Many readers of Popular About Health are interested in the drug Lozap plus 50 mg, its instructions for use, price, reviews, analogues. I will consider them especially for them. This medication belongs to the group of antihypertensive drugs.

Lozap plus - composition and release form

The pharmaceutical industry produces the medicine Lozap Plus in oblong tablets of a light yellow color, with a mark on the surface. The active components are two substances, they are losartan potassium and hydrochlorothiazide.

Among the auxiliary compounds one can note: mannitol, povidone is present, microcrystalline cellulose is added, in addition, croscarmellose sodium, as well as magnesium stearate, hypromellose, macrogol 6000, in addition, simethicone emulsion, as well as talc, yellow dye quinoline and crimson. The medicine is placed in blisters of 15 and 10 pieces. The medicine is sold by prescription. Its shelf life is three years.

Lozap plus - action

The combined pharmaceutical drug Lozap plus has a hypotensive effect. The present losartan is an antagonist of angiotensin II receptors, lowers the concentration of adrenaline and aldosterone in the blood, lowers blood pressure, in addition, reduces afterload, and also has a diuretic effect to some extent.

The second component is hydrochlorothiazide, it belongs to the so-called thiazide diuretics. Reduces the reabsorption of sodium, increases the excretion of potassium ions in the urine, as well as bicarbonate and phosphates, and also lowers blood pressure.

After taking the medication, losartan and hydrochlorothiazide are quite quickly absorbed from the gastrointestinal tract. Bioavailability of losartan is 33%. The half-life does not exceed two hours. After an hour, maximum concentration occurs. Protein binding is 99%. 30 percent is excreted in the urine, and 60 percent through the intestines.

Lozap plus - indications for use

The drug Lozap plus is indicated for use in arterial hypertension; in addition, the drug is prescribed to reduce the risk of cardiovascular pathology in people with hypertrophic processes in the left ventricle.

Lozap plus - contraindications for use

I will list the situations in which Lozap plus is contraindicated for use:

Pregnancy;
Treatment-resistant hypokalemia or hypercalcemia;
Anuria;
Severe disturbances in liver activity;
Lactation;
Obstructive pathology of the biliary tract;
Impaired kidney function;
Refractory hyponatremia;
Up to 18 years old;
Gout;
Hypersensitivity to the components of the drug.

With caution, the drug Lozap plus is prescribed for stenosis of the renal arteries, for hypovolemic conditions, for hyponatremia, for hypochloremic alkalosis, hypomagnesemia, for asthma, and for diabetes mellitus.

Lozap plus - application and dosage

The drug Lozap plus is taken orally, usually for hypertension the dosage is one tablet. If necessary, the amount of medication per day can reach two tablet forms. The medication is not chewed, it is swallowed whole.

Lozap plus - side effects

I will list the possible side effects that are observed when using Lozap plus: anemia, urticaria, Henoch-Schönlein disease, ecchymosis occurs, hemolysis is observed, anorexia, gout, insomnia, restlessness, paresthesia, anxiety, memory impairment, panic attacks, drowsiness, confusion are recorded consciousness, depression, unusual dreams, memory impairment.

Other manifestations: headache, decreased visual acuity, dizziness, characterized by increased excitability, blurred vision, peripheral neuropathy, burning in the eyes, tremor, migraine, fainting, conjunctivitis, tinnitus, hypotension, cerebrovascular disorders, tachycardia, vasculitis, myocardial infarction , arrhythmia, pharyngitis, rhinitis, ventricular tachycardia, cough, laryngitis, alopecia, dyspnea, bronchitis, constipation, nosebleeds.

Other negative reactions include: nausea, gastritis develops, vomiting and flatulence are possible, in addition, alopecia, impaired liver function, erythema, hyperemia, rhabdomyolysis, photosensitivity, itching, sweating, decreased libido, convulsions, nocturia, back pain and in the legs, swelling of the joints, arthralgia, arthritis, changes in potency, fibromyalgia, asthenia, in addition, fatigue, as well as chest pain.

In addition, the following changes are determined in the laboratory: hyperglycemia, a slight decrease in hematocrit is recorded, a decrease in hemoglobin, an increase in urea and creatinine occurs, in addition, an increase in so-called liver transaminases is observed.

Lozap plus - drug overdose

In case of an overdose of Lozap plus, tachycardia or bradycardia is observed. In such a situation, the patient is given symptomatic therapy. There is no antidote.

Lozap plus - special instructions

Sometimes the patient may develop angioedema, and the patient should be given timely assistance.

Lozap plus - analogues

The drug Lorista N, Losartan-N Richter, in addition, the pharmaceutical drug Lorista H 100, as well as Losartan-N Canon are analogues.

Lozap plus - reviews

Lozap Plus helps many patients, but there are also patients who have not felt any particular therapeutic effect from the medication.

Lozap plus – price of 50 mg tablets

Cost of 30 tablets from 348 rub.

Conclusion

The pharmaceutical drug Lozap Plus is taken after consultation with the attending physician.

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.

Catad_pgroup Combined antihypertensives

Lozap plus - instructions for use

LOZAP ® PLUS

Registration number:

LSR-000084

Trade name of the drug: LOZAP PLUS

Dosage form:

film-coated tablets

COMPOUND
1 film-coated tablet contains active substances:
Losartan potassium 50 mg and hydrochlorothiazide 12.5 mg

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

DESCRIPTION
Oblong, light yellow, film-coated tablets with a halving score on both sides.

