Dilatrand, tablets 25 mg, 30 pcs.

Carvedilol is a multifunctional adrenoreceptor blocker with beta1-, beta2- and alpha1-adrenoblocking properties. Carvedilol has an organ-protective effect. It is a powerful antioxidant that eliminates free oxygen radicals, has an antiproliferative effect against smooth muscle cells of vascular walls.

Carvedilol has no intrinsic sympathomimetic activity and, like propranololol, has membrane-stabilizing properties. By blocking beta-adrenoreceptors, it reduces the activity of the renin-angiotensin-aldosterone system, reducing the release of renin, so fluid retention (characteristic of selective alpha-adrenoblocator”) rarely occurs.

By selectively blocking a₁ adrenoreceptors, carvedilol reduces total peripheral vascular resistance.

Carvedilol has no adverse effect on the lipid profile, maintaining a normal ratio of high-density lipoproteins to low-density lipoproteins (HDL/LDL).

Indications

Arterial hypertension. Dilatrend is indicated mainly in essential hypertension (as monotherapy or combined therapy with other antihypertensive drugs, e.g., slow calcium channel blockers or diuretics).

Ischemic heart disease (including in patients with unstable angina and myocardial ischemia).

Chronic heart failure. Dilatrend is indicated for the treatment of clinically manifest mild, moderate and severe chronic heart failure of ischemic or non-ischemic genesis, to reduce complications (hospitalizations for cardiovascular causes) and mortality and to improve well-being and slow disease progression, when used in combination with ACE inhibitors, diuretics and, sometimes, digitalis preparations (standard therapy).

Dilatrand can be prescribed both in addition to standard therapy and in patients who are not receiving digitalis drugs, vasodilators, or nitrates.

Active ingredient

Composition

1 tablet contains 25 mg of carvedilol.

How to take, the dosage

The drug is taken orally with plenty of fluid.

The treatment with Dilatrand is prolonged. It should not be stopped abruptly; the dose of the drug should be gradually reduced at weekly intervals. This is especially important in patients with coronary heart disease.

Essential hypertension. The recommended starting dose is 12.5 mg once daily for the first 2 days, then 25 mg once daily. If necessary, the dose may be further increased at intervals of at least 2 weeks, up to the highest recommended dose of 50 mg once daily (or divided into two doses).

Ischemic heart disease. The recommended starting dose is 12.5 mg twice daily for the first 2 days, 25 mg twice daily thereafter. If necessary, the dose may be subsequently increased at intervals of at least two weeks, up to the highest daily dose of 100 mg divided into two doses.

Chronic heart failure. The dose should be adjusted individually, under close medical supervision In patients receiving foxglove drugs, diuretics and ACE inhibitors, their doses should be stabilized before starting treatment with Dilatrand. The recommended starting dose is 3.125 mg twice daily for two weeks. If tolerated well, the dose is increased at intervals of at least two weeks, to 6.25 mg twice daily, then to 12.5 mg twice daily, then to 25 mg twice daily. The dose should be increased to a maximum that is well tolerated by the patient.

The recommended maximum dose is 25 mg twice daily for all patients with severe chronic heart failure and for patients with mild to moderate chronic heart failure with a body weight less than 85 kg. In patients with mild to moderate chronic heart failure and body weight over 85 kg – the recommended maximum dose is 50 mg twice daily. Before each dose increase, the physician should examine the patient for possible increase in symptoms of heart failure or vasodilation. If there is a transient increase in heart failure symptoms or fluid retention, the dose of diuretics should be increased, although sometimes the dose of Dilatrand must be reduced or temporarily discontinued.

If treatment with Dilatrand is interrupted for more than 1 week, its prescription is resumed at a lower dose and then increased according to the above recommendations. If treatment with Dilatrand is interrupted for more than 2 weeks, it should be restarted at a dose of 3.125 mg twice daily, then the dose should be adjusted according to the above recommendations.

