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Lozap plus is an antihypertensive combination drug (angiotensin II receptor antagonist + diuretic).

Release form and composition

The dosage form of Lozapa plus is film-coated tablets: light yellow, oblong, with a halving line on one and the other side (in blisters of 10, 14 or 15 pcs., in a cardboard pack of 1, 3, 6 or 9 blisters of 10 pcs., 2 blisters of 14 pcs., 2, 4 or 6 blisters of 15 pcs.).

Active ingredients in 1 tablet:

• losartan potassium – 50 mg;
• hydrochlorothiazide – 12.5 mg.

Auxiliary components: magnesium stearate – 3.5 mg; povidone – 7 mg; croscarmellose sodium – 18 mg; microcrystalline cellulose – 210 mg; mannitol – 89 mg.

Shell: titanium dioxide – 0.1288 mg; simethicone emulsion – 0.3 mg; talc – 1.9 mg; macrogol 6000 – 0.8 mg; hypromellose 2910/5 – 6.8597 mg; crimson dye (E 124) – 0.0005 mg; quinoline yellow dye (E 104) – 0.011 mg.

Indications for use

• arterial hypertension (in cases where combined treatment is optimal);
• the risk of developing cardiovascular pathologies and mortality against the background of left ventricular hypertrophy and arterial hypertension (to reduce it).

Contraindications

• severe liver dysfunction;
• severe renal impairment [creatinine clearance (CC) less than 30 ml/min];
• cholestasis;
• obstructive pathologies of the biliary tract;
• refractory hyponatremia;
• refractory hypercalcemia or hypokalemia;
• anuria;
• gout and (or) symptomatic hyperuricemia;
• combination therapy with angiotensin-converting enzyme inhibitors for diabetic nephropathy, drugs that include aliskiren, against the background of diabetes mellitus, moderate and severe renal failure;
• age under 18 years;
• pregnancy;
• breastfeeding period;
• individual intolerance to the components contained in the drug, other sulfonamide derivatives.

Conditions/diseases for which Lozap plus tablets are prescribed with caution:

• hyponatremia (due to the high risk of developing arterial hypotension while following a low-salt or salt-free diet);
• stenosis of the artery of a single kidney or bilateral stenosis of the renal arteries;
• hypovolemic conditions, including vomiting and diarrhea;
• hypomagnesemia;
• hypochloremic alkalosis;
• connective tissue pathologies, including systemic lupus erythematosus;
• liver dysfunction of mild or moderate severity (including a history) and progressive pathologies of the organ;
• diabetes;
• bronchial asthma, including a history;
• complicated allergy history;
• history of angioedema;
• belonging to the Negroid race;
• heart failure with concomitant severe renal failure;
• severe chronic heart failure functional class IV according to the NYIIA classification;
• heart failure accompanied by life-threatening arrhythmias;
• cerebrovascular diseases;
• cardiac ischemia;
• aortic and mitral stenosis;
• hypertrophic obstructive cardiomyopathy;
• condition after kidney transplantation (due to lack of experience in use);
• hyperkalemia;
• primary hyperaldosteronism;
• angle-closure glaucoma and (or) acute attack of myopia;
• combination treatment with non-steroidal anti-inflammatory drugs, including cyclooxygenase-2 inhibitors, potassium-containing salt substitutes, potassium preparations, potassium-sparing diuretics, metformin;
• age over 75 years.

Lozap plus: instructions for use (method and dosage)

Lozap plus tablets are taken orally, regardless of food.

The drug is not used as initial therapy for arterial hypertension. Lozap plus is intended for the treatment of patients in whom adequate blood pressure control is not achieved with monotherapy with losartan or hydrochlorothiazide. Before prescribing the drug, a preliminary titration of the doses of its active components is carried out.

In most cases, the initial and maintenance dose is 1 pc. per day. If taking these doses does not provide adequate blood pressure control, they are increased to the maximum dose of 2 pcs. 1 time per day.

The maximum hypotensive effect is mainly achieved within 21–28 days from the start of taking Lozap plus.

To reduce the risk of developing cardiovascular pathologies and mortality in arterial hypertension and left ventricular hypertrophy, 0.05 g of losartan per day is usually prescribed. If the target blood pressure levels are not achieved, treatment is selected by combining losartan with low doses of hydrochlorothiazide (0.0125 g). If necessary, the dose of losartan can be increased to 0.1 g per day in combination with 0.0125 g of hydrochlorothiazide per day (the hypotensive effect is achieved within 21–28 days from the start of taking Lozap plus).

Before starting to take the tablets, patients with a reduced circulating blood volume (BCV) undergo correction of the circulating blood volume and (or) sodium content in the blood plasma.

Side effects

Possible adverse reactions (> 10% - very common; > 1% and< 10% – часто; >0.1% and< 1% – нечасто; >0.01% and< 0,1% – редко; < 0,01% – очень редко):

• nervous system: frequency unknown – dysgeusia;
• vessels: frequency unknown – dose-dependent orthostatic effect;
• skin and subcutaneous tissues: frequency unknown - cutaneous form of systemic lupus erythematosus;
• liver and biliary tract: rarely – hepatitis;
• laboratory and instrumental studies: rarely - increased activity of liver transaminases, hyperkalemia.

Side effects caused by losartan

• blood and lymphatic system: infrequently - hemolysis, ecchymosis, Schonlein-Henoch disease, anemia; frequency unknown - thrombocytopenia;
• immune system: rarely - hypersensitivity reactions [angioedema, including swelling of the tongue, pharynx and (or) lips or swelling of the larynx and vocal folds with the development of airway obstruction], anaphylactic reactions;
• metabolism and nutrition: infrequently – gout, anorexia;
• psyche: often – insomnia; uncommon – depression, unusual dreams, sleep disturbance, drowsiness, memory impairment, confusion, panic disorder, anxiety disorder, anxiety;
• nervous system: often – dizziness, headache; uncommon – syncope, migraine, tremor, peripheral neuropathy, paresthesia, increased excitability;
• organ of vision: infrequently - decreased visual acuity, conjunctivitis, burning sensation in the eyes, blurred vision;
• organ of hearing and labyrinthine disorders: infrequently - tinnitus, vertigo;
• heart: infrequently - arrhythmias (ventricular fibrillation, ventricular tachycardia, sinus bradycardia, tachycardia, atrial fibrillation), palpitations, myocardial infarction, cerebrovascular accident, second degree atrioventricular block, angina pectoris, pain in the sternum, orthostatic hypotension, marked decrease in blood pressure ;
• vessels: infrequently – vasculitis;
• respiratory system, chest and mediastinal organs: often – sinusitis, nasal congestion, upper respiratory tract infections, cough; uncommon – respiratory tract congestion, rhinitis, nosebleeds, bronchitis, dyspnea, laryngitis, pharyngitis, discomfort in the throat;
• gastrointestinal tract: often – dyspepsia, diarrhea, nausea, abdominal pain; uncommon – intestinal obstruction, vomiting, gastritis, flatulence, dry mouth, toothache, constipation;
• liver and biliary tract: frequency unknown - liver dysfunction;
• skin and subcutaneous tissues: uncommon - increased sweating, skin rash, urticaria, itching, photosensitivity, hyperemia, erythema, dry skin, dermatitis, alopecia;
• musculoskeletal and connective tissue: often – myalgia, pain in the lower extremities, back, muscle cramps; uncommon – muscle weakness, fibromyalgia, coxalgia, arthritis, arthralgia, joint stiffness, pain in the upper extremities, muscles and bones, in the shoulder or knee joints, swelling of the joints; frequency unknown – rhabdomyolysis;
• kidneys and urinary tract: often – renal failure, impaired renal function; uncommon – urinary tract infections, frequent urination, nocturia;
• genitals and mammary gland: uncommon – erectile dysfunction, decreased libido;
• general disorders and disorders at the injection site: often - chest pain, fatigue, asthenia; uncommon – fever, peripheral edema, swelling of the face; frequency unknown - weakness, flu-like symptoms;
• laboratory and instrumental data: often - hypoglycemia, slight decrease in hemoglobin and hematocrit, hyperkalemia; infrequently - a slight increase in the concentration of creatinine and urea in the blood plasma; very rarely - increased activity of bilirubin and liver transaminases; frequency unknown - hyponatremia.

