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

Mild to moderate arterial hypertension.

Active ingredient

Composition

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

hydrochlorothiazide 6.25 mg.

Excipients:

Silicon dioxide colloid – 0.5 mg,

magnesium stearate – 2 mg,

corn starch – 10 mg,

p> microcrystalline cellulose – 10 mg,

calcium phosphate displaced – 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.

How to take, the dosage

Lodose is recommended to be taken in the morning (with meals). The tablets should be swallowed whole with a small amount of liquid and not chewed.

Interaction

The drug is contraindicated in combination with floktafenine, sultopride.

The drug is not recommended in combination with amiodarone, lithium or with agents that may initiate arrhythmias (astemisol, bepridil, erythromycin, halofantrine, pentamidine, sparfloxacin, terfenadine, vincamycin).

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

Possible increase of the hypotensive effect if tricyclic antidepressants (including imipramine), neuroleptics, slow calcium channel blockers by dihydropyridine derivatives (including amlopidine, felopidine, latsidipine, nifedipine, nicardipine, nimodipine, nitrandipine) are used simultaneously.

The use of Lodose concomitantly with tricyclic antidepressants, including MAO inhibitors, and neuroleptics is not contraindicated. However, their combined use should be considered, as a reduction in the dose of the hypotensive agent may be required due to its additive hypotensive effect.

When co-administered with mefloquine, bradycardia may occur.

The co-administration of calcium preparations may lead to hypercalcemia.

When co-administered with cyclosporine, serum creatinine may increase.

The hypotensive effect of Lodose may be impaired when concomitantly prescribed with GCS (for systemic use), NSAIDs and tetracosactide.

Special Instructions

The treatment should not be stopped suddenly, especially in patients with CHD. The dose should be reduced gradually over a period of 2 weeks. If necessary, appropriate therapy to prevent angina attacks should be started simultaneously.
If the drug should be administered to patients with bronchial asthma or COPD, treatment should be started with the minimum initial dose. Before the start of therapy it is recommended to perform functional respiratory tests. In case of bronchospasm development beta-adrenomimetics should be prescribed during therapy.

In patients with chronic heart failure, the drug should be prescribed with caution and under medical supervision, in the lowest dose.

Dose reduction of the drug at resting heart rate is necessary Given the negative drootropic effect of beta-adrenoblockers, they should be prescribed with caution in patients with grade I AV blockade.

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

Patients with pheochromocytoma should not be treated with Lodose unless treated with alpha-adrenoblockers. BP control is necessary.

In elderly patients, treatment should be started with a low dose of the drug; close monitoring of the patient’s condition is necessary.

Patients taking Lodose 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).

With therapy with beta-adrenoblockers an exacerbation of psoriasis is possible. Bisoprolol should be used only when necessary.

If there is a history of anaphylactic reactions, regardless of the cause, especially when receiving floktafenine, or with desensitization therapy, treatment with beta-adrenoblockers may exacerbate these reactions and cause development of resistance to treatment with epinephrine (adrenaline) at normal doses.

Athletes should be informed that Lodose contains the active ingredient, which may give positive results in doping tests.

Precautionary statements regarding the use of hydrochlorothiazide:

Before starting further regularly during therapy and blood sodium levels should be monitored. Decreased sodium levels at the beginning of treatment may be asymptomatic, so regular monitoring is necessary. Particular attention is needed in the presence of risk factors, such as patients of advanced age, patients with liver cirrhosis.

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

Thiazide diuretics may decrease urinary calcium excretion, resulting in mild and temporary hypercalcemia. Temporary hypercalcemia may be associated with undiagnosed hyperparathyroidism. Thiazide treatment should be discontinued before parathyroid function is investigated.

Blood glucose levels in patients with diabetes mellitus should be monitored, especially in cases of hypokalemia.