PHARMACOTHERAPEUTIC GROUP
HYPOTENSIVE COMBINED DRUG
(angiotensin II receptor blocker + diuretic)

ATX code:С09DA01

PHARMACOLOGICAL PROPERTIES

Pharmacodynamics
The combined drug has a hypotensive effect. Contains losartan potassium - an angiotensin II receptor antagonist (AT1 subtype) and hydrochlorothiazide - a diuretic.
Losartan is a specific antagonist of angiotensin II receptors (AT1 subtype). Does not inhibit kinase II, an enzyme that destroys bradykinin. Reduces total peripheral vascular resistance (TPVR), blood concentrations of adrenaline and aldosterone, blood pressure (BP), 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- thiazide diuretic. Reduces the reabsorption of Na+, increases the excretion of K+, bicarbonate and phosphates in the urine. Lowers blood pressure by reducing circulating blood volume (CBV), changing the reactivity of the vascular wall, reducing the pressor effect of vasoconstrictors and increasing the depressor effect on the ganglia.

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

INDICATIONS FOR USE
- 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.

CONTRAINDICATIONS
- hypersensitivity to the components of the drug;
- anuria;
- severe arterial hypotension;
- severe dysfunction of the liver and kidneys (creatinine clearance? 30 ml/s);
- hypovolemia (including against the background of high doses of diuretics);
- pregnancy and 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.
The drug is prescribed with caution in patients with diabetes mellitus, hypercalcemia, hyperuricemia and/or gout, as well as patients with a history of allergy and bronchial asthma, as well as systemic connective tissue diseases (including systemic lupus erythematosus).

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

Arterial hypertension
The usual initial and maintenance dose of LOZAP PLUS is 1 tablet per day. For those patients who cannot achieve adequate blood pressure control at this dosage, the dose of LOZAP PLUS can be increased to 2 tablets once a day.
The maximum dose is 2 tablets 1 time 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 for elderly patients.

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

SIDE EFFECT
Adverse reactions are limited to those previously observed with the use of losartan potassium and/or hydrochlorothiazide. The most common side effects 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 these patients had previously experienced angioedema while using other drugs, including ACE inhibitors. Manifestations of vasculitis, including Henoch-Schönlein disease, have been reported 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 более 5,5 ммоль/л), повышение активности "печеночных" трансаминаз.

OVERDOSE
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.

INTERACTION WITH OTHER MEDICINES
Losartan enhances the effect of other antihypertensive drugs. There was no clinically significant interaction with hydrochlorothiazide, digoxin, indirect anticoagulants, cimetidine, phenobarbital, ketokenazole, 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 concomitantly:
Barbiturates, narcotic analgesics, ethanol- potentiation of orthostatic hypotension may occur.
Hypoglycemic agents(oral agents and insulin) - dose adjustment of hypoglycemic agents may be required.
Other antihypertensive drugs- an additive effect is possible.
Colistyramine reduces the absorption of hydrochlorothiazide.
Corticosteroids, ACTH- increased loss of electrolytes, especially potassium.
Pressor amines- a slight decrease in the effect of pressor amines is possible, which does not prevent their use.
Non-depolarizing muscle relaxants (eg, 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.
Nonsteroidal anti-inflammatory drugs (NSAIDs)- in some patients, the use of NSAIDs may reduce the diuretic, natriuretic and hypotensive effects of diuretics.

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

SPECIAL INSTRUCTIONS
LOZAP PLUS can be prescribed together with other antihypertensive drugs.
There is no need for special selection of the initial dose for elderly patients.
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 arterial hypotension and water-electrolyte imbalance (decrease in circulating blood volume, hyponatremia, hypochloremic alkalosis, hypomagnesemia, hypokalemia), impair glucose tolerance, reduce urinary Ca2+ excretion and cause a transient slight increase in plasma Ca2+ concentration blood, increase the concentration of cholesterol and triglycerides, provoke the occurrence of hyperuricemia and/or gout.
Taking medications 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 maternal thrombocytopenia. Diuretic therapy does not prevent the development of pregnancy toxicosis.
There is no information about the effect on the ability to drive a car and other mechanisms.

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

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

BEST BEFORE DATE
3 years.
Do not use after the expiration date stated on the package.

CONDITIONS OF VACATION FROM PHARMACIES
On prescription

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

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

Release form

Film-coated tablets.

1 film-coated tablet contains: losartan potassium 50 mg.

Package

pharmachologic effect

Lozap - losartan is a specific antagonist of angiotensin II receptors (subtype AT 1). It does not inhibit kinase II, an enzyme that catalyzes the conversion of angiotensin I to angiotensin II.

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 heart failure.

Losartan does not inhibit angiotensin-converting enzyme (ACE)-kininase II and, accordingly, does not interfere with the destruction of bradykinin, so side effects indirectly associated with bradykinin (for example, angioedema) occur quite rarely.

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

The maximum hypotensive effect develops 3-6 weeks after starting the drug.

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

Stabilizes the level of urea in blood plasma. Does not affect autonomic reflexes, and does not have a long-term effect on the concentration of norepinephrine in the blood plasma. Losartan at a dose of up to 150 mg per day does not affect the level of triglycerides, total cholesterol and high-density lipoprotein (HDL) cholesterol in the blood serum of patients with arterial hypertension. At the same dose, losartan does not affect fasting blood glucose levels.

Indications

Arterial hypertension.
- Chronic heart failure (as part of combination therapy, with intolerance or ineffectiveness of therapy with ACE inhibitors).
- To reduce the risk of developing cardiovascular diseases (including stroke) and mortality in patients with arterial hypertension and left ventricular hypertrophy.
- Diabetic nephropathy with hypercreatininemia and proteinuria (the ratio of urine albumin to creatinine more than 300 mg/g) in patients with type 2 diabetes mellitus and concomitant arterial hypertension (reducing the progression of diabetic nephropathy to end-stage chronic renal failure).

Contraindications

Hypersensitivity to the components of the drug.
- Pregnancy.
- Lactation period.
- Age up to 18 years (efficacy and safety have not been established).

Carefully:

Arterial hypotension.
- Reduced circulating blood volume.
- Violations of water and electrolyte balance.
- Bilateral renal artery stenosis.
- Stenosis of the artery of the only kidney.
- Kidney failure.
- Liver failure.

