Expiration date: 11/2025

The composition and form of issue:

Tablets, film-coated.

• 1 tablet contains:
  

bisoprolol fumarate (2:1) 2.5 mg

hydrochlorothiazide 6.25 mg

excipients: magnesium stearate crospovidone corn starch corn starch, pre-jelatinizirovanny microcrystalline cellulose (MCC) calcium phosphate odnosemjannyj 

shell: 80VS Polysorbate iron oxide yellow macrogol 400 titanium dioxide hypromellose 2910/3 hypromellose 2910/6 

10 PCs in blister. In cardboard pack of 3, 5 or 10 blisters.

• 1 tablet contains:
  

bisoprolol fumarate (2:1) 5 mg

hydrochlorothiazide 6.25 mg

excipients: silica colloidal anhydrous magnesium stearate starch corn microcrystalline cellulose (MCC) calcium phosphate odnosemjannyj 

shell: 80VS Polysorbate iron oxide yellow iron oxide red macrogol 400 titanium dioxide hypromellose 2910/3 hypromellose 2910/5 

10 PCs in blister. In cardboard pack of 3, 5 or 10 blisters.

• 1 tablet contains:
  

bisoprolol fumarate (2:1) 10 mg

hydrochlorothiazide 6.25 mg

excipients: silica colloidal anhydrous magnesium stearate starch corn microcrystalline cellulose (MCC) calcium phosphate odnosemjannyj 

shell: 80VS Polysorbate macrogol 400 titanium dioxide hypromellose 2910/3 hypromellose 2910/5 

10 PCs in blister. In cardboard pack of 3, 5 or 10 blisters.

Description pharmaceutical form:

Dosage 2.5 mg + 6.25 mg: tablets are yellow, round, biconvex, film-coated, one side is engraved a heart, and on the other is 2.5.

Dosage 5 mg + 6.25 mg: tablets are pink, round, biconvex, film-coated, one side is engraved a heart, and on the other "5".

Dosage 10 mg + 6.25 mg: tablets are white, round, biconvex, film-coated, one side is engraved a heart, and on the other "10".

Pharmacokinetics:

Bisoprolol

The time to reach Cmax in plasma ranges from 1 to 4 h bond with blood plasma proteins is about 30%. 40% of bisoprolol is metabolized in the liver. The active metabolites. T1/2 from plasma is about 11 h. Renal and hepatic clearance equivalent. Half of the administered dose is excreted in the urine as unchanged and as metabolites. Total clearance is approximately 15 l/h.

Hydrochlorothiazide

The bioavailability of hydrochlorothiazide varies from 60 to 80%. The time to reach Cmax in plasma is about 4 h (1.5 to 5 h). Relationship with blood plasma proteins is 40%. Hydrochlorothiazide is not metabolized and almost completely excreted unchanged by glomerular filtration and active tubular secretion. T1/2 of hydrochlorothiazide is approximately 8 hours.

In the case of kidney and heart failure, elderly patients renal clearance of hydrochlorothiazide is reduced and the elimination half-life increases. Hydrochlorothiazide crosses the placenta and is excreted in breast milk.

Description pharmacological action:

Clinical studies have demonstrated the potentiation of the effects of the two active components of this combination. Efficacy for the treatment of mild and moderate hypertension was noted even when using the lowest dosage 2.5 mg + 6,25 mg.

Side effects such as hypokalemia (if the application of hydrochlorothiazide) and bradycardia, asthenia and headache (with use of bisoprolol) are dose-dependent.

Bisoprolol is a highly selective &beta1-blocker without sympathomimetic and membrane stabilizing activity. The mechanism of action of bisoprolol in hypertension is primarily associated with a reduction in the level of renin in blood plasma and heart rate.

Hydrochlorothiazide is a diuretic of group tiazidov with antihypertensive effect. Its diuretic effect due to inhibition of transport of sodium ions from the renal tubules into the blood, which thus prevents its reabsorption.

Indications:

Arterial hypertension of mild and moderate severity.

Contraindications:

• hypersensitivity to bisoprololu and other components of the drug
  
• hypersensitivity to sulfonamides including hydrochlorothiazide
  
• severe forms of bronchial asthma, COPD
  
• chronic heart failure in the decompensation stage, not amenable to drug therapy
  
• cardiogenic shock
  
• the syndrome sick sinus, including sinoatrial block
  
• AV blockade II and III degree, without an artificial pacemaker
  
• bradycardia (heart rate less than 50 beats per minute)
  
• variant angina (Prinzmetal's angina)
  
• pheochromocytoma (without the simultaneous use of alpha-blockers)
  
• severe forms of peripheral circulatory disorders, including Raynaud's disease
  
• hypotension
  
• hypokalemia
  
• hypovolemia
  
• severe violations of kidney function (Cl creatinine less than 30 ml/min)
  
• severe violations of liver function
  
• simultaneous reception with floktafeninom, sultopridom, antiarrhythmic agents, lithium
  
• the age of 18 years (efficacy and safety not established).
  

