ATRAM

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: ZENTIVA a.s. (Czech Republic)

Pharmaceutical form, composition and packaging

Pills brown-yellow, with splashes, with notch mark on one side and engraved number “12” – another.

Excipients: sucrose, povidone 30, lactose monohydrate 200, silica colloidal anhydrous, sodium croscarmellose, magnesium stearate, iron oxide yellow, iron oxide red.

15 PC. – blisters (1) – packs cardboard.
15 PC. – blisters (2) – packs cardboard.

Pills brown-yellow, with splashes, with notch mark on one side and engraved number “25” – another.

Excipients: sucrose, povidone 30, lactose monohydrate 200, silica colloidal anhydrous, sodium croscarmellose, magnesium stearate, iron oxide yellow, iron oxide red.

10 PC. – blisters (3) – packs cardboard.

Pills yellow color, with splashes, with notch mark on one side and engraved number “6” – another.

Excipients: sucrose, povidone 30, lactose monohydrate 200, silica colloidal anhydrous, sodium croscarmellose, magnesium stearate, iron oxide yellow.

15 PC. – blisters (1) – packs cardboard.
15 PC. – blisters (2) – packs cardboard.

Pharmacological action

Carvedilol has a combined non-selective β₁– b₂– и a₁– blocking action. The drug does not have its own sympathomimetic activity, has membrane stabilizing properties. Due to the blockade of β-adrenergic receptors of the heart, blood pressure can decrease, cardiac output and a decrease in heart rate, Carvedilol suppresses the renin-angiotensin-aldosterone system by blocking the β-adrenergic receptors of the kidneys, causing a decrease in Renin activity plasma. Inhibiting α-adrenergic receptor, the drug may cause peripheral vessels, thereby reducing systemic vascular resistance.

The combination of β-adrenergic receptor blockade and vasodilation has the following effects: in patients with arterial hypertension – decrease in blood pressure; in patients with coronary artery disease – anti-ischemic and antianginal action; in patients with left ventricular dysfunction and circulatory failure – favorably affects hemodynamic parameters, increases left ventricular ejection fraction and reduces its size.

Pharmacokinetics

Carvedilol is rapidly absorbed from the gastrointestinal tract. High lipophilicity. C_maxblood achieved through 1-1.5 no. T_1/2 is 6-10 no. Associated with the plasma protein on 95-99 %. Bioavailability 24-28%. Eating does not affect the bioavailability of.

Metabolised in the liver with the formation of a number of active metabolites – 60-75 % the adsorbed drug is metabolized during the first passage through the liver. Metabolites have a pronounced anti-oxidant and adrenoblokirutm action. The elimination of the drug from the body occurs through the gastrointestinal tract.. Carvedilol penetrates through the placental barrier, excreted in breast milk.

If any of the kidneys carvedilol significantly the pharmacokinetic parameters do not change.

In patients with impaired liver function, the systemic bioavailability of carvedilol increases due to a decrease in metabolism during the first passage through the liver. In case of serious violations of the liver carvedilol is contraindicated.

Testimony

- Arterial hypertension (in monotherapy and in combination with diuretics);

- Congestive heart failure (in a combination therapy);

- Coronary heart disease;

- Stable angina.

Dosage regimen

Inside, regardless of the meal.

Arterial hypertension

The initial dose is 6.25 – 12.5 mg 1 once / day in the first two days of treatment. Then by 25 mg 1 time / day. In case of insufficient antihypertensive effect through 2 weeks of therapy dose can be increased in 2 times. The maximum recommended daily dose of the drug is 50 mg 1 time / day (possibly divided into 2 admission).

Coronary artery disease

The initial dose is 12.5 mg 2 times / day in the first two days of treatment. Then by 25 mg 2 times / day. With insufficient antianginal effect through 2 weeks of therapy dose can be increased in 2 times. The maximum recommended daily dose of the drug is 100 mg / day, divided by 2 admission.

Congestive heart failure

Dose picked individually, under close medical supervision. The recommended starting dose is 3.125 mg 2 times / day for 2 weeks. With good endurance dose increase at intervals of not less than 2 weeks before 6.25 mg 2 times / day , then to 12.5 mg 2 times / day, then – to 25 mg 2 times / day. The dose should be increased to a maximum of, which is well tolerated by patients. In patients weighing less than 85 kg target dose is 50 mg / day; for patients weighing more than 85 kg target dose 75 – 100 mg / day.

Side effect

CNS: dizziness, headache (usually not strong at the beginning of treatment), loss of consciousness, myasthenia (more often at the beginning of treatment), fatigue, depression, sleep disturbance, paresthesia.