The symptoms of vasodilatation can be resolved by reducing the dose of diuretics. If symptoms persist, the dose of the ACE inhibitor (if the patient is taking it) may be reduced, and then, if necessary, the dose of Dilatrand In this situation, the dose of Dilatrand should not be increased until the symptoms of increasing heart failure or arterial hypotension have stabilized. Doses in special patient groups.

Interaction

Digoxin. Concomitant administration of carvedilol and digoxin increases digoxin concentrations by approximately 15%. Regular monitoring of plasma digoxin concentrations is recommended at the beginning of therapy with carvedilol, when adjusting the dose or cancelling the drug.

Insulin or oral antidiabetic drugs. Drugs with beta-adrenoblocking properties may enhance the antidiabetic effect of insulin or oral antidiabetic drugs. Symptoms of hypoglycemia, especially tachycardia, may be masked or weakened. Patients receiving insulin or oral antidiabetic drugs are recommended to have regular blood glucose monitoring.

Hepatic metabolism inducers or inhibitors. Rifampicin reduces plasma concentrations of Carvedilol by approximately 70%.
Drugs that reduce catecholamines. Patients taking concomitant drugs with beta-adrenoblocking properties and catecholamine-lowering drugs (e.g., reserpine and monoamine oxidase inhibitors) should be closely monitored due to the risk of arterial hypotension and/or marked bradycardia.
Cyclosporine.

In administration of carvedilol in patients who have undergone renal transplantation and who developed chronic vascular rejection of transplant there was observed a moderate increase of mean minimum concentrations of cyclosporine In order to maintain cyclosporine concentrations in the therapeutic range, in approximately 30% of patients the dose of cyclosporine had to be reduced (on average by 20%), the dose adjustment was not necessary for the remaining patients. Due to pronounced individual fluctuations of the required daily dose of cyclosporine it is recommended to carefully monitor cyclosporine concentration after the start of carvedilol therapy and, if necessary, appropriate correction of daily dose of cyclosporine.

Verapamil. diltiazem and other antiarrhythmic agents (propranololol, amiodarone). Concomitant use with carvedilol may increase the risk of atrioventricular conduction disorders.

Clonidine. Concomitant administration of clonidine with drugs with beta-blocking properties may potentiate antihypertensive and cardiac arrhythmia-reducing effects. If combined therapy with a beta-adreno-blocker and clonidine is planned to be discontinued, the beta-adreno-blocker should be withdrawn first and the clonidine may be withdrawn after a few days, gradually reducing its dose.

Slow calcium channel blockers. When concomitant administration of carvedilol and diltiazem, there have been isolated cases of conduction abnormalities (rarely with abnormal hemodynamic parameters). As with other drugs with beta-adrenoblocking properties, administration of carvedilol together with “slow” calcium channel blockers such as verapamil or diltiazem is recommended under ECG and blood pressure monitoring.

As with other drugs with beta-adrenoblocking activity, carvedilol may increase the effect of other concomitant antihypertensive agents (e.g., B-adrenoblockers) or drugs that have a hypotensive effect as a side effect.

Particular attention should be paid in general anesthesia to the possibility of synergistic negative inotropic effects of carvedilol and some anesthetics.

Special Instructions

Cronic Heart Failure

In patients with chronic heart failure, an increase in symptoms of chronic heart failure or fluid retention may be noted while adjusting the dose of Dilatrand®. If such symptoms occur, it is necessary to increase the dose of diuretics and not to increase the dose of the drug Dilatrand® until hemodynamic parameters are stabilized. Sometimes it is necessary to reduce the dose of Dilatrand® or, in rare cases, temporarily discontinue the drug. Such episodes do not prevent further proper dosing of Dilatrand®.

Dilatrand® is used with caution in combination with cardiac glycosides (excessive slowing of AV conduction is possible).

