined with renal failure with creatinine clearance less than 60 ml / min;
• Renal failure with creatinine clearance below 30 ml / min;
• Anuria (lack of urine);
• Severe liver dysfunction;
• The period of pregnancy and breastfeeding;
• Age under 18;
• Uncorrected hypokalemia, hyponatremia, or hypercalcemia (only for Lozap plus);
• Obstructive diseases of the biliary tract (only for Lozap plus);
• Cholestasis (only for Lozap plus);
• Gout or hyperuricemia (increased level of uric acid in the blood) with clinical symptoms (only for Lozap plus).

Lozap and Lozap plus should be used with caution. if a person has the following conditions or diseases:

• Arterial hypotension (low blood pressure);
• Heart failure combined with severe renal failure;
• Severe chronic heart failure IV functional class according to NYHA classification;
• Heart failure with arrhythmias;
• Cerebrovascular diseases (cerebral circulation disorders, increased intracranial pressure, cerebral atherosclerosis, etc.);
• Hyperkalemia (blood potassium levels are higher than normal);
• Age over 75;
• Low circulating blood volume;
• Violations of water and electrolyte balance;
• Bilateral narrowing of both renal arteries;
• Renal or hepatic impairment;
• Postponed kidney transplant;
• Stenosis of the aortic and mitral valves;
• Angioneurotic edema in the past;
• Primary hyperaldosteronism;
• Hypertrophic obstructive cardiomyopathy;
• Diabetes mellitus (only for Lozap plus);
• Hypochloremic alkalosis (for Lozap plus);
• Hypomagnesemia (for Lozap plus);
• Connective tissue diseases, such as systemic lupus erythematosus (for Lozap plus);
• Bronchial asthma in the present or past (for Lozap plus);
• Simultaneous reception with NSAIDs, for example, Ibuprofen, Nimesulide, Nurofen, etc. (for Lozap plus);
• Acute attack of myopia or angle-closure glaucoma (for Lozap plus).

Analogs of Lozap

Lozap and Lozap plus in the pharmaceutical market of the CIS countries have two types of analogues - these are synonyms and, in fact, analogues. Synonyms include drugs that contain exactly the same active substances as Lozap and Lozap plus. Analogs include drugs that contain other active substances, but have the most similar therapeutic effect with Lozap and Lozap plus. In principle, Lozap's analogs are drugs belonging to the group of ACE inhibitors, and Lozapa plus are ACE inhibitors in combination with diuretics.

Synonyms Lozap and Lozap plus are reflected in the table.

Synonyms Lozap	Synonyms Lozap plus
Blocktran tablets	Blocktran GT tablets
Brozaar tablets	Vasotens N tablets
Vasotens tablets	Gizaar and Gizaar forte tablets
Zisakar tablets	Gizortan tablets
Cardomin-Sanovel tablets	Hydrochlorothiazide + Losartan-TAD tablets
Karzartan tablets	Cardomin plus-Sanovel tablets
Cozaar tablets	Losartan-N Richter tablets
Lakea tablets
Lozarel tablets	Lakea N tablets
Losartan tablets	Losartan / Hydrochlorothiazide-Teva tablets
Losartan-Richter, Losartan-Teva, Losartan-TAD and Losartan MacLeodz tablets	Lozarel Plus tablets
Lorista pills	Presartan N tablets
Losacor tablets	Simartan-N tablets
Lotor tablets
Presartan tablets
Renicard tablets

Analogs Lozap and Lozap plus are also reflected in the table.

Analogs of Lozap	Analogs Lozap plus
Aprovel tablets	Atacand Plus tablets
Atacand tablets	Walz N tablets
Angiakand tablets	Valsakor N80, Valsakor N160, Valsakor N320 tablets
Artinova tablets	Valsacor ND160 tablets
Walz tablets	Vanatex Combi tablets
Valsafors tablets	Ibertan Plus tablets
Valsacor tablets	Cardosal Plus tablets
Valsartan capsules and tablets	Co-Diovan tablets
Valaar tablets	Coaprovel tablets
Hyposart tablets
Diovan tablets	Kandecor ND 32 tablets
Ibertan tablets	Mikardis Plus tablets
Irbesartan tablets	Ordiss N tablets
Irsar tablets	Teveten plus tablets
Kandecor tablets	Edarby Clos pills
Cardosal 10, Cardosal 20 and Cardosal 40 tablets
Cardosten tablets
Candesar pills
Micardis tablets
Naviten tablets
Nortivan tablets
Ordiss tablets
Olimestra tablets
Pritor pills
Tantordio tablets
Tareg tablets
Teveten tablets
Telmisartan Richter tablets
Firmasta tablets
Edarbi pills

Russian analogues Lozap

Synonyms and analogues of Lozap and Lozap plus Russian production are shown in the table.

