Carvedilol Canon, tablets 25 mg 30 pcs

An antihypertensive agent of the group of alpha- and beta-adrenoblockers without intrinsic sympathomimetic activity. It blocks α1-, β1- and β2-adrenoreceptors. As a result of β1-adrenoreceptor blockade it moderately reduces conduction, force and heart rate without causing abrupt bradycardia.

As a result of blockade of α1-adrenoreceptors causes dilation of peripheral vessels. As a result of blockade of β2-adrenoreceptors may slightly increase the tone of the bronchi, some vessels of the microcirculatory bed, as well as tone and peristalsis of the intestine.

Pharmacokinetics

After oral administration, it is rapidly and almost completely absorbed from the gastrointestinal tract. Cmax in plasma is reached within 1 h. Bioavailability is 25%.

The binding to plasma proteins is 98-99%. Vd is about 2 l/kg. It penetrates through the placental barrier and is excreted with breast milk. It is subjected to the effect of “first passage” through the liver. Metabolites have a pronounced antioxidant and adrenoblocking effect.

T1/2 – 6-10 h. Plasma clearance is 590 ml/min. It is excreted mainly with bile.

Bioavailability may increase up to 80% in patients with liver dysfunction.

Indications

Active ingredient

Composition

Tablets

Active substance:

carvedilol 25 mg;

Ancillary substances:

Calcium hydrophosphate dihydrate 70 mg,

Hyprolose (hydroxypropylcellulose) 5.3 mg,

Croscarmellose sodium (primellose) 4.5 mg,

Lactose monohydrate (milk sugar) 93.7 mg,

Magnesium stearate 1.5 mg.

How to take, the dosage

– Arterial hypertension
The recommended initial dose is 6.25 – 12.5 mg (1 tablet of 6.25 mg or 1/2 tablet of 12.5 mg – 1 tablet of 12.5) once daily for the first 2 days of therapy, then 25 mg once daily. If necessary, the dose may be further increased at intervals of at least 2 weeks, up to a maximum recommended dose of 50 mg once daily (or divided into 2 doses).

Ischemic heart disease

The recommended starting dose is 12.5 mg twice daily for the first 2 days, then 25 mg twice daily. If the antianginal effect is insufficient, the dose may be increased at intervals of at least 2 weeks to the highest daily dose of 100 mg divided into 2 doses.

– Chronic heart failure

The dose is adjusted individually and should be closely monitored by a physician. In patients receiving cardiac glycosides, diuretics and ACE inhibitors, their doses should be adjusted before starting treatment with Carvedilol Canon.

The recommended starting dose is 3.125 mg (1/2 tablet of 6.25 mg) 2 times daily for 2 weeks. If tolerated well, the dose is increased at intervals of at least 2 weeks to 6.25 mg twice a day, then to 12.5 mg twice a day, then to 25 mg twice a day. The dose should be increased to the maximum dose that is well tolerated by the patient.

The recommended maximum dose is 25 mg 2 times daily for all patients with severe chronic heart failure and for patients with mild to moderate chronic heart failure with a patient body weight less than 85 kg. In patients with mild to moderate chronic heart failure and a body weight greater than 85 kg, the recommended maximum dose is 50 mg twice daily.

Before each dose increase, a physician should be seen to detect a possible increase in symptoms of chronic heart failure or vasodilation. If there is a transient increase in symptoms of chronic heart failure or fluid retention, the dose of diuretics should be increased, although sometimes the dose of the drug must be reduced or temporarily withdrawn.

The symptoms of vasodilation 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 Carvedilol Canon may be reduced. In such a situation, the dose of Carvedilol Canon should not be increased until symptoms of worsening chronic heart failure or arterial hypotension improve.

If treatment with Carvedilol Canon is interrupted for more than 1 week, its use should be resumed at a lower dose and then increased according to the above recommendations.

