Carvedilol tablets 25mg, No. 30 Ozone

Arterial hypertension (in monotherapy or in combination with other antihypertensive drugs, for example, blockers of 'slow' calcium channels or diuretics); angina pectoris (including in patients with unstable angina pectoris and painless myocardial ischemia); CHF (stable and symptomatic mild, moderate and severe CHF of ischemic and non-ischemic genesis as part of combination therapy with ACE inhibitors and diuretics, with or without cardiac glycosides).

Inside with a sufficient amount of liquid.
With arterial hypertension - an initial dose of 12.5 mg once a day for the first 2 days, then 25 mg once a day, with a possible gradual increase in the dose with an interval of at least 2 weeks. The maximum recommended daily dose of the drug is 50 mg once a day (it can be divided into two doses).
For angina pectoris - an initial dose of 12.5 mg 1 time per day for the first 2 days, then 25 mg 2 times a day (maximum up to 100 mg, divided into 2 doses).
With CHF (against the background of selected therapy with cardiac glycosides, diuretics and angiotensin-converting enzyme (ACE) inhibitors - start with 3.125 mg (1/2 tablet 6.25 mg (the tablet has a risk)) 2 times a day for 2 weeks, then (with good tolerance), this dose is increased to 6.25 mg 2 times a day, then up to 12.5 - 25 mg 2 times a day (with a patient's body weight less than 85 kg - the maximum dose is 25 mg 2 times a day, with a weight the patient's body over 85 kg - 50 mg 2 times a day).
Before each dose increase, you should consult a doctor to avoid an increase in symptoms of CHF or vasodilation.
If the symptoms of CHF or fluid retention in the body increase, the dose of diuretics should be increased, or the dose of carvedilol should be reduced or cancel it.
If treatment with Carvedilol is interrupted for more than 1 week, then its appointment is resumed at a lower dose, and then increased in accordance with the above recommendations. If the treatment is interrupted for more than 2 weeks, then its resumption begins with a dose of 3.125 mg (1/2 tablet of 6.25 mg (the tablet has a risk)) 2 times a day, followed by an increase in the dose.
In case of vasodilation, the dose of diuretics should be reduced. If symptoms persist, the dose of the ACE inhibitor (if the patient is taking it) can be reduced, and then, if necessary, the dose of carvedilol. The dose of carvedilol should not be increased until the symptoms of worsening heart failure or arterial hypotension have stabilized.

Dosing in special groups of patients:
For patients with moderate to severe renal impairment, as well as elderly patients, dose adjustment of carvedilol is not required.
For patients with clinical manifestations of liver dysfunction, carvedilol is contraindicated.

1 tablet contains:
active substance: carvedilol - 25 mg

Hypersensitivity to carvedilol and to any other component of the drug, acute and decompensated CHF requiring intravenous administration of inotropic drugs, atrioventricular (AV) block II-III stage. (without an artificial pacemaker), severe bradycardia (heart rate less than 50 beats / min), sick sinus syndrome (SSS), cardiogenic shock, severe liver failure, bronchial asthma or bronchospasm (in history), severe arterial hypotension (systolic blood pressure less than 85 mm Hg), period of breastfeeding, age up to 18 years (safety and efficacy have not been established), lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome (the drug contains lactose), pheochromocytoma without the simultaneous use of alpha-blockers.

CAREFULLY

Chronic obstructive pulmonary disease (COPD), Prinzmetal angina, 1st degree AV block, diabetes mellitus, hypoglycemia, thyrotoxicosis, occlusive peripheral vascular disease, suspected pheochromocytoma, depression, myasthenia gravis, psoriasis, major surgical interventions, general anesthesia, diabetes mellitus , pregnancy.

