Lozap Plus is a combination of losartan and hydrochlorothiazide. Lozap plus - special instructions

For the most effective treatment of arterial hypertension, it is recommended to use combination medications.

Lozap plus combines two active components that have a powerful hypotensive effect without the risk of developing severe side effects, which distinguishes this drug from other antihypertensive drugs.

However, despite the high level of safety of use, the dosage and regimen should be determined exclusively by the attending physician or other qualified specialist.

Clinical and pharmacological group

Antihypertensive drug.

Conditions for dispensing from pharmacies

Dispensed with a doctor's prescription.

Prices

How much does Lozap plus cost? The average price in pharmacies is 400 rubles.

Release form and composition

The medicine Lozap, the indications for use of which will be described below, has its own dosage form:

• Tablets of 12.5 mg are white or cream-colored, elongated, film-coated.
• Tablets of 50 mg are white or cream-colored, elongated, coated with a notch for easy division.
• Tablets of 100 mg are white or cream-colored, elongated, coated, with a notch for dose adjustment.

The active component is potassium losartan and additional components that do not have a therapeutic effect. The shell consists of white sepiphyllum, hypromelose, macrogol, MCC and titanium dioxide.

Pharmacological effect

Losartan is a specific angiotensin II receptor antagonist (AT1 subtype) that inactivates bradykinin and does not suppress the enzyme kinase II. Reduces TPVR (total peripheral vascular resistance), the concentration of aldosterone and adrenaline in the blood, blood pressure (blood pressure), pressure in the vessels of the pulmonary circulation; reduces afterload and has a diuretic effect. Prevents the appearance of myocardial hypertrophy, improves tolerance to physical activity in patients with CHF (chronic heart failure).

Hydrochlorothiazide - a thiazide diuretic inhibits the reabsorption of sodium ions, increases the excretion of bicarbonate, potassium ions and phosphates in the urine. Reduces blood pressure by reducing BCC (circulating blood volume), suppressing the pressor effect of vasoconstrictor substances, changing the reactivity of the vascular wall and increasing the inhibitory effect on the ganglia.

Indications for use

• (as part of complex therapy, in case of ineffectiveness or intolerance of treatment with inhibitors);
• , - in order to reduce the risk of heart disease;
• diabetic nephropathy, which is accompanied by proteinuria and hypercreatininemia in diabetics with concomitant arterial hypertension.

Contraindications

Contraindications for treatment are as follows:

• anuria;
• pregnancy;
• breastfeeding period;
• age under 18 years (efficacy and safety have not been established);
• 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);
• 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.

Use during pregnancy and lactation

There is no information about taking Lozapa Plus during pregnancy, but it is known that drugs that affect the renin-angiotensin system in the 2nd and 3rd trimester of pregnancy can cause developmental defects and even fetal death.

If breastfeeding, you should stop breastfeeding or stop treatment.

Dosage and method of administration

The instructions for use indicate that Lozap plus is taken orally, regardless of food intake.

1. For high blood pressure (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
2. 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.
3. 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 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.

Side effects

Controlled clinical trials of the treatment of essential hypertension with losartan and hydrochlorothiazide in combination showed the development of the only adverse reaction with a frequency of 1% or more compared with placebo - dizziness. Other side effects reported during joint therapy with losartan and hydrochlorothiazide from systems and organs:

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

Also, the use of Lozap plus may cause adverse reactions characteristic of each of the active components of the drug separately.

