Lodoz, 5 mg+6, 25 mg 30 pcs.

A combined antihypertensive drug.

Bisoprolol is a highly selective beta₁-adrenoblocker without sympathomimetic and membrane stabilizing activity. The mechanism of action of bisoprolol in arterial hypertension is associated primarily with a decrease in plasma renin levels and a decrease in HR.

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

In clinical trials, potentiation of the effects of the active substances of this combination has been observed. Efficacy for mild to moderate arterial hypertension has been observed even when used in the lowest doses of 2.5 mg + 6.25 mg.

Side effects such as hypokalemia (when using hydrochlorothiazide) and bradycardia, asthenia, and headache (when using bisoprolol) are dose dependent. Therefore, to reduce the undesirable effects, the amount of each active ingredient in Lodose has been reduced by 2-4 times.

Indications

Arterial hypertension of mild and moderate severity.

Pharmacological effect

Combined antihypertensive drug.

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

Hydrochlorothiazide is a diuretic from the group of thiazides with an antihypertensive effect. Its diuretic effect is due to inhibition of the transport of sodium ions from the renal tubules into the blood, thereby preventing its reabsorption.

In clinical studies, potentiation of the effects of the active substances of this combination was observed. Efficacy for the treatment of mild and moderate arterial hypertension was noted even when used in the lowest doses – 2.5 mg + 6.25 mg.

Side effects, such as hypokalemia (with hydrochlorothiazide) and bradycardia, asthenia and headache (with bisoprolol), are dose-dependent. Therefore, to reduce undesirable effects, the amount of each active ingredient in Lodoz is reduced by 2-4 times.

Special instructions

Treatment should not be stopped suddenly, especially in patients with coronary artery disease. It is recommended to reduce the dose gradually over 2 weeks. If necessary, appropriate therapy should be started simultaneously to prevent angina attacks.
If it is necessary to prescribe the drug to patients with bronchial asthma or COPD, treatment should begin with the minimum initial dose. Functional breathing tests are recommended before starting therapy. If bronchospasm develops during therapy, beta-agonists should be prescribed.

In patients with chronic heart failure, the drug should be prescribed with caution and under the supervision of a physician, in minimal doses.

It is necessary to reduce the dose of the drug at resting heart rate. Considering the negative dromotropic effect of beta-blockers, they should be prescribed with caution to patients with first-degree AV block.

In patients with peripheral circulatory disorders (Raynaud’s disease), beta-blockers may cause an exacerbation of the disease.

Patients with pheochromocytoma should not be prescribed Lodoz until they have been treated with alpha-blockers. Blood pressure control is necessary.

In elderly patients, treatment should begin with a low dose of the drug, and careful monitoring of the patient’s condition is necessary.

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

During therapy with beta-blockers, an exacerbation of psoriasis is possible. Bisoprolol should be prescribed only when necessary.

If there is a history of anaphylactic reactions, regardless of the cause of their occurrence, especially when taking floctafenine, or when carrying out 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 should be informed that Lodoz contains an active substance that may give positive results in doping tests.

Precautions associated with the use of hydrochlorothiazide:

Before starting further, monitoring sodium levels in the blood is necessary regularly during therapy. A decrease in sodium levels at the beginning of treatment may be asymptomatic, so regular monitoring is necessary. Particular attention is required in the presence of risk factors, for example, in elderly patients, patients with liver cirrhosis.

Blood potassium monitoring is necessary in high-risk patients, such as elderly patients, patients receiving thiazide and thiazide-like diuretics, and patients with cirrhosis accompanied by edema, ascites, patients with coronary artery disease or heart failure, prolonged QT interval.
Hypokalemia increases the risk of developing arrhythmias and toxicity of cardiac glycosides. The first determination of the level of potassium in the blood should be carried out during the first week of therapy with Lodoz.