Use during pregnancy and breastfeeding

There are no data on the use of Lozap during pregnancy. However, it is known that drugs that directly act on the renin-angiotensin system, when used in the second and third trimesters of pregnancy, can cause developmental defects or even death of the developing fetus. Therefore, if pregnancy occurs, taking Lozap should be stopped immediately.

When prescribed during lactation, a decision should be made either to stop breastfeeding or to stop treatment with the drug.

Directions for use and doses

The drug is taken orally, regardless of food intake. The frequency of administration is 1 time per day.

For arterial hypertension, the average daily dose is 50 mg. In some cases, to achieve a greater therapeutic effect, the dose is increased to 100 mg in two doses or once a day.

For heart failure, the initial dose for patients is 12.5 mg 1 time / day. Typically, the dose is increased at weekly intervals (i.e., 12.5 mg/day, 25 mg/day, 50 mg/day) to an average maintenance dose of 50 mg 1 time/day, depending on the patient's tolerability of the drug.

For patients receiving diuretics in high doses, the initial dose of the drug should be reduced to 25 mg 1 time / day. No dose adjustment is required in elderly patients.

To reduce the risk of developing cardiovascular diseases (including stroke) and mortality in patients with arterial hypertension and left ventricular hypertrophy, the initial dose of the drug is 50 mg per day once. Subsequently, hydrochlorothiazide may be added in low doses and/or the dose of the drug may be increased to 100 mg per day in one or two doses. For patients with concomitant type 2 diabetes mellitus with proteinuria: the drug is prescribed at an initial dose of 50 mg 1 time per day with a further increase in dose to 100 mg/day (taking into account the degree of blood pressure reduction) in one or two doses.

For type 2 diabetes mellitus with proteinuria, the initial dose of the drug is 50 mg 1 time per day, with a further increase in the dose to 100 mg/day (taking into account the degree of blood pressure reduction) in 1 or 2 doses.

For patients with a history of liver disease, dehydration, during hemodialysis, as well as patients over 75 years of age, a lower initial dose of the drug is recommended - 25 mg 1 time per day.

Side effects

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, occasionally reported 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: decreased blood pressure.

From the digestive tract: when taking losartan, rare (

From the respiratory system: when taking losartan - cough.

From the skin: urticaria.

Laboratory indicators: rarely (5.5 mmol/l), increased activity of liver transaminases.

special instructions

It is necessary to correct dehydration before prescribing Lozap or begin treatment with the use of the drug at a lower dose.

Drugs that affect the renin-angiotensin system may increase blood urea and serum creatinine levels in patients with bilateral renal stenosis or arterial stenosis of a solitary kidney.

During the treatment period, the concentration of potassium in the blood should be regularly monitored, especially in elderly patients with impaired renal function.

In patients with liver cirrhosis, the concentration of losartan in the blood plasma increases significantly, and therefore, in the presence of a history of liver disease, it should be prescribed in lower doses.

Instructions for medical use

medicinal product

LOZAP PLUS

Tradename

LozapPLuce

International nonproprietary name

Dosage form

Film-coated tablets

Compound

One tablet contains

active substances: losartan potassium 50 mg, hydrochlorothiazide 12.5 mg,

Excipients: mannitol, microcrystalline cellulose, croscarmellose sodium, povidone 30, magnesium stearate,

film coating:

hypromellose 2910/5, macrogol 6000, talc, titanium dioxide E171, quinoline yellow (E104) aluminum varnish, ponceau 4R aluminum varnish (E124), simethicone emulsion SE4 (purified water, polydimethylsiloxane, methylcellulose, sorbic acid).

Description

Yellow film-coated tablets, oblong in shape, with a break line on both sides

Pharmacotherapeutic group

Drugs affecting the renin-angiotensin system. Angiotensin II antagonists in combination with other drugs. Angiotensin II antagonists in combination with diuretics. Losartan in combination with diuretics.

ATX code C09DA01

Pharmacological properties

Pharmacokinetics

Absorption

Losartan

After oral administration, losartan is well absorbed from the gastrointestinal tract (GIT) and is metabolized to form a carboxyl metabolite and other inactive metabolites. Systemic bioavailability is about 33%. The maximum concentration of losartan in the blood plasma is achieved within 1 hour after administration, and its active metabolite - after 3-4 hours. Food intake does not cause clinically significant changes in the plasma concentration profile of losartan.

Hydrochlorothiazide

After oral administration, 60-80% is absorbed from the gastrointestinal tract. The time to reach maximum plasma concentration is 1.5-3 hours.

Distribution

Losartan

More than 99% of losartan and its active metabolite are bound to plasma proteins, primarily albumin. The volume of distribution of losartan is 34 liters. A study in rats showed that losartan penetrates the blood-brain barrier very poorly.

Hydrochlorothiazide

Hydrochlorothiazide crosses the placental barrier and is excreted in breast milk, but does not penetrate the blood-brain barrier.

Biotransformation

Losartan

Losartan undergoes a first-pass effect through the liver. About 14% of an oral or intravenous dose of losartan is converted to the active metabolite by carboxylation.

Inactive metabolites are also formed, of which two main ones are formed by hydroxylation of the butyl side chain and a less significant metabolite - N-2 tetrazole glucuronide.

Hydrochlorothiazide

Hydrochlorothiazide is not metabolized.

Elimination

Losartan

Plasma clearance of losartan is about 600 ml/min, plasma clearance of the active metabolite is about 50 ml/min. The renal clearance of losartan is about 74 ml/min, the active metabolite is 26 ml/min. The pharmacokinetics of losartan and its active metabolite remain linear in the range of oral doses of losartan potassium up to 200 mg.

After oral administration, the plasma concentration of losartan and its active metabolite decreases exponentially, half-life of losartan - about 2 hours, active metabolite - 6-9 hours. When losartan is administered at a dose of 100 mg once daily, neither losartan nor its active metabolite accumulates in plasma.