Side effects associated with the use of hydrochlorothiazide:

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

Side effects associated with the use of losartan:

• immune system: rarely - the occurrence of hypersensitivity, including anaphylactic reactions, angioedema of the glottis and larynx with the occurrence of airway obstruction, swelling of the face, pharynx, tongue, lips;
• genitals and mammary gland: uncommon – erectile dysfunction, decreased libido;
• organ of vision: infrequently - burning sensation in the eyes, decreased visual acuity, conjunctivitis, blurred vision;
• organ of hearing and labyrinthine disorders: infrequently – vertigo, tinnitus;
• skin and subcutaneous tissues: uncommon – dermatitis, hyperemia, rash, itching, sweating, photosensitivity, dry skin, alopecia;
• liver and biliary tract: with uncertain frequency - liver failure;
• general disorders: often - chest pain, asthenia, fatigue; uncommon – fever, swelling of the face; with uncertain frequency - weakness, flu-like symptoms;
• gastrointestinal tract: often – diarrhea, nausea, dyspepsia, abdominal pain; uncommon – vomiting, gastritis, dry mouth, constipation, flatulence, toothache;
• metabolism: uncommon – gout, anorexia;
• musculoskeletal system and connective tissue: often – pain in the back, legs, sciatica, muscle cramps; uncommon – muscle and bone pain, joint swelling, muscle weakness, fibromyalgia, arthritis, arthralgia, joint stiffness; with an unknown frequency - rhabdomyolysis;
• psyche: often – insomnia; uncommon – memory impairment, depression, confusion, sleep disturbance, unusual dreams, drowsiness, panic attacks, anxiety, restlessness;
• respiratory system, chest and mediastinal organs: often – sinusitis, nasal congestion, upper respiratory tract infections, cough; uncommon – rhinitis, nosebleeds, bronchitis, dyspnea, laryngitis, pharyngitis;
• blood and lymphatic system: infrequently - hemolysis, anemia, ecchymosis, Schönlein-Henoch disease; with an unknown frequency - thrombocytopenia;
• nervous system: often – dizziness, headache; uncommon – paresthesia, increased excitability, syncope, migraine, tremor, peripheral neuropathy;
• cardiovascular system: uncommon - vasculitis, second degree atrioventricular block, angina pectoris, pain in the sternum, orthostatic hypotension, decreased blood pressure, arrhythmias (tachycardia, sinus bradycardia, ventricular tachycardia, atrial fibrillation, ventricular fibrillation), palpitations, myocardial infarction;
• kidneys and urinary tract: often - renal dysfunction; uncommon – urinary tract infections, imperative calls to urinate, nocturia;
• laboratory and instrumental studies: often - hyperkalemia, insignificant decrease in hemoglobin and hematocrit; infrequently - a slight increase in the content of creatinine and urea in the blood plasma; very rarely - increased activity of bilirubin and liver transaminases; with an unknown frequency - hyponatremia.

Overdose

In case of an overdose of the drug Lozap plus, the following symptoms are observed: due to the content of losartan - bradycardia, tachycardia, decreased blood pressure; caused by the content of hydrochlorothiazide - loss of electrolytes and dehydration.

Treatment of overdose is symptomatic. It is necessary to stop taking the drug, rinse the stomach and take measures aimed at restoring water and electrolyte balance. If blood pressure drops excessively, maintenance fluid therapy is indicated. Hemodialysis is not effective for removing losartan. The extent to which hydrochlorothiazide is removed by hemodialysis has not been established.

special instructions

Patients with cases of angioedema in the past should be treated with the drug with caution and under the strict supervision of a physician.

In case of cirrhosis of the liver or moderate dysfunction of the organ, treatment with the drug should be prescribed under the supervision of specialists, since it is possible to increase the concentration of the active components of the drug in the blood plasma, which increases the likelihood of developing an overdose and severe side effects.

Lozap and Lozap plus can cause dizziness, drowsiness and fainting, which negatively affects the ability to control mechanisms, therefore, while using these drugs, it is recommended to avoid any activities that require high concentration and reaction speed.

Drug interactions

The drug has the property of enhancing the effect of other antihypertensive medications. There is also an increase in the effect of non-depolarizing muscle relaxants. Concomitant use of NSAIDs may weaken the effect of hydrochlorothiazide. The use of Lozap plus with lithium preparations increases the risk of intoxication. Cholestyramine helps reduce the absorption of hydrochlorothiazide.

When using Lozap plus and hypoglycemic medications simultaneously, dosage adjustments are required.

