Karvedilol

General characteristics. Structure:

Active ingredient: 12,5 mg or 25 mg of a karvedilol.

Excipients: cellulose microcrystallic, lactose (sugar milk), кросповидон (пласдон XL 10), the sodium stearylfumarating.

Anti-hypertensive cardiodrug.

Pharmacological properties:

Pharmacodynamics. Karvedilol renders combined non-selective beta1-, beta2-and alfa1 the blocking action. Drug has no own sympathomimetic activity, has membrane stabilizing properties. Thanks to blockade of beta adrenoceptors of heart the arterial pressure, cordial emission can decrease and urezhatsya heart rate. Karvedilol suppresses renin-angiotensin-aldosteronovuyu system by means of blockade of beta adrenoceptors of kidneys, causing decrease of the activity of a renin of plasma. Blocking alpha adrenoceptors, drug can cause expansion of peripheral vessels, thereby reducing system vascular resistance. The combination of blockade of adrenoceptors and vazodilatation makes the following impacts: at patients with arterial hypertension a lowering of arterial pressure; at patients with coronary heart disease antiischemic and anti-anginal action; at patients with dysfunction of a left ventricle and a circulatory unefficiency favorably influences hemodynamic indicators, raises fraction of emission of a left ventricle and reduces its sizes.

Pharmacokinetics. Karvedilol is quickly soaked up from digestive tract. Has high lipophilicity. The maximum concentration in blood is reached in 1-1,5 hours. The elimination half-life makes 6-10 hours. Contacts proteins of a blood plasma for 95-99%. Bioavailability of drug of 24-28%. Meal does not influence bioavailability. It is metabolized in a liver with formation of a number of active metabolites - 60-75% of the adsorbed drug are metabolized at first "passing" through a liver. Metabolites possess the expressed antioxidant and adrenoceptor blocking action. Removal of drug from an organism happens through digestive tract. At a renal failure pharmacokinetic parameters of a karvedilol significantly do not change.

At patients with an abnormal liver function system bioavailability of a karvedilol increases due to decrease in metabolism at first "passing" through a liver. At serious violations of function of a liver карведилол it is contraindicated.

Karvedilol gets through a placental barrier, is allocated with breast milk.

Indications to use:

• Arterial hypertension (in monotherapy and a combination with diuretics)
• Chronic heart failure (as a part of a combination therapy)
• Coronary heart disease: stable stenocardia.

Route of administration and doses:

Inside, irrespective of meal. For providing the below-mentioned mode of dosing drug use Karvedilol in a dosage form of a tablet of 6,25 mg is possible.

Arterial hypertension. The initial dose makes 6,25 - 12,5 mg of 1 times a day in the first two days of treatment. Then on 25 mg of 1 times a day. At insufficiency of anti-hypertensive effect in 2 weeks of therapy the dose can be increased twice. The maximum recommended daily dose of drug makes 50 mg of 1 times a day (perhaps divided into 2 receptions).

Coronary heart disease. The initial dose makes 12,5 mg 2 times a day in the first two days of treatment. Then on 25 mg 2 times a day. At insufficiency of anti-anginal effect in 2 weeks of therapy the dose can be increased twice. The maximum recommended daily dose of drug makes 100 mg the day divided into 2 receptions.

Chronic heart failure. The dose is selected individually, under careful observation of the doctor. The recommended initial dose makes 3,125 mg 2 times a day within 2 weeks. At good tolerance the dose is increased with an interval  by not less than 2 weeks to 6,25 mg 2 times a day, then to 12,5 mg 2 times a day, then - to 25 mg 2 times a day. The dose should be increased to maximum which is well transferred by the patient. At patients with body weight less than 85 kg the target dose makes 50 mg a day; patients with body weight have more than 85 kg a target dose of 75 - 100 mg a day.

Features of use:

Therapy has to be carried out is long and should not stop sharply, especially at patients with coronary heart disease as it can lead to deterioration in a current of a basic disease. In case of need the dose decline of drug has to be gradual, within 1-2 weeks.

At the beginning of therapy karvediloly or at increase in a dose of drug at patients, especially advanced age, the excess lowering of arterial pressure can be noted, it is preferential at a rising. Drug dose adjustment is necessary. At patients with chronic heart failure at selection of a dose increase of symptoms of heart failure, emergence of hypostases is possible. At the same time it is not necessary to increase a dose of a karvedilol, purpose of high doses of diuretics up to stabilization of a condition of the patient is recommended.

Continuous monitoring of the electrocardiogram and arterial pressure at co-administration of a karvedilol and blockers of "slow" calcium channels, derivatives of a fenilalkilamin (verapamil) and benzodiazepine (diltiazem), and also with antiarrhytmic means of the I class is recommended.

It is recommended to control function of kidneys at patients with a chronic renal failure, arterial hypotonia and chronic heart failure.

In case of carrying out surgical intervention with use of the general anesthesia it is necessary to warn the anesthesiologist about the previous therapy karvediloly.

Karvedilol does not influence concentration of glucose in blood and does not cause changes of indicators of glucose loading in patients with a non-insulin-dependent diabetes mellitus.