	For Lozap	For Lozap plus
Synonyms	Blocktran tablets	Blocktran GT tablets
	Brozaar tablets	Lorista N, Lorista N 100 and Lorista ND tablets
	Losartan tablets
	Lorista pills
	Valsafors tablets	Kandekor N 8, Kandekor N 16 and Kandekor N 32 tablets
	Valaar tablets	Kandecor ND 32 tablets
	Irsar tablets
	Kandecor tablets
	Cardosten tablets
	Candesar pills
	Tareg tablets

0010 Angiotensin II receptor antagonists (AT 1 -subtype) in combinations

INN

Losartan * + Hydrochlorothiazide *

in a contour acheikova packing 10 pcs .; in a carton box 1, 3 or 9 packages; or in a contour acheikova packing 14 pcs .; in a pack of cardboard 2 packages.

Oblong, light yellow film-coated tablets with a dividing line on both sides.

COMPOSITION

1 coated tablet contains active ingredients:
Losartan potassium 50 mg and hydrochlorothiazide 12.5 mg
Excipients
Microcrystalline cellulose, mannitol, croscarmellose sodium, povidone 30,
magnesium stearate, hypromellose, macrogol, talc, dimethicone emulsion, dye Opaspray yellow M-1-22801 (which includes: purified water, titanium dioxide, methyl alcohol BP, hypromellose, Quinolin Yellow (E 104), Pounceau 4R
(E 124))

DESCRIPTION

Oblong, light yellow film-coated tablets with a dividing line on both sides.

PHARMACOLOGICAL PROPERTIES

Pharmacodynamics
The combined drug has a hypotensive effect. Contains losartan potassium - an angiotensin II receptor antagonist (AT1 subtype) and hydrochlorothiazide - a diuretic.
Losartan is a specific angiotensin II receptor antagonist
(subtype AT1). Does not inhibit kinase II, an enzyme that degrades bradykinin. Reduces total peripheral vascular resistance (OPSS), blood concentration of adrenaline and aldosterone, blood pressure (BP), pressure in the pulmonary circulation; reduces afterload, has a diuretic effect. Prevents the development of myocardial hypertrophy, increases exercise tolerance in patients with chronic heart failure.
Hydrochlorothiazide is a thiazide diuretic. Reduces reabsorption of Na +, enhances urinary excretion of K +, bicarbonate and phosphates. Lowers blood pressure by reducing the volume of circulating blood (BCC), changing the reactivity of the vascular wall, reducing the pressor effect of vasoconstrictor substances and increasing the depressor effect on the ganglia.
Pharmacokinetics
Losartan is rapidly absorbed from the gastrointestinal tract. Bioavailability is about 33%. Has a "first pass" effect through the liver, is metabolized
by carboxylation to form an active metabolite. Communication with blood plasma proteins - 99%. The time to reach the maximum concentration of losartan is 1 hour, the active metabolite is 3-4 hours after oral administration. The half-life is 1.5 - 2 hours, and its main metabolite is 3 - 4 hours, respectively. Near
35% of the dose is excreted in the urine, about 60% through the intestines.
Hydrochlorothiazide is rapidly absorbed from the gastrointestinal tract. The half-life is 5.8-14.8 hours. It is not metabolized by the liver. About 61% is excreted by the kidneys unchanged.

INDICATION FOR USE

Arterial hypertension (in patients for whom combination therapy is optimal)

CONTRAINDICATIONS

anuria;
severe arterial hypotension;
severe liver and kidney dysfunction (creatinine clearance
≤ 30 ml / s);
hypovolemia (including against the background of high doses of diuretics);
pregnancy and lactation;
age up to 18 years (efficacy and safety have not been established)
Use caution in patients with bilateral renal stenosis or stenosis of a solitary kidney artery.
The drug is prescribed with caution in patients with diabetes mellitus, hypercalcemia, hyperuricemia and / or gout, as well as in patients with a history of allergy and bronchial asthma, as well as in systemic diseases of the connective tissue (including systemic lupus erythematosus).

METHOD OF APPLICATION AND DOSE

Inside, regardless of food intake.
The usual starting and maintenance dose of LOZAP PLUS is 1 tablet per day. For those patients who cannot achieve adequate blood pressure control at this dosage, the dose of LOZAP PLUS can be increased to 2 tablets 1 time per day.
The maximum dose is 2 tablets once a day. In general, the maximum antihypertensive effect is achieved within 3 weeks after starting treatment.
There is no need for a special selection of the initial dose in elderly patients.

