Carvedilol Sandoz, tablets 25 mg 30 pcs

Carvedilol is alpha- and beta-adrenoblocking, hypotensive, antioxidant, antianginal.

Pharmacodynamics

It has a combined non-selective beta-blocking, alpha₁-blocking and antioxidant effect. The vasodilatory effect is mainly due to blockade of alpha₁ receptors. Due to vasodilatation, it decreases RPS. It has no intrinsic sympathomimetic activity and, like propranololol, has a membrane stabilizing effect.

Powerful antioxidant, eliminates free oxygen radicals. The combination of the vasodilator action and the beta-adrenoblocking properties of carvedilol leads to the fact that in patients with arterial hypertension, a decrease in BP is not accompanied by a simultaneous increase in RPS, which is observed when taking beta-adrenoblockers. HR decreases insignificantly, renal blood flow and renal function are preserved. Because peripheral blood flow is preserved, limb cooling is very rare, unlike in patients treated with beta-adrenoblockers.

The antihypertensive effect develops quickly – 2-3 hours after a single dose and lasts for 24 hours. With prolonged treatment maximum effect is observed after 3-4 weeks. In patients with CHD, carvedilol has anti-ischemic and antianginal effects. It reduces pre- and afterload on the heart. It has no pronounced effect on lipid metabolism and plasma content of potassium, sodium and magnesium ions. In patients with left ventricular dysfunction and/or circulatory insufficiency, the alpha₁-adrenoblocking effect of carvedilol leads to dilation of arterial and, to a lesser extent, venous vessels; carvedilol has favorable effects on hemodynamic parameters: increases left ventricular ejection function and reduces its size.

Carvedilol has beneficial effects on cardiac hemodynamics and left ventricular ejection fraction in both dilated cardiomyopathy and ischemic heart failure. In heart failure, end-systolic and end-diastolic volume as well as peripheral and pulmonary vascular resistance decrease. Ejection fraction and cardiac index do not change in normal heart function.

It is established that when additionally prescribed against the background of taking cardiac glycosides, ACE inhibitors and diuretics, carvedilol decreases mortality rate, slows disease progression and improves general condition of the patient regardless of disease severity. The effect of carvedilol is more pronounced in patients with tachycardia (HR greater than 82 bpm) and low ejection fraction (less than 23%).

The HDL/LDL cholesterol ratio does not change during treatment with carvedilol.

Pharmacokinetics

Absorption of carvedilol is fast and high. T_max is 1 h after drug administration. Plasma concentration is proportional to the dose taken. The bioavailability is about 30%. Simultaneous intake of food slows down absorption of the drug, but does not affect the value of bioavailability.

The binding to plasma proteins is about 98-99%. V_d is about 2 l/kg and increases (by 80%) in case of liver dysfunction (due to reduced effect of first passage through the liver). Metabolized mainly in the liver due to intensive coupling with glucuronic acid. By demethylation and hydroxylation of the phenyl ring three active metabolites with pronounced antioxidant and adrenoblocking properties are formed. T_1/2 of carvedilol is 6-10 h, plasma clearance is about 590 ml/min. It is excreted mainly with the bile and a small part is excreted through the kidneys.

It penetrates the placental barrier and is excreted with breast milk.

Carvedilol is practically not excreted by hemodialysis. In cirrhosis, the bioavailability of carvedilol is 4 times higher and the C_max in plasma is 5 times higher than normal. Carvedilolol is mainly excreted through the gastrointestinal tract, so no cumulation of the drug is observed in renal dysfunction.

It should be noted that in elderly patients the plasma concentration of Carvedilol is 50% higher than in younger patients.

Indications

Active ingredient

Composition

Active substance:

carvedilol 25 mg;

Associates:

lactose monohydrate;

MC;

p> crospovidone;

povidone K30;

silicon dioxide colloid;

magnesium stearate

How to take, the dosage

Carvedilol is taken orally, after meals, with a small amount of liquid. The dose is chosen individually. Arterial hypertension: the recommended dose for the first 7-14 days is 12.5 mg/day in the morning after breakfast or divided into 2 doses of 6.25 mg, then 25 mg/day once in the morning or divided into 2 doses of 12.5 mg.

After 14 days, the dose may be increased again.a Stable angina pectoris: The initial dose is 12.5 mg 2 times daily, after 7-14 days, under a physician’s supervision, the dose may be increased to 25 mg 2 times daily. After 14 days, in case of insufficient efficacy and good tolerability of the drug, the dose may be increased further. The total daily dose should not exceed 100 mg (50 mg twice a day), in patients aged over 70 years – 50 mg/day (25 mg twice a day).

If the next dose is missed, Carvedilol should be taken as soon as possible; however, if the time for the next dose is approaching, only that dose is taken, without doubling. If it is necessary to cancel Carvedilol Obolensky, the dose should be reduced gradually over 1-2 weeks.

Interaction

Catecholamine depleting agents (reserpine, MAO inhibitors) may cause severe bradycardia and arterial hypotension. Concomitant administration of ACE inhibitors, thiazide diuretics, vasodilators, prescribed simultaneously with carvedilol may lead to a sharp drop in BP.

