Cordanum^® (Tablets) Instructions for Use

Marketing Authorization Holder

AWD.pharma GmbH & Co. KG (Germany)

ATC Code

C07AB13 (Talinolol)

Active Substance

Talinolol (Rec.INN registered by WHO)

Dosage Form

Cordanum®

Coated tablets, 50 mg: 50 pcs.

Dosage Form, Packaging, and Composition

10 pcs. – blister packs (5) – cardboard packs.

Clinical-Pharmacological Group

Beta₁-adrenoblocker

Pharmacotherapeutic Group

Selective beta1-adrenergic blocker

Pharmacological Action

Selective beta1-adrenergic receptor blocker without intrinsic sympathomimetic activity. In very high doses, it can block beta2-adrenergic receptors. It does not have membrane-stabilizing properties. It has antianginal, antihypertensive, and antiarrhythmic effects.

It reduces catecholamine-stimulated formation of cAMP from ATP, reduces intracellular calcium influx, decreases heart rate, inhibits conduction, and reduces myocardial contractility. Within the first 24 hours after the first dose, a decrease in cardiac output and a reactive increase in total peripheral vascular resistance are noted; the severity of the latter gradually decreases over 1-3 days.

The antianginal effect is due to a reduction in myocardial oxygen demand resulting from decreased heart rate and reduced contractility. The decrease in heart rate leads to a prolongation of diastole and improved myocardial perfusion. Due to an increase in left ventricular end-diastolic pressure and increased stretching of ventricular muscle fibers, it may increase oxygen demand, especially in patients with chronic heart failure.

The hypotensive effect is due to the inhibition of presynaptic beta-adrenergic receptors on neuron terminals, as well as a reduction in the activity of the renin-angiotensin system; it stabilizes by the end of the 2nd week of treatment.

The antiarrhythmic effect is determined by the inhibition of impulse conduction in the antegrade and, to a lesser extent, retrograde directions through the AV node and along accessory pathways. It reduces the concentration of norepinephrine, prevents increased renin synthesis, interrupting the mutual activation of the renin-angiotensin-aldosterone and sympathoadrenal systems. It reduces mortality and the frequency of recurrences in acute myocardial infarction by reducing the area of necrosis and the frequency of arrhythmias.

When used in average therapeutic doses, it has a less pronounced effect on the smooth muscles of the bronchi and peripheral arteries and on lipid metabolism than non-selective beta-adrenergic blockers. The time to onset of effect is 2-4 hours, duration is up to 24 hours.

Pharmacokinetics

After oral administration, absorption from the gastrointestinal tract is 50-70%. Absolute bioavailability is 55±15%. After a 50 mg dose of talinolol, the C_max in plasma is 168±67 ng/ml and is reached in 3.2±0.8 hours. AUC is 1321±382 ng x h/ml. Concurrent food intake slows the rate of absorption and reduces the plasma C_max level. After intravenous administration of 30 mg talinolol, the C_max in plasma is 631±95 ng/ml, AUC is 1433±153 ng x h/ml. Plasma protein binding is 60%. V_d is 3.3±0.5 L/kg. It is minimally biotransformed (<1%).

T_1/2 after oral administration is 11.9±2.4 hours, after intravenous administration – 10.6±3.3 hours. About 60% of unchanged talinolol is excreted in the urine, 40% in bile and feces.

Indications

Coronary artery disease, angina pectoris, myocardial infarction (including secondary prevention); arterial hypertension, hypertensive crisis (hyperkinetic type); rhythm disorders (including during general anesthesia, with mitral valve prolapse, congenital long QT syndrome, myocardial infarction without signs of heart failure, thyrotoxicosis): sinus tachycardia, paroxysmal atrial tachycardia, supraventricular and ventricular extrasystole, supraventricular tachycardia; pheochromocytoma (only together with alpha-adrenergic blockers); withdrawal syndrome, migraine (prevention), tremor; hyperkinetic cardiac syndrome of functional origin.

ICD codes

Dosage Regimen

The dose is set individually, depending on the indications and severity of the disease. For oral administration, the daily dose is 50-300 mg, the frequency of administration is 1-2 times/day.

For intravenous administration, a single dose is 10 mg, the frequency of administration depends on the clinical situation.

Maximum doses for oral administration – 300 mg/day, for intravenous administration – 60 mg/day.

Adverse Reactions

From the nervous system anxiety, weakness, dizziness, headache, drowsiness or insomnia, nightmares, depression, restlessness, confusion, hallucinations, impaired concentration, slowed reaction time, paresthesia in the extremities (in patients with intermittent claudication and Raynaud’s syndrome), myasthenia (usually worsening of pre-existing), seizures.

