LODOZ

Active material: Bisoprolol, Gidroxlorotiazid
When ATH: C07BB07
CCF: Antihypertensive drugs
ICD-10 codes (testimony): I10
When CSF: 01.09.16.02
Manufacturer: MERCK SANTE s.a.s. (France)

PHARMACEUTICAL FORM, COMPOSITION AND PACKAGING

Pills, coated yellow color, film; round, lenticular, engraved as a heart on the one hand and Figures “2.5” – with another.

Excipients: magnesium stearate, krospovydon, corn starch, pregelatinized corn starch, microcrystalline cellulose, calcium phosphate monobasic.

The composition of the shell: polysorbate 80 VS, iron oxide yellow, macrogol 400, Titanium dioxide, gipromelloza 2910/3, gipromelloza 2910/6.

10 PC. – blisters (3) – packs cardboard.
10 PC. – blisters (5) – packs cardboard.
10 PC. – blisters (10) – packs cardboard.

Pills, coated Pink colour, film; round, lenticular, engraved as a heart on the one hand and Figures “5” – with another.

Excipients: colloidal silicon dioxide, magnesium stearate, corn starch, microcrystalline cellulose, calcium phosphate monobasic.

The composition of the shell: polysorbate 80 VS, iron oxide yellow, iron oxide red, macrogol 400, Titanium dioxide, gipromelloza 2910/3, gipromelloza 2910/5.

10 PC. – blisters (3) – packs cardboard.
10 PC. – blisters (5) – packs cardboard.
10 PC. – blisters (10) – packs cardboard.

Pills, coated white, film; round, lenticular, engraved as a heart on the one hand and Figures “10” – with another.

Excipients: colloidal silicon dioxide, magnesium stearate, corn starch, microcrystalline cellulose, calcium phosphate monobasic.

The composition of the shell: polysorbate 80 VS, macrogol 400, Titanium dioxide, gipromelloza 2910/3, gipromelloza 2910/5.

10 PC. – blisters (3) – packs cardboard.
10 PC. – blisters (5) – packs cardboard.
10 PC. – blisters (10) – packs cardboard.

Pharmacological action

Combined antihypertensive drug.

Bisoprolol is a highly beta₁-blocker without sympathomimetic activity and membrane stabilizing. The mechanism of action of bisoprolol in hypertension is associated, primarily, with a reduction in plasma renin levels and a decrease in heart rate.

Hydrochlorothiazide is a thiazide diuretic with a group of antihypertensive effect. Its diuretic effect is due to inhibition of the transport of sodium ions from the renal tubules in the blood, warns that thus its reabsorption.

In clinical studies, there was potentiation of the effects of the combination of active substances. The efficacy for the treatment of mild to moderate hypertension has been noted, even when used in smaller doses - 2.5 mg + 6.25 mg.

Side effects, such as hypokalemia (the application of hydrochlorothiazide) and bradycardia, asthenia and headache (the application of bisoprolol), They are dose-dependent. Therefore, to reduce the undesirable effects of the amount of each active component in a reduced Lodoze 2-4 times.

Pharmacokinetics

Bisoprolol

T_max in plasma ranges from 1 to 4 no. Plasma protein binding – about 30%.

40% bisoprolol is metabolized in the liver. The metabolites are inactive.

T_1/2 from plasma is 11 no. Renal and hepatic clearance equivalent. Half of the administered dose excreted in the urine in unchanged form, as well as metabolites. The total clearance is about 15 l /.

Gidroxlorotiazid

The bioavailability of hydrochlorothiazide ranges from 60% to 80%. T_max in the blood plasma is about 4 no (from 1.5 to 5 no). Plasma protein binding – 40%. Hydrochlorothiazide is not metabolized and almost completely excreted in unchanged form by glomerular filtration and active tubular secretion. T_1/2 hydrochlorothiazide is about 8 no.

Hydrochlorothiazide crosses the placental barrier, excreted in breast milk.

Pharmacokinetics in special clinical situations

In the case of kidney and heart failure, elderly patients renal clearance of hydrochlorothiazide is reduced, T_1/2 increases.

Testimony

- Hypertension mild to moderate severity.

Dosage regimen

Lodoz recommended to take in the morning (mealtime). The tablets should be swallowed whole with a small amount of liquid and not chewed.

The dose should be selected individually, using the following formulations Lodoza:

- 2.5 bisoprolol mg / 6.25 mg of hydrochlorothiazide;

- 5 bisoprolol mg / 6.25 mg of hydrochlorothiazide;

- 10 bisoprolol mg / 6.25 mg of hydrochlorothiazide.

The initial dose matches 1 tab. (2.5 bisoprolol mg / 6.25 mg of hydrochlorothiazide) 1 time / day. In the case of lack of effectiveness of the treatment dose increased to 1 tab. (5 bisoprolol mg / 6.25 mg of hydrochlorothiazide) 1 time / day. If necessary, the dose can be increased to 1 tab. (10 bisoprolol mg / 6.25 mg of hydrochlorothiazide) 1 time / day.