Trade name: Carvedilol
International non-proprietary
name: Carvedilol
Dosage form: Tablets

Composition:
1 tablet contains:
active substance: carvedilol - 25 mg,

PHARMACOTHERAPEUTIC GROUP

Alpha and beta blocker

PHARMACHOLOGIC EFFECT

Blocks alpha1-, beta1- and beta2-adrenergic receptors, has a vasodilating, antianginal and antiarrhythmic effect. The vasodilating effect is mainly associated with the blockade of alpha1-adrenergic receptors. Due to vasodilation, it reduces the total peripheral vascular resistance (OPSS). It does not have its own sympathomimetic activity (SMA), it has membrane stabilizing properties.
It is a racemic mixture of R (+) and S (-) stereoisomers, each of which has the same alpha-adrenergic blocking and antioxidant properties.
The combination of vasodilation and blockade of beta-adrenergic receptors leads to the following effects: in patients with arterial hypertension, a decrease in blood pressure (BP) is not accompanied by an increase in OPSS, peripheral blood flow does not decrease (in contrast to beta-blockers). The heart rate (HR) decreases slightly. In patients with ischemic heart disease (CHD), it has an antianginal effect. Reduces pre- and post-stress on the heart. Does not have a pronounced effect on lipid metabolism and the content of potassium (K +), sodium (Na +) and magnesium (Mg2 +) ions in blood plasma.
In patients with impaired left ventricular (LV) function and / or heart failure (HF), it has a beneficial effect on hemodynamic parameters and improves ejection fraction and LV size.
Carvedilol reduces mortality and hospitalizations, improves symptoms and improves left ventricular function in patients with chronic heart failure (CHF) of ischemic and non-ischemic genesis, the effects of carvedilol are dose-dependent.

PHARMACOKINETICS

Absorption:
After oral administration, it is rapidly and almost completely absorbed into the gastrointestinal tract (GIT). The maximum concentration (Cmax) in blood plasma is reached after about 1.5 hours. Bioavailability is 25% (for S (-) - stereoisomer - 15%, for R (+) - stereoisomer - 31%).

Distribution:
Communication with blood plasma proteins is about 95%. The volume of distribution is about 2 l / kg. Penetrates through the placental barrier, excreted in breast milk.

Metabolism:
Metabolized in the liver (has the effect of 'primary passage' through the liver). The oxidative metabolism of carvedilol is stereoselective. The R (+) stereoisomer is metabolized mainly by the isoenzymes CYP2D6 and CYP1A2, while the S (-) stereoisomer is metabolized mainly by the isoenzyme CYP2D6. Other P450 isoenzymes involved in the metabolism of carvedilol include CYP3A4, CYP2E1 and CYP1C19 isoenzymes. The maximum concentration of the R (+) stereoisomer in blood plasma is approximately 2 times higher than that for the S (-) stereoisomer.
The R (+) stereoisomer is metabolized primarily by hydroxylation. In 'slow' metabolizers of the CYP2D6 isoenzyme, an increase in the plasma concentration of carvedilol, primarily the R (+) stereoisomer, is possible, which is reflected in an increase in the alpha-adrenergic blocking activity of carvedilol.
As a result of demethylation and hydroxylation of the phenolic ring, 3 metabolites are formed (their concentration is 10 times lower than the concentration of the starting substance) with beta-adrenoceptor blocking activity (in 4'-hydroxy-
phenolic metabolite, it is about 13 times stronger than that of carvedilol itself). The 3 active metabolites are less vasodilatory than carvedilol. The 2 hydroxycarbosolic metabolites of carvedilol are extremely powerful antioxidants, and their activity in this respect is 30-80 times higher than that of carvedilol.

Withdrawal:
The half-life (T1 / 2) is 4-7 hours (significant fluctuations are possible due to the genetic polymorphism of CYP2D6 and an increase in the half-life to 10 hours in individuals with a defective enzyme isoform). Plasma clearance - 590 ml / min. It is excreted mainly with bile through the intestines, no more than 2% of the administered carvedilol is excreted in the urine.

Pharmacokinetics in special groups of patients:
In elderly patients, the concentration of carvedilol in blood plasma is approximately 50% higher than in younger patients.
In patients with impaired liver function, bioavailability can increase up to 80%.
In case of impaired renal function, the pharmacokinetic parameters of carvedilol do not change significantly.
In heart failure, the pharmacokinetics of the R (+) and S (-) stereoisomers of carvedilol changes significantly (clearance decreases).
In patients with type 2 diabetes mellitus and arterial hypertension, carvedilol does not affect the blood glucose concentration, the level of glycated hemoglobin (HbA1) or the dose of hypoglycemic agents; does not cause a decrease in glucose tolerance.