To treat hypertension, drugs from different groups are used, as well as combination drug therapy. Drugs from the group of angiotensin II receptor antagonists, for example, Lozap tablets, are quite effective. This drug has a prolonged effect, providing round-the-clock blood pressure control.

Lozap is a pill for hypertension and heart failure. The tablets are small in size, convex on both sides, coated with a thin coating, providing prolonged action. The medicine is packaged in blisters of 10 tablets, one package contains 30, 60 or 90 tablets.

The main active ingredient of the drug is the angiotensin II antagonist losartran. The medicine is available in four dosages - 100, 50, 25 and 12.5 mg of active ingredient in one tablet. Also in pharmacies there is a drug with losartran and 12.5 mg of diuretic in the composition.

The dosage of the medicine and the presence of the excipient determines the exact name of the drug. Lozap contains only losartran and formative components in one tablet. 50 mg of losartran in combination with a diuretic are Lozap Plus tablets.

Auxiliary and formative substances in the composition of the medicine:

• cellulose;
• silica;
• talc;
• crospovidone;
• magnesium stearate;
• titanium dioxide

The prescription of Lozap Plus 50 mg with a diuretic is justified in case of low effectiveness of therapy with small doses of the drug without hydrochlorothiazide in the composition. Usually, the drug is started with a low dosage, gradually increasing it if necessary. Precise recommendations for taking the drug should be given by the doctor who prescribed Lozap to the patient.

Lozap is available in various dosages, with one and two active ingredients

Properties of the drug

Among medications for hypertension, the drug Lozap is widely popular. This is due to the mechanism of action of Lozap.

The drug acts directly on the cause of hypertension. The drug Lozap affects the renin-angiotensin-aldosterone system by blocking angiotensin-sensitive receptors. This eliminates the negative effects caused by the activity of angiotensin II:

• synthesis of the hormone aldosterone;
• vasopressin synthesis;
• norepinephrine production;
• fluid retention;
• increased peripheral vascular tone.

The use of Lozap Plus for hypertension has a complex effect on the body. The tablets not only lower blood pressure, but also block the mechanisms that lead to its increase. A jump in blood pressure causes aldosterone and norepinephrine, and the drug Lozap 50 mg or a higher dosage prevents the synthesis of these substances.

In addition to the hypotensive effect, the medicine stimulates the removal of fluid from the body. Lozap 50 mg prevents the development of edema and improves the general well-being of patients with hypertension.

Lozap tablets normalize cardiac activity, protect the myocardium from the effects of high blood pressure, and prevent the development of a heart attack.

The main feature of Lozapa Plus 50 mg and Lozapa with 12.5 mg hydrochlorothiazide is the improvement of exercise tolerance in patients with hypertension. Therapy with this medicine stabilizes the cardiovascular system, allowing hypertensive patients to live a full life, play sports and maintain performance. At the same time, the drug does not affect metabolism, which means it can be used to treat hypertensive patients with diabetes mellitus. Taking Lozap prevents the formation of protein in the urine, so the medicine is not prohibited for patients with proteinuria.

The drug acts slowly, by gradually releasing the active substance. The maximum effect is achieved 6 hours after taking the tablet and persists for some time, and then slowly declines. The minimal hypotensive effect of Lozap is observed one day after taking a therapeutic dose of the drug.

All varieties of Lozap effectively fight hypertension, and the addition of a diuretic to Lozap Plus also
prevents swelling

Indications for use

Lozap instructions suggest taking it in the following cases:

• essential hypertension;
• heart failure;
• prevention of heart attack and stroke;
• diabetes mellitus and proteinuria.

For diabetes mellitus and proteinuria, Lozap is used as part of complex therapy for hypertension aggravated by these conditions.

The medicine is prescribed for the treatment of chronic heart failure in elderly people as the most gentle remedy with a pronounced therapeutic effect. However, renal dysfunction is not a contraindication to drug therapy.

Unlike other drugs for hypertension, Lozap is allowed to be taken by children over 6 years of age and adolescents. Treatment of these age groups is carried out with minimal dosages of the drug and only as prescribed by a doctor.

