Lozap plus pills 50mg + 12.5 mg №60

Indications and usage

- arterial hypertension (in patients for whom combination therapy is optimal);

- reducing the risk of cardiovascular diseases and mortality in patients with arterial hypertension and left ventricular hypertrophy.

The drug is taken orally, regardless of the meal.

At hypertension the usual initial and maintenance dose is 1 tab. / day. If the use of the drug in this dose fails to achieve adequate control of blood pressure, 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 hypotensive effect is achieved within 3 weeks after the start of treatment.

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

WITH to reduce the risk of cardiovascular disease and mortality in patients with arterial hypertension and left ventricular hypertrophy prescribe Losartan (Lozap^®) in the standard initial dose of 50 mg / day. Patients who failed to achieve the target level of blood pressure while using losartan at a dose of 50 mg / day require selection of therapy by combining losartan with hydrochlorothiazide at a low dose (12.5 mg), which is ensured by administering Lozap^® A plus. If necessary, the dose of the drug Lozap^® Plus, you can increase to 2 tab. (100 mg of losartan and 25 mg of hydrochlorothiazide) 1 time / day.

Adverse reactions

Undesirable reactions are distributed according to the frequency of development as follows: very frequent (≥ 1/10); frequent (≥ 1/100 and up to <1/10); infrequent (≥ 1/1000 and up to <1/100); rare (≥ 1/10 000 and up to <1/1000); very rare (<1/10 000), frequency unknown (cannot be calculated based on available data).

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

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

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

Liver and biliary tract: rare - hepatitis.

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

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

Losartan

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

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

Metabolism and nutrition: infrequent - anorexia, gout.

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

From the nervous system: frequent - headache, dizziness; infrequent - hyperexcitability, paresthesia, peripheral neuropathy, tremor, migraine, syncope.

On the part 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 side of 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, sinus bradycardia, tachycardia, ventricular tachycardia, fibroids, sinus bradycardia, tachycardia, ventricular tachycardia, fibroids, sinus bradycardia, tachycardia, ventricular tachycardia, fibroids, sinus bradycardia, tachycardia, ventricular tachycardia, sinus bradycardia, tachycardia, fibrillation

From the side of the vessels: infrequent - vasculitis.

From the side 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.

Liver and biliary tract: frequency unknown - abnormal liver function.

Skin and Subcutaneous Tissues: infrequent - alopecia, dermatitis, dry skin, erythema, hyperemia, photosensitivity, itching, rash, sweating.

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

From the kidneys and urinary tract: infrequent - nocturia, imperative urination, urinary tract infections.

From the reproductive system: infrequent - decrease in a libido, decrease in a potentiality.

On the part of the body as a whole: frequent - asthenia, fatigue, chest pain; infrequent - puffiness of the person, fever.

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

Hydrochlorothiazide

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

On the part of the immune system: rare - anaphylactic reactions up to shock.

Metabolism: infrequent - anorexia, hyperglycemia, hyperuricemia, hypokalemia, hypomagnesia, hyponatremia, hypercalcemia, hypochloraemic alkalosis.

From the psyche: infrequent - insomnia.

From the nervous system: infrequent - headache.

On the part of the organ of vision: infrequent - temporary decrease in visual acuity, xanthopsia.

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

On the part of the respiratory system: infrequent - respiratory distress syndrome, including pneumonitis and non-cardiogenic pulmonary edema.

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

Liver and biliary tract: infrequent - cholestatic jaundice, cholecystitis, pancreatitis.

Skin and Subcutaneous Tissues: infrequent - photosensitivity, urticaria, toxic epidermal necrolysis.

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

From the kidneys and urinary tract: infrequent - glycosuria, interstitial nephritis, renal dysfunction, renal failure.

On the part of the body as a whole: infrequent - fever, dizziness.

- hypokalemia or hypercalcemia resistant to treatment;

- severe liver dysfunction;

- obstructive diseases of the biliary tract;

- refractory hyponatremia;

- hyperuricemia and / or gout;

- pronounced impaired renal function (CK≤30 ml / min);

- anuria;

- pregnancy;

- breastfeeding period;

- 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, which are derivatives of sulfonyl amide.

WITH caution prescribed to patients with bilateral renal artery stenosis or arterial stenosis 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), hypochloramic alkalosis, hypomagnia, connective tissue diseases (including SLE), patients with impaired liver function or with progressive liver diseases, diabetes mellitus, bronchial asthma (including history), burdened allergist cal history, simultaneously with NSAIDs, including COX-2 inhibitors, as well as the representatives of the Negroid race.

Use 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 options with a safety profile. In the case of pregnancy diagnosis during treatment with Lozap^® Plus, treatment should be stopped immediately and alternative treatment should begin.

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

In the case of Lozap^® Plus, in the II and III trimesters of pregnancy, an ultrasound examination of the kidneys and fetal skull is recommended.