Approximately 4% of an oral dose of losartan is excreted unchanged in the urine, and about 6% is excreted as an active metabolite. After administration of radiolabeled 14 C losartan, 35% of the radioactivity is found in the urine, while 58% of the radioactivity is associated with feces.

Hydrochlorothiazide

Hydrochlorothiazide is not metabolized and is quickly eliminated through the kidneys. It has been established that for at least 24 hours after taking the drug, T1/2 is 5.6-14.8 hours. At least 61% of an oral dose of hydrochlorothiazide is excreted unchanged.

Pharmacokinetics in certain groups of patients:

Elderly patients

Losartan - Hydrochlorothiazide

Plasma concentrations of losartan and its active metabolite and absorption of hydrochlorothiazide in elderly patients with arterial hypertension did not differ significantly from those in young patients.

Liver dysfunction

Losartan

After oral administration in patients with moderate to moderate severity of liver cirrhosis of alcoholic origin, plasma concentrations of losartan and its active metabolite were 5 times and 1.7 times higher, respectively, than in young male volunteers.

Losartan and its active metabolites are not removed by hemodialysis.

Pharmacodynamics

Lozap Plus is a combination drug containing losartan potassium and hydrochlorothiazide. It has a hypotensive effect, more pronounced than each component individually. Lozap Plus has a diuretic effect, hydrochlorothiazide included in its composition, increases the activity of renin in plasma, increases the secretion of aldosterone, reduces the concentration of potassium in the serum and increases the level of angiotensin II.

The use of losartan blocks all physiologically important effects of angiotensin II and (through aldosterone suppression) may reduce potassium loss induced by diuretic treatment. Losartan has a moderate and transient uricosuric effect. Hydrochlorothiazide has been shown to moderately increase blood uric acid concentrations, and losartan reduces diuretic-induced hyperuricemia.

The antihypertensive effect of Lozap Plus lasts for 24 hours. In clinical studies lasting at least 1 year, the antihypertensive effect was stable. Despite a significant decrease in blood pressure (BP), taking Lozap Plus did not have a significant clinical effect on heart rate. In clinical studies over 12 weeks, treatment with the combination of losartan 50 mg/hydrochlorothiazide 12.5 mg resulted in a reduction in mean diastolic blood pressure of 13.2 mmHg. rt. Art., measured in a sitting position before administering the medicine.

In a comparative study of the combination of losartan 50 mg/hydrochlorothiazide 12.5 mg with captopril 50 mg/hydrochlorothiazide 25 mg in young (<65 years of age) and elderly (65 years of age and older) patients with arterial hypertension, the antihypertensive effect was similar in the two age groups. groups. Overall, losartan 50 mg/hydrochlorothiazide 12.5 mg produced a dose-dependent, statistically significant reduction in the incidence of adverse reactions and the rate of treatment discontinuation due to adverse reactions, compared with the combination of captopril 50 mg/hydrochlorothiazide 25 mg.

A study of 131 patients with severe hypertension showed benefit from the combination of losartan 50 mg/hydrochlorothiazide 12.5 mg given as initial therapy, as well as in combination with other antihypertensive agents for 12 weeks of therapy.

The combination of losartan 50 mg/hydrochlorothiazide 12.5 mg had an effect on reducing blood pressure in men and women, regardless of ethnicity - in young (under 65 years of age) and elderly (65 years of age and older) patients; the drug is effective at all stages of hypertension.

Losartan

Losartan is a selective angiotensin II receptor antagonist (type AT1). Angiotensin II binds to AT1 receptors found in vascular smooth muscle, adrenal glands, kidneys and heart and induces several important biological responses, including vasoconstriction and aldosterone release. Angiotensin II also stimulates the proliferation of smooth muscle cells. Losartan and its pharmacologically active carbonic acid metabolite (E-3174) block in vitro and in vivo all physiologically significant effects of angiotensin II, regardless of its origin and route of synthesis.

The antihypertensive effect of losartan and the decrease in plasma aldosterone concentrations persist even with increasing angiotensin II levels, indicating the effectiveness of angiotensin II receptor blockade.

The binding of losartan to the AT1 receptor is selective, with no binding or blockade of other hormone receptors or ion channels that are important in the regulation of cardiovascular function. Losartan does not inhibit ACE (kinase II), the enzyme responsible for the degradation of bradykinin into non-protein peptides, in contrast to the conversion of angiotensin I to angiotensin II. Thus, effects not associated with AT1 receptor blockade, as well as intensification of bradykinin-mediated effects or the development of edema (1.7% in patients taking losartan and 1.9% in patients taking placebo) are not attributable to losartan.

Losartan acts by blocking the responses to angiotensin I and angiotensin II, without affecting the effects of bradykinin, which corresponds to the specificity of action of losartan. In contrast, ACE inhibitors, while blocking the response to angiotensin I and enhancing the response to bradykinin, do not change the response to angiotensin II. Thus, the pharmacodynamic effects of losartan differ from those of ACE inhibitors.

In a study conducted specifically to evaluate the incidence of cough in patients treated with losartan compared with patients treated with ACE inhibitors, the incidence of cough in patients treated with losartan or hydrochlorothiazide was similar, but significantly lower than in patients treated with ACE inhibitors. In an analysis of 16 double-blind studies involving 4313 patients, the incidence of spontaneous cough reporting in patients treated with losartan (3.1%) was similar to that in patients treated with placebo (2.6%) and in patients treated with losartan. treated with hydrochlorothiazide (4.1%), while the incidence of cough reported in patients treated with ACE inhibitors was 8.8%.

In patients with arterial hypertension with proteinuria, but without concomitant diabetes mellitus, the administration of losartan potassium led to a significant decrease in proteinuria and the excretion of albumin and immunoglobulin G fractions. When treated with losartan, the glomerular filtration rate is maintained and the filtration fraction decreases.

