Dilatrend

General characteristics. Structure:

Active agent: карведилол 6.25 mg, 12.5 mg or 25 mg

Excipients: lactoses monohydrate, sucrose, K25 povidone, кросповидон, silicon dioxide colloid anhydrous, magnesium stearate, dye ferrous oxide yellow (E172) (tablet of 6.25 mg and 12.5 mg), dye ferrous oxide red (E172) (tablet of 12.5 mg).

Pharmacological properties:

Pharmacodynamics. Karvedilol – a blocker of a1-, b1, - and b2-adrenoceptors, renders organoprotektivny effect, is the antioxidant eliminating free oxygen radicals, possesses anti-proliferative action concerning smooth muscle cells of walls of vessels. Karvedilol represents racemic mix R (+) and S (-) of stereoisomers, each of which has identical a-adrenoceptor blocking and antioxidant properties. Beta and adrenoceptor blocking action of a karvedilol has non-selective character and is caused by left-handed S (-) stereoisomer.
Karvedilol has no internal sympathomimetic activity and, like propranolol, has membrane stabilizing properties. Blocking beta adrenoceptors, it reduces activity system renin-angiotensin-aldosteronovoy, reducing release of a renin therefore the liquid delay (characteristic of the selection alpha adrenoblockers) arises seldom.
Selectively blocking a1-adrenoceptors, карведилол reduces the general peripheric vascular resistance.
Karvedilol does not exert adverse impact on a lipidic profile, keeping a normal ratio of lipoproteins of the high and low density (LPVP/LPNP).

Efficiency
Arterial hypertension
At patients with arterial hypertension карведилол reduces the arterial pressure (AP) due to the combined blockade of b-and a1-adrenoceptors. Decrease in the ABP is not followed by simultaneous increase in the general peripheric vascular resistance which is observed at reception of non-selective beta adrenoblockers. The Heart Rate (HR) decreases a little. The renal blood stream and function of kidneys at patients with arterial hypertension remain. It is shown what карведилол does not change a stroke output of blood and reduces the general peripheric vascular resistance; does not break blood supply of bodies and a peripheral blood stream, including in skeletal muscles, forearms, the lower extremities, integuments, a brain and a carotid artery. The cold snap of extremities and increased fatigue during an exercise stress are noted seldom. The hypotensive effect of a karvedilol at arterial hypertension remains for a long time.

Coronary heart disease
At patients with coronary heart disease карведилол has antiischemic and anti-anginal effect (increase in the general duration of an exercise stress, time up to development of a depression of a segment of ST of 1 mm in depth and time up to emergence of an attack of stenocardia), remaining at long therapy. Karvedilol authentically reduces the need of a myocardium for oxygen and activity of sympathoadrenal system. Also reduces preloading (jamming pressure in a pulmonary artery and pulmonary capillary pressure) and an afterload (the general peripheric vascular resistance).

Chronic heart failure
Karvedilol reduces rate of mortality and reduces the frequency of hospitalization, reduces symptomatology and improves function of a left ventricle at patients with chronic heart failure of ischemic and not ischemic genesis. Effects of a karvedilol are dozozavisimy.

Pharmacokinetics. Absorption. After intake карведилол it is quickly soaked up. Karvedilol is substrate of the protein carrier which is carrying out a pump role in a gleam of intestines, a glycoprotein R. Glikoprotein P plays a major role in bioavailability of certain medicines. The maximum concentration in a blood plasma (Cmax) is reached approximately in 1 hour. Absolute bioavailability of a karvedilol makes about 25%.

Distribution. Karvedilol has high lipophilicity. About 98-99% of a karvedilol contact proteins of a blood plasma. Its volume of distribution makes about 2 l/kg.

Metabolism. Karvedilol is exposed to biotransformation in a liver by oxidation and conjugation with formation of a number of metabolites. 60-75% of the absorbed drug are metabolized at "the first passing" through a liver. Existence of enterohepatic circulation of initial substance is shown.