In case of left ventricular hypertrophy, Lozap can be taken as a means of normalizing myocardial function. In this case, Lozap also helps minimize the risk of developing a heart attack. For older patients, Lozap can be prescribed to prevent stroke.

Lozap is allowed to be taken by children and adolescents, but only as prescribed by a doctor.

Detailed dosage plan

Each package of the medicine contains several blisters with Lozap tablets and instructions for use, which should be carefully studied before starting to take the medicine. On the recommendation of the attending physician, the dosage regimen may be changed. It is prohibited to independently increase the maximum permissible daily dosage of the drug.

For arterial hypertension, start taking the drug at a dosage of 50 mg. One tablet of the medicine is taken in the first half of the day. To ensure long-lasting, prolonged action, the tablet should be swallowed without chewing, with a sufficient amount of plain water. A persistent hypotensive effect is achieved after three weeks of regular use of the drug.

During the first few weeks of drug therapy, the patient should regularly measure blood pressure. If the drug is insufficiently effective, the daily dosage can be doubled (up to 100 mg). In this case, both tablets should be taken simultaneously before breakfast.

The low effectiveness of Lozap monotherapy for arterial hypertension necessitates the introduction of diuretics into the treatment regimen. In this case, the doctor may prescribe a combination drug Lozap Plus, which contains both an angiotensin antagonist and a diuretic. One tablet contains 50 mg of losartran and 12.5 mg of hydrochlorothiazide. This drug effectively removes excess fluid from the body and prevents the formation of edema. Most often, Lozap Plus is prescribed to patients with arterial hypertension of 2 and 3 degrees.

For patients with diabetes and renal impairment, including proteinuria, the drug is prescribed at a dosage of 50 mg. If necessary, after a month the dosage can be doubled. When treating such patients with Lozap, the instructions for use warn that the medicine can be combined with other drugs for hypertension and drugs for the treatment of diabetes (insulin, hypoglycemic drugs).

For heart failure in elderly patients, Lozap is started with low doses. In the first week of treatment, you need to take one tablet containing 12.5 mg of losartran. Then a gradual increase in dosage is practiced if the patient tolerates the medicine well. In the second week of treatment, you should take 25 mg of the drug daily, in the third week - tablets with 50 mg of the active substance in the composition. If there are no side effects, therapy continues with daily dosing of 50 mg of the drug.

To reduce the risk of stroke in patients over 60 years of age with arterial hypertension, it is practiced to take 50 mg of the drug per day. After two weeks, it is necessary to undergo an examination to determine the dynamics of changes in blood pressure and normalization of blood circulation. The insufficient effectiveness of the drug with 50 mg of losartran in the composition is a reason to increase the daily dosage to 100 mg, or to switch to treatment with Lozap Plus, which contains a diuretic.

The drug is started with a minimum dosage

Possible side effects

When taking Lozap and Lozap Plus, the instructions warn about the risk of developing the following side effects:

• dizziness;
• fainting state;
• drowsiness and loss of strength;
• tachycardia;
• dry cough;
• nasal congestion.

Most often, patients experience dizziness. This side effect is caused by a sharp decrease in blood pressure and persists in the first days of taking Lozap. As the body gets used to the mechanism of action of the drug, the dizziness goes away.

In rare cases, patients complain of indigestion while taking the medication. Stomach pain, diarrhea and constipation may persist during the first week of losartran therapy, but disappear fairly quickly. The occurrence of such a reaction in the body does not require treatment or discontinuation of the drug.

Drowsiness and loss of strength are also a consequence of lowering blood pressure and persist only until the body gets used to the action of the drug. This usually takes 7-10 days.

The side effects listed above occur in no more than 5% of patients. In the vast majority of cases, Lozap is well tolerated, regardless of the age and presence of concomitant diseases in the patient taking the medicine to normalize blood pressure.

It is recommended to consult a doctor if side effects persist for a long time and are so severe that they impair the patient’s quality of life. In this case, it is possible that we are talking about intolerance to the drug, which requires replacing the tablets.