In general, losartan causes a decrease in serum uric acid levels (usually less than 0.4 mg/100 ml) that persists during long-term therapy.

Losartan does not affect autonomic reflexes and does not permanently affect plasma norepinephrine levels.

In patients with left ventricular failure, positive hemodynamics and neurohormonal effects are induced by doses of 25 mg and 50 mg of losartan, this effect is characterized by an increase in cardiac index, a decrease in pulmonary capillary pressure (wedge pressure), vascular resistance in mean systemic arterial pressure and heart rate, due to a decrease circulating levels of aldosterone and norepinephrine. The incidence of hypotension was dose-dependent in patients with heart failure.

Administration of 50-100 mg of losartan once a day gives a significantly more pronounced antihypertensive effect than 50-100 mg of captopril administered once a day. The antihypertensive effect of 50 mg of losartan is close to that of 20 mg of enapril administered once a day. The antihypertensive effect of 50-100 mg of losartan 1 time per day is comparable to that of 50-100 mg of atenolol 1 time per day. Also, the antihypertensive effect of 50-100 mg of losartan 1 time per day is equivalent to the administration of 5-10 mg of felodipine, extended-release tablets in elderly patients with arterial hypertension (65 years and older) after 12 weeks of treatment.

Losartan is equally effective in men and women, young (under 65 years of age) and elderly (65 years of age and older) patients with arterial hypertension. Although the antihypertensive effect of losartan, as well as other drugs that affect the renin-angiotensin system, is consistent across all ethnic groups, black patients respond, on average, to losartan monotherapy less than non-black patients. The effect of losartan on lowering blood pressure exhibits additive properties when administered together with thiazide-type diuretics.

In clinical studies, daily administration of losartan once a day to patients with mild to moderate essential hypertension led to a statistically significant decrease in systolic and diastolic blood pressure; in clinical studies lasting up to one year, the antihypertensive effect was maintained. Measurements of blood pressure during the period of minimum (24 hours after administration), in relation to the maximum effect (5-6 hours after administration), showed a relatively slow decrease in blood pressure over 24 hours. The antihypertensive effect corresponded to natural daily fluctuations in blood pressure. The decrease in blood pressure by the end of the dose was 70-80% of the effect that developed 5-6 hours after administration of the drug. Discontinuation of losartan by patients did not lead to a sharp increase in blood pressure and did not have a clinically significant effect on heart rate.

Results and researchLIFE“Losartan Intervention For Endpoint reduction in hypertension” (LIFE) showed that treatment with losartan reduced the risk of stroke by 25% compared with taking atenol (p=0.001, 95% confidence interval 0.63-0.89), by 13. 0% showed a reduction in the risk of mortality from cardiovascular diseases, myocardial infarction (p = 0.021, 95% confidence interval 0.77-0.98) compared with the group of patients taking atenolol. StudyLIFE- a randomized controlled trial involving 9193 patients with hypertension, aged 55 to 80 years, with signs of left ventricular hypertrophy identified on the basis of a standard ECG. Patients were randomized into 2 groups: 1) receiving losartan 50 mg once a day; 2) receiving atenolol 50 mg once a day. If within 2 months it was not possible to achieve the target blood pressure (140/90 mm Hg), treatment was supplemented with hydrochlorothiazide (12.5 mg per day), and the daily dose of losartan and atenolol was increased to 100 mg.

Hydrochlorothiazide

The exact mechanism of the antihypertensive effect of thiazides is unknown. As a rule, thiazides do not change normal blood pressure values.

Hydrochlorothiazide is a diuretic and antihypertensive agent. It affects the mechanisms of electrolyte reabsorption in the distal renal tubules. Hydrochlorothiazide increases the excretion of sodium and chloride in approximately equal amounts. Natriuresis may be accompanied by significant loss of potassium and bicarbonates.

After oral administration, diuresis begins after 2 hours, reaches a peak after approximately 4 hours and persists for 6-12 hours.

Indications for use

Treatment of essential arterial hypertension in patients whose blood pressure is not controlled by monotherapy with losartan or hydrochlorothiazide

The drug is intended for adults only.

This fixed combination should not be used for initial treatment of arterial hypertension.

Directions for use and doses

Lozap plus tablets should be swallowed with water.

Lozap plus is taken orally regardless of meals.

It is recommended to adjust the dose of the individual components (losartan and hydrochlorothiazide) when a clinically appropriate need to switch from monotherapy to combination therapy is considered in patients whose blood pressure (BP) cannot be adequately controlled.

The maintenance dose of Lozap plus is 1 tablet per day. For those patients who cannot achieve adequate blood pressure control at this dosage, the dose of Lozap plus can be increased to 2 tablets once a day. The maximum dose of Lozap plus is 2 tablets once a day.

The maximum hypotensive effect is achieved within 3-4 weeks after the start of treatment.

Use in patients with renal failure and hemodialysis patients

There is no need to adjust the initial dose in patients with moderate renal failure (creatinine clearance 30-50 ml/min). Losartan and hydrochlorothiazide tablets are not recommended for hemodialysis patients. Lozap plus tablets should not be taken by patients with acute renal failure (creatinine clearance<30 мл/мин) (см. раздел противопоказания).

Use in patients with reduced circulating blood volume (CBV)

BCC and/or electrolyte disturbances must be corrected before starting Lozap plus.

Use in patients with liver failure

Lozap plus is contraindicated for use in patients with acute liver failure (see contraindications section).

Use in elderly patients

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

Use in pediatrics

The safety and effectiveness of the drug in children have not been established, therefore Lozap Plus is not recommended for children and adolescents under 18 years of age.

Side effects

The incidence of adverse reactions is estimated as follows: "Often" ( > 1/10) , "often"(from ≥ 1/100 to< 1 /10) , "infrequently" (from > 1/1000 to < 1 /100) , "rarely" (from > 1/10000 to < 1/1000) , "very rarely" (< 1/10000), "frequencynot known"(cannot be determined from available data).