Metabolism of a karvedilol by oxidation is the stereoselection. R stereoisomer is metabolized generally by means of CYP2D6 and CYP1A2, and S stereoisomer – generally by means of CYP2D9 and to a lesser extent by means of CYP2D6. CYP3A4, CYP2E1 and CYP2C19 belong to other isoenzymes of P450 participating in metabolism of a karvedilol. The maximum concentration R stereoisomers in plasma exceeds that for S stereoisomers approximately twice.

R stereoisomer is metabolized mainly by a hydroxylation. At slow metabolizator of CYP2D6 increase in plasma concentration of a karvedilol, first of all, R stereoisomers is possible that is expressed in increase in alpha and adrenoceptor blocking activity of a karvedilol.

As a result of demethylation and a hydroxylation of a phenolic ring 3 metabolites (their concentration 10 times lower, than concentration of initial substance) with beta and adrenoceptor blocking activity (at 4 ’-a hydroxyphenolic metabolite it is about 13 times stronger, than at the karvedilol) are formed. 3 active metabolites have less expressed vazodilatiruyushchy properties, than карведилол. 2 of hydroxycarbacindery metabolites of a karvedilol are extremely powerful antioxidants, and their activity in this respect at 30-80 times exceeds that at a karvedilol.

Removal. The elimination half-life of a karvedilol makes about 6 hours, plasma clearance - about 500-700 ml/min. Removal happens mainly through intestines, the main way of removal – to bile. A small part of a dose is removed by kidneys in the form of various metabolites.

Pharmacokinetics at special groups of patients.

Patients with a renal failure. At long therapy karvediloly intensity of a renal blood-groove remains, the glomerular filtration rate does not change.

At patients with arterial hypertension and a renal failure the area under a curve "concentration time" (AUC), an elimination half-life and the maximum plasma concentration do not change. Renal removal of not changed drug at patients with a renal failure decreases, however changes of pharmacokinetic parameters at the same time are expressed slightly.

Karvedilol is an effective remedy for treatment of patients with renovascular arterial hypertension, including at patients with a chronic renal failure, and also at the patients who are on a hemodialysis or transferred renal transplantation. Karvedilol causes gradual decrease in the ABP both in day of carrying out dialysis, and in days without dialysis, and its hypotensive effect is comparable to that at patients with normal function of kidneys. During dialysis карведилол it is not removed as does not pass through a dialysis membrane probably thanks to what strongly contacts proteins of a blood plasma.

On the basis of the results received in comparative researches at the patients who are on a hemodialysis the conclusion is drawn on what карведилол is more effective with the best portability in comparison with blockers of "slow" calcium channels.

Patients with an abnormal liver function. At patients with cirrhosis system bioavailability of drug increases by 80% owing to reduction of expressiveness of metabolism at "the first passing" through a liver. Therefore, карведилол it is contraindicated to patients with clinically manifest abnormal liver function (see the section "Contraindications").

Patients with heart failure. In a research at 24 patients having heart failure, the clearance of R and S stereoisomers of a karvedilol was much lower in comparison with earlier observed clearance at healthy volunteers. These results demonstrate that the pharmacokinetics of R and S stereoisomers of a karvedilol at heart failure considerably changes.

Patients of advanced and senile age. The age does not exert statistically significant impact on pharmacokinetics of a karvedilol at patients with arterial hypertension. According to data of clinical trials, portability of a karvedilol at patients with arterial hypertension or coronary heart disease of advanced and senile age does not differ from that at patients of younger age.

Children. Data on drug pharmacokinetics at patients up to 18 years are limited now.

Patients with a diabetes mellitus. At patients with a diabetes mellitus 2 types and arterial hypertension карведилол do not influence concentration of glucose in blood on an empty stomach and after food, the level of glikozilirovanny hemoglobin (HbA1) or a dose of hypoglycemic means for intake. In some clinical trials it was shown that 2 types карведилол do not cause decrease in tolerance to glucose in patients with a diabetes mellitus. At the patients with arterial hypertension who had insulin resistance (a syndrome of X), but without the accompanying diabetes mellitus, карведилол improves sensitivity to insulin. Similar results were received at patients with arterial hypertension and a diabetes mellitus 2 types.

Indications to use:

Arterial hypertension
Essential hypertensia (in monotherapy or in a combination with other anti-hypertensive means, for example, blockers of "slow" calcium channels or diuretics).

