Instructions for use
Cordaflex RD tab p.o 40mg No. 30

Dosage forms
tablets 40mg

Synonyms
Adalat
Vero-Nifedipine
Calcigard retard
Cordafen
Cordaflex
Cordipin
Cordipin retard
Kordipin HL
Corinfar
Corinfar retard
Corinfar Uno
Nifedipine

Nifecard HL
Osmo-Adalat
Phenigidine

Group
Calcium channel blockers of the dihydropyridine group

International generic name
Nifedipine

Compound
The active substance is nifedipine.

Manufacturers
Arena Pharmaceuticals GmbH, packaged by Egis Pharmaceutical Plant (Switzerland), Siegfried Ltd/Egis JSC (Switzerland)

Pharmacological action
Antianginal, hypotensive. Blocks calcium channels, inhibits the transmembrane flow of calcium ions into smooth muscle cells of arterial vessels and cardiomyocytes. Expands peripheral, mainly arterial vessels, incl. coronary, lowers blood pressure, reduces overall peripheral resistance blood vessels and afterload on the heart. Increases coronary blood flow, reduces the strength of heart contractions, heart function and myocardial oxygen demand. Improves myocardial function and helps reduce heart size in chronic heart failure. Reduces blood pressure pulmonary artery, has a positive effect on cerebral hemodynamics. Inhibits platelet aggregation, has antiatherogenic properties, improves post-stenotic circulation in atherosclerosis. Increases the excretion of sodium and water, reduces myometrial tone. When taken orally, it is quickly and completely absorbed. The bioavailability of all dosage forms is 40-60%. About 90% of the dose taken is bound to plasma proteins. After oral administration, the maximum concentration in plasma is created after 30 minutes, the half-life is 2-4 hours. It is excreted by the kidneys in the form inactive metabolites and with feces. In small quantities it passes through the blood-brain barrier and the placental barrier, and penetrates into breast milk. Does not have mutagenic or carcinogenic activity.

Side effect
From the cardiovascular system and blood (hematopoiesis, hemostasis: facial hyperemia with a feeling of heat, palpitations, tachycardia, hypotension (up to fainting), angina-like pain, very rarely - anemia, leukopenia, thrombocytopenia, thrombocytopenic purpura. From the nervous system systems and sensory organs: dizziness, headache, stunned, change visual perception, loss of sensation in the arms and legs. From the gastrointestinal tract: constipation, nausea, diarrhea, gingival hyperplasia (with long-term treatment), increased activity of liver transaminases. From the respiratory system: bronchospasm. From the musculoskeletal system: myalgia, tremor. Allergic reactions: itching, urticaria, exanthema, exfoliative dermatitis. Other: swelling and redness of the arms and legs, photodermatitis, hyperglycemia, gynecomastia (in elderly patients), burning sensation at the injection site (with intravenous administration).

Indications for use
Arterial hypertension, including hypertensive crisis, prevention of angina attacks (including Prinzmetal's angina), hypertrophic cardiomyopathy (obstructive, etc.), Raynaud's disease, pulmonary hypertension, broncho-obstructive syndrome.

Contraindications
Hypersensitivity, acute period myocardial infarction (first 8 days), cardiogenic shock, severe aortic stenosis, heart failure in the stage of decompensation, severe arterial hypotension, tachycardia, pregnancy, breastfeeding. Restrictions on use: You should refrain from using the drug in pediatric practice, since the safety and effectiveness of its use in children have not been determined.

Overdose
Symptoms: severe bradycardia, bradyarrhythmia, arterial hypotension, in severe cases - collapse, conduction slowdown. When taking a large number of retard tablets, signs of intoxication appear no earlier than after 3-4 hours and can additionally be expressed in loss of consciousness up to coma, cardiogenic shock, convulsions, hyperglycemia, metabolic acidosis, hypoxia. Treatment: gastric lavage, taking activated carbon, administration of norepinephrine, calcium chloride or calcium gluconate in atropine solution intravenously. Hemodialysis is ineffective.

Interaction
The hypotensive effect is enhanced by nitrates, diuretics, beta-blockers, tricyclic antidepressants, fentanyl, and alcohol. Increases the activity of theophylline, reduces the renal clearance of digoxin. Strengthens side effects vincristine (reduces excretion). Increases the bioavailability of cephalosporins (cefixime). Cimetidine and ranitidine increase plasma levels. Diltiazem slows metabolism (requires a reduction in the dose of nifedipine). Incompatible with rifampicin (accelerates biotransformation and does not allow the creation effective concentrations). Grapefruit juice (large quantities) increases bioavailability. Increases the concentration of cardiac glycosides in the blood.

Special instructions
Elderly patients are advised to reduce daily dose(decreased metabolism). Use with caution when working for drivers vehicles and people whose profession is associated with increased concentration. The drug should be discontinued gradually. In patients with stable angina, at the beginning of treatment, a paradoxical increase in anginal pain may occur; with severe coronary sclerosis and unstable angina, aggravation of myocardial ischemia may occur. It is not recommended to use drugs short acting For long-term treatment angina pectoris or arterial hypertension, because Unpredictable changes may occur blood pressure and reflex angina.

