Carvedilol-Teva - instructions for use, dose, side effects, contraindications

Excipients: cellulose microcrystalline 28,000 / 56,00 / 112,00 / 224,00 mg, lactose monohydrate 16,770 / 33,54 / 67,08 / 134,16 mg, low-substituted giprolose 4,545 / 9,09 / 18,18 / 36,36 mg, corn starch 6,360 / 12,72 / 25,44 / 50,88 mg, talc 0,300 / 0,60 / 1,20 / 2,40 mg, silicon dioxide colloid 0,340 / 0,68 / 1,36 / 2, 72 mg, magnesium stearate 0.560 / 1.12 / 2.24 / 4.48 mg.

Description:TOrifle, biconvex tablets white or almost white.

Pharmacotherapeutic group:Alpha- and beta-blocker

ATX: & nbsp

C.07.A.G.02 Carvedilol

Pharmacodynamics:

Has combined non-selective beta-blocking, alpha1-blocking and antioxidant effect. The vasodilating effect is mainly related to the blockade of alpha-1 receptors. Due to vasodilation reduces the overall peripheral vascular resistance. Does not have an internal sympathomimetic activity and, like propranolol, has a membrane-stabilizing effect.

A powerful antioxidant, eliminates free oxygen radicals. The combination of vasodilation and beta-adrenergic blockade has the following effect:

The combination of vasodilating action and beta-adrenergic blocking properties of carvedilol leads to the fact that in patients with arterial hypertension, a decrease in blood pressure (BP) is not accompanied by a simultaneous increase in the total peripheral resistance observed when taking beta-blockers; carvedilol slightly reduces the heart rate (heart rate), while maintaining renal blood flow and kidney function. Since peripheral blood flow is preserved, the cooling of limbs is very rare, unlike patients who are treated with beta adrenoblockers.

The antihypertensive effect develops rapidly - 2-3 hours after a single dose and lasts for 24 hours. With prolonged treatment, the maximum effect is observed after 3-4 weeks. In patients with ischemic heart disease carvedilol has anti-ischemic and antianginal action. Reduces pre- and afterload on the heart. It has no pronounced effect on the lipid metabolism and the content of potassium, sodium, magnesium ions in the blood plasma.

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

The favorable effect of carvedilol on the hemodynamics of the heart, the fraction of the ejection of the left ventricle is observed both in dilated cardiomyopathy and in the ischemic form of heart failure. With heart failure carvedilol reduces the end-systolic and end-diastolic volume, as well as peripheral and pulmonary vascular resistance. The ejection fraction and cardiac index do not change with normal heart function.

The effect of carvedilol is more pronounced in patients with tachycardia (heart rate more than 82 beats / min) and low ejection fraction (less than 23%).

During treatment with carvedilol, the ratio of high-density lipoprotein / low-density lipoprotein cholesterol does not change.

Pharmacokinetics:

After oral administration carvedilol quickly and almost completely absorbed from the gastrointestinal tract. The maximum concentration in the blood plasma is reached 1 hour after taking the drug. Bioavailability is 25%.The concentration in the blood plasma and the dose are in a linear relationship. Bioavailability and the magnitude of the maximum concentration in the blood plasma do not depend on food intake, only the time to reach the maximum concentration increases.

The connection with plasma proteins is high and is 98-99%. The volume of distribution is about 2 l / kg and increases (by 80%) in the case of liver function disorders (due to a decrease in the effect of "first passage" through the liver).

Metabolized mainly in the liver due to intensive connection with glucuronic acid. By demethylation and hydroxylation of the phenyl ring, three active metabolites are formed, which have a pronounced antioxidant and adrenoblocking effect.

The half-life of carvedilol is 6-10 hours, the plasma clearance is about 590 ml / min. It is excreted mainly with bile and a small part - through the kidneys.

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

Carvedilol is practically not removed from the blood during hemodialysis.

Indications:

- Arterial hypertension - in the form of monotherapy and in combination with other antihypertensive agents;

- stable angina pectoris;

- chronic heart failure (stage II and III stage NYHA) *, in combination with diuretics, digoxin or angiotensin-converting enzyme (ACE) inhibitors,

*NYHA - II (New York Heart Associatian): patients in this stage have no symptoms at rest, moderate physical activity is accompanied by fatigue, palpitations and difficulty breathing (short breath)

*NYHA - III (New York Heart Associatian): there are usually no symptoms in rest. Small Physical stress causes the symptoms indicated above.

Contraindications:

- Hypersensitivity to carvedilol or other components of the drug;

- heart failure in the stage of decompensation;

- syndrome of weakness of the sinus node;

- atrioventricular block II-III Art., except for patients with an artificial pacemaker;

- marked bradycardia (heart rate less than 50 beats per minute);

- cardiogenic shock;

- bronchial asthma;

- pronounced violations of the liver function;

metabolic acidosis;

- Pregnancy;

- lactation period;

- children's and adolescents under 18 years of age (effectiveness and safety not established);

- joint intravenous administration of verapamil, diltiazem or other antiarrhythmic drugs (especially anti-arrhythmic drugs of the first class).