Be wary, AV blockade degree I, psoriasis, ischemic heart disease, chronic heart failure decompensation, older age, hyperthyroidism, electrolyte disorders (hyponatremia, hypokalemia, hypercalcemia), gout.

Application of pregnancy and breast-feeding:

Apply this combination drug during pregnancy is not recommended because it contains a diuretic of group tiazidov.

At present it is not known whether bisoprolol is excreted in breast milk. Diuretics from the group of thiazides are excreted in breast milk and therefore breast-feeding during treatment with the drug Lodoz contraindicated.

Side effects:

The drug is generally well tolerated.

The side effects described less than 10% of cases. These include: a feeling of cold and numbness of the extremities sleep disturbances, depression, nausea, vomiting, diarrhea, constipation, hypertriglyceridemia and hypercholesterolemia, hyperglycemia and glycosuria, hyperuricemia, impaired fluid and electrolyte status, metabolic alkalosis, muscle weakness and cramps bradycardia, impaired AV conduction, worsening of chronic heart failure, orthostatic hypotension, bronchospasm in patients with bronchial asthma or COPD with a history of reversible elevation of creatinine and urea in blood plasma elevated levels of liver enzymes — asparaginases and albinterferon, hepatitis, jaundice impotence hearing loss, allergic rhinitis decreased secretion of the lacrimal glands (keep in mind, patients using contact lenses), blurred vision leukopenia, thrombocytopenia beta-blockers can cause or aggravate psoriasis or induce psoriasiform rash, alopecia.

Also possible: fatigue, fatigue, dizziness, headache that may occur at the beginning of treatment and usually disappear within the first or second week of treatment.

Drug interactions:

The drug is contraindicated in combination with floktafeninom, sultopridom.

The drug is not recommended in combination with amiodarone, lithium or with means that can trigger arrhythmias (astemizole, bepridil, erythromycin, halofantrine, pentamidine, sparfloxacin, terfenadine, vincamine).

Care must be taken when used together with baclofen, halogenated inhaled General anesthetics, BPC (bepridil, diltiazem, verapamil), antiarrhythmic drugs (propafenone, quinidine, hydrogenizing, disopyramide), insulin, medications, urea, lidocaine, iodinated contrast media, anticholinesterase means, high doses of salicylates, drugs, causing gipokaliemia — amphotericin b (at/in route of administration) and mineralokortikosteroidy (the systems use), tetrakozaktidom, laxatives, cardiac glycosides diuretics that can cause hyperkalemia (amiloride, canrenone, spironolactone, triamterene), ACE inhibitors Metformin.

Combinations to be taken into account

Perhaps greater hypotensive action, while the application of antidepressant drugs based on imipramine (tricyclic), neuroleptics, CCB — derived digidropiridinovmi series (amlodipine, felodipine, lacidipine, nifedipine, nicardipine, nimodipine, nitrendipine).

Application Lodosa together with tricyclic antidepressants, including MAO inhibitors, and antipsychotics, is not a contraindication. At the same time, combined their application should be taken into consideration, because may require dose reducing antihypertensive medications because of additive (summing) the hypotensive action.

The joint appointment with mefloquine may develop bradycardia.

The joint appointment with drugs calcium may develop hypercalcemia.

The joint appointment with ziklosporinom possible increase of the creatinine level in the blood.

A possible attenuation of the antihypertensive action Lodosa when administered together with corticosteroids (with systemic use), NSAIDs and tetrakozaktidom.

Method of application and dose:

Inside. Logos recommended to be taken in the morning (during the meal). Tablets should be swallowed whole with a small amount of liquid and not to chew.

For individual dose selection Lodoz is available in the following dosages containing 2.5 mg of bisoprolol and 6.25 mg hydrochlorothiazide, 5 mg bisoprolol and 6.25 mg of hydrochlorothiazide 10 mg of bisoprolol and 6.25 mg of hydrochlorothiazide.

The initial dose is equivalent to 1 table. containing 2.5 mg of bisoprolol and 6.25 mg of hydrochlorothiazide, 1 time per day.

In case of insufficient efficacy of treatment, increase the dose to 1 tab., contains 5 mg of bisoprolol and 6.25 mg of hydrochlorothiazide, 1 time per day. If necessary the dose can be increased to 1 tab., contains 10 mg of bisoprolol and 6.25 mg of hydrochlorothiazide, 1 time per day.

Changes dose is not required in the case of liver or moderate impaired renal function (Cl creatinine more than 30 ml/min).

Application in Pediatrics. Data on the use of the drug in children is not, so it is not recommended for pediatric use.

Overdose:

Symptoms: excessive lowering AD, aetiology.