Storage conditions
Store at room temperature, in a cool, dry place, away from children.

Release form

Pills

Compound

Nifedipine 40 mg excipients: cellulose - 10 mg, microcrystalline cellulose - 48.5 mg, lactose - 30 mg, hypromellose 4000 mpa.s - 20 mg, magnesium stearate - 1.5 mg, colloidal anhydrous silicon dioxide - 0.75 mg. shell composition: hypromellose 15 mpa .s - 2 mg, macrogol 6000 - 0.07 mg, macrogol 400 - 1.1 mg, red iron oxide (e172) - 0.9 mg, titanium dioxide (e171) - 2 mg, talc - 1 mg.

Pharmacological effect

Selective blocker of slow calcium channels, 1,4-dihydropyridine derivative. It has antihypertensive and antianginal effects. Nifedipine reduces the flow of extracellular calcium ions into cardiomyocytes and smooth muscle cells of the coronary and peripheral arteries. In therapeutic doses, it normalizes the transmembrane current of calcium ions, disturbed by a number of pathological conditions primarily for arterial hypertension. Reduces spasm and dilates coronary and peripheral arterial vessels, reduces peripheral vascular resistance, reduces afterload and myocardial oxygen demand. At the same time, it improves blood supply to ischemic areas of the myocardium without the development of steal syndrome, and also increases the number of functioning collaterals. Nifedipine has virtually no effect on the sinoatrial and AV node and does not have both pro- and antiarrhythmic action. Does not affect the tone of the veins. Nifedipine increases renal blood flow, causing moderate natriuresis. In high doses, it inhibits the release of calcium ions from intracellular stores. Reduces the number of functioning calcium channels without affecting the time of their activation, inactivation and recovery. After a single dose of the drug Cordaflex RD, the duration of the effect exceeds 24 hours.

Pharmacokinetics

Absorption After oral administration, the drug is quickly and almost completely (90%) absorbed from the gastrointestinal tract. When developing the dosage form of the drug Cordaflex RD, zero-order release kinetics was chosen in order to ensure constant speed release active substance. The relative bioavailability of Cordaflex RD is about 60%. Cmax in blood plasma is 29.4±12.0 ng/ml. The concentration of the drug in plasma reaches a plateau 7.4±6.4 hours after taking each dose. Cmax of nifedipine in blood plasma is achieved when taking the drug Cordaflex RD with food. However, at the end of the dosing interval, the concentration of the drug in the blood plasma does not change. After taking Cordaflex RD, after 24 hours, the concentration of nifedipine in the blood plasma reaches a minimum level of 12.0 ± 6.5 ng/ml, which is twice the concentration achieved after taking Cordaflex 20 mg tablets (regular drug form) 2 times/day. Distribution: Binding to blood plasma proteins (albumin) is 94-97%. Studies with labeled nifedipine in animals have shown that unbound nifedipine is distributed in all organs and tissues. It was found that the concentration of nifedipine is higher in the myocardium than in skeletal muscles. There is no cumulative effect. MetabolismNifedipine is mainly metabolized in the liver with the formation of inactive metabolites. Elimination: 60-80% of the drug dose taken orally is excreted in the urine in the form of inactive metabolites, the remaining part is excreted in bile and feces. T1/2 of nifedipine from blood plasma is about 2 hours However, after taking Cordaflex RD, the elimination of nifedipine occurs over a longer period - up to 14.9 ± 6.0 hours at steady state. Pharmacokinetics in special clinical conditions When renal function is impaired, the pharmacokinetics of nifedipine does not change. With a significant decrease in liver function, the clearance of nifedipine is reduced, so it is not recommended to exceed the daily dose.

Indications

Arterial hypertension; - stable angina (angina pectoris); - post-infarction angina; - angiospastic angina (Prinzmetal angina).

Contraindications

Unstable angina; - myocardial infarction with left ventricular failure; - severe arterial hypotension with the risk of collapse in cardiovascular shock with respiratory manifestations; - increased sensitivity to nifedipine, other components of the drug, other 1,4-dihydropyridine derivatives. The drug should be used with caution when acute myocardial infarction during the first 4 weeks, severe aortic stenosis, severe stenosis mitral valve, hypertrophic obstructive cardiomyopathy, severe bradycardia or tachycardia, SSSU, with chronic heart failure, severe disorders cerebral circulation, renal or liver failure (especially in patients on hemodialysis due to the high risk of excessive and unpredictable decrease in blood pressure), in patients under the age of 18 years (since safety and effectiveness have not been established), in elderly patients (due to most likely age-related disorders kidney and liver functions).

Precautions

During the treatment period, exacerbation of psoriasis is possible. For pheochromocytoma, propranolol can be used only after taking an alpha-blocker. After a long course of treatment, propranolol should be discontinued gradually, under medical supervision. During treatment with propranolol, intravenous administration of verapamil, diltiazem should be avoided. Several days before When performing anesthesia, it is necessary to stop taking propranolol or select an anesthetic agent with minimal negative inotropic effect. Impact on the ability to drive vehicles and operate machinery In patients whose activities require increased attention, the issue of using propranolol on an outpatient basis should be decided only after assessing the patient’s individual response.