Carefully:

FROM caution and controlled to treat patients with diabetes mellitus, hypoglycemia, hyperthyroidism, pheochromocytoma (only stabilized purpose alpha blockers), occlusive peripheral vascular disease, atrioventricular block 1 degree, chronic obstructive pulmonary disease, Prinzmetal angina, psoriasis, renal dysfunction, depression , myasthenia gravis for the treatment of alpha-blockers and alpha-agonists, while the use of preparations of digitalis, diuretics and / or inhibitor E monoamine oxidase (MAO); elderly people, with extensive surgical interventions and general anesthesia.

Pregnancy and lactation:

The use of the drug is contraindicated in pregnancy (see section "Contraindications").

If Carvedilol-Teva is needed during lactation, breast-feeding should be discarded.

Dosing and Administration:

For oral administration. The tablets are washed down with a sufficient amount of liquid.

It should be borne in mind that in elderly patients carvedilol concentration in the blood plasma is 50% higher than in young patients.

As carvedilol is excreted mainly through the digestive tract, renal dysfunction is not accompanied by its cumulation.

With cirrhosis of the liver, the bioavailability of carvedilol is 4 times, and the maximum concentration in blood plasma is 5 times higher than normal.

Arterial hypertension

Adults: the initial dose is 12.5 mg once a day for the first 2 days. Then 25 mg once a day. If necessary, increase the dose. The maximum dose is 50 mg / day once or twice a day (morning and evening). Increase in dosage should be carried out gradually with an interval of at least 2 weeks.

In elderly patients, in a number of cases, a dose of 12.5 mg can be effective.

Angina pectoris

Adults: the initial dose is 12.5 mg twice a day for the first 2 days. Then 25 mg twice (morning and evening) a day. If necessary, the dose is increased at intervals of 2 weeks to a maximum of 100 mg / day divided into 2 divided doses.

For elderly patients The maximum daily dose is 50 mg divided into 2 doses.

Chronic heart failure

The dose is selected individually. When the dose is increased, careful monitoring is carried out. It is necessary to observe the patient's condition within the first 2-3 hours after the first intake or after the first increased dose.Additional use of the drug Carvedilol-Teva requires a stable clinical state. The dose and administration of other medicines, such as digoxin, diuretics and ACE inhibitors, should be documented prior to the appointment of Carvedilol-Teva. Patients should take pills during meals (to reduce the risk of orthostatic hypotension).

The recommended starting dose is 3,125 mg twice daily for 14 days. With good drug tolerance and the need to increase dosage, the drug is administered at a dose of 6.25 mg twice a day, then to 12.5 mg and then to 25 mg twice daily. Patients are prescribed the maximum tolerated dose. The maximum recommended dose is 25 mg twice a day for patients weighing up to 85 kg and 50 mg twice a day for patients with a body weight of more than 85 kg. Patients with heart failure to prevent orthostatic hypotension are advised to take the drug while eating. At the beginning of treatment and until each dose is increased, the condition of the patients should be monitored, since a deterioration in the course of heart failure is possible. A fluid retention may develop, and in connection with vasodilator action - arterial hypotension and lethargy.If fluid is delayed, diuretics should be increased, and a temporary reduction in the dose of Carvedilol-Teva may be required. In some cases, treatment with Carvedilol-Teva should be temporarily suspended.

Side effects:

In recommended doses, the drug is well tolerated, but in some cases, side effects are possible:

From the digestive system: nausea, dry mouth, abdominal pain, diarrhea or constipation, vomiting, increased activity of "liver" transaminases.

From the central nervous system: headache, dizziness, fatigue, loss of consciousness, muscle weakness (usually at the beginning of treatment), sleep disturbance, depression, paresthesia.

On the part of the organs of hematopoiesis: leukopenia, thrombocytopenia,

Allergic reactions: exanthema, hives, itching, rashes, the appearance and / or exacerbation of psoriasis, sneezing, nasal congestion, very rarely anaphylactoid reaction.

From the respiratory system: dyspnea, bronchospasm (in predisposed patients).

From the side of the cardiovascular system: bradycardia, orthostatic hypotension, angina pectoris, atrioventricular blockade,progression of circulatory failure (cold extremities), progression of heart failure, swelling of the lower extremities.

From the side of metabolism: weight gain, violation of carbohydrate metabolism.

Other: occasionally - exacerbation of the syndrome of "intermittent" lameness, Raynaud's syndrome, pain in the limbs, urination disorder, renal dysfunction, flu-like syndrome, teardrop reduction.

As with the use of other alpha-blockers, latent diabetes mellitus may develop or its symptomatology may increase.

Overdose:

Symptoms: a marked decrease in blood pressure (systolic pressure 80 mm Hg and below), bradycardia (less than 50 beats / min), respiratory function disorders (bronchospasm), chronic circulatory failure, cardiogenic shock, cardiac arrest.

Treatment: During the first hours, induce vomiting and rinse the stomach.

Overdosing requires intensive treatment. Antidote beta-adrenergic blocking action is orciprenaline or isoprenaline 0.5-1 mg intravenously and / or glucagon in a dose of 1-5 mg (maximum dose of 10 mg).