Side effects usually go away on their own after a few days

Contraindications

The drug does not affect kidney function, so it can be taken by patients with impaired functioning of this organ. Metabolism of the drug occurs in the liver, so severe disturbances in its functioning are an absolute contraindication to treatment with Lozap.

Also, the medicine is not prescribed:

• with individual intolerance;
• pregnant and lactating women;
• children.

Despite the fact that the drug is officially approved for use by children over 6 years of age, large-scale studies have not been conducted on the effect of the drug on the children's body. In this regard, the medicine should not be given to children without a doctor's prescription.

If a hypersensitivity reaction occurs, the medicine should be discontinued. Long-term side effects, allergic rashes, and angioedema indicate intolerance to Lozap. If a patient develops severe angina while taking Lozap, the medication should be discontinued.

Precautions and special instructions

Patients with a history of angioedema are allowed to take Lozap, but only in a hospital under the supervision of a physician. If no negative effects from the drug are detected during the observation period, drug therapy can be continued at home. In this case, it is practiced to take only minimal dosages of the drug (12.5 mg).

Patients with water-electrolyte imbalances should take minimal dosages of the drug. This is true for hypertensive patients who have been limiting salt intake for a long time or taking strong diuretics. Lozap Plus can be combined with other antihypertensive drugs, but not with diuretics.

Simultaneous use of large doses of Lozap with drugs from the ACE inhibitor group can lead to a decrease in blood pressure to critical values. If Lozap is used as part of complex therapy for hypertension, and not as an independent remedy, the dosage of other drugs that lower blood pressure should be reduced.

Taking Lozap during pregnancy or when planning conception can lead to the development of hypotension in the fetus and severe hypoxia.

Despite the fact that Lozap does not suppress the activity of the nervous system, it is recommended to stop driving vehicles in the first days of taking the drug. This limitation is due to the likelihood of developing side effects associated with a sharp decrease in blood pressure - dizziness, drowsiness, fainting.

It is better not to drive during treatment

Overdose and drug interactions

Taking large doses of the drug Lozap can lead to the development of severe hypotension and a decrease in blood pressure below 90 to 60. This condition is dangerous for the development of oxygen starvation, fainting and coma.

An overdose of Lozap may be accompanied by bradycardia. This condition is characterized by a decrease in heart rate below 60 beats per minute. If symptoms of overdose appear, you should call an ambulance. In this case, symptomatic treatment is carried out in a hospital. In case of overdose with drugs of this group, hemodialysis is not used due to the low efficiency of the method.

Lozap enhances the effect of beta-blockers and sympatholytics. When taken simultaneously with ACE inhibitors, it is necessary to reduce the dosage to avoid the development of hypotension.

Cost and analogues

If it is necessary to replace the drug Lozap Plus with analogues, you should pay attention to the drugs Angizar Plus, Locard, Lorista N. These drugs contain the same combination of active ingredients - losartran and hydrochlorothiazide.

If symptoms of intolerance to Lozap appear, the listed medications should not be used, as they have the same effect and cause the same side effects. In this case, analogues should only be selected by a doctor.

Full analogues of the drug Lozap, which do not contain diuretics, but only losartran:

• Angizar;
• Closart;
• Losartin;
• Trosan.

All these drugs have a similar composition and differ only in price and form of release.

The cost of 30 tablets of the drug Lozap is from 250 rubles in the minimum dosage, up to 350 rubles in the dosage of 100 mg of losartran in one tablet. Lozap Plus will cost more - from 370 to 450 rubles per package of the medicine.

The most affordable analogue of the drug Lozap is Angizar tablets. Their minimum dosage is 25 mg of active substance in one tablet. A package of this drug will cost only 100 rubles.

Doctors speak positively about the drug, choosing Lozap as a first-line treatment for hypertension in older people. Due to its good tolerability and minimal side effects, Lozap is most often prescribed to patients over 65 years of age.

Patients praise Lozap; reviews note the affordable cost of the medicine, the absence of side effects and a minimum of contraindications. According to statistics, more than 80% of patients are satisfied with this medicine and note its high effectiveness.