Side effects caused by hydrochlorothiazide

• blood and lymphatic system: uncommon – thrombocytopenia, purpura, leukopenia, hemolytic or aplastic anemia, agranulocytosis;
• immune system: rarely - anaphylactic reactions;
• metabolism and nutrition: infrequently - hyponatremia, hypokalemia, hyperuricemia, hyperglycemia, anorexia;
• psyche: infrequently – insomnia;
• nervous system: often – headache;
• organ of vision: infrequently – xanthopsia, temporary decrease in visual acuity;
• vessels: infrequently - cutaneous or necrotizing vasculitis;
• respiratory system, chest and mediastinal organs: infrequently - respiratory distress syndrome, including non-cardiogenic pulmonary edema and pneumonia;
• gastrointestinal tract: uncommon - constipation, diarrhea, vomiting, nausea, gastritis, spasms, sialadenitis;
• liver and biliary tract: uncommon – pancreatitis, cholecystitis, cholestatic jaundice;
• skin and subcutaneous tissues: uncommon – toxic epidermal necrolysis, urticaria, photosensitivity;
• musculoskeletal and connective tissue: uncommon – muscle cramps;
• kidneys and urinary tract: uncommon – renal failure, impaired renal function, interstitial nephritis, glycosuria;
• general disorders and disorders at the injection site: infrequently - dizziness, fever.

Overdose

Main symptoms: decreased blood pressure, electrolyte disturbances, dehydration.

Therapy: discontinuation of Lozap plus, medical observation, symptomatic treatment, gastric lavage if you have recently taken pills.

Overdose due to losartan

Main symptoms: tachycardia, marked decrease in blood pressure, bradycardia, which may be a consequence of vagal stimulation.

Therapy: for symptomatic arterial hypotension - maintenance infusion treatment; the substance and its active metabolite are not excreted by hemodialysis.

Overdose due to hydrochlorothiazide

Main symptoms: hyponatremia, hypochloremia, hypokalemia (consequences of electrolyte deficiency), dehydration associated with excessive diuresis; When combined with cardiac glycosides, hypokalemia can aggravate the course of arrhythmias.

Therapy: there is no specific antidote; how much of the substance can be removed from the body through hemodialysis has not been established.

special instructions

A history of angioedema [of the tongue and/or pharynx, lips, face] requires careful monitoring. A decrease in blood volume and arterial hypotension with hypovolemia and (or) reduced sodium content in the blood due to limited consumption of table salt with food, intensive use of diuretics, vomiting or diarrhea can lead to the development of symptomatic arterial hypotension (especially after taking the first dose of Lozap plus). Correction of such conditions is necessary before starting therapy.

Against the background of impaired renal function, the water-electrolyte balance is often disturbed, and therefore CC and potassium content in the blood plasma must be carefully monitored. Particularly careful monitoring is required for the condition of patients with CC from 30 to 50 ml/min and heart failure.

In liver cirrhosis, according to pharmacokinetics data, there is a marked increase in the concentration of losartan in plasma.

There have been reports of renal dysfunction due to inhibition of the renin-angiotensin system (RAAS), including renal failure, particularly in renal function dependent on the RAAS, for example in the presence of impaired renal function or severe heart failure. As with therapy with other drugs that affect the RAAS, cases of increased concentrations of creatinine and urea in the blood plasma have been described with bilateral renal artery stenosis or renal artery stenosis of a single kidney. Such changes in renal function may be reversible and decrease after discontinuation of therapy.

It should be taken into account that there is no experience with the use of Lozap plus in recent kidney transplantation.

There is usually no response to therapy with antihypertensive drugs that inhibit the RAAS in patients with primary hyperaldosteronism.

An excessive decrease in blood pressure due to coronary heart disease or cerebrovascular disease in patients receiving antihypertensive drugs can lead to stroke or myocardial infarction.

In heart failure with impaired renal function while taking drugs that affect the RAAS (or without impairment), there is a risk of developing severe arterial hypotension, as well as impaired renal function, usually acute.

Losartan and other angiotensin II receptor antagonists, by analogy with other angiotensin-converting enzyme inhibitors, are less effective in lowering blood pressure in black patients compared to representatives of other races. Presumably this is due to more frequent cases of low renin levels in the black population with arterial hypertension.

There is evidence that concomitant therapy with angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists or aliskiren increases the risk of developing renal dysfunction, including renal failure, hyperkalemia and hypotension.

In some cases, when taking hydrochlorothiazide, symptomatic arterial hypotension may develop. It is important to monitor patients for clinical signs of fluid and electrolyte imbalance in the form of hypokalemia, hypomagnesemia, hypovolemic alkalosis, hyponatremia or hypovolemia, which may develop with concomitant vomiting or diarrhea. In such cases, periodic monitoring of the content of electrolytes in the blood plasma is necessary. With edema in hot weather, hypovolemic hyponatremia may occur.

Taking thiazides may impair glucose tolerance. In this regard, dose adjustment of hypoglycemic drugs, including insulin, may be required. During therapy with thiazides, the manifestation of diabetes mellitus is possible with impaired glucose tolerance.

The use of thiazides may cause a slight periodic increase in the concentration of calcium in the blood plasma and a decrease in calcium excretion by the kidneys. Severe hypercalcemia may indicate latent hyperparathyroidism. It is recommended to stop taking thiazides before examining the function of the parathyroid glands.

While taking thiazide diuretics, the concentration of triglycerides and cholesterol in the blood plasma may increase.

In some cases, thiazides can provoke the development of gout and (or) hyperuricemia. Since losartan lowers uric acid concentrations, its use in combination with hydrochlorothiazide may slow the onset of diuretic-induced hyperuricemia.

Thiazides should be used with caution in case of progressive liver pathologies or liver dysfunction, since the development of intrahepatic cholestasis is possible, and also due to the fact that minor disturbances in water and electrolyte balance may be a prerequisite for the development of hepatic coma.

It should be taken into account that the crimson dye contained in Lozapa Plus can cause allergic reactions.

Since drowsiness or dizziness may occur during therapy with antihypertensive drugs, patients must be careful when driving vehicles and performing potentially hazardous activities during treatment.

Use during pregnancy and lactation

According to the instructions, Lozap Plus is contraindicated during pregnancy and breastfeeding.

When planning pregnancy, as well as during lactation, it is recommended to switch to an alternative type of antihypertensive therapy with an established safety profile. If pregnancy is diagnosed while taking the drug, immediate discontinuation of therapy and switch to alternative treatment are required.

Angiotensin II receptor blockers in the second and third trimesters of pregnancy lead to fetotoxic effects (delayed ossification of the skull, oligohydramnios, decreased renal function) and toxicity to the newborn (hyperkalemia, arterial hypotension, renal failure). If taking Lozap plus is necessary during this period, an ultrasound examination of the fetal skull and kidneys is performed.

Children whose mothers received the drug during pregnancy should be carefully monitored for the development of arterial hypotension.

