Carvedigamma^® (Tablets) Instructions for Use

ATC Code

C07AG02 (Carvedilol)

Active Substance

Carvedilol

Clinical-Pharmacological Group

Beta₁-, beta₂-adrenoblocker. Alpha₁-adrenoblocker

Pharmacotherapeutic Group

Alpha- and beta-adrenergic blocker

Pharmacological Action

Carvedilol exerts a combined non-selective beta₁, beta₂ and alpha₁-adrenergic blocking action.

The drug has no intrinsic sympathomimetic activity and possesses membrane-stabilizing properties.

Due to the blockade of beta-adrenergic receptors in the heart, blood pressure, cardiac output may decrease, and heart rate may slow down.

Carvedilol suppresses the renin-angiotensin-aldosterone system by blocking beta-adrenergic receptors in the kidneys, causing a decrease in plasma renin activity.

By blocking alpha-adrenergic receptors, the drug can cause peripheral vasodilation, thereby reducing systemic vascular resistance.

The combination of beta-adrenergic blockade and vasodilation has the following effects: in patients with arterial hypertension – reduction of blood pressure; in patients with coronary artery disease – anti-ischemic and antianginal action; in patients with left ventricular dysfunction and circulatory insufficiency – a favorable effect on hemodynamic parameters, increased left ventricular ejection fraction and reduction of its size.

Pharmacokinetics

Carvedilol is rapidly absorbed from the gastrointestinal tract.

It has high lipophilicity.

C_max in blood is reached after 1-1.5 hours.

T_1/2 is 6-10 hours.

It binds to plasma proteins by 95-99%.

The bioavailability of the drug is 24-28%.

Food intake does not affect bioavailability.

It is metabolized in the liver with the formation of a number of active metabolites – 60-75% of the absorbed drug is metabolized during the “first pass” through the liver.

Metabolites have pronounced antioxidant and adrenergic blocking action.

Elimination of the drug from the body occurs through the gastrointestinal tract.

In case of impaired renal function, the pharmacokinetic parameters of carvedilol do not change significantly.

In patients with impaired liver function, the systemic bioavailability of carvedilol increases due to reduced metabolism during the “first pass” through the liver.

In severe liver dysfunction, Carvedilol is contraindicated.

Carvedilol penetrates the placental barrier and is excreted in breast milk.

Indications

• Arterial hypertension (in monotherapy and in combination with diuretics);
• Chronic heart failure (as part of combination therapy);
• Coronary artery disease: stable angina pectoris.

ICD codes

Dosage Regimen

Tablets

Orally, with a sufficient amount of liquid, regardless of food intake.

For arterial hypertension – the initial dose is 6.25-12.5 mg once a day for the first 2 days of treatment, then 25 mg once a day.

If the hypotensive effect is insufficient after 2 weeks of therapy, the dose can be doubled.

The maximum recommended daily dose of the drug is 50 mg once a day (possibly divided into 2 doses).

For angina pectoris – the initial dose is 12.5 mg twice a day for the first 2 days of treatment.

Then 25 mg twice a day.

If the antianginal effect is insufficient after 2 weeks of therapy, the dose can be doubled.

The maximum recommended daily dose is 100 mg/day, divided into 2 doses.

For chronic heart failure, the dose is selected individually, under strict medical supervision.

The initial dose is 3.125 mg twice a day for 2 weeks, then (if well tolerated) this 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 that is well tolerated by the patient.

In patients weighing less than 85 kg, the target dose is 50 mg/day; in patients weighing more than 85 kg, the target dose is 75-100 mg/day.

If treatment is interrupted for more than 2 weeks, it should be resumed with a dose of 3.125 mg twice a day, followed by a dose increase.

Adverse Reactions

From the central nervous system headache (usually not severe and at the beginning of treatment), dizziness, loss of consciousness, myasthenia (more often at the beginning of treatment), sleep disorders, depression, paresthesia, increased fatigue.

From the cardiovascular system bradycardia, orthostatic hypotension, angina pectoris, AV block; rarely – occlusive peripheral circulation disorders, progression of heart failure.

From the digestive system dry mouth, nausea, abdominal pain, loss of appetite, diarrhea or constipation, vomiting, increased activity of liver transaminases.

From the hematopoietic system thrombocytopenia, leukopenia.

From metabolism weight gain, impaired carbohydrate metabolism.

Allergic reactions skin allergic reactions (exanthema, urticaria, itching, rash), exacerbation of psoriasis, nasal congestion.

From the respiratory system shortness of breath and bronchospasm (in predisposed patients).

Other flu-like syndrome, limb pain, intermittent claudication, decreased tear production, sneezing, myalgia, arthralgia; rarely – urination disorder, impaired renal function.

Contraindications

• Acute and chronic heart failure (in the stage of decompensation);
• Severe hepatic insufficiency;
• AV block II-III degree;
• Severe bradycardia (less than 50 beats/min);
• Sick sinus syndrome;
• Cardiogenic shock;
• Chronic obstructive pulmonary disease;
• Arterial hypotension (systolic BP less than 85 mm Hg);
• Age under 18 years (safety and efficacy of use have not been established);
• Hypersensitivity to carvedilol or other components of the drug.