Coronary heart disease (including at patients with unstable stenocardia and bezbolevy ischemia of a myocardium).

Chronic heart failure
Treatment of stable and symptomatic slight, moderate and heavy chronic heart failure (the II-IV F.K. according to the New York association of cardiologists, NYHA) ischemic or not ischemic genesis in a combination with inhibitors of an angiotensin-converting enzyme (APF) and diuretics, with or without cardiac glycosides (standard therapy), in the absence of contraindications.

Route of administration and doses:

Inside, washing down with enough liquid.
Essential hypertensia
The recommended initial dose makes 12.5 mg of 1 times a day in the first 2 days of performing therapy, then on 25 mg of 1 times a day. In need of further it is possible to increase a dose bucketed not less than 2 weeks, bringing to the maximum recommended dose 50 mg of 1 times a day (or divided into 2 receptions).

Coronary heart disease
The recommended initial dose makes 12.5 mg 2 times a day in the first 2 days, then on 25 mg 2 times a day. If necessary afterwards it is possible to increase a dose bucketed not less than 2 weeks, bringing to the highest daily dose equal 100 mg divided into 2 receptions.

Chronic heart failure
The dose is selected individually, careful observation of the doctor is necessary. At the patients receiving cardiac glycosides, diuretics and APF inhibitors it is necessary to correct their doses prior to treatment by the drug Dilatrend®.
The recommended initial dose makes 3.125 mg (1/2 tablets on 6:25 mg) 2 times a day within 2 weeks. At good tolerance the dose is increased bucketed 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 the maximum dose which is well transferred by the patient. The recommended maximum dose – 25 mg 2 times a day for all patients with heavy chronic heart failure and for patients with easy and moderate degree of chronic heart failure with the body weight of the patient less than 85 kg. At patients with slight and moderate chronic heart failure and with a body weight more than 85 kg – the recommended maximum dose makes 50 mg 2 times a day.

Before each increase in a dose the doctor has to examine the patient for identification of possible increase of symptoms of chronic heart failure or a vazodilatation. At tranzitorny increase of symptoms of chronic heart failure or a delay of liquid in an organism it is necessary to increase a dose of diuretics though sometimes it is necessary to reduce a dose of the drug Dilatrend® or temporarily to cancel it.

Symptoms of a vazodilatation can be eliminated with reduction of a dose of diuretics. If symptoms remain, it is possible to lower an APF inhibitor dose (if the patient accepts it), and then, if necessary - a drug Dilatrend® dose. In such situation the dose of the drug Dilatrend® should not be increased, so far symptoms of the amplifying chronic heart failure or arterial hypotension will not improve.

If treatment with the drug Dilatrend® is interrupted more than for 1 week, then its appointment is resumed in a smaller dose, and then increased according to the stated above recommendations. If treatment with the drug Dilatrend® is interrupted more than for 2 weeks, then its appointment it is necessary to renew in a dose 3.125 mg (1/2 tablets on 6:25 mg) 2 times a day, then select a dose according to the stated above recommendations.

Dosing at special groups of patients
Renal failure

The existing data on pharmacokinetics at patients with various degree of a renal failure (including a renal failure) allow to believe what is not required to patients with a moderate and heavy renal failure of dose adjustment of the drug Dilatrend®.

Abnormal liver function
Дилатренд® it is contraindicated to patients with clinical manifestations of an abnormal liver function (see the section "Contraindications").

Patients of advanced age
Data which would dictate need of dose adjustment, no.

Features of use:

Chronic heart failure

At patients with chronic heart failure during selection of a dose of the drug Dilatrend® increase of symptoms of chronic heart failure or a delay of liquid can be noted. At emergence of such symptoms it is necessary to increase a dose of diuretics and not to raise a drug Dilatrend® dose to stabilization of indicators of a hemodynamics. Sometimes happens it is necessary to reduce a dose of the drug Dilatrend® or, in rare instances, temporarily to cancel drug. Similar episodes do not interfere with further correct selection of a dose of the drug Dilatrend®.