From the sensory organs visual impairment, decreased tear secretion, dry and painful eyes, conjunctivitis.

From the cardiovascular system bradycardia, palpitations, impaired myocardial conduction, AV block (up to cardiac arrest), arrhythmias, decreased myocardial contractility, development (worsening) of chronic heart failure, orthostatic hypotension, manifestations of angiospasm (cold extremities, Raynaud’s syndrome), chest pain.

From the digestive system dry mouth, nausea, vomiting, abdominal pain, constipation or diarrhea, taste changes.

From the respiratory system nasal congestion, difficulty breathing when prescribed in high doses (loss of selectivity) and/or in predisposed patients – laryngo- and bronchospasm.

From the endocrine system hyperglycemia (in patients with non-insulin-dependent diabetes mellitus), hypoglycemia (in patients receiving insulin).

Dermatological reactions increased sweating, skin hyperemia, exacerbation of psoriasis symptoms, psoriasis-like skin rashes, reversible alopecia.

From the hematopoietic system thrombocytopenia (unusual bleeding and hemorrhage), agranulocytosis, leukopenia.

Other chest pain, decreased libido, impotence, withdrawal syndrome (increased angina attacks, increased blood pressure).

Contraindications

Cardiogenic shock, AV block II-III degree, severe bradycardia (heart rate less than 40 beats/min), sick sinus syndrome, sinoatrial block, acute heart failure or decompensated chronic heart failure, cardiomegaly without signs of heart failure, acute myocardial infarction (complicated by bradycardia, arterial hypotension or left ventricular failure), Prinzmetal’s angina, pheochromocytoma (without simultaneous use of alpha-adrenergic blockers), arterial hypotension (in case of use in myocardial infarction, systolic blood pressure less than 100 mm Hg), simultaneous use of MAO inhibitors (except for MAO type B inhibitors), lactation period, hypersensitivity to talinolol.

Use in Pregnancy and Lactation

The use of talinolol during pregnancy is possible only for vital indications.

It should be borne in mind that Talinolol can cause hypoglycemia, bradycardia, and intrauterine growth retardation in the fetus.

If it is necessary to use talinolol during lactation, breastfeeding should be discontinued.

Use in Hepatic Impairment

Use with caution in hepatic insufficiency.

Use in Renal Impairment

Use with caution in chronic renal failure.

Pediatric Use

Use with caution under the age of 18 years (efficacy and safety not established).

Geriatric Use

Use with caution over the age of 60 years.

Special Precautions

Use with caution in diabetes mellitus (especially of labile course), metabolic acidosis, COPD (including bronchial asthma, pulmonary emphysema); AV block I degree, chronic heart failure (compensated), obliterating peripheral vascular diseases (intermittent claudication, Raynaud’s syndrome); in hepatic insufficiency, chronic renal failure, in myasthenia gravis, thyrotoxicosis, depression (including in history), in psoriasis, age under 18 years (efficacy and safety not established), age over 60 years.

Treatment should be discontinued gradually, over 1-2 weeks, to avoid the development of withdrawal syndrome.

When consuming alcohol during talinolol therapy, a slowdown in the speed of psychomotor reactions associated with a decrease in blood pressure is possible.

Effect on the ability to drive vehicles and operate machinery

When using talinolol, especially at the beginning of treatment and when changing the drug, a slowdown in the speed of psychomotor reactions associated with a decrease in blood pressure is possible. This should be taken into account by patients engaged in potentially hazardous activities that require increased attention and speed of psychomotor reactions.

Drug Interactions

With simultaneous use with antihypertensive agents, the hypotensive effect is enhanced.

With simultaneous use, the effects of hypoglycemic, psychotropic agents and ethanol may be enhanced.

With simultaneous use, the negative chronotropic and dromotropic effects of cardiac glycosides are enhanced; the cardiodepressant effects of class I A antiarrhythmic agents are enhanced.

With simultaneous use with ergot alkaloids (especially non-hydrogenated ones), the risk of peripheral circulation disorders increases.

With simultaneous use with verapamil, diltiazem (especially intravenous forms), an enhancement of the cardiodepressant effect of talinolol is possible.

In patients receiving beta-adrenergic blockers, sudden withdrawal of clonidine may lead to severe arterial hypertension. It is believed that this is due to an increase in the concentration of catecholamines in the circulating blood and an enhancement of their vasoconstrictor action.

With simultaneous use with reserpine, methyldioxyphenylalanine, bradycardia may be enhanced.

With simultaneous use with sulfasalazine, a significant decrease in the concentration of talinolol in the blood was noted.

With simultaneous use with erythromycin, an increase in the plasma concentration of talinolol is possible.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.