Carvedilol-OBL (Tablets) Instructions for Use

Marketing Authorization Holder

FP Obolenskoe, JSC (Russia)

Contact Information

ALIUM JSC (Russia)

ATC Code

C07AG02 (Carvedilol)

Active Substance

Carvedilol (Rec.INN registered by WHO)

Dosage Forms

	Carvedilol-OBL	Tablets 6.25 mg: 14, 20, 21, 28, 30, 35, 40, 45, 50, 56, 60, 70, 75, 80, 90, 100, 120, 150, 160, 200, 240 or 300 pcs.
		Tablets 12.5 mg: 14, 20, 21, 28, 30, 35, 40, 45, 50, 56, 60, 70, 75, 80, 90, 100, 120, 150, 160, 200, 240 or 300 pcs.
		Tablets 25 mg: 14, 20, 21, 28, 30, 35, 40, 45, 50, 56, 60, 70, 75, 80, 90, 100, 120, 150, 160, 200, 240 or 300 pcs.

Dosage Form, Packaging, and Composition

Tablets white or white with a yellowish tint, biconvex in shape.

Excipients: sugar (sucrose), magnesium stearate, potato starch, hypromellose (hydroxypropylmethylcellulose), croscarmellose sodium (primellose), colloidal silicon dioxide (aerosil), calcium phosphate.

7 pcs. – contour cell packaging (2) – cardboard packs.
7 pcs. – contour cell packaging (3) – cardboard packs.
7 pcs. – contour cell packaging (4) – cardboard packs.
7 pcs. – contour cell packaging (5) – cardboard packs.
7 pcs. – contour cell packaging (8) – cardboard packs.
7 pcs. – contour cell packaging (10) – cardboard packs.
10 pcs. – contour cell packaging (2) – cardboard packs.
10 pcs. – contour cell packaging (3) – cardboard packs.
10 pcs. – contour cell packaging (4) – cardboard packs.
10 pcs. – contour cell packaging (5) – cardboard packs.
10 pcs. – contour cell packaging (8) – cardboard packs.
10 pcs. – contour cell packaging (10) – cardboard packs.
15 pcs. – contour cell packaging (2) – cardboard packs.
15 pcs. – contour cell packaging (3) – cardboard packs.
15 pcs. – contour cell packaging (4) – cardboard packs.
15 pcs. – contour cell packaging (5) – cardboard packs.
15 pcs. – contour cell packaging (8) – cardboard packs.
15 pcs. – contour cell packaging (10) – cardboard packs.
20 pcs. – contour cell packaging (2) – cardboard packs.
20 pcs. – contour cell packaging (3) – cardboard packs.
20 pcs. – contour cell packaging (4) – cardboard packs.
20 pcs. – contour cell packaging (5) – cardboard packs.
20 pcs. – contour cell packaging (8) – cardboard packs.
20 pcs. – contour cell packaging (10) – cardboard packs.
30 pcs. – contour cell packaging (2) – cardboard packs.
30 pcs. – contour cell packaging (3) – cardboard packs.
30 pcs. – contour cell packaging (4) – cardboard packs.
30 pcs. – contour cell packaging (5) – cardboard packs.
30 pcs. – contour cell packaging (8) – cardboard packs.
30 pcs. – contour cell packaging (10) – cardboard packs.

Clinical-Pharmacological Group

Beta₁-, beta₂-adrenoblocker. Alpha₁-adrenoblocker

Pharmacotherapeutic Group

Alpha- and beta-adrenergic blocker

Pharmacological Action

Alpha- and beta-adrenoblocker. Carvedilol has a combined non-selective beta₁-, beta₂– and alpha₁-blocking action. The drug has no intrinsic sympathomimetic activity and has membrane-stabilizing properties.

Due to the blockade of beta-adrenergic receptors of the heart, a decrease in blood pressure, a decrease in cardiac output and heart rate occur. Carvedilol suppresses the RAAS by blocking beta-adrenergic receptors of 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 – a decrease in 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, increases the left ventricular ejection fraction and reduces its size.

Pharmacokinetics

Carvedilol is rapidly absorbed from the gastrointestinal tract. It has high lipophilicity. C_max in the blood is reached after 1-1.5 hours. T_1/2 is 6-10 hours. It binds to blood 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 a pronounced antioxidant and adrenoblocking effect.

The drug is eliminated from the body through the gastrointestinal tract. Carvedilol penetrates the placental barrier and is excreted in breast milk.

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 first-pass metabolism through the liver. In severe liver dysfunction, Carvedilol is contraindicated.

Indications

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

ICD codes

Dosage Regimen

Orally, regardless of meals.

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 antihypertensive 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).

Coronary artery disease

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 of the drug is 100 mg/day, divided into 2 doses.

Chronic heart failure

The dose is selected individually, under the careful supervision of a physician. The recommended initial dose is 3.125 mg twice a day for 2 weeks. If well tolerated, 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 that is well tolerated by the patient. In patients with a body weight of less than 85 kg, the target dose is 50 mg/day; in patients with a body weight of more than 85 kg, the target dose is 75-100 mg/day.

Adverse Reactions

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

From the cardiovascular system: bradycardia, orthostatic hypotension, AV block II-III degree, rarely – peripheral circulation disorders, progression of heart failure (during dose increase), lower limb edema, angina pectoris, pronounced decrease in blood pressure.

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

From the hematopoietic system: rarely – thrombocytopenia, leukopenia.

From the metabolism: weight gain, carbohydrate metabolism disorder.

Allergic reactions: skin allergic reactions, nasal congestion.

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

Other: exacerbation of psoriasis, visual impairment, decreased lacrimation, flu-like syndrome, sneezing, myalgia, arthralgia, limb pain, intermittent claudication, rarely – urination disorder, renal function impairment.

Contraindications

• Hypersensitivity to carvedilol or other components of the drug;
• 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;
• Arterial hypotension (systolic blood pressure less than 85 mm Hg);
• Cardiogenic shock;
• Chronic obstructive pulmonary disease;
• Children and adolescents under 18 years of age (efficacy and safety have not been established).

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

Use in Pregnancy and Lactation

Controlled studies of the use of carvedilol in pregnant women have not 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

Contraindication: severe hepatic insufficiency.

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 Carvedilol-OBL 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, when selecting the dose, an increase in the symptoms of heart failure and the appearance of edema is possible. In this case, the dose of Carvedilol-OBL 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 Carvedilol-OBL 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 warned about previous therapy with Carvedilol-OBL.

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

During treatment, the consumption of ethanol should be avoided.

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 lacrimation.

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-OBL. It is necessary to refrain from other activities that require high concentration of attention and quick psychomotor reactions.

Overdose

Symptoms: decrease in blood pressure (accompanied by dizziness or fainting), bradycardia. The occurrence of shortness of breath due to bronchospasm and vomiting is possible. In severe cases, cardiogenic shock, respiratory distress, confusion, and conduction disturbances are possible.

Treatment: it is necessary to monitor and correct vital signs, if necessary – in the ICU. 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 or drugs 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 the 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.

Microsomal oxidation inhibitors (cimetidine) enhance, and inducers (phenobarbital, rifampicin) weaken the hypotensive effect of carvedilol.

Drugs that reduce the content of catecholamines (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

The drug should be stored out of the reach of children, in a dry, light-protected place at a temperature not exceeding 25°C (77°F).

Shelf Life

Shelf life – 2 years.

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.