Дилатренд® with care use in a combination with cardiac glycosides (perhaps excessive delay of AV of conductivity).
Function of kidneys at chronic heart failure
At purpose of the drug Dilatrend® the patient with chronic heart failure and low arterial pressure (systolic the ABP less than 100 mm of mercury.), coronary heart disease and diffusion changes of vessels and/or a renal failure noted reversible deterioration in function of kidneys. The dose of drug is selected depending on a functional condition of kidneys.

HOBL
The patient with HOBL (including a bronkhospastichesky syndrome) which is not receiving peroral or inhalation antiasthmatic means, Dilatrend® appoint only if possible advantages of its use exceed potential risk. With initial predisposition to a bronkhospastichesky syndrome at administration of drug of Dilatrend® as a result of increase in resistance of respiratory tracts an asthma can develop. At the beginning of reception and at increase in a dose of the drug Dilatrend® of these patients it is necessary to observe carefully, reducing a drug dose at emergence of initial signs of a bronchospasm.

Diabetes mellitus
With care drug appoint a sick diabetes mellitus as it can mask or weaken hypoglycemia symptoms (especially tachycardia). At patients with chronic heart failure and a diabetes mellitus use of the drug Dilatrend® can be followed by disturbances of glycemic control.

Diseases of peripheral vessels
Care is necessary at purpose of the drug Dilatrend® for patients with diseases of peripheral vessels (including with Reynaud's syndrome) as beta adrenoblockers can strengthen symptoms of arterial insufficiency.

Thyrotoxicosis
As well as expressiveness of symptoms of a thyrotoxicosis can reduce other beta adrenoblockers, Dilatrend®.

General anesthesia and extensive surgical interventions
Care is required from patients to whom surgical intervention under the general anesthesia, because of a possibility of summation of negative effects of the drug Dilatrend® and means for the general anesthesia is carried out.

Bradycardia
Дилатренд® can cause bradycardia, at ChSS urezheniya less than 55 уд. / a min. dose of the drug Dilatrend® should be lowered.

Hypersensitivity
It is necessary to be careful at purpose of the drug Dilatrend® to patients with anamnestic instructions on heavy hypersensitivity reactions or taking desensitization course as beta adrenoblockers can increase sensitivity to allergens and severity of anaphylactic reactions.

Psoriasis
Patients with anamnestic instructions at use of beta adrenoblockers, Dilatrend® can appoint to emergence or an exacerbation of psoriasis only after the careful analysis of possible advantage and risk.

Concomitant use of blockers of "slow" calcium channels (BMKK)

At the patients who are at the same time accepting BMKK like verapamil or diltiazem and also other antiarrhytmic means, it is regularly necessary to monitorirovat an ECG and the ABP.

Pheochromocytoma
Patients with a pheochromocytoma prior to use of any beta adrenoblocker need to appoint alpha adrenoblocker. Though Dilatrend® has both beta, and alpha and adrenoceptor blocking properties, there is no experience of its use for such patients therefore with care it is necessary to appoint him the patient with suspicion to a pheochromocytoma.

Printsmetal's stenocardia
Non-selective beta adrenoblockers can provoke emergence of pains in patients with Printsmetal's stenocardia. These patients do not have experience of purpose of the drug Dilatrend®. Though its alpha and adrenoceptor blocking properties can prevent similar symptomatology, it is necessary to appoint карведилол in such cases with care.

Contact lenses
The patients using contact lenses have to remember a possibility of reduction of amount of the lacrimal liquid.

Syndrome of "cancellation"
Treatment by the drug Dilatrend® is carried out is long. It should not be stopped sharply, it is necessary to reduce gradually a drug dose with week intervals. It is especially important at patients with coronary heart disease.

In case of need carrying out surgical intervention with use of the general anesthesia it is necessary to warn the anesthesiologist about the previous therapy by the drug Dilatrend®.

During treatment alcohol intake is excluded.

Influence on ability to driving of vehicles and work with cars and mechanisms
Considering potentially possible side effects of the drug Dilatrend®, patients whose work demands bystry psychomotor reaction, especially in an initiation of treatment, and also at a concomitant use of alcohol should appoint it with care.