SIDE EFFECT

Adverse reactions are limited to those previously observed with the use of losartan potassium and / or hydrochlorothiazide.
Allergic reactions: angioedema, including edema of the larynx and / or tongue, leading to airway obstruction, and / or edema of the face, lips, pharynx and / or tongue, occasionally noted with losartan. Some of these patients have previously experienced angioedema with other drugs, including ACE inhibitors. It is extremely rare when taking losartan manifestations of vasculitis, including Shenlein-Henoch disease, were noted.
From the side of the cardiovascular system: lowering blood pressure.
From the side of the digestive tract: rare ( 1%) cases of hepatitis, diarrhea were registered when taking losartan.
From the respiratory system: when taking losartan - cough.
On the part of the skin: urticaria.
Laboratory indicators: rarely ( 1%) hyperkalemia (serum potassium more than 5.5 mmol / l), increased activity of “hepatic” transaminases.

OVERDOSE

Symptoms: losartan - a marked decrease in blood pressure, tachycardia, bradycardia (as a result of vagal stimulation). Hydrochlorothiazide - loss of electrolytes (hypokalemia, hyperchloremia, hyponatremia), as well as dehydration resulting from excessive diuresis.
Treatment: symptomatic and supportive therapy. If the drug has been recently taken, the stomach should be flushed; if necessary, correction of water-electrolyte disturbances is carried out.
Losartan and its active metabolites are not removed by hemodialysis.

INTERACTION WITH OTHER MEDICINAL PRODUCTS

Losartan enhances the effect of other antihypertensive drugs. There was no clinically significant interaction with hydrochlorothiazide, digoxin, indirect anticoagulants, cimetidine, phenobarbital, ketoconazole, erythromycin.
Like other drugs that block angiotensin II or its action, the simultaneous administration of potassium-sparing diuretics (for example, spironolactone, triamterene, amiloride), potassium preparations or salt substitutes containing potassium can lead to hyperkalemia.
Hydrochlorothiazide
The following drugs can interact with thiazide diuretics when given concomitantly:
Barbiturates, narcotics, ethanol - potentiation of orthostatic hypotension may occur.
Hypoglycemic agents (oral agents and insulin) - dose adjustment of hypoglycemic agents may be required.
Other antihypertensive drugs - an additive effect is possible.
Cholestyramine reduces the absorption of hydrochlorothiazide.
Corticosteroids, ACTH - increase the loss of electrolytes, especially potassium.
Pressor amines - a slight decrease in the effect of pressor amines is possible without interfering with their use.
Non-depolarizing muscle relaxants (for example, tubocurarine) - it is possible to enhance the action of muscle relaxants.
Lithium preparations - diuretics reduce the renal clearance of Li + and increase the risk of lithium intoxication, therefore, simultaneous use is not recommended.
Non-steroidal anti-inflammatory drugs (NSAIDs) - in some patients, the use of NSAIDs can reduce the diuretic, natriuretic and hypotensive effects of diuretics.

Impact on laboratory results
Due to their effect on calcium excretion, thiazides can interfere with the results of the analysis of the function of the parathyroid glands.

SPECIAL INSTRUCTIONS

LOZAP PLUS can be prescribed together with other antihypertensive drugs.
There is no need for a special selection of the initial dose for elderly patients.
The drug can increase the concentration of urea and creatinine in the blood plasma
in patients with bilateral renal artery stenosis or renal artery stenosis of a solitary kidney.
Hydrochlorothiazide can increase arterial hypotension and disturbances in water and electrolyte balance (decrease in circulating blood volume, hyponatremia, hypochloremic alkalosis, hypomagnesemia, hypokalemia), impair glucose tolerance, reduce the excretion of Ca2 + in the urine and cause a transient slight increase in the concentration of Ca2 + cholesterol and triglycerides, provoke the occurrence of hyperuricemia and / or gout.
Taking drugs that directly act on the renin-angiotensin system during the II and III trimesters of pregnancy can lead to fetal death. When pregnancy occurs, drug withdrawal is indicated.
The use of diuretics is usually not recommended for pregnant women due to the risk of jaundice in the fetus and newborn, maternal thrombocytopenia. Diuretic therapy does not prevent the development of pregnancy toxicosis.
There is no information on the effect on the ability to drive a car and other mechanisms.

