KARVEDILOL SANDOZ

471 9 minutes read

Active material: Karvedilol
When ATH: C07AG02
CCF: Beta₁-,beta₂-adrenoblokator. Alpha₁-adrenoblokator
ICD-10 codes (testimony): I10, i20, I50.0
When CSF: 01.01.01.01.02
Manufacturer: Hexal AG (Germany)

PHARMACEUTICAL FORM, COMPOSITION AND PACKAGING

Pills light pink, round, lenticular, scored on both sides and on the sides and with the inscription “C1” on one side.

	1 tab.
karvedilol	3.125 mg

Excipients: iron oxide red, lactose monohydrate, microcrystalline cellulose, krospovydon, povidone K30, colloidal silicon dioxide, magnesium stearate.

10 PC. – blisters (1) – packs cardboard.
10 PC. – blisters (2) – packs cardboard.
10 PC. – blisters (3) – packs cardboard.
10 PC. – blisters (4) – packs cardboard.
10 PC. – blisters (5) – packs cardboard.

Pills yellow color, round, lenticular, scored on both sides and on the sides and with the inscription “C2” on one side.

	1 tab.
karvedilol	6.25 mg

Excipients: iron oxide yellow, lactose monohydrate, microcrystalline cellulose, krospovydon, povidone K30, colloidal silicon dioxide, magnesium stearate.

Pills pinkish-beige, round, lenticular, scored on both sides and on the sides and with the inscription “C3” on one side.

	1 tab.
karvedilol	12.5 mg

Excipients: iron oxide red, iron oxide yellow, lactose monohydrate, microcrystalline cellulose, krospovydon, povidone K30, colloidal silicon dioxide, magnesium stearate.

Pills white or almost white, round, lenticular, scored on both sides and on the sides and with the inscription “C4” on one side.

	1 tab.
karvedilol	25 mg

Excipients: lactose monohydrate, microcrystalline cellulose, krospovydon, povidone K30, colloidal silicon dioxide, magnesium stearate.

Pills white or almost white, round, lenticular, scored on both sides and on the sides and with the inscription “C5” on one side.

	1 tab.
karvedilol	50 mg

Excipients: lactose monohydrate, microcrystalline cellulose, krospovydon, povidone K30, colloidal silicon dioxide, magnesium stearate.

Pharmacological action

Beta₁-,beta₂-adrenoblokator. Alpha₁-adrenoblokator. It has a combined non-selective beta-adrenoceptor blocking, alpha₁-adrenoblokiruyuschee and antioxidant effects. Vasodilator effect is due, mainly, blockade with α₁-adrenoreceptorov. Due vasodilation reduces peripheral vascular resistance. It has no intrinsic sympathomimetic activity, and, like propranololu, It has membrane stabilizing action.

Eliminates free oxygen radicals.

The totality of the vasodilating action and beta-adrenoceptor blocking properties of carvedilol causes, that in hypertensive patients blood pressure reduction is not accompanied by a simultaneous increase in systemic vascular resistance, which is celebrated when taking beta-blockers. Slightly decreased heart rate, renal blood flow and renal function are stored. Since peripheral blood flow is maintained, extremities cold snap observed very rarely, Unlike patients, who carried out the treatment of beta-blockers.

The antihypertensive effect develops rapidly – through 2-3 hours after a single dose and is continued for 24 no. In long-term treatment of the maximum effect observed after 3-4 of the week.

In patients with ischemic heart disease, carvedilol has anti-ischemic and anti-anginal action. reduces before- and afterload on the heart. It does not have a pronounced effect on lipid metabolism, and the content of potassium ions, sodium and magnesium in plasma.

In patients with impaired left ventricular function and / or circulatory failure, carvedilol has a favorable effect on hemodynamic parameters: improves the function of the left ventricular ejection and reduces its size.

Carvedilol has a beneficial effect on cardiac hemodynamics and left ventricular ejection fraction as in dilated cardiomyopathy, and in the form of ischemic heart disease. In heart failure, decreased end-systolic and end-diastolic volume, as well as peripheral and pulmonary vascular resistance. Ejection fraction and cardiac index in the normal function of the heart do not change.

In the case of left ventricular dysfunction alpha₁-adrenoceptor blocking effect of carvedilol leads to arterial and expansion, less, veins. Established, that the supplemental taken against the background of cardiac glycosides, ACE inhibitors and diuretics carvedilol reduces mortality, It slows the progression of the disease and improves the general condition of the patient regardless of the severity of the disease. Effect of carvedilol was more pronounced in patients with tachycardia (HR more 82 u. / min) and low ejection fraction (less 23%).

During treatment carvedilol ratio HDL cholesterol / not modified LDL.

Pharmacokinetics

Absorption

carvedilol absorption fast and high. C_max plasma levels achieved after 1 h after dosing. The plasma concentration is proportional to the dose. Bioavailability is about 30%. Simultaneous food intake slows down the absorption of the drug, but it does not affect the bioavailability of.

Distribution

Plasma protein binding is about 98-99%. V_d – about 2 l / kg.

