2010/09/17

Acridilole

Composition, structure and packing

Tablets are square with rounded corners, biconvex, with a Phillips notch on one side and engraved "AL1" - on the other, from white to white with kremovatym color allowed light marbling.

1 tab. carvedilol 12.5 mg.

Excipients: ludipress LTSE (lactose, povidone), sodium starch glycolate (sodium karboksimetilkrahmal), magnesium stearate.

The tablets are oval, biconvex, with a partial notch on both sides and engraved "AL2" on one side, white to white with kremovatym color allowed easy marbling.

1 tab. Carvedilol 25 mg.

Excipients: ludipress LTSE (lactose, povidone), sodium starch glycolate (sodium karboksimetilkrahmal), magnesium stearate.

Clinico-pharmacological group: beta1-, beta2-blocker. Alpha 1-blocker.

Pharmacological action

Alpha-and beta-blocker. Akridilol blocking β1-, β2-and α1-adrenergic receptors. Has vasodilatation, antianginal and antiarrhythmic action. The drug has no internal sympathomimetic activity, has membrane stabilizing properties. Due to the blockade of β-adrenergic receptors of the heart may decrease blood pressure, decrease cardiac output and decrease in heart rate. Akridilol suppresses the renin-angiotensin-aldosterone system blockade by β-adrenergic receptors of the kidneys, causing a decrease in plasma renin. By blocking α-adrenergic receptors, the drug can cause expansion of peripheral blood vessels, which leads to a decrease TPVR.

Through the combination of β-adrenoceptor blockade and vasodilation drug lowers blood pressure in hypertension, with CHD has antiischemic and antianginal effect, with left ventricular dysfunction and heart failure improves hemodynamic parameters, improves left ventricular ejection fraction and reduces its size.

It has no distinct effect on lipid metabolism and the content of potassium, sodium and magnesium in plasma. Antioxidant effect, eliminating free oxygen radicals.

Pharmacokinetics

Absorption

After oral carvedilol is rapidly absorbed from the gastrointestinal tract. Has high lipophilicity. Cmax plasma levels achieved after 1-1.5 h. bioavailability - 24-28%. Eating does not affect the bioavailability of carvedilol.

Distribution

Plasma protein binding is 95-99%. Carvedilol crosses the placenta, excreted in breast milk.

Metabolism

Metabolised in the liver with the formation of several active metabolites, 60-75% of the absorbed drug is metabolized in the "first pass" through the liver. Metabolites possess antioxidant and adrenoceptor blocking action.

Withdrawal

T1 / 2 of 6-10 h. Withdrawal of the drug from the body occurs mainly with the bile.

Pharmacokinetics in special clinical situations

In case of violation of renal function the pharmacokinetic parameters of carvedilol did not significantly change.

In patients with impaired liver function systemic bioavailability of carvedilol is increased by reducing the metabolism in the "first pass" through the liver. When serious liver Carvedilol is contraindicated.

Statement
hypertension (as monotherapy and combination with diuretics);
Chronic heart failure (in a combination therapy);
Coronary heart disease: stable angina.

Dosage regimen

When hypertension the initial dose for adults is 6.25-12.5 mg / day for 2 days. Then assign to 25 mg / day 1 times per day in the morning. If necessary, after 14 days you can still increase the dose in 2 times. The maximum daily dose is 50 mg 1 time / day (possibly in 2 divided doses).

With CHD in the early treatment of drug prescribed to 12.5 mg 2 times / day during the first 2 days of treatment, then - 25 mg 2 times / day. In case of insufficiency antianginal effect after 2 weeks of therapy dose can be increased by a factor of 2. The maximum daily dose is 100 mg (50 mg 2 times / day).

In chronic heart failure treated with doses of 3.125 mg 2 times / day for 2 weeks. If well tolerated dose increased at intervals of not less than 2 weeks to 6.25 mg 2 times / day, then to 12.5 mg 2 times / day, and then to 25 mg 2 times / day. The dose should be increased to the maximum, which is well tolerated by patients. Patients weighing less than 85 kg target dose is 50 mg / day; patients with body weight over 85 kg target dose of 75-100 mg / day. The drug should be taken irrespective of food intake, drinking a small amount of liquid.

Side effect

From the side of the central nervous system and peripheral nervous system: dizziness, headache (usually not severe and early treatment), loss of consciousness, myasthenia gravis (usually at the beginning of treatment), fatigue, depression, sleep disturbance, paresthesia.

Since the cardiovascular system: bradycardia, orthostatic hypotension, AV-block II-III degree, rarely - a violation of the peripheral circulation, the progression of heart failure (in the period increased doses), edema of the lower extremities, angina, marked reduction of BP.

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

On the part of the hemopoietic system: rarely - thrombocytopenia, leukopenia.