Side effects:

The undesirable reactions meeting with frequency? 10%, are regarded as it is very frequent.
The undesirable reactions meeting with frequency from? 1% to <10%, are regarded as it is frequent.
The undesirable reactions meeting with frequency from? 0.1% to <1%, are regarded as infrequently.
The undesirable reactions meeting with frequency from? 0.01% to <0.1%, are regarded as it is rare.
The undesirable reactions meeting with frequency <0.01%, including separate messages, are regarded as it is very rare.

Frequency of undesirable reactions, except for dizziness, a vision disorder and bradycardia, does not depend on a drug dose.

Undesirable reactions at patients with chronic heart failure

Central nervous system: very often - dizziness, a headache (usually easy and arising more often in an initiation of treatment); adynamy (including, increased fatigue), depression.

Cardiovascular system: often - bradycardia, postural hypotension, the expressed decrease in the ABP, hypostases (including the generalized, peripheral, depending on situation bodies, crotch hypostases, hypostases of the lower extremities, a hypervolemia, a liquid delay); infrequently - syncopal states (including presinkopalny), an atrioventricular block and heart failure during increase in a dose.

Digestive tract: often - nausea, diarrhea, vomiting.

System of a hemopoiesis: seldom - thrombocytopenia; very seldom - a leukopenia.

Disbolism: often - increase in body weight, a hypercholesterolemia; patients with already available diabetes mellitus have a hyperglycemia or a hypoglycemia, disturbances of glycemic control (see the section "Special Instructions").

Others: often - vision disorders; seldom - a renal failure and a renal failure at patients with a diffusion vasculitis and/or a renal failure (see the section "Special Instructions").

Undesirable reactions at patients with arterial hypertension and coronary heart disease

The nature of side effects from cardiovascular system at treatment of arterial hypertension and long therapy of coronary heart disease is similar to that at chronic heart failure, however their frequency is slightly less.

Central nervous system: often - the dizziness, a headache and the general weakness usually slight and arising, in particular, in an initiation of treatment; infrequently - lability of mood, a sleep disorder, paresthesia.

Cardiovascular system: often - bradycardia, postural hypotension, syncopal states (infrequently), especially at the beginning of therapy; infrequently - disturbances of peripheric circulation (a cold snap of extremities, an aggravation of a syndrome of the "alternating" lameness and Reynaud's syndrome), an atrioventricular block, stenocardia (thorax pain), development or aggravation of symptoms of heart failure and peripheral hypostases.

Respiratory organs: often - a bronchospasm and an asthma at predisposed patients; seldom - a nose congestion.

Digestive tract: often - dispepsichesky frustration (including nausea, abdominal pains, diarrhea); infrequently - a lock, vomiting.

Integuments: infrequently - skin reactions (skin rash, dermatitis, a small tortoiseshell and a skin itch).

Laboratory indicators: very seldom - increase in activity of "hepatic" transaminases - alaninaminotranspherases (ALT), aspartate aminotransferases (nuclear heating plant) and gamma глутамилтрансферазы, thrombocytopenia and a leukopenia.

Others: often - extremity pains, reduction of a slezootdeleniye and irritation of eyes; infrequently - decrease in a potentiality, a vision disorder; seldom - dryness in a mouth and disturbances of an urination; very seldom - an exacerbation of psoriasis, sneezing, a grippopodobny syndrome.

Separate cases of allergic reactions.

Post-marketing observations

Exceptional cases of an incontience of urine at women, reversible after drug withdrawal of Dilatrend® are registered.
Existence at drug of beta and adrenoceptor blocking properties does not exclude a possibility of manifestation latentno of the proceeding diabetes mellitus, a decompensation of already available diabetes mellitus or oppression of kontrinsulyarny system.

Interaction with other medicines:

Pharmacokinetic interaction

As карведилол is both substrate, and inhibitor of a glycoprotein P, at its concomitant use with the drugs transported by a glycoprotein P, bioavailability of the last can increase. Besides, bioavailability of a karvedilol can change under the influence of inductors or inhibitors of a glycoprotein of River.
Inhibitors and the inductors CYP2D6 and CYP2C9 can stereoselektivno change system and/or presistemny metabolism of a karvedilol, leading to increase or decrease in concentration of R and S stereoisomers of a karvedilol in a blood plasma. Some examples of the similar interactions observed at patients or at healthy volunteers are listed below, however this list is not full.