In clinical studies with losartan potassium and hydrochlorothiazide, no adverse reactions associated with the drug combination were observed. Adverse reactions are limited to those previously observed with the use of losartan potassium and/or hydrochlorothiazide alone. In controlled clinical trials in patients with essential hypertension, the only drug-related adverse reaction was dizziness, which occurred more frequently than with placebo and occurred in 1% or more of patients treated with losartan potassium and hydrochlorothiazide. In controlled clinical trials in patients with hypertension and left ventricular hypertrophy, the most common drug-related adverse reactions were:

Rare

Hepatitis,

Hyperglycemia, increased activity of “liver” transaminases

Frequency unknown

Dysgeusia

Dose-dependent orthostatic conditions

Cutaneous lupus erythematosus

In addition, the following adverse reactions may occur when using losartan potassium/hydrochlorothiazide, which have been observed with each component.

Losartan

In post-marketing studies, the following adverse reactions were reported (it was not possible to accurately determine the frequency of their occurrence):

Often

Insomnia, headache, dizziness,

Cough, upper respiratory tract infections, nasal congestion, sinusitis, sinus pathologies;

Abdominal pain, nausea, diarrhea, dyspepsia

Muscle cramps, back pain, leg pain, ischalgia

Renal dysfunction, renal failure

Asthenia, fatigue, chest pain

Hyperglycemia, slight decrease in hematocrit and hemoglobin, hypoglycemia

Infrequently

Anemia, Henoch-Schönlein disease, ecchymosis, hemolysis

Anorexia, gout

Restlessness, anxiety, panic attacks, confusion, depression, unusual dreams, sleep disturbance, drowsiness, memory impairment

Increased excitability, paresthesia, peripheral neuropathy, tremor, migraine, syncope

Blurred vision, burning sensation in the eyes, conjunctivitis, decreased visual acuity

Vertigo, ringing in the ears

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)

Vasculitis

Pharyngeal discomfort, pharyngitis, laryngitis, dysponoea, bronchitis, nosebleeds, rhinitis, respiratory congestion

Constipation, toothache, dry mouth, flatulence, gastritis, vomiting

Alopecia, dermatitis, dry skin, erythema, hyperemia, photosensitivity, itching, rash, urticaria, sweating

Arm pain, joint swelling, knee pain, muscle and bone pain, shoulder pain, joint stiffness, arthralgia, arthritis, coxalgia, fibromyalgia, muscle weakness

Nocturia, urinary urgency, urinary tract infection

Decreased libido, erectile dysfunction/impotence

Facial swelling, swelling, fever

Slight increase in serum urea and creatinine levels

Rarely

Anaphylactic reactions, angioedema, including swelling of the larynx and glottis leading to airway obstruction and/or swelling of the face, lips, pharynx and/or tongue, cases of angioedema associated with other medications have been described in some of these patients, including ACE inhibitors

Frequencyunknown

Thrombocytopenia

Pancreatitis

Liver dysfunction

Rhabdomyolysis

Inflammatory symptom, dysphoria

Hyponatremia

Hydrochlorothiazide

Often

Headache

Infrequently

- agranulocytosis, aplastic anemia, hemolytic anemia, leukopenia, purpura, thrombocytopenia

Anorexia, hyperglycemia, hyperuricemia, hypokalemia

Insomnia

Temporary decrease in visual acuity, xanthopsia

Necrotizing angiitis (necrotizing vasculitis, cutaneous vasculitis)

Respiratory distress syndrome, including pneumonitis and noncardiogenic pulmonary edema

Sialadenitis, cramps, gastritis, nausea, vomiting, diarrhea, constipation

Jaundice (intrahepatic cholestasis), pancreatitis

Photosensitivity, urticaria, toxic epidermal necrolysis

Muscle cramps

Glycosuria, interstitial nephritis, renal dysfunction, renal failure

Fever, dizziness

Rarely

- anaphylactic reactions

Contraindications

Hypersensitivity to the active and auxiliary components of the drug

Hypersensitivity to other drugs - sulfonamide derivatives

Treatment-resistant hypokalemia, hypercalcemia,

Refractory hyponatremia

Severe liver dysfunction, cholestasis, biliary obstruction

Symptomatic hyperuricemia/gout

Severe renal impairment (creatinine clearance below 30 ml/min)

• pregnancy and lactation
• children and teenagers up to 18 years of age

Prescribe losartan-containing medicinal products with aliskiren with caution in patients with diabetes mellitus or renal failure (GFR<60 мл/мин/1,73 м 2).

Drug interactions

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.

When treated with 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 simultaneous use of ARA II and nonsteroidal anti-inflammatory drugs (NSAIDs) (for example, selective COX-2 inhibitors, acetylsalicylic acid in doses used for anti-inflammatory effect), and non-selective NSAIDs, a decrease in the antihypertensive effect may be observed. Concomitant use of II receptor antagonists or diuretics and NSAIDs may cause an increased risk of deterioration of renal function, including 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.

Concomitant use of the drug and angiotensin II receptor antagonists in patients with impaired renal function receiving treatment with NSAIDs, incl. Selective cyclooxygenase-2 inhibitors may worsen renal dysfunction. These effects are usually reversible.

Dual blockade (eg, by adding an ACE inhibitor or aliskiren to an angiotensin II receptor antagonist) should be limited on a case-by-case basis and require careful monitoring of blood pressure, renal function and electrolytes. Some studies have shown that in patients with established atherosclerosis, heart failure, or diabetes with end-organ damage, dual blockade of the renin-angiotensin-aldosterone system is associated with a higher incidence of hypotension, syncope, hyperkalemia, and changes in renal function (in including acute renal failure), compared with the use of a single renin-angiotensin-aldosterone agent. The simultaneous use of aliskiren with losartan in patients with diabetes mellitus or in patients with renal failure (GFR) is prohibited.<60 мл / мин).

