Lodose - instructions for use, doses, side effects, contraindications

The core of the tablet: active substances: * bisoprolol hemifumarate 2.50 mg, hydrochlorothiazide 6.25 mg; Excipients: magnesium stearate vs 1.00 mg; crospovidone 3.00 mg; corn starch, fine powder 6,75 mg; corn starch, pregelatinized 6.75 mg; cellulose microcrystalline 37.50 mg; calcium hydrophosphate, anhydrous, fine powder 75.00 mg;

Film sheath: opadraj® yellow 3,5000 mg (polysorbate 80 vs 0.0350 mg; ferric iron oxide yellow E172 0.0890 mg; macrogol 400 0.2800 mg; titanium dioxide 0.8910 mg; hypromellose 2910/3 1,1025 mg; hypromellose 2910/6 1,1025 mg)

1 tablet, film-coated, 5 mg + 6.25 mg contains:

The core of the tablet: active substances: * Bisoprolol hemifumarate 5.00 mg, hydrochlorothiazide 6.25 mg; Excipients: silicon dioxide colloidal, anhydrous 0.50 mg; magnesium stearate vs 2.00 mg; corn starch, fine powder 10.00 mg; cellulose microcrystalline 10.00 mg; calcium hydrophosphate, anhydrous, fine powder 136.25 mg.

Film sheath: opadrai® pastel pink 4,50000 mg (polysorbate 80 vs 0.04500 mg; ferric iron oxide yellow E172 0.01260 mg; ferric dye oxide red E172 0.04500 mg; Macrogol 400 0.36000 mg; titanium dioxide 1.33290 mg; hypromellose 2910/3 1,35225 mg; hypromellose 2910/5 1.35225 mg).

1 tablet, film-coated, 10 mg + 6.25 contains:

The core of the tablet: active substances: * Bisoprolol hemifumarate 10.00 mg, hydrochlorothiazide 6.25 mg Excipients: silicon dioxide colloidal, anhydrous 0.50 mg; magnesium stearate vs 2.00 mg; corn starch, fine powder 10.00 mg; cellulose microcrystalline 10.00 mg; calcium hydrophosphate, anhydrous, fine powder 131.25 mg;

Film sheath: opadraj® white 4,50000 mg (polysorbate 80 vs 0.04500 mg; Macrogol 400 0.36000 mg; titanium dioxide 1.40625 mg; hypromellose 2910/3 1,34438 mg; hypromellose 2910/5 1.34438 mg).

* Bisoprolol fumarate (2: 1) and bisoprolol hemifumarate are synonymous.

Description:

Dosage 2.5 mg + 6.25 mg:

The tablets are yellow, round, biconvex, covered with a film shell, with engraving in the form of a heart on one side and "2.5" on the other.

Dosage 5 mg + 6.25 mg:

Tablets are pastel pink color, round, biconcave, covered with a film shell, with engraving in the form of a heart on one side and "5" on the other.

Dosage of 10 mg + 6.25 mg:

Tablets are white, round, biconvex, covered with a film sheath, with engraving in the form of a heart on one side and "10" on the other.

Pharmacotherapeutic group:antihypertensive drug combined (beta 1-blocker selective + diuretic)

ATX: & nbsp

C.07.B.B.07 Bisoprolol in combination with thiazides

Pharmacodynamics:

Lodose is a combination of a selective blocker beta₁adrenoreceptors - bisoprolol, and thiazide diuretic hydrochlorothiazide.

Bisoprolol is a highly selective beta₂adrenoblocker without adrenomimetic and membrane-stabilizing activity. The mechanism of action of bisoprolol in hypertension is associated primarily with a decrease in renin content in the blood plasma and heart rate (heart rate). Hydrochlorothiazide is a diuretic from the group of thiazides with antihypertensive activity. Its diuretic effect is due to the inhibition of active transport of sodium ions from the renal tubules into the blood, which prevents its reabsorption.

Pharmacokinetics:

Bisoprolol

Suction. Bisoprolol almost completely (more than 90%) is absorbed from the gastrointestinal tract. The time to reach the maximum concentration in the blood plasma ranges from 1 to 4 hours. It has a high bioavailability (88%) with a very low effect of the first passage through the liver. Eating food for bioavailability is not affected. For doses from 5 to 40 mg, the kinetics is linear.