If treatment with Carvedilol Canon is interrupted for more than 2 weeks, it should be restarted at a dose of 3.125 mg (1/2 tablet of 6.25 mg) twice daily, then the dose should be adjusted according to the above recommendations.

Dosing in special patient groups

Disorders of renal function

In patients with moderate to severe renal impairment, no dose adjustment of Carvedilol Canon is required.

Hepatic impairment

Carvedilol Canon is contraindicated in patients with clinical manifestations of hepatic impairment (see section “Contraindications”).

Patients in the elderly

There are no data that would dictate the need for dose adjustment.

Interaction

In concomitant administration of carvedilol and digoxin, the concentration of the latter is increased by approximately 15%. At the beginning of therapy with carvedilol, when adjusting the dose or cancelling the drug, regular monitoring of plasma concentrations of digoxin is recommended. At the same time, combined therapy with carvedilol and digoxin may lead to additional slowing of atrioventricular conduction.

Due to marked individual fluctuations in cyclosporine concentrations, careful monitoring of its concentration after initiation of therapy with carvedilol and, if necessary, appropriate adjustment of the daily dose of cyclosporine is recommended. In case of intravenous administration of cyclosporine, no interaction with carvedilol is expected.

Rifampicin decreases plasma concentrations of carvedilol, leading to a decrease in its antihypertensive effect.
Fluoxetine, ketoconazole, cimetidine, haloperidol increase the hypotensive effect of carvedilol.

Carvedilol may increase the hypoglycemic effect of insulin or hypoglycemic agents for oral administration. When concomitant use, regular monitoring of blood glucose concentrations is recommended.

Patients taking simultaneously carvedilol and catecholamine reducing drugs (e.g., reserpine and monoamine oxidase inhibitors) should be closely monitored due to the risk of arterial hypotension and/or marked bradycardia.

In patients with heart failure, concomitant administration of carvedilol with amiodarone or other antiarrhythmic agents is accompanied by the risk of increased beta-adrenoblocking effect. At the same time, amiodarone may increase the risk of AV conduction abnormalities.

The concomitant use of carvedilol with clonidine may potentiate antihypertensive and bradycardic effects. If combination therapy with these drugs is planned to be discontinued, carvedilol should be stopped first, and clonidine should be stopped after a few days, gradually reducing its dose.

The simultaneous use of slow calcium channel blockers (CMBs) such as verapamil, diltiazem and carvedilolol may increase the risk of atrioventricular conduction disturbances. Administration of carvedilol together with BMCCs is recommended under control of ECG and blood pressure.

Carvedilol may increase the effect of other concomitantly taken hypotensive drugs (e.g., alpha1-adrenoblockers) or drugs that cause arterial hypotension as a side effect.
For general anesthesia, the negative inotropic and hypotensive effect of carvedilol increases.

Non-steroidal anti-inflammatory drugs (NSAIDs) decrease the antihypertensive effect of carvedilol.
Bronchodilators (beta-adrenoreceptor agonists). Since noncardioselective beta-adrenoblockers interfere with the bronchodilator effect of beta-adrenoreceptor stimulator bronchodilators, careful monitoring of patients receiving these drugs is necessary.

Special Instructions

Chronic heart failure.

In patients with chronic heart failure, an increase in symptoms of chronic heart failure or fluid retention may be noted during dose adjustment. If these symptoms occur, the dose of diuretics should be increased and the drug dose should not be increased until hemodynamic parameters have stabilized. Sometimes it may be necessary to reduce the dose of Carvedilol Canon or, in rare cases, to temporarily cancel the drug. Such episodes do not prevent further correct dosing of Carvedilol Canon.

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

At the beginning of therapy with Carvedilol Canon or when increasing the drug dose, especially in elderly patients, an excessive decrease of blood pressure may be noted, especially when changing from lying to standing position. Correction of the drug dose is necessary.

Kidney function in chronic heart failure.