Digoxin
At a concomitant use of a karvedilol and digoxin of concentration of digoxin increase approximately by 15%. At the beginning of therapy karvediloly, at selection of its dose or drug withdrawal, regular control of concentration of digoxin in a blood plasma is recommended.

Cyclosporine
In two researches at purpose of a karvedilol to the patients who transferred renal transplantation and hearts and receiving cyclosporine orally, increase in concentration of cyclosporine was noted. It turned out that owing to inhibition of activity of a glycoprotein P in intestines, карведилол increases absorption of cyclosporine at its oral administration. To maintain concentration of cyclosporine in the therapeutic range, reduction of a dose of cyclosporine on average for 10-20% was required. Due to the expressed individual fluctuations of concentration of cyclosporine careful monitoring of its concentration after the beginning of therapy karvediloly and, if necessary, the corresponding correction of a daily dose of cyclosporine is recommended. In case of intravenous administration of cyclosporine, any interaction with karvediloly it is not expected.

Rifampicin
In a research with participation of 12 healthy volunteers rifampicin reduced plasma concentration of a karvedilol, most likely, by induction of a glycoprotein P, leading to decrease in absorption of a karvedilol in intestines and to decrease in its anti-hypertensive action.

Amiodaronum
At patients with heart failure Amiodaronum reduced clearance S stereoisomers of a karvedilol, suppressing CYP2C9. Average concentration R stereoisomers of a karvedilol did not change. Therefore, in connection with increase in concentration S stereoisomers of a karvedilol, the risk of increase in beta and adrenoceptor blocking action is possible.

Fluoxetine
In a randomized research with cross design at 10 patients with heart failure the concomitant use of fluoxetine (CYP2D6 inhibitor) led to the stereoselection suppression of metabolism of a karvedilol - to increase in an average value of AUC for R (+) for 77%. However, the difference in side effects, size ABP or ChSS between two groups was not noted.

Pharmakodinamichesky interaction
Insulin or hypoglycemic means for intake
Drugs with beta and adrenoceptor blocking properties can strengthen hypoglycemic effect of insulin or hypoglycemic means for intake. Hypoglycemia symptoms, especially tachycardia, can mask or weaken. Regular control of content of glucose of blood is recommended to the patients receiving insulin or hypoglycemic means for intake.

The drugs reducing the maintenance of catecholamines
The patients accepting at the same time means with beta and adrenoceptor blocking properties and the means reducing the maintenance of catecholamines (for example, Reserpinum and inhibitors of a monoaminooxidase), have to be under careful observation in connection with risk of development of arterial hypotension and/or the expressed bradycardia.

Digoxin
The combination therapy of means with beta and adrenoceptor blocking properties and digoxin can lead to additional delay of atrioventricular conductivity.

Verapamil, diltiazem, Amiodaronum or other antiarrhytmic means
The concomitant use with karvediloly can increase risk of disturbance of atrioventricular conductivity.

Clonidine
Co-administration of a clonidine with drugs with beta and adrenoceptor blocking properties can exponentiate anti-hypertensive and bradikarditichesky effect. If is planned to stop a combination therapy drug with beta and adrenoceptor blocking properties and a clonidine, the first should cancel beta adrenoblocker, and in several days it is possible to cancel a clonidine, gradually reducing its dose.

Blockers of "slow" calcium channels (BMKK)
At co-administration of a karvedilol and diltiazem separate cases of disturbances of conductivity were noted (seldom – with disturbances of indicators of a hemodynamics). As well as in a case with other drugs with beta and adrenoceptor blocking properties, purpose of a karvedilol together with BMKK like verapamil or diltiazem is recommended to be carried out under control of an ECG and the ABP.

Anti-hypertensive means
As well as with beta and adrenoceptor blocking activity, карведилол action of other at the same time accepted anti-hypertensive means (for example, alfa1-adrenoblockers) or drugs which cause arterial hypotension as side effect can strengthen other drugs.

Means for the general anesthesia
It is necessary to make careful observation of the main vital signs of an organism when carrying out the general anesthesia in connection with a possibility of synergistic negative inotropic action of a karvedilol and means for the general anesthesia.