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

Hydrochlorothiazide

Experience with hydrochlorothiazide during pregnancy, especially during the first trimester, is limited. Animal studies are insufficient. Hydrochlorothiazide penetrates the placental barrier and is determined in the blood of the umbilical cord. Based on the pharmacological mechanism of action of hydrochlorothiazide, its use during pregnancy may worsen the feto-placental blood flow and lead to abnormalities in the fetus and newborn, such as jaundice, electrolyte imbalance and thrombocytopenia.

Use of the drug Lozap^® Plus is contraindicated during pregnancy.

Use during breastfeeding

Angiotensin II Receptor Antagonists

Due to the lack of information on the use of the drug Lozap^® Plus, during the breastfeeding period, the prescription of the drug during this period is contraindicated.During the period of breastfeeding, preference is given to alternative treatment with a more studied safety profile.

Hydrochlorothiazide

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

Lozap^® Plus is contraindicated in patients with severe liver dysfunction.

These pharmacokinetics indicate a pronounced increase in plasma concentrations of losartan in patients with cirrhosis of the liver. Based on this data, Lozap^® Plus, it should be used with caution in patients with mild or moderate hepatic impairment in history. Experience with losartan in patients with severely impaired liver function is absent.

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

Contraindicated in marked impaired renal function (CK≤30 ml / min).

Reported renal dysfunction due to depression of the RAAS, incl. about renal failure (in particular, in patients whose kidney function depends on the RAAS, for example, in severe heart failure or existing renal impairment).As in the case of the use of other drugs that affect the RAAS, there have been described cases of increased levels of urea and serum creatinine 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 diminish after discontinuation of treatment. Lozap^® Plus, it should be used with caution in patients with bilateral stenosis of the renal arteries or stenosis of the renal artery of a single kidney.

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

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

Losartan

Angioedema

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

Hypotension and decreased BCC

Patients with hypovolemia and / or low sodium levels resulting from intensive use of diuretics, restriction of salt intake with food, diarrhea or vomiting may develop symptomatic arterial hypotension (especially after taking the first dose). It is necessary to carry out the correction of such conditions before taking the drug Lozap^® A plus.

Electrolyte imbalance

Electrolyte imbalance often occurs in patients with impaired renal function, therefore the potassium content in blood plasma and QC are carefully monitored, and the condition of patients with heart failure and QC of 30-50 ml / min should be carefully monitored. Not recommended joint use of the drug Lozap^® Plus, with potassium-sparing diuretics, potassium preparations and potassium-containing salt substitutes.

Liver dysfunction

These pharmacokinetics indicate a pronounced increase in plasma concentrations of losartan in patients with cirrhosis of the liver. Based on this data, Lozap^® Plus, it should be used with caution in patients with mild or moderate hepatic impairment in history. Experience with losartan in patients with severely impaired liver function is absent. Therefore, the drug Lozap^® Plus is contraindicated in patients with severe liver dysfunction.

Renal dysfunction

Reported renal dysfunction due to depression of the RAAS, incl. about renal failure (in particular, in patients whose kidney function depends on the RAAS, for example, in severe heart failure or existing renal impairment). As in the case of the use of other drugs that affect the RAAS, there have been described cases of increased levels of urea and serum creatinine 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 diminish after discontinuation of treatment. Lozap^® Plus, it should be used with caution in patients with bilateral stenosis of the renal arteries or with stenosis of the renal artery of a single kidney.

Kidney transplantation

The experience of using the drug in patients who have recently undergone kidney transplantation is absent.

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 the drug Lozap^® Plus not recommended.

CHD and cerebrovascular disease

As with any other antihypertensive drugs, 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 kidney dysfunction) are at risk of developing severe arterial hypotension, as well as kidney dysfunction (often acute).

Aortic and mitral valve stenosis, obstructive hypertrophic cardiomyopathy

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

Ethnicity Differences

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

Hydrochlorothiazide

Hypotension and impaired water-electrolyte balance

As with the treatment of any other antihypertensive drugs, symptomatic arterial hypotension may develop in individual patients. Patients should be monitored for clinical signs of impaired water and electrolyte balance, 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 the levels of electrolytes in the serum. Patients with edema in hot weather may develop hypervolemic hyponatremia.

Endocrine and metabolic effects

Treatment with thiazides may result in impaired glucose tolerance. It may be necessary to adjust the dose of antidiabetic drugs, incl. insulin . During treatment with thiazides in patients with impaired glucose tolerance, diabetes can occur.

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

Treatment with thiazide diuretics may be accompanied by increased levels of cholesterol and triglycerides in the blood.

In some patients, thiazide treatment may trigger hyperuricemia and / or gout. Since losartan reduces uric acid levels, the use of losartan in combination with hydrochlorothiazide may slow the development of hyperuricemia due to the action of a diuretic.

Liver dysfunction

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

Lozap^® Plus is contraindicated in patients with severe liver dysfunction.

Other

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

The preparation contains the dye Puntsovy [Ponso 4R], which can cause allergic reactions.