When prescribing Carvedilol Canon in patients with chronic heart failure and low BP (systolic BP less than 100 mm Hg), coronary heart disease and diffuse vascular changes and/or renal failure, reversible worsening of renal function has been observed. The dose of the drug is adjusted depending on the functional state of renal function.
It is recommended to monitor renal function in patients with chronic renal insufficiency, arterial hypotension and chronic heart failure.

COPD.

Patients with COPD, including those with bronchospastic syndrome, who are not receiving oral or inhaled anti-asthmatic agents, Carvedilol Canon is prescribed only if the possible benefits of its use exceed the potential risk. In the presence of an initial predisposition to bronchospastic syndrome when taking Carvedilol Canon, dyspnea may develop as a result of increased airway resistance. These patients should be closely monitored at the beginning of therapy and when increasing the dose of Carvedilol Canon, reducing the dose of the drug when the initial signs of bronchospasm appear.

Diabetes mellitus.

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

Caution is required when prescribing Carvedilol Canon 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, Carvedilol Canon may decrease the severity of symptoms of thyrotoxicosis.

General anesthesia and major surgical interventions.

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

Bradycardia.

Carvedilol Canon may cause bradycardia. If the HR is less than 55 bpm, the drug dose should be reduced.
Hypersensitivity.

Cautious use of Carvedilol Canon should be made in patients with a history of severe hypersensitivity reactions or who are undergoing desensitization, because beta-adrenoblockers may increase allergen sensitivity and the severity of anaphylactic reactions.

Psoriasis.

In patients with a history of onset or exacerbation of psoriasis when using beta-adrenoblockers, Carvedilol Canon should only be prescribed after careful analysis of possible benefits and risks.

Pheochromocytoma.

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

Prinzmetal angina.

Nonselective beta-adrenoblockers may cause pain in patients with Prinzmetal angina. There is no experience with prescribing carvedilol in these patients. Although its alpha-adrenoblocking properties may prevent these symptoms, Carvedilol Canon should be prescribed with caution in these cases.

Contact lenses.

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

The “withdrawal” syndrome.

The treatment with Carvedilol Canon is long-term. It should not be stopped abruptly, the dose of drug should be gradually reduced at intervals of 1-2 weeks. This is especially important in patients with coronary heart disease.
If it is necessary to perform a surgical intervention using general anesthesia it is necessary to warn the anesthesiologist about the previous therapy with Carvedilol Canon.

The use of alcohol is excluded during treatment.

Impact on the ability to drive vehicles and machines:

Caution should be exercised when driving motor vehicles and engaging in potentially hazardous activities requiring increased concentration and speed of psychomotor reactions due to the possible development of dizziness.

Contraindications

AV-blockade of degree II and III, severe bradycardia, decompensated heart failure, shock, bronchial asthma, chronic lung diseases with bronchoobstructive syndrome in anamnesis, liver failure, pregnancy, lactation, hypersensitivity to carvedilol.

Side effects

Blood and lymphatic system disorders

Rare: thrombocytopenia.
Very rare: leukopenia.

Endocrine system disorders
Often: in patients with preexisting diabetes mellitus – hyperglycemia or hypoglycemia, impaired glycemic control.
The presence of beta-adrenoblocking properties of the drug does not exclude the possibility of manifestation of latent diabetes mellitus, decompensation of existing diabetes mellitus or suppression of the counterinsulatory system.

Disorders of metabolism and nutrition
Often: weight gain, hypercholesterolemia.

Nervous system disorders
Often: dizziness, headache (usually mild and occurring more frequently at the beginning of treatment), asthenia (including increased fatigue), depression.
Rarely: changes in mood/thought, sleep disorders, paresthesias, loss of consciousness.

Visual disorders
Often: eye irritation, decreased tear production (pay attention when using contact lenses).
Very rare: visual impairment.