In the case of severe bradycardia or excessive loss AD/injected the following drugs:

• atropine 1-2 mg
  
• glucagon — 1 mg slow bolus and then if necessary in the form of infusion — 1-10 mg/h.
  
• further, if necessary, administered either epinephrine (adrenaline) — 15-85 µg, the introduction can be repeated, but the total number should not exceed 300 µg, or dopamine at 2.5–10 mcg/kg/min.
  

Neonates born to mothers treated with beta-blockers, possibly an overdose, manifested by decompensation. You must assign:

• glucagon at the rate of 0.3 mg/kg
  
• monitoring in the NICU
  
• epinephrine (adrenaline) and dobutamine. Usually used high-dose long-term treatment is carried out under the supervision of a specialist.
  

Special instructions:

Precautions associated with bisoprololum

Termination of therapy

You should not suddenly stop treatment, particularly in patients with coronary artery disease. The dose should be reduced gradually over two weeks. If necessary, simultaneously initiate appropriate therapy to prevent angina attacks.

Bronchial asthma and COPD

If necessary, the appointment, the treatment is to begin with minimal initial dose. Before starting therapy it is recommended to conduct functional respiratory tests. In the case of the development of bronchospasm during therapy, prescribed beta-agonists.

Chronic heart failure

Be administered with caution and under the supervision of a physician, in minimal doses.

Bradycardia

If reduced heart rate less than 50-55 BPM at rest and in patients experiencing symptoms associated with bradycardia, it is necessary to decrease the dose of the drug.

AV blockade I of a degree

Given the negative Chrono dromotroponoe the action of beta-blockers should be administered with caution to patients with AV blockade of I degree.

Peripheral circulatory disorders

In patients suffering from peripheral circulatory disorders (Raynaud's disease), beta-blockers may cause worsening of the disease.

Pheochromocytoma

Patients with pheochromocytoma should not be administered Logos until then, until the prescribed treatment alpha-blockers. Need to control blood pressure.

Elderly patients

Start treatment with low dosages of the drug requires careful monitoring of the patient's condition.

Diabetes

Patients taking Lodoz should be warned about the possibility of hypoglycemia and the need for regular monitoring of glucose levels in the blood. Bisoprolol may mask signs of hypoglycemia — tachycardia, palpitations and sweating.

Psoriasis

Therapy beta-blockers can exacerbate psoriasis. Bisoprolol is prescribed only if necessary.

Allergic reactions

Patients that have a history of anaphylactic reactions observed, regardless of their causes, especially when taking floctafenine or conducting desensitizing therapy, treatment with beta-blockers may exacerbate the occurrence of these reactions and cause the development of resistance to treatment with epinephrine (adrenaline) in normal doses.

Athletes

Athletes must be informed that this license agreement contains an active substance that can give positive results when conducting doping test.

Precautions associated with hydrochlorothiazide

The level of sodium in the blood

Before starting therapy and then regularly necessary to control the level of sodium in the blood. Reducing the level of sodium in the beginning of treatment may be asymptomatic, so requires regular monitoring. Special attention should be paid to high-risk patients, such as elderly patients, patients with liver cirrhosis.

The level of potassium in the blood

Requires monitoring of potassium in the blood in patients at high risk, such as older patients and in patients with cirrhosis, accompanied by edema, ascites in patients with coronary artery disease or heart failure, an increased QT interval.

Hypokalemia increases risk of arrhythmias, toxicity of cardiac glycosides. The first definition of the level of potassium blood should be held during the first week of therapy Lodosa.

Blood calcium

Thiazide diuretics can reduce the excretion of calcium in the urine, which leads to a slight and temporary hypercalcemia. Temporary hypercalcemia may be related to undiagnosed hyperparathyroidism. Before the study of parathyroid function thiazide-treatment should be discontinued.

Blood glucose

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

Uric acid

In patients with hyperuricemia are at increased risk of attacks of gout: the dose should be individualized.

Renal function

Thiazide diuretics are effective with normal renal function or slightly reduced renal function (Cl creatinine less than 25 mg/ml or 220 µmol/l).

In elderly patients the creatinine level can be calculated based on the age, body weight and sex of the patient on the basis of equation Cockroft. For Example: Cl = (140?age) × body weight/0,814 x creatinine of blood, where age (years) body weight (kg) creatinine (µmol/l).

This formula is applicable for male patients. For women need the result to be multiplied by 0,85.

Hypovolemia (loss of fluid and sodium) arising out of the use of diuretics at the beginning of therapy, leading to decrease in glomerular filtration, which in turn leads to increased levels of urea and creatinine in the blood in patients with normal renal function.

Temporary impairment of renal function occurs without consequences in patients with normal renal function. In patients with impaired renal function may increase existing violations.

In the case of appointment of the drug with other hypotensive means, recommended dose reduction at the beginning of treatment.

Effects on ability to drive and use machines

Be used with caution when driving and operating machinery in connection with the possibility of dizziness.