During pregnancy, especially in the first trimester, experience with the use of hydrochlorothiazide is limited. The substance penetrates the placental barrier and is detected in the umbilical cord blood. Given the pharmacological mechanism of action of hydrochlorothiazide, its use during pregnancy may worsen fetoplacental blood flow and cause disturbances in the fetus and newborn (thrombocytopenia, electrolyte imbalance and jaundice).

Hydrochlorothiazide is excreted in breast milk. Thiazides may inhibit milk production and cause increased diuresis.

Use in childhood

Lozapa plus is contraindicated for children under 18 years of age due to the lack of data on the safety and effectiveness of its use in patients in this age group.

For impaired renal function

• severe renal impairment: use is contraindicated;
• condition after kidney transplantation, bilateral renal artery stenosis, stenosis of the artery of a single kidney: Lozap plus is prescribed with caution.

For liver dysfunction

• severe liver dysfunction: contraindicated;
• progressive liver pathologies, mild or moderate liver dysfunction (including history): Lozap plus is used with caution.

Use in old age

For patients over 75 years of age, Lozap plus is prescribed with caution.

Drug interactions

There is evidence of a decrease in the concentration of the active metabolite with the combined use of fluconazole and rifampicin.

When Lozap plus is used in combination with certain drugs/substances, the following effects may develop:

• potassium-containing salt substitutes, potassium preparations, potassium-sparing diuretics (amiloride, triamterene, spironolactone): increase the level of potassium in the blood plasma;
• drugs affecting sodium excretion: may slow down lithium excretion;
• non-steroidal anti-inflammatory drugs, angiotensin receptor antagonists: may weaken the antihypertensive effect of Lozap plus;
• amifostine, baclofen, antipsychotics, tricyclic antidepressants: possible increased risk of arterial hypotension;
• antidepressants, narcotic substances, barbiturates, ethanol: may increase the risk of orthostatic hypotension;
• ion exchange resins: interfere with the absorption of hydrochlorothiazide;
• cholestyramine, colestipol: lead to the binding of hydrochlorothiazide, reducing its absorption from the gastrointestinal tract;
• adrenocorticotropic hormone, corticosteroids: may aggravate electrolyte deficiency, especially hypokalemia;
• pressor amines (adrenaline): hydrochlorothiazide may reduce their effect;
• non-depolarizing muscle relaxants (tubocurarine chloride): hydrochlorothiazide may enhance their effect;
• lithium preparations: hydrochlorothiazide reduces the renal clearance of lithium, significantly increasing the risk of its toxic effects;
• Anticholinergic drugs: may increase the bioavailability of hydrochlorothiazide;
• cytotoxic drugs: hydrochlorothiazide can inhibit their excretion by the kidneys and enhance their myelosuppressive effect;
• salicylates (high doses): hydrochlorothiazide may enhance their toxic effect on the central nervous system;
• cyclosporine: possible increased risk of complications of gout and hyperuricemia;
• calcium salts: hydrochlorothiazide can increase their content in blood plasma;
• carbamazepine: symptomatic hyponatremia may develop.

When Lozap plus is used in combination with drugs whose effect depends on the potassium content in the blood plasma, regular monitoring of the potassium content in the blood plasma and electrocardiogram monitoring are required. Such measures are also necessary when using the drug simultaneously with certain neuroleptics, class 1A and class III antiarrhythmic drugs, and other drugs (vincamine/erythromycin for intravenous administration, terfenadine, pentamidine, mizolastine, halofantrine, difemanil, cisapride, bepridil).

Analogs

Analogues of Lozap plus are Simartan-N, Presartan N, Lorista N, Losartan-N, Losarel Plus, GIZAAR Forte, Hydrochlorothiazide + Losartan, Bloktran GT.

Terms and conditions of storage

Store in a place protected from light and moisture, at temperatures up to 30 °C. Keep away from children.

Shelf life – 3 years.

Conditions for dispensing from pharmacies

Dispensed by prescription.

Price for Lozap plus in pharmacies

Approximate price of Lozap plus film-coated tablets, 30 pcs. per package – 325 rubles, 60 pcs. per package – 678 rubles, 90 pcs. per package – 780 rubles.

The drug should be stored in a dry place, out of reach of children, at a temperature not exceeding 30°C.

Expiration date from date of manufacture

Product description

pharmachologic effect

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 (AT1 subtype). Does not inhibit kinase II, an enzyme that destroys bradykinin. Reduces peripheral vascular resistance, blood concentrations of adrenaline and aldosterone, blood pressure, pressure in the pulmonary circulation; reduces afterload and has a diuretic effect. Prevents the development of myocardial hypertrophy, increases exercise tolerance in patients with chronic heart failure.
Hydrochlorothiazide is a thiazide diuretic. Reduces the reabsorption of sodium ions, increases the excretion of potassium, bicarbonate and phosphate ions in the urine. Lowers blood pressure by reducing blood volume, changing the reactivity of the vascular wall, reducing the pressor effect of vasoconstrictors 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 Cmax of losartan is 1 hour, its active metabolite is 3-4 hours.
Distribution
The binding of losartan to plasma proteins is 99%.
Metabolism
Losartan undergoes a first-pass effect through the liver and is metabolized by carboxylation to form an active metabolite.
Hydrochlorothiazide is not metabolized in the liver.
Removal
T1/2 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 feces.
T1/2 of hydrochlorothiazide is 5.8-14.8 hours. About 61% is excreted unchanged in the urine.

Indications for use

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

Use during pregnancy and lactation

Use during pregnancy
Angiotensin II receptor antagonists (ARA II)
The use of angiotensin II receptor antagonists during pregnancy is contraindicated.
Patients planning pregnancy should switch to alternative antihypertensive therapy options 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 second and third 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 second and third trimesters of pregnancy, an ultrasound scan of the fetal kidneys and skull is recommended.
Children whose mothers took Lozap® Plus during pregnancy should be carefully monitored for the development of arterial hypotension.
Hydrochlorothiazide
Experience with the use of hydrochlorothiazide during pregnancy, especially during the first trimester, is limited. Animal studies are insufficient. Hydrochlorothiazide penetrates the placental barrier and is detected in the umbilical cord blood. Based on the pharmacological mechanism of action of hydrochlorothiazide, its use during pregnancy may impair feto-placental blood flow and lead to fetal and neonatal disorders such as jaundice, electrolyte imbalance and thrombocytopenia.
The use of Lozap® Plus is contraindicated during pregnancy.
Use during breastfeeding
Angiotensin II receptor antagonists
Due to the lack of information on the use of Lozap® Plus during breastfeeding, the use of the drug during this period is contraindicated. During breastfeeding, preference is given to alternative treatments with a better studied safety profile.
Hydrochlorothiazide
Hydrochlorothiazide is excreted in breast milk. Thiazides can cause intense diuresis and may inhibit milk production. Therefore, the use of Lozap® Plus during breastfeeding is contraindicated.