Distribution. Link with blood plasma proteins about 30%, volume distribution is large (about 3 l / kg).

Metabolism. 40% of bisoprolol is metabolized in the liver. Metabolites are inactive.

Excretion. The half-life of plasma is 11 hours. Kidney and liver clearance are approximately comparable. Half of the administered dose is excreted unchanged by the kidneys, as well as metabolites. The total ground clearance is about 15 liters per hour.

Hydrochlorothiazide

Suction. After oral administration, about 80% of hydrochlorothiazide is absorbed from the gastrointestinal tract. The bioavailability of hydrochlorothiazide ranges from 60% up to 80%. The time to reach the maximum concentration in the blood plasma is about 4 hours (from 1.5 to 5 hours).

Distribution. Connection with blood plasma proteins 40%.

Excretion. Hydrochlorothiazide is not metabolized and almost completely eliminated by glomerular filtration and active tubular secretion. The half-life of hydrochlorothiazide is about 8 hours.

In the case of renal and cardiac failure, renal clearance of hydrochlorothiazide decreases and the half-life increases.

In elderly patients, it is also possible to increase the maximum concentration in blood plasma (C_mOh).

Hydrochlorothiazide penetrates the placenta and is excreted in breast milk.

Indications:

Arterial hypertension of mild to moderate severity.

Contraindications:

- Hypersensitivity to bisoprolol, hydrochlorothiazide, other thiazides, sulfonamides or other components of the drug;

- severe forms of bronchial asthma and chronic obstructive pulmonary disease (COPD);

- acute heart failure or chronic heart failure (CHF) in the stage of decompensation, requiring inotropic therapy;

- cardiogenic shock;

- syndrome of weakness of the sinus node;

- sinoatrial blockade;

- atrioventricular (AV) of blockade II and III degree without an artificial pacemaker;

- symptomatic bradycardia (heart rate less than 50 beats per minute);

- arterial hypotension (systolic blood pressure (BP) less than 100 mm Hg);

- pheochromocytoma (without simultaneous use of alpha-blockers);

- severe forms of peripheral circulatory disorders, including Raynaud's syndrome;

- metabolic acidosis;

- severe renal dysfunction (creatinine clearance less than 30 ml / min);

- severe violations of liver function;

- simultaneous application with sultopride;

- age to 18 years (efficacy and safety not established).

Carefully:

Chronic heart failure; diabetes mellitus with significant fluctuations in the concentration of glucose in the blood; strict diet; AV blockade of the 1st degree; angina of Prinzmetal; violations of peripheral circulation; hypovolemia; abnormal liver function; hyperuricemia, psoriasis, thyrotoxicosis, pheochromocytoma (against the background of treatment with alpha-blockers), water-electrolyte disorders (hyponatremia, hypokalemia, hypercalcemia), depression (including history), myasthenia gravis, elderly age, myopia (myopia) and angle-closure glaucoma.

Pregnancy and lactation:

Use this combination drug during pregnancy is not recommended because it contains a diuretic from the group of thiazides. Diuretics can lead to fetoplacental ischemia with a concomitant risk of fetal hypotrophy. It is assumed that hydrochlorothiazide can cause thrombocytopenia in newborns.

At the present time, it is not known whether bisoprolol with breast milk. Diuretics from the group of thiazides are excreted in breast milk, so breastfeeding during treatment with Lodose is not recommended.

Hydrochlorothiazide can inhibit the secretion of breast milk.

Dosing and Administration:

Lodoz should be taken orally once a day, in the morning before breakfast, during or after it. Tablets should be swallowed whole, not liquid, squeezed with a small amount of liquid.

The dose of the drug should be selected individually.

The initial dose corresponds to 1 tablet containing 2.5 mg of bisoprolol + 6.25 mg of hydrochlorothiazide once a day.

If the therapeutic effect is insufficient, the dose can be increased to 1 tablet containing 5 mg of bisoprolol + 6.25 mg of hydrochlorothiazide, once a day.If the therapeutic effect is not enough expressed, you can increase the dose of Lodose to 1 tablet containing 10 mg of bisoprolol + 6.25 mg of hydrochlorothiazide once a day.