Thiazide diuretics may reduce urinary calcium excretion, resulting in mild and temporary hypercalcemia. Transient hypercalcemia may be associated with undiagnosed hyperparathyroidism. Before studying the function of the parathyroid glands, treatment with thiazides must be discontinued.

Monitoring blood glucose levels is necessary in patients with diabetes mellitus, especially in the case of hypokalemia.

Patients with hyperuricemia have an increased risk of developing gout attacks: the dose of the drug must be selected individually.
Thiazide diuretics are effective with normal renal function or slightly reduced renal function (creatinine clearance 220 µmol/l). In elderly patients, serum creatinine can be calculated taking into account the age, body weight and gender of the patient using the Cockroft formula:

For men:

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

For women: obtained value x 0.85

Hypovolemia (loss of fluid and sodium) resulting from the use of diuretics at the beginning of therapy leads to a decrease in glomerular filtration rate, which leads to an increase in blood urea and creatinine levels 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, existing disorders may worsen.

If the drug is prescribed with another antihypertensive drug, it is recommended to reduce the dose at the beginning of treatment.
Use in pediatrics: The effectiveness and safety of the drug in children and adolescents under 18 years of age have not been established, therefore the use of the drug is contraindicated.

Impact on the ability to drive vehicles and operate machinery:

use with caution when driving a car or operating machinery due to the possibility of dizziness.

Active ingredient

Bisoprolol, Hydrochlorothiazide

Composition

1 table contains bisoprolol fumarate (2:1) 5 mg,

hydrochlorothiazide 6.25 mg.

Excipients:

colloidal silicon dioxide – 0.5 mg,

magnesium stearate – 2 mg,

corn starch – 10 mg,

microcrystalline cellulose – 10 mg,

monosubstituted calcium phosphate – 136.25 mg.

Shell composition:

polysorbate 80 VS – 0.045 mg, iron oxide yellow – 0.0126 mg, iron oxide red – 0.045 mg, macrogol 400 – 0.36 mg, titanium dioxide – 1.3329 mg, hypromellose 2910/3 – 1.35225 mg, hypromellose 2910/5 – 1.35225 mg.

Pregnancy

It is not recommended to use this combination drug during pregnancy, because it contains a diuretic from the thiazide group. It is currently unknown whether bisoprolol is excreted in breast milk.

Diuretics from the thiazide group are excreted in breast milk, and therefore breastfeeding during treatment with Lodoz is contraindicated.

There is no data on the use of the drug in children, so it is not recommended for use in pediatrics.

Contraindications

– Severe forms of bronchial asthma, COPD.
– Chronic heart failure in the stage of decompensation, not amenable to drug therapy.
– Cardiogenic shock.
– SSSU, incl. sinoatrial blockade.
– AV block II and III degrees without artificial pacemaker.
– Severe bradycardia (HR – Variant angina (Prinzmetal angina).
– Pheochromocytoma (without simultaneous use of alpha-blockers).
– Severe forms of peripheral circulatory disorders (including Raynaud’s disease).
– Arterial hypotension.
– Hypokalemia.
– Hypovolemia.
– Severe renal dysfunction (creatinine clearance – Severe liver dysfunction.
– Simultaneous use with floctafenine, sultopride, antiarrhythmic drugs, lithium preparations
– Children and adolescents under 18 years of age (efficacy and safety have not been established).
– Hypersensitivity to bisoprolol and other components of the drug.
– Hypersensitivity to hydrochlorothiazide and other sulfonamides.

Caution should be used in case of 1st degree AV blockade, psoriasis, coronary artery disease, chronic heart failure in the stage of decompensation, thyrotoxicosis, water and electrolyte disorders (hyponatremia, hypokalemia, hypercalcemia), gout, as well as in elderly patients.

Side Effects

From the central nervous system: sleep disturbances, depression; possible – fatigue, fatigue, dizziness, headache (may occur at the beginning of treatment and usually disappear during the first or second week of treatment).