special instructions

Losartan
Angioedema
Patients with a history of angioedema (swelling of the face, lips, pharynx and/or tongue) should be closely monitored.
Hypotension and decreased blood volume
In patients with hypovolemia and/or reduced sodium levels resulting from intensive use of diuretics, dietary salt restriction, diarrhea or vomiting, symptomatic arterial hypotension may develop (especially after taking the first dose). It is necessary to correct such conditions before starting to take Lozap® Plus.
Electrolyte imbalance
Electrolyte imbalances often occur in patients with impaired renal function, so the content of potassium in the blood plasma and creatinine clearance should be carefully monitored; the condition of patients with heart failure and creatinine clearance of 30-50 ml/min should be monitored especially carefully. The combined use of Lozap® Plus with potassium-sparing diuretics, potassium supplements and potassium-containing salt substitutes is not recommended.
Liver dysfunction
Pharmacokinetic data indicate a marked 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 the use of losartan in patients with severe liver dysfunction. Therefore, Lozap® Plus is contraindicated in patients with severe liver dysfunction.
Renal dysfunction
Impaired renal function has been reported due to inhibition of the RAAS, incl. about renal failure (in particular, in patients whose kidney function depends on the RAAS, for example, with severe heart failure or existing renal impairment). As with the use of other drugs that affect the RAAS, cases of increased serum urea and creatinine levels 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 treatment is discontinued. Lozap® Plus should be used with caution in patients with bilateral renal artery stenosis or with renal artery stenosis of a single kidney.
Kidney transplant
There is no experience with the use of the drug in patients who have recently undergone kidney transplantation.
Primary hyperaldosteronism
Patients with primary hyperaldosteronism generally do not respond 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 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 act on the RAAS, patients with heart failure (with or without renal impairment) are at risk of developing severe hypotension as well as renal impairment (often acute).
Aortic and mitral valve stenosis, obstructive hypertrophic cardiomyopathy
As with other vasodilators, special caution should be exercised when treating patients with aortic or mitral stenosis or obstructive hypertrophic cardiomyopathy.
Differences due to ethnicity
By analogy with other ACE inhibitors, losartan and other angiotensin antagonists are markedly less effective in reducing blood pressure in blacks compared to patients of other races. This may be due to more frequent cases of low renin levels in the black population with arterial hypertension.
Hydrochlorothiazide
Arterial hypotension and water-electrolyte imbalance
As with any other antihypertensive drug, symptomatic hypotension may develop in some patients. Patients should be monitored for clinical signs of fluid and electrolyte imbalance, such as hypovolemia, hyponatremia, hypochloremic alkalosis, hypomagnesemia, or hypokalemia, which may develop with 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 may lead to impaired glucose tolerance. Dosage 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 may reduce urinary calcium excretion and cause small intermittent increases in serum calcium levels. Severe hypercalcemia may be a sign of hidden hyperparathyroidism. Before testing 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 may provoke the occurrence of hyperuricemia and/or gout. Because losartan reduces uric acid levels, use of losartan in combination with hydrochlorothiazide may slow the development of diuretic-induced hyperuricemia.
Liver dysfunction
Thiazides should be prescribed with caution to patients with impaired liver function or progressive liver disease due to the risk of developing intrahepatic cholestasis, as well as due to the fact that minor disturbances in 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 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 during treatment with thiazides have been described.
The drug contains the dye Crimson dye [Ponceau 4R], which can cause allergic reactions.
Impact on the ability to drive vehicles and operate machinery
Studies have not been conducted to study the effect of the drug on the ability to drive vehicles or operate machinery. However, it must be taken into account that during treatment with antihypertensive drugs, dizziness or drowsiness may occur when driving or operating machinery, especially when starting treatment or when increasing the dosage of the drug.

With caution (Precautions)

Prescribe with caution to patients with bilateral renal artery stenosis or stenosis of the 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 connective tissue diseases (including SLE), patients with impaired liver function or with progressive liver diseases, diabetes mellitus, bronchial asthma (including a history), aggravated allergic history, simultaneously with NSAIDs, in incl. COX-2 inhibitors, as well as representatives of the Negroid race.

Contraindications

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

Directions for use and doses

The drug is taken orally, regardless of food intake.
For arterial hypertension, the usual initial and maintenance dose is 1 tablet/day. If, when using the drug at this dose, it is not possible to achieve adequate blood pressure control, the dose of Lozap® Plus can be increased to 2 tablets. 1 time/day
The maximum dose is 2 tablets. 1 time/day In general, the maximum hypotensive effect is achieved within 3 weeks after the start of treatment.
There is no need for special selection of the initial dose in elderly patients.
In order 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 starting 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 require selection of therapy by combining losartan with hydrochlorothiazide at a low dose (12.5 mg), which is ensured by prescribing Lozap® Plus. If necessary, the dose of Lozap® Plus can be increased to 2 tablets. (100 mg losartan and 25 mg hydrochlorothiazide) 1 time/day.

Overdose

There is no data on the specific treatment of overdose with Lozap® Plus. Taking Lozap® Plus should be discontinued and the patient should be monitored. In case of overdose, symptomatic therapy is indicated: gastric lavage if the drug has been taken recently, as well as eliminating dehydration, electrolyte disturbances and lowering blood pressure using standard methods (restoring blood volume and water-electrolyte balance).
Losartan
The most common symptoms of overdose are a pronounced decrease in blood pressure and tachycardia; bradycardia may be a consequence of parasympathetic (vagal) stimulation.
In case of symptomatic arterial hypotension, maintenance fluid therapy is indicated. Losartan and its active metabolite are not eliminated by hemodialysis.
Hydrochlorothiazide
The most common symptoms of overdose are due to electrolyte deficiency (hypokalemia, hypochloremia, hyponatremia) and dehydration due to excessive diuresis. When taking cardiac glycosides simultaneously, hypokalemia may aggravate the course of arrhythmias.
There is no specific antidote for an overdose of hydrochlorothiazide. It has not been established to what extent hydrochlorothiazide can be removed from the body by hemodialysis.

Side effect

Adverse reactions are distributed according to frequency as follows: very common (≥ 1/10); frequent (≥ 1/100 and up to In clinical studies with losartan - hydrochlorothiazide, no adverse reactions associated with the combination of drugs were observed.
Adverse reactions are limited to those previously observed with the use of losartan and/or hydrochlorothiazide alone.
In controlled clinical trials for the treatment of essential hypertension in patients receiving losartan and hydrochlorothiazide, the only adverse reaction occurring at an incidence of 1% or more compared with placebo was dizziness. In addition, there are other adverse reactions that have been reported with the use of the losartan/hydrochlorothiazide combination:
From the liver and biliary tract: rare – hepatitis.
From laboratory and instrumental studies: rare – hyperglycemia, increased activity of liver transaminases.
In addition, when using losartan/hydrochlorothiazide, the following adverse reactions may occur, which were observed with the use of each of the components:
Losartan
From the blood and lymphatic system: uncommon - anemia, Henoch-Schönlein 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.
Metabolism and nutrition: uncommon – anorexia, gout.
From the mental side: frequent – ​​insomnia; Uncommon – restlessness, anxiety, panic attacks, confusion, depression, unusual dreams, sleep disturbance, drowsiness, memory impairment.
From the nervous system: frequent – ​​headache, dizziness; uncommon – increased excitability, paresthesia, peripheral neuropathy, tremor, migraine, fainting.
From the organ of vision: infrequent - blurred vision, burning sensation in the eyes, conjunctivitis, decreased visual acuity.
From the organ of hearing and labyrinthine disorders: infrequent - vertigo, ringing in the ears.
From the heart: infrequent - arterial hypotension, orthostatic hypotension, pain in the sternum, angina pectoris, AV block of the second degree, cerebrovascular disorders, myocardial infarction, palpitations, arrhythmias (atrial fibrillation, sinus bradycardia, tachycardia, ventricular tachycardia, ventricular fibrillation).
Vascular disorders: uncommon – vasculitis.
From the respiratory system: frequent - cough, upper respiratory tract infections, nasal congestion, sinusitis; uncommon – pharyngitis, laryngitis, dyspnea, bronchitis, nosebleeds, rhinitis.
From the gastrointestinal tract: frequent – ​​abdominal pain, nausea, diarrhea, dyspepsia; uncommon - constipation, toothache, dry mouth, flatulence, gastritis, vomiting.
From the liver and biliary tract: frequency unknown - impaired liver function.
From the skin and subcutaneous tissues: uncommon - 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; Uncommon – joint swelling, muscle and bone pain, joint stiffness, arthralgia, arthritis, fibromyalgia, muscle weakness; frequency unknown – rhabdomyolysis.
From the kidneys and urinary tract: infrequently - nocturia, imperative urge to urinate, urinary tract infections.
From the reproductive system: infrequent – ​​decreased libido, decreased potency.
From the body as a whole: frequent – ​​asthenia, fatigue, chest pain; Uncommon: swelling of the face, fever.
From laboratory and instrumental studies: frequent - hyperglycemia, slight decrease in hematocrit and hemoglobin; infrequently - a slight increase in serum urea and creatinine levels; very rare – increased levels of liver transaminases and bilirubin.
Hydrochlorothiazide
From the hematopoietic system: uncommon - agranulocytosis, aplastic anemia, hemolytic anemia, leukopenia, purpura, thrombocytopenia.
From the immune system: rare - anaphylactic reactions up to shock.
From the metabolic side: infrequent - anorexia, hyperglycemia, hyperuricemia, hypokalemia, hypomagnesemia, hyponatremia, hypercalcemia, hypochloremic alkalosis.
From the mental side: infrequent – ​​insomnia.
From the nervous system: infrequent – ​​headache.
From the organ of vision: infrequent - temporary decrease in visual acuity, xanthopsia.
Vascular disorders: uncommon – necrotizing vasculitis, cutaneous vasculitis.
From the respiratory system: uncommon - respiratory distress syndrome, including pneumonitis and non-cardiogenic pulmonary edema.
From the gastrointestinal tract: infrequent - sialadenitis, spasms, gastritis, nausea, vomiting, diarrhea, constipation.
From the liver and biliary tract: uncommon – cholestatic jaundice, cholecystitis, pancreatitis.
From the skin and subcutaneous tissues: uncommon – photosensitivity, urticaria, toxic epidermal necrolysis.
From the musculoskeletal system and connective tissue: infrequent – ​​muscle cramps.
From the kidneys and urinary tract: uncommon - glycosuria, interstitial nephritis, renal dysfunction, renal failure.
From the body as a whole: infrequent – ​​fever, dizziness.