RELEASE FORM

14 tablets in a blister, 2 blisters (28 tablets) together with instructions for use are placed in a cardboard box.

STORAGE CONDITIONS

List B.

Store in a dry place out of the reach of children at temperatures up to 30 ° C.

SHELF LIFE

2 years.
Do not use later than the date indicated on the package.

TERMS OF RELEASE FROM PHARMACIES

On prescription.

MANUFACTURER

ZENTIVA a.s., 130, 102 37 Prague 10,
Czech Republic

Losartan enhances the effect of other antihypertensive drugs. There was no clinically significant interaction with digoxin, indirect anticoagulants, cimetidine, phenobarbital, ketoconazole, erythromycin.

As with other drugs that block angiotensin II or its action, the simultaneous administration of potassium-sparing diuretics (for example spironolactone, triamterene, amiloride), potassium preparations or salt substitutes containing potassium can lead to hyperkalemia.

Hydrochlorothiazide. The following drugs can interact with thiazide diuretics while prescribing the following drugs:

barbiturates, narcotic pain relievers, ethanol - potentiation of orthostatic hypotension may occur;

hypoglycemic agents (oral agents and insulin) - dose adjustment of hypoglycemic agents may be required;

other antihypertensive drugs - an additive effect is possible;

cholestyramine - reduced absorption of hydrochlorothiazide;

corticosteroids, ACTH - increased loss of electrolytes, especially potassium;

non-depolarizing muscle relaxants (for example tubocurarine) - it is possible to enhance the action of muscle relaxants;

lithium preparations - diuretics reduce the renal clearance of Li + and increase the risk of lithium intoxication, therefore, simultaneous use is not recommended;

NSAIDs - in some patients, the use of NSAIDs can reduce the diuretic, natriuretic and hypotensive effects of diuretics.

Due to their effect on calcium excretion, thiazides can interfere with the results of the analysis of the function of the parathyroid glands.

Losartan is rapidly absorbed from the gastrointestinal tract. Bioavailability is about 33%. Has the effect of "first pass" through the liver, is metabolized by carboxylation to form an active metabolite. Plasma protein binding - 99%. The time to reach C max of losartan is 1 hour, the active metabolite is 3-4 hours after ingestion. T 1/2 - 1.5-2 hours, and its main metabolite - 3-4 hours, respectively. About 35% of the dose is excreted in the urine, about 60% through the intestines.

Hydrochlorothiazide is rapidly absorbed from the gastrointestinal tract. T 1/2 - 5.8-14.8 hours Not metabolized by the liver. About 61% is excreted by the kidneys unchanged.

The combined drug has a hypotensive effect. Contains losartan potassium - an angiotensin II receptor antagonist (AT 1 subtype) - and hydrochlorothiazide - a diuretic.

Losartan is a specific angiotensin II receptor antagonist (AT 1 subtype).

Does not inhibit kinase II, an enzyme that degrades bradykinin. Reduces OPSS, blood concentration of adrenaline and aldosterone, blood pressure, pressure in the pulmonary circulation; reduces afterload, has a diuretic effect. Prevents the development of myocardial hypertrophy, increases exercise tolerance in patients with chronic heart failure.

Hydrochlorothiazide is a thiazide diuretic. Reduces reabsorption of Na +, enhances urinary excretion of K +, bicarbonate and phosphates. Lowers blood pressure by reducing the BCC, changing the reactivity of the vascular wall, reducing the pressor effect of vasoconstrictor substances.

Arterial hypertension (in patients for whom combination therapy is optimal).

hypersensitivity to drug components;

severe arterial hypotension;

severe violations of liver and kidney function (Cl creatinine<30 мл/с);

hypovolemia (including against the background of high doses of diuretics);

pregnancy;

lactation period;

age up to 18 years (efficacy and safety have not been established).

Carefully:

patients with bilateral renal stenosis or stenosis of a solitary kidney artery;

patients with diabetes mellitus, hypercalcemia, hyperuricemia and / or gout;

patients with a burdened allergic history and bronchial asthma, as well as with systemic diseases of the connective tissue (including systemic lupus erythematosus).

Taking drugs that directly affect the renin-angiotensin system during the II and III trimesters of pregnancy can lead to fetal death. When pregnancy occurs, drug withdrawal is indicated.

The use of diuretics is usually not recommended for pregnant women due to the risk of jaundice in the fetus and newborn, thrombocytopenia in the mother. Diuretic therapy does not prevent the development of pregnancy toxicosis.

Inside, regardless of food intake.