Duration of treatment

Treatment with Lodose is usually a long-term therapy.

Patients with impaired hepatic or renal function

Dose adjustment is not required in the case of a violation of the liver or kidney function (creatinine clearance more than 30 ml / min) from mild to moderate degree.

Elderly patients

Correction of the dose is usually not required.

Children

There are no data on the use of the drug in children, therefore it is not recommended for use in children under the age of 18 years.

Side effects:

The incidence of adverse reactions listed below was determined as follows:

- very frequent ≥ 1/10;

- Frequent ≥ 1/100, <1/10;

- infrequent ≥ 1/1000, <1/100;

- rare ≥ 1/10 000, <1/1000;

- Very rare <1/10000, including individual messages;

- The frequency is not set (can not be calculated from available data).

Violations of the blood and lymphatic system

Rare: leukopenia, thrombocytopenia;

Very rare: agranulocytosis.

Disorders from the metabolism and nutrition

Infrequent: loss of appetite, hyperglycemia, hyperuricemia,violation of water-electrolyte balance (in particular hypokalemia and hyponatremia, hypomagnesemia and hypochloraemia, as well as hypercalcemia);

Very rare: metabolic alkalosis.

Disorders of the psyche

Infrequent: depression, insomnia;

Rare: hallucinations, nightmares.

Disturbances from the nervous system

Frequent: dizziness *, headache *.

Disturbances on the part of the organ of sight

Rare: decreased lacrimal production fluid (should be considered when wearing contact lenses), impaired vision;

Very rare: conjunctivitis.

Hearing disorders and labyrinthine disorders

Rare: hearing impairment.

Heart Disease

Infrequent: bradycardia, violation AV conduction, aggravation of symptoms of CHF flow.

Vascular disorders

Frequent: feeling cold or numb in the limbs;

Infrequent: orthostatic hypotension;

Rare: syncope (syncope).

Disturbances from the respiratory system, chest and mediastinal organs

Infrequent: bronchospasm in patients with bronchial asthma or airway obstruction in anamnesis;

Rare: allergic rhinitis;

Frequency not established: interstitial pulmonary disease.

Disorders from the digestive system

Frequent: nausea, vomiting, diarrhea, constipation;

Infrequent: pain in the abdomen;

Very rare: pancreatitis.

Disturbances from the liver and bile ducts

Rare: hepatitis, jaundice.

Disturbances from the skin and subcutaneous tissues

Rare: hypersensitivity reactions, such as pruritus, sudden "tides" of blood to the face, skin rash, photodermatitis, purpura (hemorrhagic rash), urticaria;

Very rare: alopecia, cutaneous lupus erythematosus. Beta-blockers can exacerbate the course of psoriasis or cause a psoriasis-like rash.

Disturbances from musculoskeletal and connective tissue

Infrequent: muscle weakness, muscle cramps.

Violations of the genitals and mammary gland

Rare: a violation of potency.

General disorders and disorders at the site of administration

Frequent: increased fatigue;

Infrequent: asthenia;

Very rare: chest pain.

Impact on the results of laboratory and instrumental studies

Infrequent: increased concentration amylase, reversible increase concentration of serum creatinine and urea, increased concentration of triglycerides and cholesterol, glucosuria;

Rare: increased activity "hepatic" transaminases in the blood (aspartate aminotransferase (ACT), alanine aminotransferase (ALT)).

* Especially often these symptoms appear at the beginning of the course of treatment. Usually, these phenomena are of an easy nature and usually pass within 1-2 weeks after the start of treatment.

It is necessary to inform the attending physician of all arising side effects.

Overdose:

Symptoms

The most common symptoms overdose beta-blockers: bradycardia, marked decrease in blood pressure, AV blockade, bronchospasm, acute heart failure and hypoglycemia.

The sensitivity to a single administration of a high dose of bisoprolol varies widely among individual patients and, probably, patients with CHF have high sensitivity.

Clinical manifestations of acute or chronic overdose of hydrochlorothiazide are due to a significant loss of fluid or electrolytes.

The most frequent symptoms of hydrochlorothiazide overdose are: dizziness, nausea, drowsiness, hypovolemia, hypotension, hypokalemia.