Compound

In 1 tab.
losartan potassium 50 mg,
hydrochlorothiazide 12.5 mg: Excipients: mannitol - 89 mg, microcrystalline cellulose - 210 mg, croscarmellose sodium - 18 mg, povidone - 7 mg, magnesium stearate - 3.5 mg. Film shell composition: hypromellose 2910/5 - 6.8597 mg, macrogol 6000 - 1.9 mg, talc - 0.8 mg, simethicone emulsion - 0.3 mg, titanium dioxide - 0.1288 mg, quinoline yellow dye (E104) - 0.011 mg, dye crimson [Pounceau 4R] (Pounceau 4R) (E124) - 0.0005 mg.

Interaction with other drugs

Losartan
Cases of decreased concentrations of the active metabolite have been described with the combined use of rifampicin and fluconazole. Clinical evidence for such interactions has not been evaluated.
As with other drugs that block angiotensin II or its effects, concomitant use of potassium-sparing diuretics (eg, spironolactone, triamterene, amiloride), potassium supplements, or potassium-containing salt substitutes may result in increased 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, when prescribing lithium salts and ARA II simultaneously, 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 COX-2 inhibitors, acetylsalicylic acid in doses used for anti-inflammatory effect, and non-selective NSAIDs, a weakening of the antihypertensive effect of Lozap® Plus may be observed. The simultaneous use of ARB II or diuretics and NSAIDs may cause an increased risk of deterioration of renal function, incl. acute renal failure and increased serum potassium levels, especially in patients with underlying renal impairment. Combination treatment should be prescribed with caution, especially in elderly patients. Patients should be adequately hydrated and renal function monitored after initiation of combination treatment and periodically during treatment.
In some patients with impaired renal function receiving treatment with NSAIDs, incl. selective COX-2 inhibitors, simultaneous use of angiotensin II receptor antagonists may aggravate renal dysfunction. These effects are usually reversible.
Other drugs that cause hypotension, such as tricyclic antidepressants, antipsychotic drugs, baclofen, amifostine: simultaneous use of Lozap® Plus with these drugs that lower blood pressure may increase the risk of developing arterial hypotension.
Hydrochlorothiazide
When taken simultaneously with thiazide diuretics, interactions with the following substances may occur:
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. Dosage 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 cholestyramine 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: may worsen electrolyte deficiency, especially hypokalemia.
Pressor amines (for example, adrenaline): the effect of pressor amines may be reduced, but this does not preclude their use.
Non-depolarizing muscle relaxants (for example, tubocurarine chloride): the effect of muscle relaxants may be enhanced.
Lithium preparations: Diuretics reduce the 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.
Drugs for the treatment of gout (probenecid, sulfinpyrazone and allopurinol): Dosage adjustment of anti-gout drugs may be necessary 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 the rate of gastric emptying.
Cytotoxic drugs (eg, cyclophosphamide, methotrexate): Thiazide diuretics can inhibit the renal excretion of cytotoxic drugs and enhance their myelosuppressive effect.
Salicylates: When high doses of salicylates are used, hydrochlorothiazide may enhance their toxic effects on the central nervous system.
Methyldopa: Isolated cases of hemolytic anemia have been described in patients receiving hydrochlorothiazide and methyldopa concomitantly.
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: When Lozap® Plus is co-administered with medicines whose effect is influenced 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 using Lozap® Plus simultaneously with the following drugs that can cause torsades de pointes (including antiarrhythmics), since hypokalemia is a factor predisposing to the development of torsades de pointes: class IA antiarrhythmics (for example , quinidine, hydroquinidine, disopyramide), class III antiarrhythmics (eg, amiodarone, sotalol, dofetilide, ibutilide), some antipsychotics (eg, thioridazine, chlorpromazine, levomepromazine, trifluoperazine, cyamemazine, sulpride, sultopride, amisulpride, tiapride, pimozide, haloperidol, droperidol), others (for example, bepridil, cisapride, difemanil, erythromycin IV, halofantrine, mizolastine, pentamidine, terfenadine, vincamycin IV).
Calcium salts: Thiazide diuretics may increase serum calcium levels by decreasing calcium excretion. If the patient is taking calcium supplements, it is necessary to monitor the level of calcium in the blood serum and, accordingly, adjust the dosage of calcium supplements.
Effect on laboratory results: Due to their effect on calcium metabolism, thiazides may interfere with test results to assess parathyroid function.
Carbamazepine: There is a risk of developing symptomatic hyponatremia. Clinical observation and laboratory monitoring of blood sodium levels are necessary in patients taking carbamazepine.
Iodine-containing contrast agents: in case of dehydration caused by the use of diuretics, the risk of acute renal failure increases, especially when taking high doses of iodine preparations. Patients should be rehydrated before administration.
Amphotericin B (parenteral), corticosteroids, ACTH, stimulant laxatives or glycyrrhizin (found in licorice): Hydrochlorothiazide may cause electrolyte deficiency, especially hypokalemia.

Release form

The tablets are light yellow, oblong, film-coated, with a halving line on both sides.

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

in a blister pack 10 pcs.; in a cardboard pack 1, 3 or 9 packages; or in a blister pack 14 pcs.; in a cardboard pack 2 packs.

Oblong tablets, coated with a light yellow color, with a halving line on both sides.