During treatment to avoid the ethanol uses.

Patients with a pheochromocytoma prior to therapy need to appoint alpha adrenoblockers.
The patients carrying contact lenses should consider that drug can cause reduction of a slezootdeleniye.

It is not recommended to drive the car at the beginning of therapy and at increase in a dose of a karvedilol. It is necessary to refrain from other types of activity connected with need of high concentration of attention and bystry psychomotor reactions.

Use at pregnancy and in the period of a lactation. Controlled researches of use of a karvedilol for pregnant women were not conducted therefore purpose of drug of this category of patients is possible only in cases when the advantage for mother exceeds potential risk for a fruit. Breastfeeding is not recommended during treatment karvediloly.

Side effects:

From the central nervous system: dizziness, a headache (usually not strong and in an initiation of treatment), a loss of consciousness, a myasthenia (is more often in an initiation of treatment), increased fatigue, a depression, a sleep disorder, paresthesias.

From cardiovascular system: bradycardia, orthostatic hypotension an atrioventricular block of the II-III Art., disturbance of peripheric circulation, progressing of heart failure (during increase in doses), hypostases of the lower extremities, stenocardia, the expressed decrease in the ABP is rare.

From a digestive tract: dryness in a mouth, nausea, diarrhea or a lock, vomiting, an abdominal pain, appetite loss, increase in activity of "hepatic" transaminases.

From system of a hemopoiesis: seldom thrombocytopenia, leukopenia.

From a metabolism: increase in body weight, disturbance of carbohydrate metabolism.

Allergic reactions: skin allergic reactions, exacerbation of psoriasis, nose congestion.

From respiratory system: an asthma and a bronchospasm (at predisposed patients).

Others: the vision disorder, reduction of a slezootdeleniye, a grippopodobny syndrome, sneezing, a mialgiya, an arthralgia, extremity pains, the "alternating" lameness, is rare disturbance of an urination, a renal failure.

Interaction with other medicines:

Karvedilol can exponentiate action of other at the same time accepted anti-hypertensive means or drugs which render hypotensive effect (nitrates).

At combined use of a karvedilol and diltiazem disturbances of conductivity of heart and disturbance of a hemodynamics can develop.

At a concomitant use of a karvedilol and digoxin concentration of the last increases and time of atrioventricular carrying out can increase.

Karvedilol can potentsiirovat effect of insulin and peroral hypoglycemic means, at the same time hypoglycemia symptoms (especially tachycardia) can mask therefore at patients with a diabetes mellitus regular control of level of sugar in blood is recommended.

Inhibitors of a microsomal oxidation strengthen (Cimetidinum), and inductors (phenobarbital, rifampicin) weaken hypotensive effect of a karvedilol.

The drugs reducing the maintenance of catecholamines (Reserpinum, monoaminooxidase inhibitors) increase risk of development of arterial hypotension and the expressed bradycardia.

At simultaneous use of cyclosporine concentration of the last increases (correction of a daily dose of cyclosporine is recommended).

Co-administration of a clonidine can exponentiate an anti-hypertensive and urezhayushchy cordial rhythm effects of a karvedilol.

The general anesthetics strengthen negative inotropic and hypotensive effect of a karvedilol.

Contraindications:

Hypersensitivity to a karvedilol or other components of drug, the acute and dekompensirovanny chronic heart failure demanding intravenous administration of inotropic means, a heavy liver failure, an atrioventricular block of the II-III Art., the expressed bradycardia (less than 50 beats/min), a syndrome of weakness of a sinus node, arterial hypotension (systolic arterial pressure less than 85 mm of mercury.), cardiogenic shock, bronchial asthma, a chronic obstructive pulmonary disease, age up to 18 years (efficiency and safety are not established).

With care. Bronkhospastichesky syndrome, chronic bronchitis, emphysema of lungs, Printsmetal's stenocardia, thyrotoxicosis, occlusal diseases of peripheral vessels, pheochromocytoma, psoriasis, renal failure, atrioventricular block of the I degree, extensive surgical interventions and general anesthesia, diabetes mellitus, hypoglycemia, depression, myasthenia.

Overdose:

Symptoms: the lowering of arterial pressure (which is followed by dizziness or a faint), bradycardia. Developing of short wind owing to a bronchospasm and vomiting is possible. In hard cases cardiogenic shock, breath disturbance, confusion of consciousness, conductivity disturbance are possible.

Treatment: it is necessary to carry out monitoring and correction of zhiznennovazhny indicators, if necessary - in intensive care unit. Symptomatic treatment. Reasonablly intravenous use of m-holinoblokatorov (atropine), adrenomimetik (Epinephrinum, Norepinephrinum).

Storage conditions:

List B. To store in the dry, protected from light place, at a temperature not above 25 °C. To store in the place, unavailable to children. Period of validity: 2 years. Not to use after a period of validity.

Issue conditions:

According to the recipe

Packaging:

Tablets on 12,5 mg and 25 mg. On 10 tablets in a blister strip packaging or on 10, 20 or 30 tablets in bank of polymeric. 1, 2 either 3 blister strip packagings or each can together with the application instruction in a pack from a cardboard.