Carvenal (Tablets) Instructions for Use

Marketing Authorization Holder

Shin Poong Pharmaceutical, Co. Ltd. (Republic Of Korea)

ATC Code

C07AG02 (Carvedilol)

Active Substance

Carvedilol

Dosage Form

Carvenal

Tablets 25 mg: 100 pcs.

Dosage Form, Packaging, and Composition

10 pcs. – blisters (10) – cardboard packs.

Clinical-Pharmacological Group

Beta₁-, beta₂-adrenoblocker. Alpha₁-adrenoblocker

Pharmacotherapeutic Group

Alpha- and beta-adrenergic blocker

Pharmacological Action

An antihypertensive agent from the group of alpha- and beta-adrenergic blockers without intrinsic sympathomimetic activity. It blocks α₁-, β₁-, and β₂-adrenergic receptors.

As a result of β₁-adrenergic receptor blockade, it moderately reduces conductivity, force, and frequency of heart contractions without causing a sharp bradycardia.

As a result of α₁-adrenergic receptor blockade, it causes peripheral vasodilation.

As a result of β₂-adrenergic receptor blockade, it may slightly increase the tone of the bronchi, some vessels of the microcirculatory bed, as well as the tone and peristalsis of the intestine.

Pharmacokinetics

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

Plasma protein binding is 98-99%. V_d is about 2 L/kg. It penetrates the placental barrier and is excreted in breast milk. It undergoes a significant first-pass effect through the liver. Metabolites have pronounced antioxidant and adrenoblocking action.

T_1/2 is 6-10 hours. Plasma clearance is 590 ml/min. It is excreted mainly with bile.

In patients with impaired liver function, bioavailability may increase to 80%.

Indications

Arterial hypertension.

Coronary artery disease: prevention of attacks of stable angina pectoris.

Chronic heart failure (as part of combination therapy).

ICD codes

Dosage Regimen

Take Carvenal tablets orally, with food, to minimize the risk of orthostatic hypotension.

For arterial hypertension, initiate therapy at 12.5 mg once daily for two days. Increase the dose to 25 mg once daily thereafter. If an adequate therapeutic response is not achieved after one to two weeks, increase the dose to a maximum of 50 mg once daily.

For stable angina pectoris, the recommended maintenance dose is 25 mg to 50 mg twice daily. Initiate treatment at 12.5 mg twice daily and titrate upwards as tolerated.

For chronic heart failure, begin with 3.125 mg twice daily for a minimum of two weeks. Double the dose every two weeks as tolerated by the patient. The maximum recommended dose is 25 mg twice daily for patients weighing less than 85 kg (187 lbs) and 50 mg twice daily for patients weighing 85 kg or more.

In elderly patients, initiate therapy at 12.5 mg once daily. This dose may be sufficient for maintenance; titrate cautiously based on clinical response.

For all indications, do not abruptly discontinue therapy. Taper the dose gradually over one to two weeks under medical supervision.

Monitor blood pressure and heart rate closely during dose titration and at regular intervals thereafter. In patients with heart failure, monitor for worsening symptoms during the initial titration phase.

Adverse Reactions

From the cardiovascular system: at the beginning of treatment (first-dose effect) and when increasing the dose, episodes of excessive blood pressure reduction are possible (usually these phenomena resolve on their own and the patient’s condition stabilizes without special correction); with further use of carvedilol, bradycardia is also possible; less frequently, peripheral blood flow disorders, angina attacks, AV block, episodes of intermittent claudication are observed; in some cases – increased manifestations of heart failure.

From the central and peripheral nervous system: weakness, fatigue, headache are possible; in some cases – sleep disorders, mental depression, paresthesia.

From the digestive system: increased intestinal tone and motility; in some cases – changes in plasma transaminase activity.

Allergic reactions: rarely – allergic exanthema, itching.

Dermatological reactions: urticaria, reactions resembling lichen planus, appearance of psoriatic plaques or exacerbation of a pre-existing psoriatic process.

From the respiratory system: in some cases – nasal congestion.