It enhances the effect of insulin and sulfonylurea derivatives (while masking or weakening the severity of symptoms of hypoglycemia, reducing the breakdown of liver glycogen to glucose).

When concomitantly administered with insulin or oral hypoglycemic agents, blood glucose levels should be monitored. CYP2D6 isoenzyme inhibitors (quinidine, fluoxetine, propafenone) may increase the concentration of R(+)-enantiomer of Carvedilol.

Co-administration with antiarrhythmic agents (especially class I) and BMCCs (verapamil, diltiazem) may provoke severe arterial hypotension and heart failure. Intravenous administration of these drugs together with taking carvedilol is contraindicated.

Elevates digoxin concentrations, which requires monitoring of digoxin concentrations because concomitant administration with cardiac glycosides may lead to AV blockade.

General anesthetics increase negative inotropic and hypotensive effects. Phenobarbital and rifampicin accelerate metabolism and decrease plasma concentration of carvedilol. Microsomal oxidation inhibitors (cimetidine), diuretics and ACE inhibitors increase the concentration and increase the hypotensive effect of carvedilol. Carvedilol delays the metabolism of cyclosporine.

Special Instructions

If the heart rate decreases to 55 bpm, the drug should be discontinued. In allergic persons or persons undergoing desensitization, administration of Carvedilol may increase allergic sensitivity.

Persons wearing contact lenses should be warned that the drug reduces tear production. When completing treatment with Carvedilol Sandoz concomitantly with clonidine, the dosage of clonidine should first be gradually reduced and then clonidine and then carvedilol should be withdrawn first.

If it is necessary to use Carvedilol Sandoz during lactation, breastfeeding should be stopped. Alcohol intake should be excluded during treatment.

In case of progression of circulatory insufficiency during treatment, it is recommended to increase the dose of diuretics; in case of renal insufficiency, the dose should be adjusted taking into account the parameters of the functional state of the kidneys.

If surgical intervention with general anesthesia is necessary, the anesthesiologist should be warned about previous therapy with carvedilol. It should be noted that the drug may mask symptoms of thyrotoxicosis and hypoglycemia, therefore, regular monitoring of blood glucose levels and dosage adjustment if necessary are recommended.

Contraindications

Side effects

In the recommended doses, Carvedilol is well tolerated, but in some cases, side effects may occur.

Digestive system disorders: nausea, dry mouth, abdominal pain, diarrhea or constipation, vomiting, increased liver transaminase activity.

Nervous system disorders: headache, dizziness, fatigue, loss of consciousness, muscle weakness (usually at the beginning of treatment), sleep disorders, depression, paresthesias.

Sensory organs: decrease in lacrimation.

Urinary system disorders: renal dysfunction, edema, urinary disorders.

Hematopoietic disorders: leukopenia, thrombocytopenia.

Allergic reactions: urticaria, itching, rash, appearance and/or exacerbation of psoriasis, sneezing, nasal congestion, bronchospasm, shortness of breath (in predisposed patients), very rare – anaphylactoid reaction.

Systemic diseases: bradycardia, orthostatic hypotension, angina pectoris, AV blockade, progression of circulatory failure (cold extremities), progression of heart failure, worsening of intermittent claudication and Raynaud’s syndrome.

Endocrine disorders: weight gain.

Others: pain in extremities, flu-like symptoms.

As with other drugs that block alpha-adrenoreceptors, latent diabetes mellitus may appear or increase its symptoms.

Overdose

Symptoms: marked BP decrease (BP 80 mmHg or lower), marked bradycardia (less than 50 bpm), respiratory disorders (bronchospasm, etc.), chronic circulatory failure, cardiogenic shock, cardiac arrest.

Treatment: within the first two hours induce vomiting and gastric lavage. Overdose requires intensive treatment, control of vital functions is necessary. The patient should be in a position with elevated legs, i.e. in Trendelenburg position. Beta-blocking antidotes are orciprenaline or isoprenaline 0.5-1 mg IV and/or glucagon at a dose of 1-5 mg (maximum dose 10 mg). Severe hypotension is treated with parenteral administration of fluids and repeated adrenaline at a dose of 5-10 mg (or its intravenous infusion at a rate of 5 µg/min).

In case of excessive bradycardia, administer IV atropine at a dose of 0.5-2 mg. To maintain cardiac activity: glucagon is administered rapidly (within 30 s) by IV, followed by a continuous infusion at a rate of 2-5 mg/h. If peripheral vasodilator effect prevails (warm limbs, in addition to significant arterial hypotension), norepinephrine should be administered 5-10 mcg as an IV infusion – 5 mcg/min.

Beta-adrenomimetics (as an aerosol or intravenously) or aminophylline intravenously are prescribed to relieve bronchospasm. If seizures develop, slow administration of diazepam or clonazepam is recommended. In severe cases of intoxication when symptoms of shock dominate, treatment should be continued until the patient’s condition is stabilized, taking into account the T1/2 of carvedilol, which is 6-10 h.

Pregnancy use

The drug is contraindicated in pregnancy.

If it is necessary to use the drug Carvedilol Sandoz during lactation, breastfeeding should be stopped.

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