Lozap is intended for long-term use. A sustained therapeutic effect occurs three weeks after the start of treatment. However, the tablets are not suitable as an emergency remedy for relieving a hypertensive crisis. After discontinuation of the drug, the hypotensive effect persists for a week.

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.

Detailed instructions for use are published on this page. Lozapa. The available dosage forms of the drug are listed (tablets 12.5 mg, 50 mg and 100 mg, Plus in combination with a diuretic), as well as its analogues. Information is provided on the side effects that Lozap can cause and on interactions with other medications. In addition to information about the diseases for the treatment and prevention of which the drug is prescribed (arterial hypertension and blood pressure reduction), administration algorithms, possible dosages for adults and children are described in detail, and the possibility of use during pregnancy and breastfeeding is clarified. The abstract for Lozap is supplemented with reviews from patients and doctors.

Instructions for use and dosage

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 daily dose can be increased to 100 mg in 2 or 1 dose.

The initial dose for patients with chronic heart failure is 12.5 mg 1 time per day. Typically, the dose is increased at weekly intervals (i.e., 12.5 mg per day, 25 mg per day, 50 mg per day) to a mean maintenance dose of 50 mg once daily, depending on drug tolerability.

When prescribing the drug to patients receiving diuretics in high doses, the initial dose of Lozap should be reduced to 25 mg 1 time per day.

For elderly patients there is no need for dose adjustment.

When prescribing the drug to reduce the risk of cardiovascular diseases (including stroke) and mortality in patients with arterial hypertension and left ventricular hypertrophy, the initial dose is 50 mg per day. In the future, hydrochlorothiazide may be added at a low dose and/or the dose of Lozap may be increased to 100 mg per day in 1-2 doses.

For patients with concomitant type 2 diabetes mellitus with proteinuria, the initial dose of the drug is 50 mg 1 time per day, then the dose is increased to 100 mg per day (taking into account the degree of blood pressure reduction) in 1-2 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 (1/2 tablet of 50 mg) once a day.

Release forms

Film-coated tablets 12.5 mg, 50 mg and 100 mg.

Lozap plus tablets (in combination with the diuretic hydrochlorothiazide to enhance the effect).

Lozap- antihypertensive drug. Specific angiotensin 2 receptor antagonist (AT1 subtype). Does not suppress kininase 2, an enzyme that catalyzes the reaction of converting angiotensin 1 into angiotensin 2. Reduces peripheral vascular resistance, the concentration of adrenaline and aldosterone in the blood, 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. Losartan (the active ingredient of the drug Lozap) does not inhibit ACE kininase 2 and, accordingly, does not prevent the destruction of bradykinin, therefore side effects indirectly associated with bradykinin (for example, angioedema) occur quite rarely.

In patients with arterial hypertension without concomitant diabetes mellitus with proteinuria (more than 2 g per 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 levels of triglycerides, total cholesterol and HDL cholesterol in the blood serum in patients with arterial hypertension. At the same dose, losartan does not affect fasting blood glucose levels.

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.

The combined drug Lozap plus additionally contains hydrochlorothiazide, 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.

The maximum antihypertensive effect is achieved within 3 weeks after the start of treatment.

Pharmacokinetics

When taken orally, Lozap is well absorbed. Food intake does not affect the bioavailability of losartan. Approximately 14% of losartan administered to a patient intravenously or taken orally is converted into an active metabolite. When taken orally, approximately 4% of the dose taken is excreted unchanged by the kidneys and about 6% is excreted by the kidneys in the form of an active metabolite.

Neither losartan nor its active metabolite is removed from the body by hemodialysis.

Plasma concentrations of losartan and its active metabolite in elderly men with arterial hypertension do not differ significantly from the values ​​of these parameters in young men with arterial hypertension.

Plasma concentrations of losartan in women with arterial hypertension are 2 times higher than the corresponding values ​​in men with arterial hypertension. Concentrations of the active metabolite do not differ between men and women. This pharmacokinetic difference is not clinically significant.