With severe bradycardia, intravenously atropine in a dose of 0.5-2 mg.

For maintenance of cardiac activity: intravenously struino (within 30 seconds) enter glucagon, followed by a long infusion at a rate of 2-5 mg / h.

If peripheral vasodilator action prevails (warm limbs, in addition to significant arterial hypotension), norepinephrine in repeated doses of 5-10 μg or 5 μg / min of infusion should be prescribed.

To stop bronchospasm appoint beta-adrenomimetics (in the form of an aerosol or intravenously) or aminophylline intravenously.

If seizures develop, slow diazepam or clonazepam is recommended.

In severe cases of intoxication, when symptoms of shock predominate, treatment with antidotes should continue until the patient's condition stabilizes, taking into account the half-life of carvedilol 6-10 hours.

In the intensive care unit, monitor and correct vital signs.

Interaction:

Carvedilol can potentiate the effect of other concurrently taken antihypertensive drugs or drugs that have an antihypertensive effect (nitrates).

With the combined use of carvedilol and diltiazem may develop violations of cardiac conduction and hemodynamic disorders.

With the simultaneous administration of carvedilol and digoxin the concentration of the latter increases and the time of atrioventricular conduction may increase.

Carvedilol may potentiate the action insulin and oral hypoglycemic agents, while the symptoms of hypoglycemia (especially tachycardia) can be masked, so patients with diabetes recommended regular monitoring of blood sugar levels.

Inhibitors of microsomal oxidation (cimetidine) strengthen, and inducers (phenobarbital, rifampicin) weaken the hypotensive effect of carvedilol.

Drugs that reduce the content of catecholamines (reserpine, monoamine oxidase inhibitors), increase the risk of developing arterial hypotension and severe bradycardia.

With simultaneous application cyclosporine the concentration of the latter increases (a correction of the daily dose of cyclosporine is recommended).

Simultaneous appointment clonidine can potentiate antihypertensive and heart rhythm-reducing effects of carvedilol.

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

Special instructions:

Therapy should be carried out for a long time and should not abruptly cease, especially in patients with coronary heart disease, since this can lead to a worsening of the course of the underlying disease. If necessary, the dose reduction should be gradual, within 1-2 weeks.

At the beginning of therapy with the drug Karvedilol-Teva or with increasing the dose of the drug in patients, especially the elderly, there may be an excessive decrease in blood pressure, mainly on rising. A dose adjustment is necessary. In patients with chronic heart failure, the choice of a dose may increase the symptoms of heart failure, the appearance of edema. In this case, do not increase the dose of Carvedilol-Tevaa, recommended the appointment of large doses of diuretics until stabilization of the patient.

It is recommended to monitor the electrocardiogram and blood pressure continuously while prescribing Carvedilol-Teva and blockers of "slow" calcium channels, phenylalkylamine derivatives (verapamil) and benzothiazepine (diltiazem), and also with antiarrhythmic drugs of the first class.

It is recommended to monitor kidney function in patients with chronic renal failure, arterial hypotension and chronic heart failure.

In the case of a surgical procedure using general anesthesia, an anesthesiologist should be warned about prior carvedilol therapy.

Carvedilol-Teva does not affect the concentration of glucose in the blood and does not cause changes in the glucose tolerance test in patients with non-insulin-dependent diabetes mellitus.

During treatment avoid the use of ethanol.

Patients with pheochromocytoma prior to initiation of therapy should be assigned alpha-blockers.

Patients wearing contact lenses should note that the drug can cause a decrease in tearing.

In case of a reduction in the heart rate (heart rate) to 55 beats / min, the drug should be discarded.

In individuals with allergies or under the course of desensitization, carvedilol can increase allergensensitivity.

Effect on the ability to drive transp. cf. and fur:It is not recommended to drive at the beginning of therapy and with an increase in the dose of Carvedilol-Teva.It is necessary to refrain from other activities associated with the need for high concentration of attention and rapid psychomotor reactions.

Form release / dosage:

Tablets of 3,125, 6,25, 12,5 and 25 mg.

Packaging:

Tablets of 3,125, 6,25, 12,5 mg: 14 or 15 tablets in a blister of PVC / PVDC / aluminum foil. 2 blisters together with instructions for use in a cardboard box.

Tablets of 25 mg: 30 tablets per blister of PBX / PVDC / aluminum foil. 1 blister together with instructions for use in a cardboard box.

Storage conditions:

At a temperature of no higher than 25 ° C, in a place protected from light.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the date shown on the package.

Terms of leave from pharmacies:On prescription

Registration number:LS-001085

Date of registration:17.08.2010

The owner of the registration certificate:Pliva of Hrvatska dooPliva of Hrvatska doo Croatia

Manufacturer: & nbsp

TEVA Operations Poland, Sp. z o.o. Poland

Representation: & nbspPliva of Hvartska dooPliva of Hvartska doo

Information update date: & nbsp01.06.2012

Illustrated instructions

Instructions

Carvedilol-Teva (Carvedilol-Teva)