INDICATIONS FOR USE

Arterial hypertension (in monotherapy or in combination with other antihypertensive drugs, for example, blockers of 'slow' calcium channels or diuretics); angina pectoris (including in patients with unstable angina pectoris and painless myocardial ischemia); CHF (stable and symptomatic mild, moderate and severe CHF of ischemic and non-ischemic genesis as part of combination therapy with ACE inhibitors and diuretics, with or without cardiac glycosides).

CONTRAINDICATIONS

Hypersensitivity to carvedilol and to any other component of the drug, acute and decompensated CHF requiring intravenous administration of inotropic drugs, atrioventricular (AV) block II-III stage. (without an artificial pacemaker), severe bradycardia (heart rate less than 50 beats / min), sick sinus syndrome (SSS), cardiogenic shock, severe liver failure, bronchial asthma or bronchospasm (in history), severe arterial hypotension (systolic blood pressure less than 85 mm Hg), period of breastfeeding, age up to 18 years (safety and efficacy have not been established), lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome (the drug contains lactose), pheochromocytoma without the simultaneous use of alpha-blockers.

CAREFULLY

Chronic obstructive pulmonary disease (COPD), Prinzmetal angina, 1st degree AV block, diabetes mellitus, hypoglycemia, thyrotoxicosis, occlusive peripheral vascular disease, suspected pheochromocytoma, depression, myasthenia gravis, psoriasis, major surgical interventions, general anesthesia, diabetes mellitus , pregnancy.

APPLICATION DURING PREGNANCY AND DURING BREASTFEEDING

Carvedilol is contraindicated during pregnancy and breastfeeding.

Beta blockers reduce placental blood flow, which can lead to fetal death and premature birth.

The fetus and newborn may experience undesirable reactions (in particular, hypoglycemia and bradycardia, complications from the heart and lungs).

Animal studies have not shown a teratogenic effect with carvedilol.

The potential risk to humans is unknown.

In animals, carvedilol and its metabolites pass into breast milk. There are no data on the penetration of carvedilol into human breast milk. If taking CARVEDILOL is necessary during breastfeeding, then breastfeeding should be discontinued.

DOSAGE AND APPLICATION

Inside with a sufficient amount of liquid.
With arterial hypertension - an initial dose of 12.5 mg once a day for the first 2 days, then 25 mg once a day, with a possible gradual increase in the dose with an interval of at least 2 weeks. The maximum recommended daily dose of the drug is 50 mg once a day (it can be divided into two doses).
For angina pectoris - an initial dose of 12.5 mg 1 time per day for the first 2 days, then 25 mg 2 times a day (maximum up to 100 mg, divided into 2 doses).
With CHF (against the background of selected therapy with cardiac glycosides, diuretics and angiotensin-converting enzyme (ACE) inhibitors - start with 3.125 mg (1/2 tablet 6.25 mg (the tablet has a risk)) 2 times a day for 2 weeks, then (with good tolerance), this dose is increased to 6.25 mg 2 times a day, then up to 12.5 - 25 mg 2 times a day (with a patient's body weight less than 85 kg - the maximum dose is 25 mg 2 times a day, with a weight the patient's body over 85 kg - 50 mg 2 times a day).
Before each dose increase, you should consult a doctor to avoid an increase in symptoms of CHF or vasodilation.
If the symptoms of CHF or fluid retention in the body increase, the dose of diuretics should be increased, or the dose of carvedilol should be reduced or cancel it.
If treatment with Carvedilol is interrupted for more than 1 week, then its appointment is resumed at a lower dose, and then increased in accordance with the above recommendations. If the treatment is interrupted for more than 2 weeks, then its resumption begins with a dose of 3.125 mg (1/2 tablet of 6.25 mg (the tablet has a risk)) 2 times a day, followed by an increase in the dose.
In case of vasodilation, the dose of diuretics should be reduced. If symptoms persist, the dose of the ACE inhibitor (if the patient is taking it) can be reduced, and then, if necessary, the dose of carvedilol. The dose of carvedilol should not be increased until the symptoms of worsening heart failure or arterial hypotension have stabilized.

Dosing in special groups of patients:
For patients with moderate to severe renal impairment, as well as elderly patients, dose adjustment of carvedilol is not required.
For patients with clinical manifestations of liver dysfunction, carvedilol is contraindicated.