Patients with hyperuricemia have an increased risk of gout attacks: the dose should be adjusted accordingly.
Thiazide diuretics are effective with normal renal function or slightly reduced renal function (CK 220 μmol/L). In elderly patients serum creatinine can be calculated taking into account the patient’s age, body weight and sex by Cockroft formula:

For men:

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

For women: value obtained x 0.85

Hypovolemia (loss of fluid and sodium) resulting from the use of diuretics at the start of therapy leads to decreased glomerular filtration, which leads to elevated blood levels of urea and creatinine in patients with normal renal function.

Transient impairment of renal function is unaffected in patients with normal renal function. In patients with impaired renal function, existing impairments may worsen.

If the drug is prescribed with another hypotensive agent, it is recommended to reduce the dose at the beginning of treatment.
Pediatric use: The effectiveness and safety of the drug in children and adolescents under the age of 18 years has not been established, so the use of the drug is contraindicated.

Impact on the ability to drive and operate machinery:

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

Contraindications

– Severe forms of bronchial asthma, COPD.
– Chronic heart failure in the decompensation stage, not amenable to drug therapy.
– Cardiogenic shock.
– CCSU, including sinoatrial block.
– AV-blockade of II and III degree without artificial pacemaker.
– Severe bradycardia (HR – variant angina (Prinzmetal angina).
– Pheochromocytoma (without simultaneous use of alpha-adrenoblockers).
– Severe forms of peripheral circulatory disorders (including Raynaud’s disease).
– Arterial hypotension.
– Hypokalemia.
– Hypovolemia.
– Severe renal function disorders (creatinine clearance – Severe liver function disorders.
– Concomitant use with floktafenin, sultopride, antiarrhythmic agents, lithium preparations
– Children and adolescents under 18 years of age (effectiveness and safety is not established).
– Hypersensitivity to bisoprolol and other components of the drug.
– Hypersensitivity to hydrochlorothiazide and other sulfonamides.

With caution when using with AV-blockade of 1st degree, psoriasis, CHD, decompensated chronic heart failure, thyrotoxicosis, water-electrolyte disorders (hyponatremia, hypokalemia, hypercalcemia), gout and elderly patients.

Side effects

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

Cardiovascular system disorders: bradycardia, AV conduction disorders, worsening of chronic heart failure, orthostatic hypotension.

Respiratory system: bronchospasm in patients with bronchial asthma or COPD in history.

Digestive system disorders: nausea, vomiting, diarrhea, constipation, hepatitis, jaundice, increased AST and ALT activity.

Urinary system disorders: reversible increase in serum creatinine and urea.

Muscular system disorders: feeling of cold and numbness of extremities, muscle weakness, cramps.

Sensory system disorders: hearing disorders, decreased lacrimal gland production (should be considered in patients who use contact lenses), visual impairment.

Metabolism disorders: hypertriglyceridemia, hypercholesterolemia, hyperglycemia, glucosuria, hyperuricemia, electrolyte and water disorders, metabolic alkalosis.

Hematopoietic system: leukopenia, thrombocytopenia.

Dermatological reactions: beta-adrenoblockers may cause or aggravate psoriasis or cause psoriasis-like rashes and alopecia.

Others: impotence, allergic rhinitis.

The drug is usually well tolerated.

Side effects have been described in less than 10% of cases.

Overdose

Symptoms: excessive BP reduction, bradycardia. In newborns from mothers treated with beta-adrenoblockers, development of overdose is possible, manifested by decompensation of cardiac activity.

Treatment: in case of marked bradycardia or excessive BP decrease, the following drugs are administered by IV/v: Atropine in a dose of 1-2 mg; glucagon in a dose of 1 mg slowly bolus and then, if necessary, as an infusion in a dose of 1-10 mg/h; then, if necessary, either epinephrine (adrenaline) in a dose of 15-85 µg, the injection can be repeated, its total amount should not exceed 300 µg, or dopamine in a dose of 2.5-10 µg/kg/min.

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

Pregnancy use

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

The thiazide diuretics are excreted with breast milk, and therefore breast-feeding during treatment with Lodoz is contraindicated.

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