In patients impaired liver function or moderate renal impairment (CC>30 ml / min) dose modification is not required.

Side effect

CNS: sleep disorders, depression; possible – fatigue, fatiguability, dizziness, headache (may occur at the beginning of treatment and usually disappear within the first or second week of treatment).

Cardio-vascular system: bradycardia, violation of AV-conduction, exacerbation of chronic heart failure, orthostatic hypotension.

The respiratory system: bronchospasm in patients with asthma or COPD history.

From the digestive system: nausea, vomiting, diarrhea, constipation, hepatitis, jaundice, increased activity of AST and ALT.

From the urinary system: reversible elevation of serum creatinine and urea.

On the part of the musculoskeletal system: feeling cold and numb limbs, muscular weakness, convulsions.

From the senses: hearing loss, decreased production of lacrimal gland (should take into account patients, using contact lenses), blurred vision.

Metabolism: hypertriglyceridemia, hypercholesterolemia, giperglikemiâ, glycosuria, hyperuricemia, disruption of water and electrolyte status, metabolic alkalosis.

From the hematopoietic system: leukopenia, thrombocytopenia.

Dermatological reactions: Beta-blockers can cause or aggravate psoriasis or induce psoriasis-like rash, alopecia.

Other: impotence, nasal allergy.

The drug is generally well tolerated. Side effects have been described at least in 10% cases.

Contraindications

- Severe bronchial asthma, COPD;

- Chronic heart failure decompensation, not amenable to drug therapy;

- Cardiogenic shock;

- SSS, incl. sinoatrialynaya blockade;

- AV-block II and III degree, without artificial pacemaker;

- Vыrazhennaya bradycardia (Heart Rate<50 u. / min);

- variant angina (Prinzmetal angina);

- Pheochromocytoma (without the simultaneous use of alpha-blockers);

- Severe peripheral circulatory disorders (incl. Raynaud's disease);

- Hypotension;

- Hypokalemia;

- Gipovolemiя;

- Severe renal dysfunction (CC<30 ml / min);

- Severe liver;

- Simultaneous application of floctafenine, sultoprydom, antiarrhythmics, lithium preparations;

- Childhood and adolescence up 18 years (efficacy and safety have not been established);

- Hypersensitivity to bisoprolol and other ingredients;

- Hypersensitivity to hydrochlorothiazide or other sulphonamides.

FROM caution It should be applied to AV-blockade of I degree, psoriaze, CHD, chronic heart failure, decompensated, thyrotoxicosis, fluid and electrolyte disorders (giponatriemiya, kaliopenia, hypercalcemia), podagre, as well as in elderly patients.

Pregnancy and lactation

Not recommended for use during pregnancy Lodoz, because it contains a group of thiazide diuretic.

It is currently unknown, whether bisoprolol is released in breast milk. Diuretics group of thiazides are excreted in breast milk. Breastfeeding during treatment with Lodoz contraindicated.

Cautions

Precautions, associated with the use of bisoprolol

Do not suddenly stop treatment, especially in patients with coronary artery disease. The dose recommended to reduce gradually over 2 weeks. If necessary, at the same time initiate appropriate therapy, warning angina.

If necessary, the appointment of the drug to patients with bronchial asthma or COPD, Treatment begins with a minimum initial dose. Before therapy is recommended for functional respiratory tests. In the case of bronchospasm during therapy should be prescribed beta-agonists.

Patients with chronic heart failure drug should be used with caution and under medical supervision, in minimal doses.

It is necessary to decrease the dose of the drug in heart rate at rest <50-55 u. / min, and the presence of clinical symptoms bradycardia.

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

Patients c peripheral circulatory disorders (Raynaud's disease) Beta-blockers may exacerbate the disease.

Patients with pheochromocytoma should not be administered until Lodoz, has not yet been treated alpha-blockers. Necessary to control blood pressure.

In elderly patients treatment should be started with a low dose, careful monitoring of the patient.

Patients, taking Lodoz, should be warned about the possibility of hypoglycemia and the need for regular monitoring of blood glucose. Bisoprolol may mask the symptoms of hypoglycemia (tachycardia, palpitation and sweating).

The therapy beta-blockers may increase the flow of psoriasis. Bisoprolol should be administered only if necessary.

When specifying a history of anaphylactic reactions, regardless of their causes, especially when taking floctafenine, or during desensitizing therapy, treatment with beta-blockers may exacerbate the occurrence of these reactions and cause the development of resistance to treatment with epinephrine (adrenaline) at conventional doses.

Athletes should be informed that, Lodoz that contains the active substance, which may give positive results in the doping test.