Non-steroidal anti-inflammatory drugs (NPVS)
Joint reception of NPVS and beta adrenoblockers can lead to increase in the ABP and decrease in control of the ABP.

Bronchodilators (agonists of beta adrenoceptors)
As not cardioselective beta adrenoblockers interfere with bronkholitiruyushchy effect of the bronchodilators which are stimulators of beta adrenoceptors careful control of the patients receiving these drugs is necessary.

Contraindications:

Hypersensitivity to a karvedilol or any component of drug; the acute and chronic heart failure in a decompensation stage demanding intravenous administration of inotropic means; clinically significant abnormal liver function; age up to 18 years (efficiency and safety of the drug Dilatrend® are not established); an atrioventricular block of II and III degrees (except for patients with an artificial pacemaker); the expressed bradycardia (ChSS less than 50 beats/min); a sick sinus syndrome (including a sinoauricular block); the expressed arterial hypotension (systolic the ABP less than 85 mm of mercury.); cardiogenic shock; anamnestic instructions on a bronchospasm and bronchial asthma; lactose intolerance, deficit of lactase, glyukozo-galaktozny malabsorption.

With care use drug at the chronic obstructive pulmonary disease (COPD), a depression, a myasthenia, a hypoglycemia, an atrioventricular block of the I degree, a thyrotoxicosis, at extensive surgical interventions and carrying out the general anesthesia, Printsmetal's stenocardia, a diabetes mellitus, occlusal diseases of peripheral vessels, at suspicion on a pheochromocytoma, a renal failure, psoriasis.

Pregnancy and period of feeding by a breast
Beta adrenoblockers reduce a placental blood stream that can lead to pre-natal death of a fruit and premature births. Besides, the fruit and the newborn can have undesirable reactions (in particular, a hypoglycemia and bradycardia, complications from heart and lungs). Researches on animals did not reveal at a karvedilol of teratogenic effect.
There is no sufficient experience of use of the drug Dilatrend® for pregnant women. Karvedilol is contraindicated at pregnancy, except for cases when possible advantages of its use for women exceed potential risk for a fruit.
At animals карведилол and its metabolites get into breast milk. Data on penetration of a karvedilol into breast milk at the person are absent therefore if administration of drug is necessary in the period of a lactation, breastfeeding needs to be stopped.

Overdose:

Symptoms: the expressed decrease in the ABP, bradycardia, heart failure, cardiogenic shock, a cardiac standstill; breath disturbances, a bronchospasm, vomiting, confusion of consciousness and generalized spasms are possible.

Treatment: in addition to actions of the general character it is necessary to carry out monitoring and correction of the vital indicators, if necessary - in intensive care unit. It is possible to use the following events:

to lay the patient on a back (with the raised legs);
at the expressed bradycardia - atropine on 0.5-2 mg intravenously;
for maintenance of cardiovascular activity - a glucagon on 1-10 mg intravenously struyno, then on 2-5 mg an hour in the form of long infusion;
sympathomimetics (Dobutaminum, изопреналин, орципреналин or Epinephrinum (adrenaline) in various doses, depending on body weight and the response to treatment.
If in a clinical picture of overdose arterial hypotension dominates, enter Norepinephrinum (noradrenaline); it is appointed in the conditions of continuous control of indicators of blood circulation.
At bradycardia, resistant to treatment, use of an artificial pacemaker is shown.
At a bronchospasm enter beta-adrenergic agonists in the form of an aerosol (at inefficiency - intravenously) or Aminophyllinum intravenously.
At spasms intravenously slowly enter diazepam or clonazepam.

As at heavy overdose with symptomatology of shock lengthening of an elimination half-life of a karvedilol and removal of drug from depot is possible, it is necessary to continue a maintenance therapy rather long time. Duration of the supporting / disintoxication therapy depends on severity of overdose, it should be continued before stabilization of a clinical condition of the patient.

Storage conditions:

List B.
At a temperature not above 25 °C in the dry, protected from light place.
To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

Tablets of 6.25 mg, 12.5 mg, 25 mg
On 10 tablets in the blister from a film of three-layered (OPA/Al/PVC) and aluminum foil.
3 blisters together with the application instruction place in a cardboard pack.