From the Metabolic: weight gain, carbohydrate metabolism. Allergic reactions: skin allergic reactions (rash, hives, itching, rash), exacerbation of psoriasis, nasal congestion.

On the part of the respiratory system: dyspnea, and bronchospasm (in predisposed patients).

Other: blurred vision, decrease watery, flu-like syndrome, sneezing, myalgia, arthralgia, pain in the limbs, intermittent claudication; rarely - a violation of urination, renal failure.

Contraindications
and acute decompensated chronic heart failure, which requires a / in the introduction of inotropic funds;
severe hepatic impairment;
AV-block II-III degree;
pronounced bradycardia (less than 50 bpm);
SSS;
hypotension (systolic blood pressure less than 85 mm Hg. Art.)
cardiogenic shock;
COPD;
the age of 18 years (effectiveness and safety have not been established);
Hypersensitivity to carvedilol or other components of the drug.

With care use in patients with angina

Prinzmetal, thyrotoxicosis, peripheral vascular occlusive disease, pheochromocytoma, psoriasis, kidney failure, AV-blockade of I degree, extensive surgery and general anesthesia, diabetes, hypoglycemia, depression, myasthenia gravis.

Pregnancy and lactation

There are no adequate and strictly controlled studies of carvedilol in pregnancy has not been, so use of the drug in this category of patients is only possible in cases where the expected benefit of therapy to the mother outweighs the potential risk to the fetus. Avoid breastfeeding during treatment with carvedilol.

Application for violations of liver function

The drug is contraindicated in severe hepatic insufficiency.

Application for violations of renal function

It is recommended to monitor renal function in patients with chronic renal failure.

Cautions

Therapy should be prolonged and not stop abruptly, especially in ischemic heart disease, because this can lead to poor flow of the underlying disease. If necessary, the dose should be reduced gradually over 1-2 weeks.

At the beginning of therapy Akridilolom or with increasing doses of the drug in patients, especially the elderly, there may be excessive lowering of BP, mainly during epistaxis. In such cases, dosage adjustment is necessary. In the treatment of chronic heart failure in the selection of the dose may increase symptoms of heart failure, leading to swelling. One should not increase the dose Akridilola, recommended use of diuretics in higher doses up to stabilize the patient.

It is recommended that continuous monitoring of ECG and blood pressure, while the appointment Akridilola and slow calcium channel blockers, derivatives of phenylalkylamine (verapamil) and benzothiazepines (diltiazem), as well as with class I antiarrhythmics.

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

In the case of surgical intervention with general anesthesia should notify the anesthesiologist of previous therapy Akridilolom. Akridilol not affect the concentration of glucose in the blood and causes no changes in indicators of glucose tolerance test in patients with insulin-dependent diabetes mellitus. Patients with pheochromocytoma before therapy to assign alpha-blockers. Patients who use contact lenses, be aware that the drug may cause a decrease watery. In the period of treatment should avoid alcohol.

Effects on ability to drive vehicles and management mechanisms

Do not drive a car at the beginning of therapy and with increasing doses Akridilola. It should refrain from other activities related to the need of high concentration and rapid psychomotor reactions.

Overdose

Symptoms: reduced blood pressure (accompanied by dizziness or fainting, systolic blood pressure below 80 mm Hg), bradycardia. You may experience shortness of breath due to bronchospasm and vomiting. In severe cases, possible cardiogenic shock, respiratory failure, confusion, conduction disorders.

Treatment: the holding of symptomatic therapy. Monitoring and correction of vital parameters, if necessary - in the intensive care unit. It is advisable to / in the introduction of m-holinoblokatorov (atropine), sympathomimetics (epinephrine, norepinephrine).

Drug Interactions

With simultaneous application of Carvedilol may potentiate the action of other antihypertensive drugs or drugs which have a hypertensive effect (nitrates). When the joint application of carvedilol and diltiazem may develop heart conduction disorders and hemodynamic disturbances. Inhibitors of microsomal oxidation (cimetidine) increase, and inducers (phenobarbital, rifampicin) weaken the hypotensive effect of carvedilol.

At the same time receiving carvedilol and digoxin increased the concentration of the latter and can be increased while AV-holding. Carvedilol may potentiate the action of insulin and oral hypoglycemic funds, with the symptoms of hypoglycaemia (especially tachycardia) may be masked, so patients with diabetes should regularly monitor blood glucose.

Drugs that reduce the content of catecholamines (reserpine, MAO inhibitors), increase the risk of arterial hypotension and marked bradycardia.

With simultaneous application of cyclosporine increased the concentration of the latter (recommended daily dose of cyclosporine correction). The simultaneous appointment of clonidine may potentiate the hypotensive and negative chronotropic effects of carvedilol. General anesthetics enhance the negative inotropic and hypotensive effects of carvedilol.

Terms and Conditions of storage

List B. The drug should be stored in dry, light, reach of children, at a temperature not above 25 ° C. Shelf life - 3 years.