Precautions, associated with gidroxlorotiazida

Before beginning continue regularly during therapy, and need to control the level of sodium in the blood. Reducing sodium in the beginning of treatment may be asymptomatic, therefore requires regular monitoring. Particular attention is required in the presence of risk factors, eg, elderly patients, patients with cirrhosis.

Requires control of potassium in the blood of high-risk patients, eg, in elderly patients, patients, receiving thiazide diuretics and thiazide, as well as in patients with cirrhosis, accompanied by edema, ascites, in patients with coronary artery disease or heart failure, increased QT interval.

Hypokalemia increases the risk of arrhythmias, the toxicity of cardiac glycosides. First determine the level of potassium in the blood must be held during the first week of therapy Lodozom.

Thiazide diuretics may reduce urinary excretion of calcium, that leads to slight and temporary hypercalcaemia. Temporary hypercalcemia may be associated with undiagnosed hyperparathyroidism. Before examining the function of the parathyroid glands thiazide treatment should be discontinued.

Requires monitoring of blood glucose levels in patients with diabetes, particularly in the case of hypokalemia.

In patients with hyperuricemia increased risk of gout attacks: dose should be adjusted individually.

Thiazide diuretics are effective in normal renal function or slightly reduced renal function (CC<60 ml / min or serum creatinine content > 220 mmol / l). In elderly patients, the content of serum creatinine can be calculated based on age, body weight and sex of the patient by Cockcroft:

For men:

CC (ml / min)= [140-age] x body weight (kg)/72 x serum creatinine (mg / dL)

For women: the resulting value of x 0.85

Gipovolemiя (loss of fluid and sodium), arising from the use of diuretics in the early treatment, It leads to a decrease in the glomerular filtration, which leads to higher levels of urea and creatinine levels in patients with normal renal function.

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

In the case of the appointment of the drug to other antihypertensive agents recommended dose reduction at the beginning of treatment.

Use in Pediatrics

The efficacy and safety of the drug in children and adolescents under the age of 18 years not set, so the use of the drug is contraindicated.

Effects on ability to drive vehicles and management mechanisms

Use caution when driving and operating machinery due to the possibility of dizziness.

Overdose

Symptoms: excessive reduction of blood pressure, bradycardia. Newborns of mothers, treated with beta-blockers, possible development of an overdose, manifested cardiac decompensation.

Treatment: in the case of bradycardia or excessive decrease in blood pressure / injected these drugs: atropine at a dose 1-2 mg; glucagon doze 1 mg bolus and then slowly, if necessary, in the form of an infusion in a dose of 1-10 mg / h; Further, if necessary, introduce or epinephrine (adrenaline) dose 15-85 g, administration can be repeated, its total amount shall not exceed 300 g, or dopamine at a dose 2.5-10 ug / kg / min.

In overdose in newborns, manifested cardiac decompensation, glucagon administered is based 0.3 mg / kg; epinephrine (adrenaline) and dobutamine (usually high doses) necessary to ensure the observation in the ICU newborn. Prolonged treatment is carried out under the supervision of a specialist).

Drug Interactions

The drug is contraindicated for use in combination with floctafenine, sultoprydom.

The drug is not recommended for use in combination with amiodarone, lithium or with means, that can trigger arrhythmias (astemizol, bepridil, Erythromycin, galofantrin, pentamidine, sparfloxacine, terfenadine, vinkamicin).

Caution is required while using the drug with baclofen, halogenated inhaled anesthetics general, blockers of slow calcium channels (bepridil, diltiazemom, verapamil), antiarrhythmics (propafenone, xinidinom, gidroxinidinom, dizopiramidom), insulinom, urea drugs, lidokainom, iodine-containing contrast agents, anticholinesterases, high doses of salicylates, Drug, cause hypokalemia – amphotericin (in / introduction) and mineralocorticoid (systemic administration), tetrakozaktidom, laxatives; cardiac glycosides, Diuretics, causing hyperkalemia (amiloridom, canrenone, spironolactone, Triamteren); ACE inhibitors, metforminom.

Perhaps increased hypotensive effect, while the use of tricyclic antidepressants (incl. imipramine), neuroleptics, blockers of slow calcium channel dihydropyridine derivatives (incl. amlopidin, felopidin, lacidipine, nifedipine, nikardipin, nimodipine, nitrendipine).

Application Lodoza concurrently with tricyclic antidepressants, incl. MAO inhibitors, as well as neuroleptics, not a contraindication. At the same time, the combined use of them must be taken into account, as it may be necessary to decrease the dose of the antihypertensive agent of the additive hypotensive effect.

The joint appointment with mefloquine may develop bradycardia.

When coadministered with calcium may develop hypercalcemia.

When coadministered with cyclosporine may increase the content of serum creatinine.

Perhaps the weakening of hypotensive action Lodoza while the appointment with SCS (for systemic use), NSAIDs and tetrakozaktidom.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

The drug should be stored out of reach of children at temperature from 18 ° to 25 ° C. Shelf life – 3 year.