Renal function in chronic heart failure

When Dilatrend® was administered to patients with chronic heart failure and low blood pressure (systolic BP less than 100 mm Hg), coronary heart disease and diffuse vascular changes and/or renal failure, a reversible deterioration of renal function was observed. The dose of the drug is adjusted depending on the functional state of the kidneys.

Patients with COPD (including bronchospastic syndrome) who do not receive oral or inhaled antiasthmatic agents, Dilatrand® is administered only if possible benefits of its use exceed the potential risk. In the presence of initial predisposition to bronchospastic syndrome when taking Dilatrand® due to the increase of airway resistance, dyspnea may develop. At the beginning of use and when increasing the dose of Dilatrand® these patients should be carefully monitored, reducing the dose of the drug when the initial signs of bronchospasm appear.

Diabetes mellitus

The drug is prescribed with caution in diabetic patients because it may mask or attenuate the symptoms of hypoglycemia (especially tachycardia). In patients with chronic heart failure and diabetes mellitus the use of Dilatrand® may be accompanied by impaired glycemic control.

Peripheral vascular disease

Perhaps caution should be exercised when using Dilatrand® in patients with peripheral vascular disease (including Raynaud’s syndrome) because beta-adrenoblockers may increase the symptoms of arterial insufficiency.

Thyrotoxicosis

Like other beta-adrenoblockers, Dilatrand® may decrease the severity of symptoms of thyrotoxicosis.

General anesthesia and major surgical interventions

Caution is required in patients who are undergoing surgery under general anesthesia because of the possibility of summation of the negative effects of Dilatrend® and general anesthesia agents.

Bradycardia

Dilatrand® may cause bradycardia; if heart rate falls below 55 bpm the dose of Dilatrand® should be decreased.

We should use caution when prescribing Dilatrand® in patients with a history of severe hypersensitivity reactions or undergoing desensitization therapy, since beta-adrenoblockers may increase sensitivity to allergens and the severity of anaphylactic reactions.

Persons with a history of psoriasis occurrence or exacerbation when using beta-adrenoblockers, Dilatrand® should be prescribed only after a careful analysis of the possible benefits and risks.

Concomitant use of “slow” calcium channel blockers (CMBs)

In patients simultaneously taking CMBs such as verapamil or diltiazem as well as other antiarrhythmic agents, ECG and BP should be monitored regularly.

Pheochromocytoma

Pheochromocytoma patients should be prescribed an alpha-adrenoblocker before starting any beta-adrenoblocker. Although Dilatrand® has both beta- and alpha-adrenoblocking properties, there is no experience with its use in such patients, so it should be prescribed with caution in patients with suspected pheochromocytoma.

Prinzmetal angina

Nonselective beta-adrenoblockers may provoke pain in patients with Prinzmetal angina. There is no experience with Dilatrand® in these patients. Although its alpha-adrenoblocking properties may prevent this symptomatology, caution should be exercised when prescribing carvedilol in these cases.

Contact lenses

Patients who wear contact lenses should be aware of the possibility of decreased tear fluid.

The “withdrawal” syndrome

The treatment with Dilatrand® is prolonged. It should not be stopped abruptly; the dose of the drug should be gradually reduced at weekly intervals. This is especially important in patients with coronary heart disease.

If there is a need for surgical intervention with general anesthesia it is necessary to warn the anesthesiologist about the previous therapy with dilatrend®.

At the time of treatment the use of alcohol is excluded.

Impact on driving and operating machinery

With regard to the potential side effects of Dilatrand® , caution should be exercised when prescribing it in patients whose work requires rapid psychomotor reaction, especially at the start of treatment, and when alcohol is taken concomitantly.

Contraindications

Hypersensitivity to carvedilol or any component of the drug, acute heart failure, clinically significant liver dysfunction, breast-feeding period.