From the cardiovascular system: bradycardia, impaired AV conduction, exacerbation of chronic heart failure, orthostatic hypotension.

From the respiratory system: bronchospasm in patients with a history of bronchial asthma or COPD.

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

From the urinary system: a reversible increase in serum creatinine and urea.

From the musculoskeletal system: feeling of cold and numbness of the extremities, muscle weakness, cramps.

From the senses: hearing impairment, decreased production of lacrimal glands (must be taken into account in patients using contact lenses), visual impairment.

From the metabolic side: hypertriglyceridemia, hypercholesterolemia, hyperglycemia, glucosuria, hyperuricemia, impaired water-electrolyte status, metabolic alkalosis.

From the hematopoietic system: leukopenia, thrombocytopenia.

Dermatological reactions: beta-blockers can cause or aggravate psoriasis or cause psoriasis-like rashes and alopecia.

Other: impotence, allergic rhinitis.

The drug is usually well tolerated.

Side effects are described in less than 10% of cases.

Interaction

The drug is contraindicated for use in combination with floctafenine and sultopride.

The drug is not recommended for use in combination with amiodarone, lithium or with drugs that can initiate arrhythmias (astemizole, bepridil, erythromycin, halofantrine, pentamidine, sparfloxacin, terfenadine, vincamycin).

Caution is required when using the drug simultaneously with baclofen, inhaled halogenated general anesthetics, slow calcium channel blockers (bepridil, diltiazem, verapamil), antiarrhythmic agents (propafenone, quinidine, hydroquinidine, disopyramide), insulin, urea preparations, lidocaine, iodine-containing contrast agents, anticholinesterase drugs, high doses of salicylates, drugs that cause hypokalemia – amphotericin (IV administration) and mineralocorticoids (systemic use), tetracosactide, laxatives; cardiac glycosides, diuretics that cause hyperkalemia (amiloride, canrenone, spironolactone, triamterene); ACE inhibitors, metformin.

It is possible to enhance the hypotensive effect with the simultaneous use of tricyclic antidepressants (including imipramine), neuroleptics, slow calcium channel blockers and dihydropyridine derivatives (including amlopidine, felopidine, lacidipine, nifedipine, nicardipine, nimodipine, nitrendipine).

The use of Lodoz simultaneously with tricyclic antidepressants, incl. MAO inhibitors, as well as antipsychotics, are not a contraindication. At the same time, their combined use should be taken into account, since it may be necessary to reduce the dose of the antihypertensive drug due to additive hypotensive effects.

When co-administered with mefloquine, bradycardia may develop.

When co-administered with calcium supplements, hypercalcemia may develop.

When co-administered with cyclosporine, an increase in serum creatinine levels is possible.

The hypotensive effect of Lodoz may be weakened when administered simultaneously with GCS (for systemic use), NSAIDs and tetracosactide.

Overdose

Symptoms: excessive decrease in blood pressure, bradycardia. Newborns from mothers treated with beta-blockers may develop an overdose, manifested by cardiac decompensation.

Treatment: in case of severe bradycardia or excessive decrease in blood pressure, the following drugs are administered intravenously: atropine at a dose of 1-2 mg; glucagon at a dose of 1 mg as a slow bolus and then, if necessary, in the form of an infusion at a dose of 1-10 mg/hour; then, if necessary, either epinephrine (adrenaline) is administered at a dose of 15-85 mcg, the administration can be repeated, its total amount should not exceed 300 mcg, or dopamine at a dose of 2.5-10 mcg/kg/min.

In case of overdose in newborns, manifested by cardiac decompensation, glucagon is prescribed at a rate of 0.3 mg/kg; epinephrine (adrenaline) and dobutamine (usually in high doses) should be monitored in the neonatal ICU. Long-term treatment is carried out under the supervision of a specialist.

Storage conditions

At a temperature of 18–25 °C

Shelf life

3 years

Manufacturer

Merck Healthcare KGaA, Germany