SIDE EFFECT

To describe the frequency of adverse reactions, the following gradation of the frequency of development of adverse reactions was used: very often -> 10%, often -> 1% and <10%, not often -> 0.1% and <1%, rarely -> 0.01% and <0.1%, very rarely - <0.01%, including isolated messages.
From the nervous system: very often - dizziness, headache, loss of consciousness, myasthenia gravis (more often at the beginning of treatment), often - sleep disturbances, depression, paresthesia.

From the side of the cardiovascular system (CVS):
often - bradycardia, orthostatic hypotension, angina pectoris, AV block, marked decrease in blood pressure, hypervolemia; infrequently - occlusive disorders of peripheral circulation, progression of heart failure, syncope and presyncopal states; rarely - 'intermittent' claudication.

From the digestive system:
often - nausea, diarrhea or constipation, abdominal pain, vomiting, rarely - dryness of the oral mucosa, very rarely - increased activity of 'hepatic' transaminases.

From the side of metabolism:
often - hypercholesterolemia, hyperglycemia or hypoglycemia in patients with pre-existing diabetes mellitus.

From the side of hematopoietic organs:
often - anemia, rarely - thrombocytopenia, very rarely - leukopenia.

From the respiratory system:
often - pulmonary edema, pneumonia, bronchitis, upper respiratory tract infections, rarely - nasal congestion.

From the urinary system:
often - edema, urinary tract infections, rarely - severe renal dysfunction.

Allergic reactions:
not often - allergic skin reactions (exanthema, urticaria, pruritus, rashes), very rarely - exacerbation of psoriatic eruptions, sneezing, nasal congestion, bronchospasm (in predisposed patients).

Others:
often - flu-like syndrome, pain in the limbs, decreased tearing, eye irritation; increase in body weight; not often - violation of potency; visual impairment (often in patients with chronic heart failure); rarely - urinary incontinence in women, reversible after drug withdrawal, alopecia.

OVERDOSE

Symptoms: vomiting, confusion, marked decrease in blood pressure (systolic blood pressure 80 mm Hg and below), bradycardia (less than 50 beats / min), impaired respiratory function (including bronchospasm), HF, cardiogenic shock, arrest heart, generalized convulsions.
Treatment: cardiotonics, control of CVS, functions of the respiratory system and kidneys. Hemodialysis is not effective.

INTERACTION WITH OTHER DRUGS

Pharmacokinetic interaction:
Carvedilol is both a substrate and an inhibitor of glycoprotein P, when used simultaneously with drugs transported by glycoprotein P, the bioavailability of the latter may increase. In addition, the bioavailability of carvedilol can be altered by inducers or inhibitors of glycoprotein P.
Inhibitors and inducers of CYP2D6 and CYP2C9 can stereoselectively alter the systemic and / or first-pass metabolism of carvedilol, leading to an increase or decrease in the concentrations of R (+) and S (-) stereoisomers of carvedilol in blood plasma.
Some examples of such interactions observed in patients or in healthy volunteers are listed below, but this list is not complete.

Digoxin:
With the simultaneous use of carvedilol and digoxin, digoxin concentrations increase by about 15%. At the beginning of therapy with carvedilol, when selecting its dose or discontinuing the drug, it is recommended to regularly monitor the concentration of digoxin in the blood plasma.

Cyclosporine:
Carvedilol increases the plasma concentration of cyclosporine when taken orally. To maintain the concentration of cyclosporine in the therapeutic range, a decrease in the dose of cyclosporine by an average of 10-20% is required. Due to the pronounced individual fluctuations in the concentration of cyclosporine, careful monitoring of its concentration is recommended after starting therapy with carvedilol and, if necessary, an appropriate correction of the daily dose of cyclosporine. With intravenous (IV) cyclosporine, no interaction with carvedilol is expected.

Rifampicin, phenobarbital:
Rifampicin, phenobarbital accelerate metabolism and reduce plasma concentrations of carvedilol, leading to a decrease in its antihypertensive effect.