With caution Prinzmetal’s angina, diabetes mellitus, hypoglycemia, thyrotoxicosis, occlusive peripheral vascular diseases, pheochromocytoma, depression, myasthenia, psoriasis, renal failure, AV block I degree, extensive surgical interventions and general anesthesia.

Use in Pregnancy and Lactation

No controlled studies on the use of carvedilol in pregnant women have been conducted, so the prescription of the drug to this category of patients is possible only in cases where the benefit to the mother outweighs the potential risk to the fetus.

Breastfeeding is not recommended during treatment with carvedilol.

Use in Hepatic Impairment

Contraindicated

• Severe hepatic insufficiency.

Use in Renal Impairment

With caution.

Pediatric Use

Contraindicated in children under 18 years of age.

Geriatric Use

At the beginning of therapy with Carvedigamma or when increasing the dose of the drug in elderly patients, excessive lowering of blood pressure may be noted, mainly when standing up.

Dose adjustment of the drug is necessary.

Special Precautions

Therapy should be long-term and should not be abruptly discontinued, especially in patients with coronary artery disease, as this may lead to a worsening of the underlying disease.

If necessary, the dose of the drug should be reduced gradually, over 1-2 weeks.

At the beginning of therapy with Carvedigamma or when increasing the dose of the drug in patients, especially the elderly, excessive lowering of blood pressure may be noted, mainly when standing up.

Dose adjustment of the drug is necessary.

In patients with chronic heart failure during dose selection, an increase in the symptoms of heart failure and the appearance of edema are possible.

In this case, the dose of Carvedigamma should not be increased; it is recommended to prescribe larger doses of diuretics until the patient’s condition stabilizes.

Constant monitoring of ECG and blood pressure is recommended when Carvedigamma is prescribed simultaneously with slow calcium channel blockers, phenylalkylamine derivatives (verapamil) and benzothiazepine (diltiazem), as well as with class I antiarrhythmic agents.

It is recommended to monitor renal function in patients with chronic renal failure, arterial hypotension and chronic heart failure.

In case of surgical intervention using general anesthesia, the anesthesiologist should be informed about the previous therapy with Carvedigamma.

Carvedilol does not affect blood glucose concentration and does not cause changes in glucose tolerance test parameters in patients with non-insulin-dependent diabetes mellitus.

Avoid ethanol consumption during treatment.

Patients with pheochromocytoma should be prescribed alpha-blockers before starting therapy.

Patients wearing contact lenses should take into account that the drug may cause decreased tear production.

Effect on the ability to drive vehicles and mechanisms

It is not recommended to drive a car at the beginning of therapy and when increasing the dose of carvedilol.

Refrain from other activities that require high concentration and rapid psychomotor reactions.

Overdose

Symptoms pronounced decrease in blood pressure (accompanied by dizziness or fainting), bradycardia (less than 50 beats/min).

The occurrence of shortness of breath due to bronchospasm and vomiting is possible.

In severe cases, cardiogenic shock, respiratory distress, confusion, conduction disturbance, cardiac arrest are possible.

Treatment monitoring and correction of vital signs is necessary, if necessary – in the intensive care unit.

Treatment is symptomatic.

Intravenous administration of m-cholinolytics (atropine), adrenomimetics (epinephrine, norepinephrine) is advisable.

Drug Interactions

Carvedilol may potentiate the effect of other simultaneously taken antihypertensive agents (ACE inhibitors, thiazide diuretics, vasodilators) or agents that have a hypotensive effect (nitrates).

With the combined use of carvedilol and diltiazem, cardiac conduction disorders and hemodynamic disturbances may develop.

With simultaneous administration of carvedilol and digoxin, the concentration of the latter increases and AV conduction time may increase.

Carvedilol may potentiate the effect of insulin and oral hypoglycemic agents, while the symptoms of hypoglycemia (especially tachycardia) may be masked, so in patients with diabetes mellitus, regular monitoring of blood glucose levels is recommended.

Inhibitors of microsomal oxidation (nizatidine) enhance, and inducers (phenobarbital, rifampicin) weaken the hypotensive effect of carvedilol.

Drugs that reduce catecholamine content (reserpine, MAO inhibitors) increase the risk of arterial hypotension and severe bradycardia.

With simultaneous use of cyclosporine, the concentration of the latter increases (correction of the daily dose of cyclosporine is recommended).

Simultaneous administration of clonidine may potentiate the antihypertensive and heart rate-lowering effects of carvedilol.

General anesthetics enhance the negative inotropic and hypotensive effect of carvedilol.

Storage Conditions

Store the drug in a place protected from light, at a temperature not exceeding 25°C (77°F).

Keep out of reach of children.

Shelf Life

Shelf life – 3 years.

Do not use after the expiration date indicated on the packaging.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.