Amlodipine + Atenolol - instructions for use, dose, side effects, contraindications

Clinical and pharmacological group: & nbsp

Antiarrhythmics

Calcium channel blockers

Included in the formulation

Tenochek ®

pills inwards

Ipka Laboratories Ltd. India

Included in the list (Order of the Government of the Russian Federation No. 2782-r of 30.12.2014):

VED

ONLS

АТХ:

C.07.F.B.03 Atenolol in combination with other antihypertensive agents

Pharmacodynamics:

Combined drug, the effect of which is due to the properties of its components.

Atenolol - cardioselective beta-1-blocker, has antianginal, antihypertensive and antiarrhythmic effect. Does not possess membrane stabilizing and internal sympathomimetic activity. Reduces the formation of cAMP and ATP, stimulated by catecholamines, reduces the intracellular current of calcium ions. In the first 24 hours after taking the drug inside against the background of a decrease in cardiac output, there is a reactive increase in OPSS, the severity of which decreases gradually over the course of 1-3 days.

The antihypertensive effect is associated with a decrease in cardiac output, a decrease in the activity of the renin-angiotensin system, sensitivity of the baroreceptors, and effects on the central nervous system. The hypotensive effect is manifested by a decrease in systolic and diastolic blood pressure, a decrease in the impact and minute volume.When used in medium recommended doses, it has no effect on the tone of peripheral arteries. The hypotensive effect persists for 24 hours, with regular use of BP stabilized by the end of 2 weeks of treatment.

The antianginal effect is determined by the decrease in myocardial oxygen demand as a result of a decrease in heart rate (diastolic elongation and improvement of myocardial perfusion) and a decrease in myocardial contractility, as well as a decrease in myocardial sensitivity to sympathetic innervation. Reduces heart rate at rest and under physical exertion. By increasing the tension of the ventricular muscle fibers and the final diastolic pressure in the left ventricle, it can increase the demand for myocardium in oxygen, especially in patients with chronic heart failure.

Negative chronotropic effect is manifested after 1 hour after administration, reaches a maximum after 2-4 hours and lasts up to 24 hours.

Antiarrhythmic effect is manifested by suppression of sinus tachycardia and is associated with elimination of arrhythmogenic sympathetic influences on the conduction system of the heart, inhibition of heterogeneous automatism, decrease in the rate of spread of excitation through the sinoatrial node and prolongation of the refractory period.Oppresses impulses in antegrade and to a lesser extent - retrograde directions through the AV node and along additional paths.

Increases the survival rate of patients who underwent myocardial infarction (reduces the incidence of ventricular arrhythmias and angina attacks).

In therapeutic concentrations does not affect β2-adrenergic receptors, in contrast to non-selective beta-blockers has a less pronounced effect on the smooth muscles of the bronchi, peripheral arteries and lipid metabolism. Slightly reduces the vital capacity of the lungs, almost does not weaken the bronchodilating effect of isoproterenol. When taking more than 100 mg / day. can affect β2-adrenergic receptors.

Amlodipine - a blocker of slow calcium channels, is a derivative of dihydropyridine. Has antihypertensive, antianginal, antispasmodic and vasodilating effect. It blocks the flow of calcium ions through the cell membranes into the smooth muscle cells of the vessels and the myocardium. The mechanism of antihypertensive action is caused by a direct effect on the smooth muscles of the vessels.

The antianginal effect of amlodipine is due to the dilating effect on the peripheral arterioles, which leads to a decrease in OPSS. At the same time, a decrease in heart burden leads to a decrease in myocardial oxygen demand, and at the same time, oxygen supply to the myocardium increases due to the expansion of the coronary arteries (which is especially important in angiospastic angina).

Amlodipine does not adversely affect the metabolism and lipid composition of the blood plasma, has antiatherosclerotic, antithrombotic activity, increases the glomerular filtration rate, and has a weakly expressed natriuretic effect. When diabetic nephropathy does not increase the severity of microalbuminuria.

Pharmacokinetics:

Atenolol

After taking the drug inside atenolol quickly absorbed from the digestive tract (approximately 50% of the dose taken). Bioavailability is 40-50%. Cmax is achieved 2-4 hours after ingestion.

Poorly penetrates through the BBB and through the placental barrier, in small quantities excreted in breast milk. Binding to plasma proteins - 6-16%.