Amiodarone:
In patients with heart failure, amiodarone decreased the clearance of the
S (-) stereoisomer of carvedilol by suppressing CYP2C9. The average concentration of the R (+) stereoisomer of carvedilol did not change. Therefore, in connection with an increase in the concentration of the S (-) stereoisomer of carvedilol, there is a risk of an increase in the beta-adrenergic blocking action.

CYP2D6 isoenzyme inhibitors:
The use of CYP2D6 isoenzyme inhibitors, incl. quinidine, fluoxetine, paroxetine, propafenone, can lead to stereoselective suppression of the metabolism of carvedilol (possibly an increase in the concentration of the R (+) stereoisomer).

PHARMACODYNAMIC INTERACTION

Oral insulin or hypoglycemic agents:
Preparations with beta-adrenergic blocking properties may enhance the hypoglycemic effect of insulin or oral hypoglycemic agents. Symptoms of hypoglycemia, especially tachycardia, may be masked or subside. Patients receiving insulin or oral hypoglycemic agents are advised to regularly monitor their blood glucose levels.

Drugs that reduce the content of catecholamines:
Patients taking simultaneously drugs with beta-adrenergic blocking properties and drugs that reduce the content of catecholamines (for example, reserpine and monoamine oxidase (MAO) inhibitors) should be closely monitored due to the risk of arterial hypotension and / or severe bradycardia.

Digoxin
Combination therapy with beta-blockers and digoxin can lead to an additional slowdown in AV conduction.

Verapamil, diltiazem, amiodarone or other antiarrhythmics:
Their concomitant use with carvedilol may increase the risk of AV conduction disturbance.

With the simultaneous use of carvedilol and diltiazem, there have been isolated cases of cardiac conduction disorders (rarely - with violations of hemodynamic parameters). The use of carvedilol together with blockers of 'slow' calcium channels (for example, verapamil or diltiazem) is recommended under the control of ECG and blood pressure.

Clonidine: The
simultaneous use of clonidine with beta-blockers can potentiate the hypotensive and bradycardic effect. If it is planned to discontinue combination therapy with a beta-blocker and clonidine, the beta-blocker should be canceled first, and after a few days, clonidine can be canceled, gradually decreasing its dose.

Antihypertensive drugs:
Like other drugs with beta-adrenergic blocking activity, carvedilol can enhance the effect of other antihypertensive drugs (for example, alpha-blockers) or drugs that cause arterial hypotension as a side effect.

—редства дл¤ общей анестезии:
—ледует проводить тщательное наблюдение за основными показател¤ми жизнеде¤тельности организма при проведении общей анестезии в св¤зи с возможностью синергичного отрицательного инотропного действи¤ карведилола и средств дл¤ общей анестезии.

Ќестероидные противовоспалительные препараты (Ќѕ¬ѕ):
ќдновременное применение Ќѕ¬ѕ и бета-адреноблокаторов снижает антигипертензивный эффект карведилола.

Ѕронходилататоры (агонисты бета-адренорецепторов):
ѕоскольку некардиоселективные бета-адреноблокаторы преп¤тствуют бронхолитическому эффекту бронходилататоров, ¤вл¤ющихс¤ стимул¤торами ?-адренорецепторов, необходимо тщательное наблюдение за пациентами, получающими данные препараты.

»нгибиторы микросомального окислени¤ (циметидин), диуретики и ингибиторы јѕ‘ усиливают антигипертензивный эффект карведилола.

ќ—ќЅџ? ” ј«јЌ»я

—ледует с осторожностью назначать пациентам, работа которых требует быстрой психомоторной реакции (во врем¤ работы с машинами и механизмами, при управлении транспортными средствами), пациентам, использующим контактные линзы (уменьшение слезоотделени¤).

ќтмена должна осуществл¤тьс¤ постепенно (во избежании развити¤ синдрома Ђотменыї), в течение нескольких дней (особенно у пациентов с »Ѕ—).

ѕри хранении на свету возможно изменение цвета таблеток.

ћожет маскировать симптомы тиреотоксикоза, гипогликемии.

 линический опыт применени¤ карведилола в педиатрической практике отсутствует.
¬ случае необходимости проведени¤ хирургического вмешательства с применением общей анестезии необходимо предупредить анестезиолога о предшествующей терапии карведилолом, из-за возможности суммации отрицательных эффектов препарата  ј–¬??»ЋќЋ и средств дл¤ общей анестезии.