It penetrates through the placental barrier and is excreted in breast milk.

Metabolism

It is metabolized primarily in the liver due to intensive compound with glucuronic acid. By demethylation and hydroxylation of the phenyl ring are formed three active metabolites with strong antioxidant properties and adrenoblokiruyuschee.

Deduction

T_1/2 carvedilol is 6-10 no, plasma clearance – about 590 ml / min. Write mainly in the bile and a small part – through the kidneys.

Carvedilol is practically not appear in hemodialysis.

Pharmacokinetics in special clinical situations

Liver cirrhosis bioavailability carvedilol 4 times higher, and the maximum plasma concentration in 5 times higher, than normal.

V_d increases (on 80%) in the case of liver disease (by reducing the first pass effect through the liver).

It should be taken into account, that elderly patients carvedilol plasma concentration on 50% higher, than at a young age.

Carvedilol is derived mainly through the digestive tract, so when kidney function drug accumulation is not observed.

Testimony

- hypertension in the form of mono- or combination therapy (in combination with thiazide diuretics);

- Stable angina;

- chronic heart failure in combination with a diuretic, digoxin or ACE inhibitors.

Dosage regimen

Karvedilol Sandoz^® is inwards, drinking plenty of fluids.

Arterial hypertension

The initial dose – 12.5 mg 1 time / day (the morning after breakfast) within the first 2 days, then – by 25 mg 1 time / day. Through the if necessary 14 day dose may be increased. The maximum dose – 50 mg / day 1 or 2 admission (in the morning and in the evening).

In elderly patients in some cases the dose 12.5 mg may be effective.

Angina

The initial dose – by 12.5 mg 2 times / day for the first 2 days, then – by 25 mg 2 times / day (in the morning and in the evening). If necessary, after 7-14 days daily dose may be increased to a maximum, component 100 mg / day, razdelennoy of 2 admission.

In elderly patients The maximum daily dose is 50 mg, divided by 2 admission.

Congestive heart failure

Dose picked individually, conducting close monitoring. Should monitor the patient's condition during the first 2-3 hours after the first dose, or increased after the first dose. The dose and administration of other drugs, such as digoxin, diuretics and ACE inhibitors should be fixed before drug administration Carvedilol Sandoz^®.

Karvedilol Sandoz^® It should be taken with food (to reduce the risk of orthostatic hypotension).

The recommended starting dose is 3.125 mg 2 times / day for 14 days. With good tolerability and the need to increase the dosage of drug administered in a dose of 6.25 mg 2 times / day, then – to 25 mg 2 times / day. Patients received the maximum tolerated dose. The maximum recommended dose – by 25 mg 2 times / day for patients weighing up 85 kg and 50 mg 2 times / day – to patients weighing more 85 kg.

At the beginning of treatment and before each dose increase the patient should be monitored, tk. possibly worsening heart failure. It may develop fluid retention, and due to the presence vasodilating effect – hypotension and lethargy. When fluid retention should increase the dose of diuretics, Besides, may require temporary dose reduction of the drug Carvedilol Sandoz^®. Sometimes you need a temporary discontinuation of treatment.

Side effect

The recommended doses Carvedilol Sandoz^® well tolerated, however, in some cases, possible side effects.

From the digestive system: nausea, dry mouth, stomach ache, diarrhea or constipation, vomiting, increase in liver transaminases.

CNS: headache, dizziness, feeling tired, loss of consciousness, muscular weakness (usually, at the beginning of treatment), sleep disturbance, depression, paresthesia.

From the senses: reduction slezovydeleniya.

With the genitourinary system: disorders of the kidney function, swelling.

From the side of hematopoiesis: leukopenia, thrombocytopenia.

Cardio-vascular system: bradycardia, otrostaticheskaya hypotension, angina, AV блокада, progression of circulatory failure (cold extremities), progression of heart failure.

Allergic reactions: hives, itch, rashes, the emergence and / or worsening of psoriasis, chikhaniye, nasal congestion, bronchospasm, breathlessness (in predisposed patients); rarely – anaphylactoid reactions.

Other: rare syndrome exacerbation of intermittent claudication, Raynaud's syndrome, pain in the limbs, violation of urination, flu-like symptoms, weight gain.

As with other alpha-blockers, It can manifest the latent current diabetes or worsen its symptoms.

Contraindications

- Chronic heart failure decompensation;

- SSS;

— AV-blockade II and III degrees, except in patients with an artificial pacemaker;

- Vыrazhennaya bradycardia (HR less 50 u. / min);

- Cardiogenic shock, collapse;

- Bronchial asthma;

- Severe liver;

- Metabolic acidosis;

- joint in / with the introduction of verapamil, diltiazem or other antiarrhythmics (Class I especially);

- Pregnancy;

- Lactation (breast-feeding);

- Up to 18 years (efficacy and safety have not been established);

- Hypersensitivity to the drug.