Concomitant use of the drug with drugs that lower blood pressure and cause hypotension, such as tricyclic antidepressants, antipsychotics, baclofen, amifostine: may increase the risk of developing arterial hypotension.

Hydrochlorothiazide

The following drugs may interact with concomitantly administered thiazides:

• Alcohol, barbiturates or general anesthetics may worsen existing orthostatic hypotension.
• Antidiabetic medications (oral or insulin) - The dose of antidiabetic medications may need to be adjusted.
• Other antihypertensive drugs - may provide additional antihypertensive effect.
• Cholestyramine and colestipol resins - weakening of the absorption of hydrochlorothiazide in the presence of an ion exchange resin. A single dose of cholestyramine or colestipol can bind hydrochlorothiazide, and as a result, reduce absorption in the gastrointestinal tract by 43-85%.
• Corticosteroids, ACTH - increase electrolyte deficiency, especially in conditions of hypokalemia.
• Pressor amines (eg, adrenaline) - the effect of pressor amines may be reduced, however, not to such an extent that their withdrawal is required.
• Non-depolarizing muscle relaxants (eg, tubocurarine) - potential for increased sensitivity to muscle relaxants.
• Lithium diuretics reduce the renal clearance of lithium, which leads to an increased risk of lithium toxicity. Coadministration of these drugs is not recommended.
• Drugs for the treatment of gout (probenecid, sulfinpyrazone and allopurinol) will require dose adjustment of anti-gout drugs, because hydrochlorothiazide may increase serum uric acid levels. The dose of probenecid or sulfinpyrazone may need to be increased. Concomitant use with thiazides may increase the incidence of hypersensitivity reactions to allopurinol.
• Anticholinergic drugs (atropine, biperidine) increase the bioavailability of thiazide diuretics by reducing gastrointestinal motility and the rate of gastric emptying.
• Cytotoxic drugs (cyclophosphamide, methotrexate): Thiazide diuretics can inhibit the renal excretion of cytotoxic drugs and enhance their myelosuppressive effect.
• When using high doses of salicylates, hydrochlorothiazide may enhance their toxic effects on the central nervous system.
• Isolated cases of the development of hemolytic anemia in patients simultaneously receiving hydrochlorothiazide and methyldopa have been described.
• Concomitant treatment with cyclosporine may increase the risk of hyperuricemia and complications of gout.
• Digitalis glycosides: Hypokalemia or hypomagnesemia caused by thiazide diuretics may contribute to the development of digitalis-induced arrhythmias.
• Drugs whose effect is affected by changes in serum potassium levels: When losartan/hydrochlorothiazide is co-administered with drugs whose effect is affected by changes in potassium levels (for example, digitalis glycosides and antiarrhythmic drugs), regular monitoring of serum potassium levels and ECG monitoring is recommended. These measures are also recommended when used 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 antiarrhythmic drugs (quinidine, hydroquinidine, disopyramide);

Class III antiarrhythmic drugs (amiodarone, sotalol, dofetilide, ibutilide);

Antipsychotic drugs (thioridazine, chlorpromazine, levomepromazine, trifluoperazine, cyamemazine, sulpride, sultopride, amisulpride, tiapride, pimozide, haloperidol, droperidol);

Others (bepridil, cisapride, difemanil, erythromycin IV, halofantrine, mizolastine, pentamidine, terfenadine, vincamycin IV).

• Calcium salts: Thiazide diuretics may increase serum calcium concentrations due to decreased calcium excretion. If calcium supplementation is necessary, serum calcium concentrations should be continuously monitored and the calcium dose adjusted accordingly.

Effect on laboratory parameters.

Thiazides may interfere with parathyroid function tests due to their effect on calcium metabolism.

• Carbamazepine: There is a risk of developing symptomatic hyponatremia. Clinical observation and laboratory monitoring are necessary.
• 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), corticosteroid hormones, ACTH, stimulant laxatives, or glycyrrhizin (found in licorice): Hydrochlorothiazide may cause electrolyte deficiency, especially hypokalemia.

special instructions

Losartan

Quincke's edema

Monitoring is required for patients with a history of angioedema (swelling of the face, lips, throat, and/or tongue)

Hypotension and decreased circulating blood volume.

In patients with a decrease in blood volume and/or hyponatremia, due to diuretic therapy, restrictions in dietary salt intake, diarrhea or vomiting, symptoms of hypotension may appear, especially after taking the first dose. Such conditions must be corrected before taking Lozap Plus.

Electrolyte imbalance

Electrolyte imbalance is common in patients with impaired renal function, with or without diabetes, and should be taken into account. Therefore, plasma potassium concentrations and creatinine clearance should be carefully monitored, especially in patients with heart failure and creatinine clearance between 30 and 50 ml/min.

The simultaneous use of potassium-sparing diuretics, potassium supplements and potassium-containing salt substitutes with Lozap Plus is not recommended.

Functional liver disorders

Based on pharmacokinetic data showing a significant increase in plasma concentrations of Lozap Plus in patients with cirrhosis, lower starting dosages should be selected for patients with a history of impaired liver function. There is no therapeutic experience in patients with severely impaired liver function. Therefore, Lozap Plus should not be used in patients with severe liver dysfunction.

Functional kidney disorders

Impaired renal function may occur as a consequence of suppression of the renin-angiotensin system. These disorders may be reversible after stopping treatment.

Losartan, like other drugs that affect the renin-angiotensin system, may increase serum urea and creatinine concentrations in patients with bilateral renal artery stenosis or solitary renal artery stenosis. These changes in renal dysfunction may be reversible after discontinuation of the drug.

In patients in whom renal function may be dependent on the activity of the renin-angiotensin-aldosterone system (patients with low renal blood flow, such as severe congestive heart failure), treatment with ACE inhibitors has been associated with oliguria and/or progressive azotemia and acute renal failure (rarely). ) and/or a fatal condition. The same cases occurred during treatment with losartan.