Treatment

In case of an overdose, first of all, it is necessary to stop taking the drug, rinse the stomach, prescribe adsorptives and start supporting symptomatic therapy.

With severe bradycardia: intravenous atropine. If the effect is insufficient, with caution, you can enter a drug that has a positive chronotropic effect. Sometimes it may be necessary to temporarily set up an artificial pacemaker.

At the expressed arterial hypotension: intravenous introduction plazmozameshchajushchih solutions and appointment vazopressora.

When AV blockade (II or III degree): patients should be under constant supervision, and receive treatment with beta-adrenomimetics, it is possible to use epinephrine. If necessary - staging an artificial pacemaker.

With exacerbation of CHF flow: intravenous injection of diuretics, drugs with a positive inotropic effect, as well as vasodilators.

When bronhospazme: the appointment of bronchodilators, beta₂adrenomimetics and / or aminophylline.

When hypoglycemia: intravenous administration of a solution of dextrose (glucose).

The limited data available indicate that bisoprolol only to a small extent is excreted in hemodialysis; The degree of excretion of hydrochlorothiazide by hemodialysis has not been established.

Interaction:

Contraindicated combinations

Sultopride: simultaneous use with bisoprolol may increase the risk of developing ventricular arrhythmia.

Unrecommended combinations

Lithium: hydrochlorothiazide, can enhance the cardiotoxic and neurotoxic effects of lithium, reducing the excretion of the latter from the body.

Blockers of "slow" calcium channels (BCCC) like verapamil to a lesser extent, diltiazem: when used with bisoprolol may lead to a decrease in the contractility of the myocardium and the violation of AV conduction. In particular, intravenous administration of verapamil to patients taking beta-blockers can lead to severe arterial hypotension and AV blockade.

Hypotensive agents of central action (such as clonidine, methyldopa, moxonidine, rilmenidine): with simultaneous application with the drug Lodose can lead to a decrease in heart rate and a decrease in cardiac output, as well as to vasodilation due to a decrease in the central sympathetic tone. However, do not interrupt treatment without consulting a doctor. Abrupt cancellation, especially before the abolition of beta-blockers, may increase the risk of developing "ricochet" arterial hypertension.

Combinations that should be used with caution

BCCC derivatives, dihydropyridine (for example, nifedipine, amlodipine): with simultaneous use with bisoprolol may increase the risk of developing arterial hypotension. In patients with heart failure, the risk of subsequent deterioration in the function of the ventricles of the heart can not be ruled out.

Hypotensive drugs and other means with a possible antihypertensive effect (tricyclic antidepressants, barbiturates, phenothiazine derivatives, baclofen): in combination with the drug Lodose may increase the risk of developing hypotension;

Angiotensin converting enzyme (ACE) inhibitors (eg, captopril, enalapril), angiotensin II receptor antagonists: the risk of a significant reduction in blood pressure and / or acute renalinsufficiency at the beginning of treatment with ACE inhibitors or angiotensin II receptor antagonists in patients with hyponatremia (especially in patients with renal artery stenosis). If the previous intake of diuretics caused hyponatremia, it is necessary either to stop taking diuretics three days before the start of treatment with ACE inhibitors, or to start treatment with the latter in small doses, with a gradual increase in them.

Antiarrhythmic drugs of the first class (for example, quinidine, disopyramide; lidocaine, phenytoin; flecainide, propafenone): with simultaneous application with bisoprolol may reduce AV conduction and enhance the negative inotropic effect.

Antiarrhythmic drugs of the III class (for example, amiodarone): with simultaneous application with bisoprolol may increase the disturbance of AV conduction.

Antiarrhythmic agents that can cause tachycardia as pirouettes (class IA, for example, chinidium, hydroquinidine, disopyramide and class III, for example, amiodarone, sotalol, dofetilid, ibutilid): hypokalemia can provoke the occurrence of ventricular arrhythmia, including tachycardia of the type "pirouette".

Other drugs that can cause tachycardia as pirouettes (for example, astemizole, erythromycin for intravenous administration, halofantrine, pentamidine, sparfloxacin, terfenadine, wincamine, some neuroleptics): hypokalemia can provoke the occurrence of ventricular arrhythmia, including tachycardias of the "pirouette" type.