It is not biotransformed in the liver.It is excreted by the kidneys through glomerular filtration, while 85-100% - in unchanged form. T1 / 2 is 6-9 hours.

It is in hemodialysis.

Amlodipine

After taking the drug inside amlodipine quickly and almost completely (90%) is absorbed from the digestive tract, Cmax is reached after 6-12 hours. Bioavailability is 60-65%.

Css is established after 7-8 days of continuous intake of the drug. Vd is 20 l / kg. Binding to plasma proteins is more than 95%. Penetrates through the BBB.

Biotransformed mainly in the liver with the formation of inactive metabolites. Less than 10% is unchanged, about 60% - in the form of inactive metabolites by the kidneys, 20-25% - in the form of metabolites with bile and through the intestine, as well as with breast milk.

Indications:

Arterial hypertension; prevention of angina attacks.

ICD-10

IX.I10-I15.I10 Essential [primary] hypertension

IX.I20-I25.I20 Angina pectoris [angina pectoris]

Contraindications:

Pronounced arterial hypotension; AV blockade II and III degree; SSSU; sinoatrial blockade; acute heart failure; chronic heart failure IIB - III stage in the phase of decompensation; severe bradycardia; metabolic acidosis; bronchial asthma,chronic obstructive pulmonary disease; angina of Prinzmetal; Cardiomegaly without symptoms of heart failure; simultaneous administration of MAO inhibitors; children and adolescents under 18; hypersensitivity to the components of the drug. With cautiousness appoint at AV blockade of I degree, violations of liver function, stenosis of the aortic aorta, chronic heart failure (in the phase of compensation), chronic renal failure, pheochromocytoma, diabetes, hypoglycemia, thyrotoxicosis, obliterating diseases of peripheral vessels (symptom of intermittent claudication, syndrome Reynaud), myasthenia gravis, depression (including history), psoriasis, as well as elderly patients. Caution should be given to patients who engage in potentially hazardous activities, due to the possible decrease in concentration.

Carefully:

With caution appoint with AV-blockade I degree, violations of liver function, stenosis of the aortic aorta, chronic heart failure (in the phase of compensation), chronic kidney failure, pheochromocytoma, diabetes mellitus, hypoglycemia, thyrotoxicosis,obliterating diseases of peripheral vessels (a symptom of intermittent claudication, Raynaud's syndrome), myasthenia gravis, depression (including anamnesis), psoriasis, as well as elderly patients.

Caution should be given to patients who engage in potentially hazardous activities, due to the possible decrease in concentration.

Pregnancy and lactation:

In pregnancy, the drug is prescribed only in cases where the intended benefit to the mother exceeds the potential risk to the fetus.

During lactation (breastfeeding), the drug should be taken only in exceptional cases with great caution.

Dosing and Administration:

With arterial hypertension, the recommended dose is 1 tab. / Day. If necessary, the daily dose can be increased to 2 tablets / day. The maximum daily dose is 2 tablets.

It is impossible to severely interrupt treatment because of the risk of developing severe arrhythmias and myocardial infarction, especially in patients with ischemic heart disease. Cancellation is carried out gradually, reducing the dose for 2 weeks or more (dose reduced by 25% in 3-4 days).

Tablets are taken orally by washing down with the necessary amount of liquid.

Side effects:

From the cardiovascular system: the appearance or worsening of symptoms of heart failure, violation of AV-conduction, bradycardia, marked decrease in blood pressure, palpitation, dyspnea, flushing of the skin to the face, peripheral edema.

On the part of the digestive system: dry mouth, nausea, vomiting, diarrhea, abdominal pain, constipation, gingival hyperplasia; rarely - increased activity of hepatic transaminases, cholestatic jaundice, dyspepsia.

From the side of the central nervous system and peripheral nervous system: dizziness, sleep disturbance, decreased ability to concentrate, drowsiness, depression, hallucinations, lethargy, fatigue, headache; rarely - a change in mood, asthenia, impaired vision, paresthesia.

From the musculoskeletal system: muscle cramps, myalgia.

On the part of the respiratory system: dyspnea, bronchospasm, apnea.

From the hemopoietic system: thrombocytopenic purpura, anemia (aplastic), thrombosis.

On the part of the endocrine system: decreased potency, decreased libido, gynecomastia, hyperlipidemia, hypoglycemia.

Dermatological reactions: urticaria, dermatitis, pruritus, photosensitization; rarely - multiforme exudative erythema.