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

As with other drugs that block angiotensin II or its action, concomitant administration of potassium-sparing diuretics (eg, spironolactone, triamterene, amiloride), potassium supplements, or potassium-containing salt substitutes may result in hyperkalemia.

Hydrochlorothiazide. The following drugs may interact with thiazide diuretics when administered simultaneously:

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

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

other antihypertensive drugs—an additive effect is possible;

cholestyramine - decreased absorption of hydrochlorothiazide;

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

non-depolarizing muscle relaxants (for example tubocurarine) - the effect of muscle relaxants may be enhanced;

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

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

Due to their effect on calcium excretion, thiazides may interfere with parathyroid function tests.

Losartan is rapidly absorbed from the gastrointestinal tract. Bioavailability - about 33%. It has a “first pass” effect through the liver and is metabolized by carboxylation to form an active metabolite. Plasma protein binding - 99%. The time to reach Cmax of losartan is 1 hour, the active metabolite is 3-4 hours after oral administration. T1/2 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 is rapidly absorbed from the gastrointestinal tract. T1/2 - 5.8-14.8 hours. Not metabolized by the liver. About 61% is excreted unchanged by the kidneys.

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

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

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

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

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

hypersensitivity to the components of the drug;

severe arterial hypotension;

severe dysfunction of the liver and kidneys (Cl creatinine<30 мл/с);

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

pregnancy;

lactation period;

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

Carefully:

patients with bilateral renal stenosis or stenosis of the artery of a single kidney;

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

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

Taking drugs that directly act on the renin-angiotensin system during the second and third trimesters of pregnancy can lead to fetal death. If pregnancy occurs, discontinuation of the drug is indicated.

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

Inside, regardless of food intake.

The usual initial and maintenance dose is 1 tablet. in a day. For those patients in whom it is not possible to achieve adequate blood pressure at this dosage, 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 hypotensive effect is achieved within 3 weeks after the start of treatment.

There is no need for 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.

The most common side effects in the treatment of essential hypertension include dizziness.

Allergic reactions: Angioedema, including swelling of the larynx and/or tongue leading to airway obstruction, and/or swelling of the face, lips, pharynx and/or tongue, has been reported occasionally with losartan.

Some of the patients with the allergic reactions mentioned above previously experienced angioedema when using other drugs, incl. and ACE inhibitors. Manifestations of vasculitis, including Henoch-Schönlein disease, have been observed extremely rarely when taking losartan.

From the cardiovascular system: decrease in blood pressure.

From the digestive tract: Rare (<1%) случаи гепатита, диарея.

From the respiratory system: when taking losartan - cough.

From the skin: hives.

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

Symptoms: losartan - 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 excess diuresis.

Treatment: symptomatic and supportive therapy. If the drug has been taken recently, the stomach should be rinsed; If necessary, correct water and electrolyte disturbances.

Losartan and its active metabolites are not removed by hemodialysis.

Lozap plus can be prescribed together with other antihypertensive drugs.

The drug may increase plasma urea and creatinine concentrations in patients with bilateral renal artery stenosis or renal artery stenosis of a solitary kidney.

Hydrochlorothiazide may increase water-electrolyte imbalance (decrease in blood volume, 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, increase the concentration of cholesterol and triglycerides, provoke the occurrence of hyperuricemia and/or gout.

There is no information on the effect on the ability to drive a car or use other machinery.

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

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

The question of which of the many antihypertensive drugs are most effective in the treatment of cardiovascular diseases has occupied the minds of cardiologists for decades. As numerous clinical trials have shown, the effectiveness of “old-time” drugs (diuretics, beta-blockers) and representatives of the new pharmacological “wave” (angiotensin-converting enzyme inhibitors, calcium antagonists, BAR) differs, if at all, very slightly. Another conclusion that was made based on 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 we can note an increase in effectiveness due to the influence on various mechanisms of the pathogenesis of arterial hypertension, and a reduction in the risk of side effects due to the use of lower dosages, and a potentiation of the organ-protective effect.

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 a wide range of patients, incl. persons over 45-50 years old. The high hypotensive activity of lozap plus is explained by its 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 incidence 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 the RAAS and SNS, and hydrochlorothiazide, in turn, promoting the removal 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 to be the best. Thus, during the pharmacotherapeutic course, patients experienced a steady decrease in blood pressure to the target level: systolic pressure of 140 mmHg. Art. and lower was achieved in 83% of patients. During treatment, study participants showed a significant decrease in left ventricular hypertrophy, which is a harbinger of an unfavorable outcome of arterial hypertension (against its background, the risk of myocardial infarction increases fourfold, and the risk of stroke increases by 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. The pronounced decrease in glycemia caused by taking 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. The unconditional positive quality of Lozap plus, as well as all BARs, is the best safety profile and tolerability compared to drugs of other pharmacological groups, which, coupled with the high efficiency and organ-protective properties of the drug, determines an improvement in the patient’s quality of life (and this can be achieved in more than 80% of cases). cases) and the prognosis for 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 subtype 1) and hydrochlorothiazide - a diuretic.

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

Hydrochlorothiazide is a thiazide diuretic. Reduces the reabsorption of sodium ions, increases the excretion of potassium, bicarbonate and phosphate ions in the urine. Lowers blood pressure by reducing blood volume, changing the reactivity of the vascular wall, reducing the pressor effect of vasoconstrictors 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 Cmax of losartan is 1 hour, its active metabolite is 3-4 hours.

Distribution

The binding of losartan to plasma proteins is 99%.

Metabolism

Losartan undergoes a first-pass effect through the liver and is metabolized by carboxylation to form an active metabolite.

Hydrochlorothiazide is not metabolized in the liver.

Removal

T1/2 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 feces.

T1/2 of hydrochlorothiazide is 5.8-14.8 hours. About 61% is excreted unchanged in the urine.

Release form

The tablets are light yellow, oblong, film-coated, with a halving 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, dye Opaspray yellow M-1-22801 - 0.5 mg (purified water, titanium dioxide, denatured ethanol (methylated alcohol BP: ethanol 99% and methanol 1%), hypromellose, dye Quinolin Yellow (E104), 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.

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

The maximum dose is 2 tablets. 1 time/day In general, the maximum hypotensive effect is achieved within 3 weeks after the start of treatment.

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

In order to reduce the risk of developing cardiovascular diseases and mortality in patients with arterial hypertension and left ventricular hypertrophy, losartan (Lozap ®) is prescribed at a standard starting 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 require selection of therapy by combining losartan with hydrochlorothiazide at a low dose (12.5 mg), which is ensured by prescribing the drug Lozap ® Plus. If necessary, the dose of Lozap ® Plus can be increased to 2 tablets. (100 mg losartan and 25 mg hydrochlorothiazide) 1 time/day.

Overdose

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

Losartan

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

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

Hydrochlorothiazide

The most common symptoms of overdose are due to electrolyte deficiency (hypokalemia, hypochloremia, hyponatremia) and dehydration due to excessive diuresis. When taking cardiac glycosides simultaneously, hypokalemia may aggravate the course of arrhythmias.

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

Interaction

Losartan

Cases of decreased concentrations of the active metabolite have been described with the combined use of rifampicin and fluconazole. Clinical evidence for such interactions has not been evaluated.

As with other drugs that block angiotensin II or its effects, concomitant use of potassium-sparing diuretics (eg, spironolactone, triamterene, amiloride), potassium supplements, or potassium-containing salt substitutes may result in increased 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, when prescribing lithium salts and ARA II simultaneously, 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 COX-2 inhibitors, acetylsalicylic acid in doses used for anti-inflammatory effect, and non-selective NSAIDs, a weakening of the antihypertensive effect of Lozap ® Plus may be observed. The simultaneous use of ARB II or diuretics and NSAIDs may cause an increased risk of deterioration of renal function, incl. acute renal failure and increased serum potassium levels, especially in patients with underlying renal impairment. Combination treatment should be prescribed with caution, especially in elderly patients. Patients should be adequately hydrated and renal function monitored after initiation of combination treatment and periodically during treatment.