Influence on ability to drive motor transport and control mechanisms

Studies on the effects 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 during treatment with antihypertensive drugs, dizziness or drowsiness may occur while driving or working with mechanisms, especially when starting treatment or increasing the dosage of the drug.

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

Losartan

Most frequent by symptoms overdose are marked reduction in blood pressure and tachycardia; bradycardia may be a consequence of parasympathetic (vagal) stimulation.

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

Hydrochlorothiazide

Most frequent by symptoms overdose results from electrolyte deficiency (hypokalemia, hypochloremia, hyponatremia) and dehydration due to excessive diuresis. With simultaneous intake of cardiac glycosides, hypokalemia can aggravate the course of arrhythmias.

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

Losartan

Cases of a decrease in the concentration of the active metabolite with the combined use of rifampicin and Fluconazole have been described. Evaluation of the clinical data of such interactions was not conducted.

As with 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 may lead to an increase in serum potassium. The combined use of these drugs is not recommended. As with other drugs that affect the excretion of sodium, the drug can slow 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 simultaneous use of ARA II and NSAIDs, for example, selective COX-2 inhibitors, Acetylsalicylic acid in doses used for the anti-inflammatory effect, and non-selective NSAIDs, a weakening of the antihypertensive effect of Lozap may be observed.^® A plus.The simultaneous use of ARA II or diuretic drugs and NSAIDs may be the reason for the increased risk of deterioration of renal function, including acute renal failure and increased serum potassium levels, especially in patients with initial impaired renal function. Combined treatment should be prescribed with caution, especially in elderly patients. Patients should be adequately hydrated and renal function should be monitored after the start of the combined treatment and periodically during the treatment process.

In some patients with impaired renal function, receiving NSAIDs, including selective inhibitors of COX-2, the simultaneous use of angiotensin II receptor antagonists can exacerbate renal dysfunction. These effects are usually reversible.

Other drugs that cause hypotension, such as tricyclic antidepressants, antipsychotics, Baclofen, amifostine: simultaneous use of Lozap^® Plus, with these drugs that reduce 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 preparations): treatment with thiazide diuretics may affect glucose tolerance. May require dose adjustment of antidiabetic drugs. Metformin should be used with caution because of the risk of lactic acidosis caused by possible functional renal failure associated with the use of hydrochlorothiazide.

Other antihypertensive drugs: additive effect.

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

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

Pressor amines (eg, adrenaline): It is possible to reduce the effect of pressor amines, however, not precluding their use.

Non-polarizing muscle relaxants (for example, tubocurarine chloride): may increase the action of muscle relaxants.

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

Preparations for the treatment of gout (probenecid, sulfinpirazon and allopurinol): Dosage adjustment of anti-gout drugs may be necessary, since hydrochlorothiazide may increase serum uric acid levels.Combined 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 the rate of gastric emptying.

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

Salicylates: in the case of the use of high doses of salicylates, hydrochlorothiazide may enhance 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 arrhythmias induced by digitalis preparations.

Drugs that are affected by changes in serum potassium levels: while appointing lozap^® Plus, with drugs that are affected by changes in potassium levels (for example, digitalis glycosides and antiarrhythmic drugs), it is recommended to regularly monitor serum potassium levels and ECG monitoring.These measures are also recommended when simultaneous application of Lozap^® Plus with the following drugs that can cause ventricular tachycardia of the "pirouette" type (including antiarrhythmic), since hypopotassemia is a factor predisposing to the development of pirouette tachycardia: class IA antiarrhythmic drugs (for example, quinidine, hydroquinidine, disopyramide), antiarrhythmic drugs class III (for example, Amiodarone, sotalol, dofetilide, ibutilid), some antipsychotic drugs (for example, thioridazine, chlorpromazine, levomepromazine, trifluoperazin, cyamemazine, sulpride, sultrided, amisulpri, Tiapride, pimozide, Haloperidol, droperidol), others (e.g., bepridil, cisapride, difemanil, Erythromycin w / w, halofantrine, mizolastine, pentamidine, terfenadine, vinkamitsin w / w).

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

Impact on laboratory results: due to the effect on calcium metabolism, thiazides may distort test results to evaluate the function of the parathyroid glands.

Carbamazepine: there is a risk of symptomatic hyponatremia. Clinical observation and laboratory monitoring of sodium in the blood in patients taking Carbamazepine is necessary.

Iodine-containing contrast agents: in the case of dehydration caused by the use of diuretics, the risk of developing acute renal failure increases, especially when taking high doses of Iodine preparations. Before their introduction, patients should be rehydrated.

Amphotericin B (for parenteral administration), GCS, ACTH, stimulant laxatives or glycyrrhizin (contained in licorice): hydrochlorothiazide may cause the development of electrolyte deficiency, especially hypokalemia.

List B. The drug should be stored in a dry place inaccessible to children at a temperature not exceeding 30 ° C.