Other: increased frequency of urination.

The drug, as a rule, is well tolerated by patients.

Overdose:

Symptoms: pronounced bradycardia, AV blockade of II and III degree, increase in symptoms of heart failure, pronounced decrease in blood pressure, bronchospasm, hypoglycemia.

Treatment: symptomatic. Hemodialysis is not effective.

Interaction:

When used simultaneously with insulin (or oral hypoglycemic agents), the symptoms of hypoglycemia are masked (due to the action of atenolol).

When combined with antihypertensive agents of other groups, the hypotensive effect is mutually reinforced.

The hypotensive effect of the drug is weakened by estrogens, GCS, mineralocorticoids, NSAIDs (due to sodium retention).

With simultaneous use of atenolol and cardiac glycosides, the risk of bradycardia and AV-conduction disorders increases.

With the simultaneous administration of atenolol with reserpine, methyldopa, clonidine, verapamil, a pronounced bradycardia may occur.

With simultaneous administration with derivatives of ergotamine and xanthine, the efficacy of atenolol is reduced.

Simultaneous use with lidocaine can slow the withdrawal of atenolol and amlodipine from the body and increase the risk of toxic effects of the drug.

Application in conjunction with phenothiazine derivatives promotes an increase in the concentration of active substances in the blood serum.

Phenytoin (with in / in the introduction) and funds for in / in anesthesia increase the severity of the cardiodepressive effect of atenolol.

Allergens used for immunotherapy, or allergen extracts for skin tests and iodine-containing radiocontrast agents for IV administration increase the risk of severe systemic allergic reactions or anaphylaxis.

Means for inhalation of general anesthesia (derivatives of hydrocarbons) increase the risk of oppression of myocardial function and marked decrease in blood pressure.

When combined amiodarone increases the risk of bradycardia and slowing AV-conduction.

Cimetidine increases the concentration of atenolol in the blood plasma (by inhibiting its metabolism).

When combined, prolongs the effect of nondepolarizing muscle relaxants and the anticoagulant effect of coumarins.

Special instructions:

In thyrotoxicosis, the drug may mask certain clinical signs of hyperthyroidism (eg, tachycardia).Abrupt withdrawal of the drug in patients with thyrotoxicosis is contraindicated, since it can strengthen symptoms.

The drug slightly increases insulin-induced hypoglycemia and does not delay the restoration of blood glucose to normal levels.

Selection of the dose in patients with chronic heart failure (compensated) should be done with caution.

If surgery is required under general anesthesia, the drug should be discontinued 48 hours before surgery. As an anesthetic, a drug with a possible minimal negative inotropic effect should be chosen.

With simultaneous application with clonidine, the drug is stopped for several days before clonidine in order to avoid the withdrawal syndrome of the latter.

It is possible to increase the severity of allergic reactions and the lack of effect on the usual doses of epinephrine in patients with a history of allergic anamnesis.

Drugs that reduce catecholamine stocks (for example, reserpine), can enhance the action of beta-adrenoblockers, so patients receiving such a combination of drugs,should be under constant surveillance to detect a marked decrease in blood pressure or bradycardia.

In the case of severe bradycardia (heart rate less than 50 / min), a significant decrease in blood pressure (systolic blood pressure below 100 mm Hg), AV blockade, bronchospasm, ventricular arrhythmias, severe liver and kidney dysfunction, it is necessary to reduce the dose or cancel the drug.

When developing depression on the background of taking the drug is recommended to stop therapy.

If necessary, in / in the introduction of verapamil, this administration should be done at least 48 hours after the last dose.

With the use of atenolol, tear production can be reduced, which is important for patients using contact lenses.

It is necessary to cancel the drug before examining the concentration in the blood and urine of catecholamines; titers of antinuclear antibodies.

In smokers, the effectiveness of beta-blockers is lower.

It is necessary to monitor heart rate and blood pressure (at the beginning of treatment - daily, then 1 time in 3-4 months), the concentration of glucose in the blood in patients with diabetes (1 time in 4-5 months.). In elderly people, it is recommended to assess kidney function (1 time in 4-5 months).

You should teach the patient how to calculate heart rate and instruct you about the need for medical consultation at a heart rate of less than 50 beats. / min.

Instructions

Amlodipine + Atenolol (Amlodipinum + Atenololum)