Indications

• arterial hypertension;
• chronic heart failure (as part of combination therapy, with intolerance or ineffectiveness of therapy with ACE inhibitors);
• reducing 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

• pregnancy;
• lactation period;
• age under 18 years (efficacy and safety have not been established);
• hypersensitivity to the components of the drug.

special instructions

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

Drugs that affect the RAAS may increase blood urea and serum creatinine levels in patients with bilateral renal artery stenosis or solitary renal artery stenosis.

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.

Taking alcohol together also increases the concentration of Lozap in the body.

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

Impact on the ability to drive vehicles and operate machinery

Lozap does not affect the ability to drive vehicles or operate machinery.

Side effect

• orthostatic hypotension (dose-dependent);
• nose bleed;
• bradycardia;
• arrhythmias;
• angina pectoris;
• vasculitis;
• myocardial infarction;
• anorexia;
• dryness of the oral mucosa;
• toothache;
• vomit;
• flatulence;
• constipation;
• liver dysfunction;
• dry skin;
• erythema;
• ecchymoses;
• photosensitivity;
• increased sweating;
• hives;
• skin rash;
• angioedema (including swelling of the larynx and tongue, causing airway obstruction and/or swelling of the face, lips, pharynx);
• anemia (slight decrease in hemoglobin concentration and hematocrit, on average by 0.11 g% and 0.09 volume%, respectively, rarely of clinical significance), thrombocytopenia, eosinophilia;
• arthralgia (joint pain);
• anxiety;
• sleep disturbance;
• drowsiness;
• memory disorders;
• paresthesia;
• tremor;
• depression;
• fainting;
• migraine;
• tinnitus;
• taste disturbance;
• visual impairment;
• conjunctivitis;
• imperative urge to urinate;
• renal dysfunction;
• decreased libido;
• impotence;
• gout.

Drug interactions

The drug can be prescribed with other antihypertensive drugs. There is a mutual enhancement of the effects of beta-blockers and sympatholytics. When losartan is used together with diuretics, an additive effect is observed.

There was no pharmacokinetic interaction of losartan with hydrochlorothiazide, digoxin, warfarin, cimetidine, phenobarbital, ketoconazole and erythromycin.

Rifampicin and fluconazole have been reported to reduce plasma concentrations of the active metabolite losartan. The clinical significance of this interaction is not yet known.

As with other drugs that inhibit angiotensin 2 or its action, concomitant use of losartan with potassium-sparing diuretics (for example, spironolactone, triamterene, amiloride), potassium supplements and potassium-containing salts increases the risk of hyperkalemia.

Nonsteroidal anti-inflammatory drugs, including selective COX-2 inhibitors, may reduce the effect of diuretics and other antihypertensive drugs.

When used together, angiotensin 2 receptor antagonists and lithium may increase the concentration of lithium in the blood plasma. Taking this into account, it is necessary to weigh the benefits and risks of combined use of losartan with lithium salts. If combined use is necessary, the concentration of lithium in the blood plasma should be regularly monitored.

Analogues of the drug Lozap

Structural analogues of the active substance:

• Blocktran;
• Brozaar;
• Vasotens;
• Vero Losartan;
• Zisakar;
• Cardomin Sanovel;
• Carzartan;
• Kozaar;
• Lakea;
• Losarel;
• Losartan;
• Lorista;
• Losakor;
• Presartan;
• Renicard.

Use in children

The safety and effectiveness of Lozap in children and adolescents under 18 years of age have not been established.

Use during pregnancy and breastfeeding

There are no data on the use of Lozap during pregnancy. However, it is known that drugs that directly affect the RAAS, when used in the 2nd and 3rd trimesters of pregnancy, can cause developmental defects or even death of the developing fetus. Therefore, if pregnancy occurs, taking Lozap should be stopped immediately.

If it is necessary to use Lozap during lactation, a decision should be made either to stop breastfeeding, or to stop breastfeeding, or to stop treatment with the drug.

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. Hg 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 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

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