ѕри прогрессировании —Ќ на фоне лечени¤ рекомендуетс¤ увеличить дозу диуретиков, при почечной недостаточности дозу регулируют в зависимости от функционального состо¤ни¤ почек.
¬ период лечени¤ исключаетс¤ употребление алкогол¤.

ѕациентам с ’ќЅЋ, не получающим ингал¤ционных препаратов или препаратов дл¤ приЄма внутрь (противоастматических средств),  ј–¬??»ЋќЋ назначают только в том случае, если возможные преимущества его применени¤ превышают потенциальный риск.

— осторожностью препарат назначают пациентам с сахарным диабетом, поскольку он может маскировать или ослабл¤ть симптомы гипогликемии (особенно тахикардию).

” пациентов с ’—Ќ и сахарным диабетом применение  ј–¬??»ЋќЋј может сопровождатьс¤ колебани¤ми гликемии.

 ак и другие бета-адреноблокаторы,  ј–¬??»ЋќЋ может уменьшать выраженность симптомов тиреотоксикоза.

ѕациентам с анамнестическими указани¤ми на возникновение или обострение псориаза при применении бета-адреноблокаторов, препарат  ј–¬??»ЋќЋ можно назначать после тщательного анализа возможной пользы и риска.

ѕациентам с феохромоцитомой до начала применени¤ любого бета-адреноблокатора необходимо назначить альфа-адреноблокатор.

’от¤  ј–¬??»ЋќЋ обладает как бета-, так и альфа-адреноблокирующими свойствами, опыта его применени¤ у таких пациентов нет, поэтому с осторожностью следует назначать пациентам с подозрением на феохромоцитому.
Ќеселективные бета-адреноблокаторы могут провоцировать по¤вление болей у пациентов со стенокардией ѕринцметала.

’от¤ его альфа-адреноблокирующие свойства могут предотвратить подобную симптоматику, назначать  ј–¬??»ЋќЋ в таких случа¤х следует с осторожностью.
Ќеобходимо соблюдать осторожность у пациентов с депрессией, метаболическим ацидозом и злокачественной миастенией (myasthenia gravis).
ќсторожность необходима при употреблении препарата  ј–¬??»ЋќЋ пациентам с заболевани¤ми периферических сосудов (в том числе с синдромом –ейно), поскольку бета-адреноблокаторы могут усиливать симптомы артериальной недостаточности.
 ј–¬??»ЋќЋ с осторожностью примен¤ют в комбинации с сердечными гликозидами у пациентов с AV блокадой I степени из-за возможности чрезмерного замедлени¤ AV проводимости.
” пациентов с почечной недостаточностью при применении карведилола отмечалось обратимое ухудшение функции почек.

?озу препарата следует подбирать в зависимости от функционального состо¤ни¤ почек.
?остаточного опыта применени¤ препарата  ј–¬??»ЋќЋ у беременных нет.

ѕоэтому он противопоказан к применению при беременности.

¬Ћ»яЌ»? Ќј —ѕќ—ќЅЌќ—“№ ”ѕ–ј¬Ћ?Ќ»я ј¬“ќ“–јЌ—ѕќ–“ќћ » –јЅќ“” — ћ?’јЌ»«ћјћ»

—ледует иметь в виду, что в начале лечени¤ и при повышении дозы  ј–¬??»ЋќЋј ј? может чрезмерно снижатьс¤, вызыва¤ головокружение. ѕоэтому в период лечени¤ пациентам следует воздерживатьс¤ от зан¤тий потенциально опасными видами де¤тельности, требующими повышенного внимани¤ и быстроты психомоторных реакций.

‘ќ–ћј ¬џѕ”— ј

Tablets of 6.25 mg, 12.5 mg, 25 mg.
7 tablets in a blister strip packaging. 2, 3, 4 blister packs together with instructions for use are placed in a carton box.
10 tablets in a blister strip packaging. 1, 2, 3, 4, 5 blister packs together with instructions for use are placed in a cardboard box.

STORAGE CONDITIONS

Store in a dry, dark place at a temperature not exceeding 25 ? C.
Keep out of the reach of children.

SHELF LIFE

2 years.
Do not use after the expiration date printed on the package.