Kidney transplantation

No data exist for kidney transplant patients.

Primary hyperaldosteronism

Patients with primary hyperaldosteronism generally do not respond to antihypertensive drugs that act by inhibiting the RAAS. Therefore, the use of Lozap Plus is not recommended.

Coronary heart disease and cerebrovascular disease

As with other antihypertensive drugs, an excessive decrease in blood pressure in such pathologies leads to myocardial infarction or strokes.

Heart failure

In patients with heart failure, with or without impaired renal function, there is a risk of acute arterial hypotension and impaired renal function (often acute).

Stenosis of the aortic and mitral valves, obstructive hypertrophic cardiomyopathy

As with other vasodilators, you should be especially careful with these pathologies.

Ethnic differences

Like other angiotensin-converting enzyme inhibitors, losartan and other angiotensin 2 antagonists are less effective in lowering blood pressure in African-Americans than in Caucasians, probably due to the higher incidence of low renin levels in African-Americans with hypertension.

Double blockadeRenin-angiotensin-aldosterone system (RAAS) Cases of hypotension, syncope, stroke, hyperkalemia and changes in renal function (including acute renal failure) have been reported in sensitive patients, especially when taking drugs in combination that affect this system. Dual blockade of the renin-angiotensin-aldosterone system by combining an angiotensin II receptor blocker (ARB) with an angiotensin I-converting enzyme inhibitor (ACEI) or aliskiren is not recommended. The combination of the drug with aliskiren is contraindicated in patients with diabetes mellitus or renal failure (GFR<60 мл/мин/1,73 м 2).
Use during pregnancy

The use of angiotensin II receptor antagonists (ARA II) during pregnancy is contraindicated. If taking ARA II is necessary, patients planning pregnancy should switch to treatment with alternative antihypertensive drugs with an established safety profile. If pregnancy is diagnosed during treatment with APA II, therapy should be stopped immediately and alternative treatment initiated.

Hydrochlorothiazide

Hypotension and water-salt imbalance

As with all antihypertensive therapy, symptomatic hypotension may occur in some patients. Hydrochlorothiazide may increase fluid imbalance, such as symptoms of hypovolemia, hyponatremia, hypochloremic alkalosis, hypomagnesemia or hypokalemia, which may develop with concomitant diarrhea or vomiting. Every patient taking diuretics requires regular monitoring of serum electrolyte concentrations at appropriate time intervals.

Metabolic and endocrine effects

Treatment with thiazides may result in decreased glucose tolerance and therefore may require dosage adjustments of antidiabetic medications, including insulin.

Thiazides may decrease urinary calcium excretion, thereby increasing serum calcium levels. Significant hypercalcemia may be a sign of latent increased function of the parathyroid glands. Thiazides should be discontinued before testing to evaluate parathyroid function.

Thiazide diuretics may increase serum cholesterol and triglyceride levels.

In some patients, treatment with thiazides may lead to sudden hyperuricemia and/or gout. Because losartan reduces uricemia, the combination of hydrochlorothiazide with losartan reduces diuretic-induced hyperuricemia.

Miscellaneous

In patients receiving treatment with thiazides, hypersensitivity reactions, including bronchial asthma, can occur with both a positive and negative allergic history. There are known cases of exacerbation or occurrence of systemic lupus erythematosus after administration of thiazides.

The drug contains Ponceau 4R dye, which may cause an allergic reaction.

Features of the influence on the ability to drive a vehicle or potentially dangerous mechanisms

The drug may have a slight or moderate effect on activities that require increased attention, coordination of movements and urgent actions, for example, when driving cars and motor vehicles, operating machinery, working at height, etc.

Overdose

Symptoms: hypotension, tachycardia or bradycardia, hypokalemia, hypochloremia, hyponatremia, dehydration, cardiac arrhythmias.

L treatment: symptomatic and adjuvant.

Administration of Lozap Plus should be discontinued and the patient should be closely monitored. Possible therapeutic measures include induction of vomiting, gastric lavage if the drug is recently taken, dehydration therapy and restoration of electrolyte balance, treatment of hepatic coma and hypotension using routine methods.

Losartan

There are only limited data on overdose of losartan in humans. The most likely manifestations of overdose are hypotension and tachycardia, however, bradycardia may also occur due to parasympathetic (vagal) stimulation. If symptomatic hypotension occurs, adjuvant therapy should be initiated.

Losartan and its active metabolite are not removed by hemodialysis.

Hydrochlorothiazide

The most common subjective and objective symptoms were caused by electrolyte deficiency (hypokalemia, hypochloremia, hyponatremia) and dehydration caused by excess diuresis. When digoxin is administered, hypokalemia may exacerbate existing cardiac arrhythmia. Increased excretion of hydrochlorothiazide by dialysis has not been proven.

Release form and packaging

15 tablets are placed in a blister pack made of polyvinyl chloride/polyvinyl dichloride film and aluminum foil.

2 and 6 contour packages together with instructions for medical use in the state and Russian languages ​​are placed in a cardboard box.

Storage conditions

Store at a temperature not exceeding 30°C.

Keep out of the reach of children!

Shelf life

Do not use after the expiration date.

Conditions for dispensing from pharmacies

On prescription

Manufacturer

Name and country of the marketing authorization holder

Zentiva K.S., Prague, Czech Republic.

Address of the organization that accepts claims from consumers regarding the quality of products (products) on the territory of the Republic of Kazakhstan

Sanofi-aventis Kazakhstan LLP

050013 Almaty, st. Furmanova 187B

phone: 8-727-244-50-96

Have you taken out sick leave due to back pain?

How often do you face the problem of back pain?

Can you tolerate pain without taking painkillers?

Find out more how to deal with back pain as quickly as possible