M-holinomimetiki: with simultaneous application with bisoprolol may increase the disturbance of AV conduction and increase the risk of bradycardia.

Beta-blockers for topical use (eg, eye drops for the treatment of glaucoma) can enhance systemic effects of bisoprolol (lowering blood pressure, decreasing heart rate).

Insulin or hypoglycemic agents for oral administration: hypoglycemic action may be intensified. Blockade of beta-adrenoreceptors can mask signs of hypoglycemia, for example, tachycardia. Such interactions are more likely when using nonselective beta-blockers.

Means for general anesthesia: may increase the risk of cardio-depressant action of bisoprolol, leading to arterial hypotension (see section "Special instructions").

Cardiac glycosides: with simultaneous application with bisoprolol may increase the time of the pulse, cause the development of a bradycardia. If hypokalemia and / or hypomagnesemia occur during treatment with Lodose, increased sensitivity of the myocardium to cardiac glycosides may occur, which leads to an increase in the effect and side effects of glycosides.

Non-steroidal anti-inflammatory drugs (NSAIDs): can reduce the antihypertensive effect of bisoprolol. In patients with hypovolemia, concurrent use of NSAIDs can initiate acute renal failure.

Beta-adrenomimetics (eg, isoprenaline, dobutamine): simultaneous use with the drug Lodose can lead to a decrease in the effect of both drugs.

Adrenomimetics acting on beta and alpha-adrenergic receptors (for example, norepinephrine, epinephrine): in combination with bisoprolol may increase vasoconstrictor effects of these drugs that occur with the involvement of alpha-adrenergic receptors, leading to an increase in blood pressure and aggravate intermittent claudication. Such interactions are more likely when using nonselective beta-blockers.

Medicines that promote the removal of potassium from the body (eg, corticosteroids, adrenocorticotropic hormone (ACTH), tetracosactide, carbenoxolone, amphotericin B, furosemide or laxatives): with simultaneous use with hydrochlorothiazide increases the loss of potassium.

Methyldopa: in separate reports, hemolysis is described as a result of the formation of antibodies to hydrochlorothiazide.

Drugs that reduce the concentration of uric acid in the blood plasma: the effect of these drugs can be weakened when they are used together with hydrochlorothiazide.

Colestramine, colestipol: reduce the absorption of hydrochlorothiazide.

Iodine-containing contrast agents: in case of dehydration caused by taking a diuretic, the risk of developing acute liver failure increases, especially when taking high doses of iodine-containing contrast agents.

Calcium salts: the risk of developing hypercalcemia with simultaneous use with hydrochlorothiazide, due to a reduction in the excretion of calcium by the kidneys.

Potassium-sparing diuretics: the risk of hypo- or hyperkalemia with concomitant use with hydrochlorothiazide.The latter condition most often occurs with diabetes or liver failure.

Combinations that should be considered

Mefloquine: with simultaneous use with bisoprolol may increase the risk of developing bradycardia.

Monoamine oxidase (MAO) inhibitors, with the exception of MAO B inhibitors: can enhance the antihypertensive effect of beta-blockers. Simultaneous application can also lead to the development of hypertensive crisis.

Glucocorticosteroids: reduce the antihypertensive effect of the drug (due to the delay of water and sodium in the body caused by glucocorticosteroids).

Special instructions:Precautions associated with bisoprolol

Discontinuation of therapy

Do not suddenly stop treatment, especially in patients with ischemic heart disease. The dose should be reduced gradually within two weeks. If necessary, simultaneous initiation of appropriate therapy to prevent angina attacks should be started.

Bronchial asthma and chronic obstructive pulmonary disease

In patients with mild asthma or COPD, treatment is started with a minimal dose.Preliminary exercise of functional respiratory tests. Symptomatic manifestations of bronchial asthma or COPD show the simultaneous use of bronchodilating agents.

In patients with bronchial asthma, an increase in airway resistance may be required, which requires a higher dose of beta₂-adrenomimetics.

Chronic heart failure

Patients with compensated CHF who are treated with beta-blockers should begin treatment with minimal doses of the drug, gradually increasing the dose, under the supervision of a doctor.