In some patients with impaired renal function receiving treatment with NSAIDs, incl. selective COX-2 inhibitors, simultaneous use of angiotensin II receptor antagonists may aggravate renal dysfunction. These effects are usually reversible.

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

Hydrochlorothiazide

When taken simultaneously with thiazide diuretics, interactions with the following substances may occur:

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. Dosage 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 cholestyramine 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: may worsen electrolyte deficiency, especially hypokalemia.

Pressor amines (for example, adrenaline): the effect of pressor amines may be reduced, but this does not preclude their use.

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

Lithium preparations: Diuretics reduce the 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.

Drugs for the treatment of gout (probenecid, sulfinpyrazone and allopurinol): Dosage adjustment of anti-gout drugs may be necessary 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 the rate of gastric emptying.

Cytotoxic drugs (eg, cyclophosphamide, methotrexate): Thiazide diuretics can inhibit the renal excretion of cytotoxic drugs and enhance their myelosuppressive effect.

Salicylates: When high doses of salicylates are used, hydrochlorothiazide may enhance their toxic effects on the central nervous system.

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

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.

Medicinal products whose effect is influenced by changes in serum potassium levels: When Lozap ® Plus is co-administered with drugs whose effect is influenced 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 using Lozap ® Plus simultaneously with the following drugs that can cause torsades de pointes (including antiarrhythmics), since hypokalemia is a factor predisposing to the development of torsades de pointes: class IA antiarrhythmics (for example , quinidine, hydroquinidine, disopyramide), class III antiarrhythmics (eg, amiodarone, sotalol, dofetilide, ibutilide), some antipsychotics (eg, thioridazine, chlorpromazine, levomepromazine, trifluoperazine, cyamemazine, sulpride, sultopride, amisulpride, tiapride, pimozide, haloperidol, droperidol), others (for example, bepridil, cisapride, difemanil, erythromycin IV, halofantrine, mizolastine, pentamidine, terfenadine, vincamycin IV).

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

Effect on laboratory results: Due to their effect on calcium metabolism, thiazides may interfere with test results to assess parathyroid function.

Carbamazepine: There is a risk of developing symptomatic hyponatremia. Clinical observation and laboratory monitoring of blood sodium levels are necessary in patients taking carbamazepine.

Amphotericin B (parenteral), corticosteroids, ACTH, stimulant laxatives or glycyrrhizin (found in licorice): Hydrochlorothiazide may cause electrolyte deficiency, especially hypokalemia.

Side effects

Adverse reactions are distributed according to frequency as follows: very common (≥ 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, no adverse reactions associated with the drug combination were observed.

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

In controlled clinical trials for the treatment of essential hypertension in patients receiving losartan and hydrochlorothiazide, the only adverse reaction occurring at an incidence of 1% or more compared with placebo was dizziness. In addition, there are other adverse reactions that have been reported with the use of the losartan/hydrochlorothiazide combination:

From the liver and biliary tract: rare – hepatitis.

From laboratory and instrumental studies: rare – hyperglycemia, increased activity of liver transaminases.

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

Losartan

From the blood and lymphatic system: uncommon - anemia, Henoch-Schönlein 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.

Metabolism and nutrition: uncommon – anorexia, gout.

From the mental side: frequent – ​​insomnia; Uncommon – restlessness, anxiety, panic attacks, confusion, depression, unusual dreams, sleep disturbance, drowsiness, memory impairment.

From the nervous system: frequent – ​​headache, dizziness; uncommon – increased excitability, paresthesia, peripheral neuropathy, tremor, migraine, fainting.

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

From the organ of hearing and labyrinthine disorders: infrequent - vertigo, ringing in the ears.

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

Vascular disorders: uncommon – vasculitis.

From the respiratory system: frequent - cough, upper respiratory tract infections, nasal congestion, sinusitis; uncommon – pharyngitis, laryngitis, dyspnea, bronchitis, nosebleeds, rhinitis.

From the gastrointestinal tract: frequent – ​​abdominal pain, nausea, diarrhea, dyspepsia; uncommon - constipation, toothache, dry mouth, flatulence, gastritis, vomiting.

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

From the skin and subcutaneous tissues: uncommon - 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; Uncommon – joint swelling, muscle and bone pain, joint stiffness, arthralgia, arthritis, fibromyalgia, muscle weakness; frequency unknown – rhabdomyolysis.

From the kidneys and urinary tract: infrequently - nocturia, imperative urge to urinate, urinary tract infections.

From the reproductive system: infrequent – ​​decreased libido, decreased potency.

From the body as a whole: frequent – ​​asthenia, fatigue, chest pain; Uncommon: swelling of the face, fever.

From laboratory and instrumental studies: frequent - hyperglycemia, slight decrease in hematocrit and hemoglobin; infrequently - a slight increase in serum urea and creatinine levels; very rare – increased levels of liver transaminases and bilirubin.

Hydrochlorothiazide

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

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

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

From the mental side: infrequent – ​​insomnia.

From the nervous system: infrequent – ​​headache.

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

Vascular disorders: uncommon – necrotizing vasculitis, cutaneous vasculitis.

From the respiratory system: uncommon - respiratory distress syndrome, including pneumonitis and non-cardiogenic pulmonary edema.

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

From the liver and biliary tract: uncommon – cholestatic jaundice, cholecystitis, pancreatitis.

From the skin and subcutaneous tissues: uncommon – photosensitivity, urticaria, toxic epidermal necrolysis.

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

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

From the body as a whole: infrequent – ​​fever, dizziness.

Indications

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

Contraindications

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

Prescribe with caution to patients with bilateral renal artery stenosis or stenosis of the 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 connective tissue diseases (including SLE), patients with impaired liver function or with progressive liver diseases, diabetes mellitus, bronchial asthma (including a history), aggravated allergic history, simultaneously with NSAIDs, in incl. COX-2 inhibitors, as well as representatives of the Negroid race.

Features of application

Use during pregnancy and breastfeeding

Use during pregnancy

Angiotensin II receptor antagonists (ARA II)

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

Patients planning pregnancy should switch to alternative antihypertensive therapy options 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 second and third 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 second and third trimesters of pregnancy, an ultrasound scan of the fetal kidneys and skull is recommended.

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

Hydrochlorothiazide

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

The use of 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 breastfeeding, the use of the drug during this period is contraindicated. During breastfeeding, preference is given to alternative treatments with a better studied safety profile.

Hydrochlorothiazide

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

Use for liver dysfunction

Pharmacokinetic data indicate a marked 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 liver dysfunction. There is no experience with the use of losartan in patients with severe liver dysfunction.

Use for renal impairment

Contraindicated in cases of severe renal impairment (creatinine clearance≤30 ml/min).

Impaired renal function has been reported due to inhibition of the RAAS, incl. about renal failure (in particular, in patients whose kidney function depends on the RAAS, for example, with severe heart failure or existing renal impairment). As with the use of other drugs that affect the RAAS, cases of increased serum urea and creatinine levels 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 treatment is discontinued. Lozap ® Plus should be used with caution in patients with bilateral renal artery stenosis or renal artery stenosis of a single kidney.