Cardio-vascular system: bradycardia, orthostatic hypotension, atrioventricular block II - III century., rarely – the peripheral blood circulation, progression of heart failure (at a time of increased doses), edema of the lower extremities, angina, marked reduction in blood pressure.

On the part of the digestive tract: dry mouth, nausea, diarrhea or constipation, vomiting, abdominal pain, loss of appetite, increase in liver transaminases.

From the hematopoietic system: rarely – thrombocytopenia, leukopenia.

Metabolism: weight gain, violation of carbohydrate metabolism.

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

The respiratory system: Dyspnea and bronchospasm (prone patients).

Other: blurred vision, decrease in lacrimation, flu-like symptoms, sneezing, myalgia, arthralgia, pain in the limbs, “intermittent” claudication, rarely - urination disorder, impairment of renal function.

Contraindications

- acute and chronic heart failure (decompensated);

- Severe hepatic impairment;

- atrioventricular block II-lll st.;

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

sick sinus syndrome;

- Hypotension (systolic blood pressure less than 85 mm Hg. Art.);

- Cardiogenic shock;

- Chronic obstructive pulmonary disease;

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

-hypersensitivity to karvedilolu or other components of the drug.

Carefully: Prinzmetal angina, thyrotoxicosis, occlusive peripheral vascular disease, pheochromocytoma, psoriasis, renal failure, AV block I degrees, major surgery and general anesthesia, diabetes, gipoglikemiâ, depression, myasthenia.

Pregnancy and lactation

There have been no controlled studies of the use of carvedilol in pregnant women, therefore, the appointment of a drug in this category of patients is possible only in cases, when the benefit to the mother outweighs the potential risk to the fetus.

Breastfeeding is not recommended during treatment with carvedilol.

Cautions

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

At the beginning of therapy with carvedilol or when the dose of the drug is increased in patients, particularly the elderly, There may be an excessive decline ad, mainly to stand up. Dose adjustment is required. In patients with chronic heart failure, when the dose is adjusted, the symptoms of heart failure may increase, the appearance of edema. In this case, you should not increase the dose of Atram., the appointment of large doses of diuretics is recommended until the patient's condition is stabilized.

It is recommended to continuously monitor the electrocardiogram and blood pressure while prescribing Atram and blockers “slow” calcium channel blockers, derived fenilalkilamina (verapamil) and benzodiazepines (diltiazem), and – with class I antiarrhythmics.

It is recommended to monitor kidney function in patients with chronic renal insufficiency, arterial hypotension and chronic heart failure. In case of surgical intervention using general anesthesia, the anesthesiologist should be warned about previous therapy with carvedilol..

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

Avoid ethanol during treatment.

Patients with pheochromocytoma should be prescribed alpha-blockers before starting therapy.

Patients, wear contact lenses, should be considered, that the drug can cause a decrease in tear production.

Effects on ability to drive vehicles and management mechanisms

It is not recommended to drive a car at the beginning of therapy and when increasing the dose of carvedilol. Should refrain from other activities, related to high concentration and psychomotor quick reactions.

Overdose

Symptoms: decrease in blood pressure (accompanied by dizziness or fainting), bradycardia. Possibly wheezing due to bronchoconstriction and vomiting. In severe cases there may be cardiogenic shock, respiratory failure, confusion, conduction disorders.

Treatment: it is necessary to monitor and correct vital indicators, if necessary – in the intensive care unit. Treatment – symptomatic. It is advisable to use m-anticholinergics intravenously (atropyn), adrenomimetikov (epinephrine, norepinephrine).

Drug Interactions

Carvedilol may potentiate the effect of other concurrently taken antihypertensive drugs or drugs, which have gipotenzivny effect (nitrates).

When coupled with enalapril and diltiazem can develop violations conductivity heart and hemodynamics.

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 of insulin and oral hypoglycemic agents, When the symptoms of hypoglycemia (especially the tachycardia) can camouflage, therefore, in patients with diabetes mellitus, regular monitoring of blood sugar levels is recommended.

Inhibitors of microsomal oxidation (cimetidine) increase, and inductors (phenobarbital, rifampicin) weaken gipotenzivny effect of carvedilol.

Preparations, reduced catecholamine (reserpine, monoamine oxidase inhibitors), increase the risk of developing arterial hypotension and severe bradycardia.

While the application of Cyclosporine increases the concentration of the latter (correction is recommended daily dose of Cyclosporine).

Concomitant administration of clonidip may potentiate the antihypertensive and heart rate-slowing effects of carvedilol.

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

Conditions of supply of pharmacies

On prescription.

Conditions and terms

Store at a temperature of 10-25 ° C in a dry place out of the reach of children.

Shelf life – 2 year.