Bradycardia

At a heart rate of less than 50-55 beats / min at rest and patients who have symptoms associated with bradycardia, it is necessary to reduce the dose of the drug.

Atrioventricular block of degree I

Given the negative dromotropic effect of beta-blockers, they should be administered with caution to patients with AV blockade of the I degree.

Angina pectoris

Beta-blockers can increase the frequency and duration of vasospastic episodes in patients with Prinzmetal angina. Beta₁-selective adrenoblockers can be used for mild or mixed manifestationsPrinzmetal angina with simultaneous application of vasodilators.

Peripheral disorders blood circulation

In patients with impaired peripheral circulation or Reynaud's syndrome, beta-adrenoblockers may cause an exacerbation of the course of the disease.

Pheochromocytoma

Patients with pheochromocytoma should not be prescribed Lodose until treatment with alpha-blockers is performed. A thorough control of blood pressure is necessary.

Elderly patients

Treatment should be carried out under close monitoring of the patient's condition (see Water-electrolyte balance).

Diabetes

Patients taking Lodose should be warned about the possibility of hypoglycemia and the need for regular monitoring of blood glucose concentrations at the beginning of treatment.

Symptoms of marked decrease in glucose concentration (hypoglycemia) such as tachycardia, palpitations or increased sweating may be masked.

Psoriasis

Therapy with beta-blockers can aggravate the course of psoriasis. Bisoprolol can be assigned only if necessary.

Allergic reactions

In patients who have a history of anaphylactic reactions regardless of the cause of their occurrence, especially when using iodine-containing contrast agents, or with desensitizing therapy, treatment with beta-blockers may aggravate the occurrence of these reactions and cause the development of resistance to epinephrine (adrenaline) treatment in conventional doses.

General anesthesia

In general anesthesia, beta-adrenergic blockade reduces the likelihood of arrhythmia and myocardial ischemia during introductory anesthesia and intubation, and also in the postoperative period. Currently, it is recommended to continue therapy with beta-blockers and intraoperatively. An anesthesiologist should consider the risk of blockade of beta-adrenergic receptors because of the potential interaction with other drugs, which can cause bradyarrhythmia, suppression of reflex tachycardia, and a decrease in the reflex capacity to compensate for blood loss. If it is necessary to stop therapy with Lodose before surgical intervention, it should be done gradually,and complete 48 hours before the general anesthesia.

Thyrotoxicosis

In the treatment of bisoprolol, the symptoms of thyrotoxicosis can be masked.

Strict diet

Lodose should be used with caution to patients who follow a strict diet.

Combination with verapamil, diltiazem or bepridilom

Such combinations require careful monitoring of the patient's condition and ECG, especially in elderly patients and at the beginning of treatment.

Precautions associated with hydrochlorothiazide

In patients with impaired liver function, thiazide diuretics and their derivatives can cause hepatic encephalopathy. In this case, you must immediately stop taking the drug.

Water-electrolyte balance

With prolonged use of the drug Lodose, it is recommended to regularly monitor the content of blood serum electrolytes (especially potassium, sodium, calcium), creatinine and urea, serum lipids (cholesterol and triglycerides), uric acid and glucose.

Prolonged use of thiazide diuretics can lead to disruption of the water electrolyte balance, in particular hypokalemia and hyponatremia, as well as hypomagnesemia and hypochloraemia, and hypercalcemia.

The content of sodium in the blood plasma

Before the start of therapy and further regular monitoring of the sodium content in the blood is necessary. Taking diuretics can provoke hyponatraemia, in some cases with serious consequences.

Decreasing the sodium content at the beginning of treatment can be asymptomatic, therefore regular monitoring is needed, special attention is required by high-risk patients, for example, elderly patients, patients with cirrhosis of the liver.

The content of potassium in blood plasma

The greatest risk associated with taking thiazide and thiazide-like diuretics is loss of potassium, leading to hypokalemia (<3.5 mmol / l).