Use in children

special instructions

Losartan

Angioedema

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

Hypotension and decreased blood volume

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

Electrolyte imbalance

Electrolyte imbalances often occur in patients with impaired renal function, so the content of potassium in the blood plasma and creatinine clearance should be carefully monitored; the condition of patients with heart failure and creatinine clearance of 30-50 ml/min should be monitored especially carefully. The combined use of Lozap ® Plus with potassium-sparing diuretics, potassium supplements and potassium-containing salt substitutes is not recommended.

Liver dysfunction

Pharmacokinetic data indicate a marked 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 liver dysfunction. There is no experience with the use of losartan in patients with severe liver dysfunction. Therefore, Lozap ® Plus is contraindicated in patients with severe liver dysfunction.

Renal dysfunction

Impaired renal function has been reported due to inhibition of the RAAS, incl. about renal failure (in particular, in patients whose kidney function depends on the RAAS, for example, with severe heart failure or existing renal impairment). As with the use of other drugs that affect the RAAS, cases of increased serum urea and creatinine levels 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 treatment is discontinued. Lozap ® Plus should be used with caution in patients with bilateral renal artery stenosis or with renal artery stenosis of a single kidney.

Kidney transplant

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

Primary hyperaldosteronism

Patients with primary hyperaldosteronism generally do not respond 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 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 act on the RAAS, patients with heart failure (with or without renal impairment) are at risk of developing severe hypotension as well as renal impairment (often acute).

Aortic and mitral valve stenosis, obstructive hypertrophic cardiomyopathy

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

Differences due to ethnicity

By analogy with other ACE inhibitors, losartan and other angiotensin antagonists are markedly less effective in reducing blood pressure in blacks compared to patients of other races. This may be due to more frequent cases of low renin levels in the black population with arterial hypertension.

Hydrochlorothiazide

Arterial hypotension and water-electrolyte imbalance

As with any other antihypertensive drug, symptomatic hypotension may develop in some patients. Patients should be monitored for clinical signs of fluid and electrolyte imbalance, such as hypovolemia, hyponatremia, hypochloremic alkalosis, hypomagnesemia, or hypokalemia, which may develop with 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 may lead to impaired glucose tolerance. Dosage 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 may reduce urinary calcium excretion and cause small intermittent increases in serum calcium levels. Severe hypercalcemia may be a sign of hidden hyperparathyroidism. Before testing 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 may provoke the occurrence of hyperuricemia and/or gout. Because losartan reduces uric acid levels, use of losartan in combination with hydrochlorothiazide may slow the development of diuretic-induced hyperuricemia.

Liver dysfunction

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

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

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 during treatment with thiazides have been described.

The drug contains the dye Crimson dye [Ponceau 4R], which can cause allergic reactions.

Impact on the ability to drive vehicles and operate machinery

Studies have not been conducted to study the effect of the drug on the ability to drive vehicles or operate machinery. However, it must be taken into account that during treatment with antihypertensive drugs, dizziness or drowsiness may occur when driving or operating machinery, especially when starting treatment or when increasing the dosage of the drug.

Instructions for use Lozap
Buy Lozap plus tab at the pharmacy. 50mg+12.5mg No. 30

Dosage forms
tablets 50mg+12.5mg

Synonyms
Bloktran GT
Vasotens N
Gizaar
Gizaar forte
Losarel Plus
Losartan-N Richter
Losartan/Hydrochlorothiazide-Teva
Lorista N
Lorista N 100
Lorista ND

Group
Combination of angiotensin II receptor antagonists and diuretics

International nonproprietary name
Losartan+Hydrochlorothiazide

Compound
Losartan + Hydrochlorothiazide.

Manufacturers
Zentiva a.s. (Czech Republic)

pharmachologic effect
Combination antihypertensive drug. The maximum antihypertensive effect is achieved within 3 weeks after the start of treatment. After oral administration, losartan and hydrochlorothiazide are rapidly absorbed from the gastrointestinal tract. The time to reach the maximum concentration of losartan is 1 hour, its active metabolite is 3-4 hours. Losartan undergoes a first-pass effect through the liver and is metabolized by carboxylation to form an active metabolite. Hydrochlorothiazide is not metabolized in the liver. The half-life 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 feces. The half-life of hydrochlorothiazide is 5.8-14.8 hours. About 61% is excreted unchanged in the urine.

Side effect
From the side of the central nervous system: often - dizziness. Allergic reactions: urticaria, angioedema, including swelling of the face, lips, pharynx, tongue, larynx; in some cases - vasculitis, including Henoch-Schönlein disease. From the cardiovascular system: arterial hypotension. From the digestive system: rarely - diarrhea, hepatitis, increased activity of liver transaminases. From the respiratory system: - cough. From the side of water-salt metabolism: - hyperkalemia.

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

Contraindications
- anuria; - severe arterial hypotension; - severe dysfunction of the liver and kidneys; - hypovolemia (including against the background of high doses of diuretics); - pregnancy; - lactation period; - children and adolescents up to 18 years of age; - hypersensitivity to the components of the drug.

Directions for use and dosage
The average initial and maintenance dose is 1 tablet per day. If, when taking the drug at this dose, it is not possible to achieve adequate blood pressure control, the dose of the drug can be increased to 2 tablets 1 time per day. The maximum dose is 2 tablets 1 time per day. The drug is taken orally, regardless of food intake.

Overdose
Symptoms: losartan - marked decrease in blood pressure, tachycardia, bradycardia; hydrochlorothiazide - loss of electrolytes (hypokalemia, hyperchloremia, hyponatremia), as well as dehydration resulting from excess diuresis. Treatment: if the drug has been taken recently, the stomach should be rinsed; carry out symptomatic and supportive therapy, and, if necessary, correction of water and electrolyte disturbances.

Interaction
Losartan enhances the effect of other antihypertensive drugs. The simultaneous administration of losartan and potassium-sparing diuretics, potassium supplements or potassium-containing salt substitutes can lead to hyperkalemia. When hydrochlorothiazide is used simultaneously with barbiturates, opioid analgesics, and ethanol, potentiation of orthostatic hypotension may occur. When using hydrochlorothiazide concomitantly with hypoglycemic drugs, their dose may need to be adjusted. When hydrochlorothiazide is co-administered with other antihypertensive drugs, an additive effect is possible. With simultaneous use of hydrochlorothiazide with corticosteroids, ACTH, increased loss of electrolytes, especially potassium, occurs. With simultaneous use of hydrochlorothiazide with non-depolarizing muscle relaxants (for example, tubocurarine), their effect may be enhanced. In some cases, simultaneous use of NSAIDs may reduce the diuretic, natriuretic and hypotensive effects of hydrochlorothiazide. Cholestyramine reduces the absorption of hydrochlorothiazide. Hydrochlorothiazide reduces the renal clearance of lithium and increases the risk of lithium toxicity, so their simultaneous use is not recommended.

special instructions
Prescribe with caution to patients with bilateral renal stenosis or stenosis of the artery of a single kidney, patients with diabetes mellitus, hypercalcemia, hyperuricemia and/or gout, systemic connective tissue diseases, as well as patients with a burdened allergic history and bronchial asthma. When using the drug, the concentration of urea and creatinine in the blood plasma may increase in patients with bilateral renal artery stenosis or stenosis of the artery of a single kidney. Hydrochlorothiazide may increase hypotension and fluid and electrolyte imbalances, impair glucose tolerance, reduce urinary calcium excretion and cause a transient slight increase in plasma calcium concentrations, increase cholesterol and triglyceride concentrations, and provoke hyperuricemia and/or gout. Hydrochlorothiazide, due to its effect on calcium metabolism, may interfere with the results of parathyroid function tests.

Storage conditions
List B. Store in a dry place, out of reach of children, at a temperature not exceeding 30°C.