From the hematopoietic system: in some cases – thrombocytopenia, leukopenia.

Contraindications

AV block of II and III degree, severe bradycardia, heart failure in the stage of decompensation, shock, bronchial asthma, chronic lung diseases with a history of broncho-obstructive syndrome, hepatic insufficiency, pregnancy, lactation, hypersensitivity to carvedilol.

Use in Pregnancy and Lactation

Carvedilol is contraindicated for use during pregnancy and during the lactation (breastfeeding) period.

Although there is no direct evidence of embryo- or fetotoxic effects of carvedilol, it is known that it penetrates the placental barrier and is excreted in breast milk. Blockade of α- and β-adrenergic receptors in the fetus or newborn may induce perinatal or neonatal distress syndrome, manifested by bradycardia, respiratory depression, hypothermia, and hypoglycemia.

Use in Hepatic Impairment

Contraindicated in hepatic insufficiency.

Pediatric Use

There is no clinical experience with the use of carvedilol in pediatrics.

Geriatric Use

In elderly patients, a dose of 12.5 mg/day may be effective.

Special Precautions

Use with caution in patients with coronary artery disease and heart failure. Before starting treatment with carvedilol for heart failure, adequate therapy should be carried out to eliminate symptoms of decompensation.

When using carvedilol in patients with coronary artery disease, a reduction in myocardial oxygen demand is possible (due to β₁-adrenergic receptor blockade). In this regard, discontinuation of carvedilol should be carried out gradually to avoid the development of angina attacks.

In patients with endocrine disorders, Carvedilol may mask the symptoms of hyperthyroidism and early signs of acute hyperglycemia (which should be warned to patients with insulin-dependent diabetes mellitus).

Alcohol consumption is not recommended during treatment.

There is no clinical experience with the use of carvedilol in pediatrics.

Effect on the ability to drive vehicles and machinery

At the beginning of treatment, as well as when increasing the dose of carvedilol during treatment, one should refrain from driving a car and other activities that require high concentration of attention and quick psychomotor reactions.

Drug Interactions

With simultaneous use of carvedilol with antiarrhythmic agents, anesthetic agents, antihypertensive drugs, antianginal drugs, other beta-adrenergic blockers (including in the form of eye drops), there is a risk of undesirable drug interaction.

With simultaneous use with inhibitors of the CYP2D6 isoenzyme, an enhancement of the effect of carvedilol is theoretically possible.

With simultaneous use with inducers of the CYP2D6 isoenzyme system, a decrease in the effect of carvedilol is possible.

With simultaneous use with verapamil, diltiazem for intravenous administration, the development of severe arterial hypotension is possible.

With simultaneous use with digoxin, an increase in the plasma concentration of digoxin and an increased risk of severe bradycardia and AV conduction disorders are possible.

With simultaneous use with insulin, oral hypoglycemic drugs, an increased risk of hypoglycemia is possible.

With simultaneous use with clonidine, severe bradycardia, arterial hypotension, and conduction disturbances are possible. In case of sudden withdrawal of clonidine in patients receiving Carvedilol, a sharp increase in blood pressure is possible.

With simultaneous use with reserpine, MAO inhibitors, there is a risk of developing severe arterial hypotension and bradycardia.

With simultaneous use with rifampicin, the AUC and C_max of carvedilol in plasma decrease.

Fluoxetine inhibits the CYP2D6 isoenzyme, which leads to inhibition of carvedilol metabolism and its accumulation. This may enhance the cardiodepressive effect (including bradycardia). Fluoxetine and, mainly, its metabolites are characterized by a long T_1/2, so the likelihood of drug interaction persists even several days after discontinuation of fluoxetine.

With simultaneous use with cimetidine, the AUC of carvedilol increases without changing its C_max in plasma.

With simultaneous use with cyclosporine, an increase (from small to moderate) in the plasma concentration of cyclosporine is possible.

With simultaneous use with ergotamine derivatives, a deterioration in peripheral circulation is possible.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

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.