FROM caution and under the control should be prescribed for patients with diabetes, gipoglikemii, thyrotoxicosis, pheochromocytoma (Only stable destination alpha-blockers), occlusive peripheral vascular disease, AV-blockade I degree, chronic obstructive pulmonary disease, Prinzmetal angina, psoriaze, renal impairment, depression, myasthenia, in the treatment of alpha-blockers and alpha-agonists, while the use of digitalis preparations, diuretics and / or MAO inhibitors, and elderly patients.

Pregnancy and lactation

The drug is contraindicated in pregnancy.

If necessary, the drug carvedilol Sandoz^® lactation, should be discontinued breastfeeding.

Cautions

In the case of rate to 55 u. / min should stop taking the drug.

In patients with an allergy or undergoing desensitization course, receiving carvedilol can increase allergochuvstvitelnost.

Patients, using contact lenses, should be warned that, that the drug reduces the slezovydelenie.

Upon completion of the course of treatment with Carvedilol Sandoz^® simultaneously with clonidine first gradually reduce the dosage of clonidine and then cancel the first clonidine, and then carvedilol.

During treatment to eliminate alcohol intake.

With the progression of circulatory failure during treatment is recommended to increase the dose of diuretics, in renal failure to conduct correction dose based on indicators of renal function.

If necessary, surgery using general anesthesia should notify the anesthesiologist of previous treatment with carvedilol.

It should be taken into account, that the drug may mask the symptoms of hyperthyroidism and hypoglycemia, therefore recommended the regular control of blood glucose and if necessary to carry out adjustment of dose.

Cancel the drug should be done gradually (during 1-2 weeks) in order to prevent the development of withdrawal syndrome, especially in patients with CHD.

Effects on ability to drive vehicles and management mechanisms

Caution should be used in patients, who require rapid psychomotor reactions (vehicle management, Working with technology).

Overdose

Symptoms: marked reduction in blood pressure (systolic blood pressure 80 mm Hg. Article. and lower), vыrazhennaya bradycardia (less 50 u. / min), impairment of respiratory function (bronchospasm), chronic circulatory insufficiency, cardiogenic shock, cardiac arrest.

Treatment: during the first 2 h, induce vomiting and stomach wash. Overdose requires intensive treatment. The patient must be in a position with the raised feet (in the Trendelenburg position). Antidote beta-adrenoceptor blocking action is ortsiprenalin or isoprenaline at a dose 0.5-1 mg in / in and / or glucagon in a doze 1-5 mg (the maximum dose 10 mg). Severe hypotension treated by parenteral administration of fluids and repeated administration of epinephrine (adrenaline) dose 5-10 mg (or on / in infusion at a rate 5 mcg / min).

If excessive bradycardia administered in / in a dose of atropine 0.5-2 mg. In order to maintain cardiac performance I / fast (during 30 sec) glucagon formulation results, then conduct a constant infusion rate of 2-5 mg / h. If the predominant peripheral vasodilator effect (warm extremities, in addition to significant hypotension), you must assign norepinephrine in repeated doses 5-10 ug or as an infusion – 5 mcg / min.

For the relief of bronchospasm prescribe beta-blockers (in an aerosol or /) or aminophylline in /.

If you develop seizures, recommended slow diazepam or clonazepam.

In severe cases of intoxication, when dominated by symptoms of shock, treatment with antidotes must be continued until the patient's condition has stabilized, given T_1/2karvedilola 6-10 no.

In intensive care to hold control over the performance of vital organs.

Drug Interactions

With the simultaneous application of the drug carvedilol Sandoz^® with means, deplete catecholamines (reserpine, MAO inhibitors), can develop severe bradycardia and hypotension.

Simultaneous administration of ACE inhibitors with carvedilol, thiazide diuretics, vasodilators, appointed at the same time, It may lead to a sharp drop in blood pressure.

Carvedilol enhances the action of insulin and sulfonylureas (simultaneously weakening or masking the severity of symptoms of hypoglycemia, reducing splitting of glycogen to glucose by the liver). When concomitant administration of insulin or oral hypoglycemic agents, should monitor the level of glucose in the blood.

While the use of inhibitors of CYP2D6 isozyme (quinidine, fluoxetine, propafenone) may increase the concentration of R(+) enantiomera karvedilola.

The combined use of carvedilol with antiarrhythmics (especially class I) and calcium channel blockers slow (verapamil, diltiazem) can cause pronounced hypotension and heart failure. B / in the administration of these drugs, together with reception of carvedilol contraindicated.

Carvedilol increases the concentration of digoxin, which requires monitoring of its concentration, tk. co-administration with cardiac glycosides may lead to AV-blockade.

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

Phenobarbital and rifampin accelerate metabolism and reduce the concentration of carvedilol in the plasma.

Inhibitors of microsomal oxidation (cimetidine), diuretics and ACE inhibitors increase the concentration and enhance the antihypertensive effect of carvedilol.

Carvedilol delays the metabolism of cyclosporin.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

The drug should be stored out of reach of children at or above 25 ° C. Shelf life – 3 year.

Vladimir Andreevich Didenko

471 9 minutes read