Cardiovascular system disorders
Very common: orthostatic hypotension.
Often: bradycardia.
Rarely: cardiac conduction disorders, aggravation of angina pectoris, worsening of the clinical picture of heart failure (especially with increasing dose), marked BP decrease, palpitations, fainting, cold hands and feet, fluid retention, hypervolemia, edema (including generalized, peripheral, position-dependent, perineal edema, edema of lower extremities).
Very rarely: syncopal states (including presyncopal states), occlusive disorders of peripheral circulation, exacerbation of “intermittent” claudication and Raynaud’s syndrome.

Respiratory system disorders, thoracic and mediastinal organs
Rare: bronchospasm and dyspnea in susceptible patients, nasal congestion.
Very rarely: sneezing.

Gastrointestinal disorders
Often: nausea, diarrhea, abdominal pain, dry oral mucosa.
Rarely: vomiting, decreased appetite, flatulence, constipation.
Very rarely: increased activity of “liver” transaminases – alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyltransferase (GGT).

Skin and subcutaneous tissue disorders
Very rare: exacerbation of psoriasis, exfoliative dermatitis, alopecia.

Muscular and connective tissue disorders
Rare: myasthenia, pain in muscles, bones, spine.

Rare: urinary disorders and urinary tract disorders
Rare: urinary disorders, incontinence in women, reversible after drug withdrawal.
Very rare: renal failure and renal function disorders in patients with diffuse vasculitis and/or impaired renal function, edema.

Disorders of the genitals and the breast
Infrequent: decreased potency.

General disorders and disorders at the site of administration
Often: general weakness.
Infrequent: hypersensitivity reaction (skin itching, rash, urticaria).
Very rare: “rushes” of blood to the skin, flu-like syndrome.

Unwanted reactions in patients with chronic heart failure

Nervous system disorders
Very common: dizziness, headache (usually mild and occurring at the beginning of treatment), asthenia (including increased fatigue), depression.

Cardiovascular system disorders
Often: bradycardia, postural hypotension, marked BP decrease, edema (including generalized, peripheral, position-dependent, perineal edema, edema of lower extremities, hypervolemia, fluid retention).
Infrequent: syncopal states (including presyncopal states), atrioventricular block and heart failure during dose escalation.

Gastrointestinal disorders
Often: nausea, diarrhea, vomiting.

Blood and lymphatic system disorders
Rare: thrombocytopenia.
Very rare: leukopenia.

Mechanism and nutrition disorders
Often: weight gain, hypercholesterolemia; in patients with preexisting diabetes mellitus – hyperglycemia or hypoglycemia, carbohydrate metabolism disorders.

Other disorders
Often: visual impairment.
Rarely: renal failure and impaired renal function in patients with diffuse vasculitis and/or impaired renal function.

Overdose

Symptoms:a marked decrease in BP, 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, if necessary, in the intensive care unit should be carried out. The following measures can be used:
– lay the patient on his back with his legs elevated;

– if bradycardia is pronounced – atropine 0.5-2 mg intravenously;
– to maintain cardiovascular activity – glucagon 1-10 mg intravenously by trickle, then 2-5 mg per hour as a prolonged infusion;

– sympathomimetics (dobutamine, isoprenaline, orciprenaline or epinephrine (adrenaline)) in different doses, depending on body weight and response to ongoing treatment.

If the clinical picture of overdose is dominated by a pronounced decrease in BP, norepinephrine (noradrenaline) is administered; it is administered with continuous monitoring of circulatory parameters. In treatment-resistant bradycardia an artificial pacemaker is indicated. In bronchospasm beta-adrenomimetics are administered in the form of aerosol (if ineffective – intravenously) or intravenous aminophylline.

In case of seizures, diazepam or clonazepam is slowly administered intravenously. Since in severe overdose with symptoms of shock the half-life of carvedilol may be prolonged and the drug withdrawn from the depot, it is necessary to continue supportive therapy for quite a long time. Duration of maintenance/detoxification therapy depends on the severity of overdose, it should be continued until the patient’s clinical condition is stabilized.

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