CORVASAN®

Composition

active ingredient: carvedilol;

1 tablet contains carvedilol 12.5 mg or 25 mg;

excipients:microcrystalline cellulose, povidone, lactose monohydrate, potato starch, talc, calcium stearate, Opadry II Pink.

Indications

• Essential hypertension (as a monotherapy or combined therapy);
•  Chronic stable angina;
•  Chronic heart failure (as adjunctive therapy).

Contraindications

• Hypersensitivity to carvedilol or other ingredients of the drug;
• Bronchial asthma or chronic obstructive lung disease;
• Hepatic impairment;
• Marked bradycardia (less than 50 beats per minute);
• Sick sinus syndrome;
• Atrio-ventricular block of II-III degree (unless a permanent pacemaker is fitted);
• Decompensated heart failure (NYHA class IV );
• Cardiogenic shock;
• Marked arterial hypotension (systolic blood pressure less than 85 mm Hg);
• Metabolic acidosis;
• Prinzmetal’s angina;
• Phaeochromocytoma;
• Severe peripheral circulatory disorders;
• Coadministration of verapamil, dilthiazem;
• Galactosemia;
• Pregnancy and lactation.

Dosage and administration

The drug should be taken orally with plenty of liquid.

Duration of therapy.

Treatment with Corvasan ® is long-term and should not be discontinued abruptly. The dose should be reduced gradually at weekly intervals. This is particularly important for patients with ischemic heart disease.

Essential hypertension. The recommended initial dose is 12.5 mg once daily during the first 2 days, followed by 25 mg once daily. If necessary, the dose may be further increased at no less than two week intervals up to the maximum recommended dose of 50 mg once daily (in 2 divided doses).

Chronic stable angina. The recommended initial dose is 12.5 mg twice daily during the first 2 days, followed by 25 mg twice daily. If necessary, the dose may be further increased at no less than two week intervals up to the maximum recommended dose of 100 mg in 2 divided doses.

Chronic heart failure.The dose is selected individually under close supervision of a physician. In patients receiving digitalis medicines, diuretics and ACE inhibitors, their doses should be stabilized before the treatment with Corvasan ®. The recommended initial dose is 3.125 mg (1/4 of the tablet with a strength of 12.5 mg, which can be divided into 4 parts with the help of breaking lines) twice daily for two weeks. If well tolerated, the dose should be increased at no less than 2-week intervals to 6.25 mg (1/2 of the tablet with a strength of 12.5 mg, which can be divided into 4 parts with the help of breaking lines) twice daily, then to 12.5 mg, and then up to 25 mg twice daily. The dose should be increased to the maximum tolerable dose. The recommended maximum dose is 25 mg twice daily for all patients with severe congestive heart failure and for patients with mild to moderate chronic heart failure weighing less than 85 kg. In patients with mild to moderate chronic heart failure and a bodyweight over 85 kg, the recommended maximum dose is 50 mg twice daily. Each time prior to increasing the dose, the physician must examine the patient for symptoms of worsening heart failure or vasodilation. In patients with transient aggravation of heart failure symptoms and fluid retention, doses of diuretics should be increased; however, it may be necessary to lower the dose of Corvasan ® or to discontinue the drug temporarily in isolated cases.

Should treatment with Corvasan ® be discontinued for more than 1 week, it is advised that therapy be reinstated in a lower dose and the dose then increased in line with the abovementioned dosage recommendations. Should treatment be discontinued for two weeks or more, it is advised that therapy be reinstated in a dose of 3.125 mg twice daily and the dose then selected in line with the abovementioned dosage recommendations.

Symptoms of vasodilation may be managed by lowering the dose of diuretics. Should the symptoms persist, the dose of ACE inhibitor may be reduced (if the patient is receiving this drug), followed by a reduction in the dose of Corvasan®, if necessary. Under these circumstances the dose of Corvasan® should not be increased until symptoms of worsening heart failure or arterial hypotension have been stabilized.

Dosage in specific populations.

Renal impairment. Pharmacokinetic data available in patients with various severity of renal impairment (including renal failure) suggest that no dose adjustment is needed in patients with moderate to severe renal failure.

Side effects

The frequency of AE is estimated as follows:

very common (≥ 10%), common (≥ 1%, <10%), uncommon (≥ 0.1%, <1%), rare (≥ 0.01%, <1%), very rare, including isolated cases (0.01%).

Central nervous system disorders: common - headache, dizziness, fatigue; rare - depression, sleep disturbances, paresthesia, hyperesthesia, vertigo.

Cardiovascular disorders: common - postural hypotension, bradycardia, hypertension, loss of consciousness, particularly at the beginning of the treatment, angina, palpitation; rare – reduced peripheral circulation (coldness of the extremities), intermittent claudication or Raynaud's disease, peripheral edema, atrio-ventricular block, progression of heart failure.

Respiratory disorders: dyspnea, asthma, rare - nasal congestion.

Gastrointestinal disorders: nausea, diarrhea, abdominal pain; rare - dry mouth, constipation, vomiting, periodontitis, melena.

Skin disorders: rash, pruritus, urticaria, lichen ruber planus.

Eye disorders: rare - dry eyes, blurred vision, eye irritation.

Metabolic disorders: weight gain.

Musculoskeletal disorders: rare - pain in the extremities, arthralgia, cramps.

Urogenital disorders: rare – micturition impairment, impotence.

Very rare - renal dysfunction in patients with diffuse impairment of peripheral arteries, renal failure, hematuria, albuminuria.

Laboratory investigations: rare - elevated serum transaminases, thrombocytopenia, leukopenia, anemia, reduced prothrombin levels, hyperglycemia in patients with diabetes, hypercholesterolemia, glycosuria, hyperkalemia, hypertriglyceridemia, hyponatremia, elevated levels of alkaline phosphatase, creatinine, urea, hyperuricemia.

Other side effects: rare - flu-like symptoms, fever; very rare - anaphylactic reactions; manifestations of latent diabetes may occur, the symptoms of pre-existing diabetes may exacerbate during the therapy.

Except for dizziness, visual impairment and bradycardia, none of the above side effects are dose-dependent