The usual starting and maintenance dose is 1 table. in a day. For those patients in whom, at this dosage, it is not possible to achieve adequate blood pressure, the dose of the drug can be increased to 2 tablets. 1 per day.

The maximum dose is 2 tablets. 1 per day. In general, the maximum antihypertensive effect is achieved within 3 weeks after starting treatment.

There is no need for a special selection of the initial dose in elderly patients.

Adverse reactions are limited to those previously observed with the use of losartan potassium and / or hydrochlorothiazide.

Dizziness is the most common side effect of essential hypertension.

Allergic reactions: angioedema, including edema of the larynx and / or tongue, leading to airway obstruction, and / or edema of the face, lips, pharynx and / or tongue, occasionally noted with losartan.

Some of the patients with the aforementioned allergic reactions have previously experienced angioedema when using other drugs, incl. and ACE inhibitors. It is extremely rare when taking losartan manifestations of vasculitis, including Shenlein-Henoch disease, were noted.

On the part of the cardiovascular system: decrease in blood pressure.

From the digestive tract: while taking losartan, rare (<1%) случаи гепатита, диарея.

From the respiratory system: when taking losartan - cough.

From the side of the skin: hives.

Laboratory indicators: seldom (<1%) — гиперкалиемия (калий сыворотки >5.5 mmol / l), increased activity of hepatic transaminases.

Symptoms: losartan - a marked decrease in blood pressure, tachycardia, bradycardia (as a result of vagal stimulation);

hydrochlorothiazide - loss of electrolytes (hypokalemia, hyperchloremia, hyponatremia), as well as dehydration resulting from excessive diuresis.

Treatment: symptomatic and supportive therapy. If the drug has been recently taken, the stomach should be flushed; if necessary, correction of water-electrolyte disturbances is carried out.

Losartan and its active metabolites are not removed by hemodialysis.

Lozap plus can be prescribed together with other antihypertensive drugs.

The drug can increase the concentration of urea and creatinine in the blood plasma in patients with bilateral renal artery stenosis or renal artery stenosis of a single kidney.

Hydrochlorothiazide can increase disturbances in water-electrolyte balance (decrease in BCC, hyponatremia, hypochloremic alkalosis, hypomagnesemia, hypokalemia), impair glucose tolerance, reduce the excretion of Ca 2+ in the urine and cause a transient slight increase in the concentration of Ca 2+ in the blood plasma of cholesterol, increase and triglycerides, provoke the occurrence of hyperuricemia and / or gout.

There is no information on the effect on the ability to drive a car and other mechanisms.

In a dry place, at a temperature not exceeding 30 ° C

90 tablets for oral administration in a pack.

pharmachologic effect

The combined drug has a hypotensive effect. Contains losartan potassium - an angiotensin II receptor antagonist (AT1 subtype) and hydrochlorothiazide - a diuretic.

Indication for use

• arterial hypertension (in patients for whom combination therapy is optimal);
• reducing the risk of cardiovascular disease and mortality in patients with arterial hypertension and left ventricular hypertrophy.

Method of administration and dosage

The drug is taken orally, regardless of food intake.

• When arterial hypertension the usual initial and maintenance dose is 1 tablet / day. If, when using the drug in this dose, it is not possible to achieve adequate blood pressure control, the dose of Lozap Plus can be increased to 2 tab. 1 time / day

The maximum dose is 2 tab. 1 time / day In general, the maximum antihypertensive effect is achieved within 3 weeks after starting treatment.

• FROM to reduce the risk of cardiovascular disease and mortality in patients with arterial hypertension and left ventricular hypertrophy losartan (Lozap) is prescribed at a standard initial dose of 50 mg / day. Patients who failed to achieve the target blood pressure level while using losartan at a dose of 50 mg / day need to select therapy by combining losartan with hydrochlorothiazide at a low dose (12.5 mg), which is ensured by the appointment of Lozap Plus. If necessary, the dose of Lozap Plus can be increased to 2 tab. (Losartan 100 mg and hydrochlorothiazide 25 mg) 1 time / day.

Contraindications

• therapy-resistant hypokalemia or hypercalcemia;
• severe liver dysfunction;
• obstructive diseases of the biliary tract;
• refractory hyponatremia;
• hyperuricemia and / or gout;
• severe renal dysfunction (CC≤30 ml / min);
• anuria;
• pregnancy;
• period of breastfeeding;
• age up to 18 years (efficacy and safety have not been established);
• hypersensitivity to any of the components of the drug or to other drugs that are derivatives of sulfonylamide.

Storage conditions

The drug should be stored out of the reach of children at a temperature not exceeding 30 ° C.