Carvidil (Tablets) Instructions for Use

Marketing Authorization Holder

Grindeks, JSC (Latvia)

ATC Code

C07AG02 (Carvedilol)

Active Substance

Carvedilol (Rec.INN registered by WHO)

Dosage Forms

	Carvidil	Tablets 6.25 mg: 28 pcs.
		Tablets 12.5 mg: 28 pcs.
		Tablets 25 mg: 28 pcs.

Dosage Form, Packaging, and Composition

Tablets round, biconvex, yellowish in color with barely noticeable inclusions, with a score on one side.

Excipients: lactose monohydrate, microcrystalline cellulose, crospovidone, colloidal silicon dioxide, magnesium stearate, yellow iron oxide.

14 pcs. – blisters (2) – cardboard packs.

Tablets round, biconvex, pink in color with barely noticeable inclusions, with a score on one side.

Excipients: lactose monohydrate, microcrystalline cellulose, crospovidone, colloidal silicon dioxide, magnesium stearate, yellow iron oxide, red iron oxide.

14 pcs. – blisters (2) – cardboard packs.

Tablets round, biconvex, white in color, with a score on one side.

Excipients: lactose monohydrate, microcrystalline cellulose, crospovidone, colloidal silicon dioxide, magnesium stearate.

14 pcs. – blisters (2) – 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 β₁-, β₂– and α₁-blocking action. The drug has no intrinsic sympathomimetic activity and has membrane-stabilizing properties. Due to the blockade of β-adrenergic receptors of the heart, a decrease in blood pressure, a decrease in cardiac output and a decrease in heart rate are possible. Carvedilol suppresses the renin-angiotensin-aldosterone system by blocking the β-adrenergic receptors of the kidneys, causing a decrease in plasma renin activity. By blocking α-adrenergic receptors, the drug can cause peripheral vasodilation, which leads to a decrease in total peripheral vascular resistance.

Due to the combination of β-adrenergic blockade and vasodilation, the drug reduces blood pressure in arterial hypertension; in coronary artery disease, it has anti-ischemic and antianginal effects; in left ventricular dysfunction and circulatory insufficiency – improves hemodynamic parameters, increases left ventricular ejection fraction and reduces its size.

Pharmacokinetics

Absorption

After oral administration, Carvedilol is rapidly absorbed from the gastrointestinal tract. It has high lipophilicity. C_max in blood plasma is reached after 1-1.5 hours. The bioavailability of the drug is 24-28%. Food intake does not affect the bioavailability of carvedilol.

Distribution

Plasma protein binding is 95-99%.

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

Metabolism

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 adrenoblocking effects.

Excretion

T_1/2 is 6-10 hours.

The drug is eliminated from the body through the gastrointestinal tract.

Pharmacokinetics in special clinical cases

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

ICD codes

Dosage Regimen

It is administered orally, 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 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 in 2 doses).

For 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 in 2 doses.

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

Adverse Reactions

From the central 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 circulatory disorders, progression of heart failure (during dose increase), edema of the lower extremities, 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, impaired carbohydrate metabolism. Allergic reactions: skin allergic reactions, exacerbation of psoriasis; nasal congestion.

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

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

Contraindications

• Acute and decompensated chronic heart failure requiring intravenous administration of inotropic agents;
• 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;
• Age under 18 years (efficacy and safety have not been established);
• Hypersensitivity to carvedilol or other components of the drug.

With caution the drug should be used for 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

Adequate and strictly controlled studies of the use of carvedilol during pregnancy have not been conducted, so the prescription of the drug to this category of patients is possible only in cases where the expected benefit of therapy for the mother outweighs the potential risk to the fetus.

Breastfeeding is not recommended during treatment with carvedilol.

Use in Hepatic Impairment

The drug is contraindicated in severe hepatic insufficiency.

Use in Renal Impairment

With caution the drug should be used in renal failure.

Pediatric Use

The efficacy and safety of the drug in patients under 18 years of age have not been established.

Special Precautions

Therapy should be long-term and not abruptly discontinued, especially in 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 Carvidil 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. In such cases, dose adjustment is necessary.

When treating chronic heart failure when selecting a dose, an increase in the symptoms of heart failure and the appearance of edema is possible. In this case, the dose of Carvidil should not be increased; it is recommended to prescribe diuretics in higher doses until the patient’s condition stabilizes.

Constant monitoring of ECG and blood pressure is recommended when Carvidil 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 Carvidil.

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

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

Patients using contact lenses should take into account that the drug may cause decreased lacrimation.

Alcohol consumption should be avoided during treatment.

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

Overdose

Symptoms: decreased 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: symptomatic therapy. Monitoring and correction of vital signs, if necessary – in the intensive care unit. Intravenous administration of m-cholinoblockers (atropine), adrenomimetics (epinephrine, norepinephrine) is advisable.

Drug Interactions

With simultaneous use, Carvedilol may potentiate the effect of other 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 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 sugar levels is recommended.

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

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

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

Simultaneous administration of clonidine may potentiate the hypotensive and negative chronotropic effects of carvedilol.

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

Storage Conditions

The drug should be stored out of the reach of children, in a dry, dark 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.