More frequent monitoring of potassium in the blood of high-risk patients, for example, elderly patients and / or malnourished and / or taking several medicines at the same time, as well as patients with coronary artery disease or heart failure, in which hypokalemia increases the risk of developing arrhythmia, cardiac glycosides toxicity. Patients with an increased QT interval, both congenital and acquired, are also at risk.Hypokalemia (as well as bradycardia) potentiates the development of severe arrhythmia, including tachycardia of the type "pirouette".

The first determination of the potassium content in blood plasma should be carried out during the first week of therapy with Lodose.

Calcium in the blood plasma

Thiazide diuretics can reduce the excretion of calcium by the kidneys, which leads to minor and temporary hypercalcemia. Significant hypercalcemia may be associated with undiagnosed hyperparathyroidism. Before the study of parathyroid function, treatment with thiazides should be discontinued.

The concentration of glucose in the blood

It is necessary to control the concentration of glucose in the blood in patients with diabetes mellitus, especially in the case of hypokalemia.

Uric acid

In patients with hyperuricemia, the risk of developing gout attacks is increased: the dose of the drug must be selected individually.

Kidney function

Thiazide diuretics are effective in normal or slightly reduced renal function (creatinine clearance less than 25 mg / ml or 220 μmol / L in adults). The creatinine clearance is calculated taking into account the patient's age, body weight and sex, using the Cockcroft equation. For example:

ClCr = (140 - age) x body weight / 0.814 x serum creatinine where: age (years) body weight (kg) serum creatinine (in micromol / l)

This calculation formula is applicable for elderly male patients.

For older female patients, the result should be multiplied by 0.85.

Hypovolemia in addition to the loss of fluid and sodium resulting from the use of diuretics at the beginning of therapy leads to a decrease in the glomerular filtration rate, which in turn leads to an increase in urea and creatinine in the blood serum in patients with normal renal function. Temporary impairment of kidney function occurs without consequences in patients with normal renal function. In patients with impaired renal function, exacerbation of existing disorders is possible.

Combination with other antihypertensive agents

If the drug is prescribed with another antihypertensive drug, a dose reduction is recommended, at least at the beginning of the treatment.

Photosensitivity

The use of thiazide diuretics can cause photosensitivity reactions. When such reactions occur, it is recommended to protect sensitive areas from sunlightor artificial UV radiation. In severe cases, treatment may be discontinued.

Myopia (nearsightedness) and angle-closure glaucoma

Hydrochlorothiazide, as sulfanilamide, can cause idiosyncratic reactions, manifested as acute short-term myopia and acute closed-angle glaucoma. Symptoms include a sharp decrease in visual acuity or pain in the eye and usually occur between a few hours and a few weeks from the start of the drug. The absence of treatment for an angle-closure glaucoma can lead to irreversible loss of vision. The first step in treatment is to stop taking hydrochlorothiazide as soon as possible. If intraocular pressure remains uncontrolled, surgical or surgical treatment may be required. The risk factor for the development of angle-closure glaucoma is the allergic reactions to sulfanylamide derivatives or penicillin in the anamnesis.

Precautions associated with bisoprolol and hydrochlorothiazide

Athletes

Athletes should be informed that the drug contains active substances that can give positive results in doping tests.

Effect on the ability to drive transp. cf. and fur:The drug Lodose does not affect the ability to drive vehicles. However, due to the individual reaction of the body to therapy with Lodose, the ability to drive vehicles or work with technically complex mechanisms can be disrupted. This should be paid special attention at the beginning of treatment, with the change of the drug, as well as with the simultaneous use of alcohol.

Form release / dosage:

Film-coated tablets, 2.5 mg + 6.25 mg, 5 mg + 6.25 mg and 10 mg + 6.25 mg.

Packaging:

For 10 tablets per blister of PVC / Al or PP / Al; 3 blisters per cardboard pack together with instructions for use.

The blister and cardboard tutu bear the symbol "M" to protect against tampering.

Storage conditions:

At a temperature of 18-25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LS-001912

Date of registration:29.09.2011

The owner of the registration certificate:Merck Sante ca.c.Merck Sante ca.c. France

Manufacturer: & nbsp

MERCK, KGaA Germany

Representation: & nbspTakeda Pharmaceuticals Ltd.Takeda Pharmaceuticals Ltd.

Information update date: & nbsp27.11.2015

Illustrated instructions

Instructions

Lodose (Lodoz)