Like other beta-adrenoblockers, Dilatrand should not be prescribed in patients with atrioventricular block of II and III degree (if no permanent pacemaker is installed), significant bradycardia (less than 50 bpm), sinus node weakness syndrome, significant arterial hypotension (systolic blood pressure less than 85 mm Hg), cardiogenic syndrome. st), cardiogenic shock, anamnestic signs of bronchospasm and bronchial asthma. The drug is used with caution in pulmonary emphysema, depression, myasthenia gravis, pregnancy.

Side effects

Adverse events in patients treated for arterial hypertension and ischemic heart disease
The nature of adverse events of Dilatrand in the treatment of arterial hypertension and long-term therapy of ischemic heart disease is similar to that in heart failure, but their frequency is somewhat lower.

The following adverse events have been reported in clinical studies in patients with arterial hypertension and coronary heart disease.

Central nervous system. Frequent: dizziness, headache and general weakness, usually mild and occurring particularly at the beginning of treatment. Infrequent: decreased mood, sleep disturbances, paresthesias.

The cardiovascular system. Frequent: bradycardia, postural hypotension, syncope, especially at the beginning of therapy.

Infrequent: peripheral circulatory disorders (coldness of extremities, worsening of “intermittent” claudication and Raynaud’s syndrome), atrioventricular block angina pectoris (chest pain), symptoms of heart failure and peripheral edema.

Respiratory organs. Frequent: bronchospasm and dyspnea in predisposed patients. Rare: nasal congestion.

Gastrointestinal tract. Frequent: dyspeptic disorders (including nausea, abdominal pain, diarrhea). Infrequent: constipation, vomiting.
Skin. Infrequent: skin reactions (allergic rash, dermatitis, urticaria and itching).

Laboratory indicators. Individual cases of increased activity of “liver” transaminases – alanine aminotransferase (ALT), aspartate aminotransferase (ACT) and gamma-glutamyltransferase, thrombocytopenia and leukopenia.

Others. Frequent: pain in extremities, decreased lacrimation and eye irritation. Infrequent: decreased potency, visual impairment. Rare: dry mouth and urinary disorders.

Some cases of skin allergic reactions (exanthema, urticaria, itching, rashes), exacerbation of psoriatic rashes, sneezing, nasal congestion, bronchospasm, shortness of breath (in predisposed patients). Occasional cases of flu-like syndrome.

The presence of beta-adrenoblocking properties of the drug does not exclude the possibility of manifestation of latent diabetes mellitus, worsening of compensation of existing diabetes mellitus or suppression of the counterinsulatory system.

Overdose

Symptoms: marked BP decrease, bradycardia, heart failure, cardiogenic shock, cardiac arrest; possible respiratory disorders, bronchospasm, vomiting, confusion and generalized convulsions.

Treatment: in addition to general measures, monitoring and correction of vital signs should be carried out, if necessary – in the intensive care unit. The following measures can be used:
a) lay the patient on his back
b) in case of marked bradycardia – atropine 0.5-2 mg intravenously;
c) to maintain cardiovascular activity – glucagon by 1-10 mg intravenous stream, then by 2-5 mg per hour as a long infusion;
d) sympathomimetics (dobutamine, isoprenaline, orciprenaline or adrenaline) in different doses, depending on body weight and therapeutic efficiency. If it is necessary to administer drugs with positive inotropic action, phosphodiesterase inhibitors are prescribed. If arterial hypotension dominates the clinical picture of overdose, norepinephrine shall be administered; it shall be administered with continuous monitoring of circulatory parameters.

In treatment-resistant bradycardia, an artificial pacemaker is indicated.

In case of bronchospasm, beta-adrenomimetics in the form of aerosol (intravenously if ineffective) or intravenous aminophylline are administered. In convulsions, diazepam or clonazepam should be given slowly intravenously. Since in severe overdose with shock symptoms the half-life of carvedilol may be prolonged and the drug may be eliminated from the depot, maintenance therapy should be continued for a sufficiently long time. Duration of maintenance/detoxification therapy depends on the severity of overdose, it should be continued until the patient’s condition stabilizes.

Similarities