Use during pregnancy and breastfeeding

Prescribing the drug Cordaflex RD during pregnancy may be recommended if it is impossible to use other drugs that do not have restrictions on use. Since nifedipine is released with breast milk, you should refrain from prescribing the drug during lactation, or stop breast-feeding during treatment.

Directions for use and doses

The dose should be selected individually, depending on the severity of the patient’s condition and the effectiveness of treatment. For arterial hypertension, Cordaflex RD is prescribed 40 mg (1 tablet) 1 time/day. If necessary, the dose can be increased to 80 mg (2 tablets in 1-2 doses). Increasing the dose to more than 80 mg is not recommended. For ischemic heart disease, 40 mg (1 tablet) is prescribed 1 time/day. If necessary, the dose can be increased to 80 mg (2 tablets in 1 or 2 doses). Doses greater than 80 mg may be given in exceptional cases under medical supervision. The daily dose should not exceed 120 mg. Tablets should be taken with meals (for example, breakfast), swallowed whole and washed down with enough water. In case of impaired renal or liver function, the drug is recommended to be used with caution in the same doses as for normal function kidneys or liver. Tolerance may develop. If there is a significant decrease in liver function, the dose should not exceed 40 mg/day.

Side effects

From the cardiovascular system: at the beginning of treatment - facial skin flushing, marked decrease in blood pressure, tachycardia; peripheral edema (ankles, feet, legs); rarely - increased frequency of angina attacks (which is typical for other vasoactive drugs and requires discontinuation of the drug), heart failure. From the central nervous system and peripheral nervous system: headache, dizziness, fatigue, drowsiness; with long-term use in high doses - paresthesia in the limbs, tremor. digestive system: nausea, heartburn, diarrhea or constipation; rarely with long-term use - intrahepatic cholestasis, increased activity of liver transaminases (disappears after discontinuation of the drug); in some cases - gum hyperplasia. From the hematopoietic system: rarely - thrombocytopenia, thrombocytopenic purpura, leukopenia; in some cases - anemia. From the urinary system: increased daily diuresis; rarely - deterioration of kidney function in patients with chronic renal failure From the musculoskeletal system: myalgia; very rarely - arthritis, arthralgia. Allergic reactions: rarely - urticaria, exanthema, itchy skin; very rarely - photodermatitis. Others: in some cases - visual impairment, gynecomastia, hyperglycemia (completely disappear after discontinuation of the drug), changes in body weight, galactorrhea. In the vast majority of cases, the drug Cordaflex RD is well tolerated by patients.

Overdose

Symptoms: headache, arterial hypotension, and also (as under the influence of other vasodilators) disruption of the energy supply to the myocardium (angina attack). Treatment: immediately after an overdose, as first aid, you can rinse the stomach and give activated charcoal. If necessary, small intestinal lavage can be done, which is especially appropriate in the case of an overdose of controlled-release drugs. Since nifedipine is highly bound to plasma proteins, dialysis is not effective, but plasmapheresis may be effective. Symptoms of the disorder heart rate Bradycardia can be treated with the administration of beta sympathomimetics. At life threatening bradycardia should be used artificial driver rhythm. For severe arterial hypotension, infusion of norepinephrine (norepinephrine) in standard doses is indicated. If symptoms of heart failure develop, intravenous administration of fast-acting digitalis glycosides is recommended. Due to the lack of a specific antidote, symptomatic therapy is indicated. Dopamine, isoprenaline and 10% calcium gluconate (10-20 ml IV) can be used as antidotes.

Interaction with other drugs

Cordaflex RD can be successfully used in the composition combination therapy.Rational from the point of view of antihypertensive and antianginal effects is the combination of Cordaflex RD with beta-blockers, diuretics, ACE inhibitors, nitrates. Combined use Cordaflex RD with beta-blockers is safe and highly effective in most clinical situations, because leads to summation and potentiation of effects, however, in some cases there is a risk of developing arterial hypotension and worsening heart failure. An increase in the hypotensive effect is also observed in combination therapy with cimetidine, ranitidine and tricyclic antidepressants. During treatment with corticosteroids and NSAIDs, the effectiveness of Cordaflex RD does not decrease. Cordaflex RD increases the concentration of digoxin and theophylline; therefore, the clinical effect and/or the content of digoxin and theophylline in the blood plasma should be monitored. When administered simultaneously with rifampicin and calcium preparations, the effect of Cordaflex RD is weakened. Procaine, quinidine and other drugs that cause prolongation of the interval QT, increase the negative inotropic effect and increase the risk of QT prolongation. Under the influence of Cordaflex RD, the concentration of quinidine in the blood serum is significantly reduced, which is apparently due to a decrease in its bioavailability, as well as the induction of enzymes involved in the metabolism of quinidine. When Cordaflex RD is discontinued, a transient increase in quinidine concentration is observed (approximately 2 times), which reaches a maximum level on days 3-4. The use of such a combination requires caution, especially in patients with impaired left ventricular function. Nifedipine can displace drugs characterized by a high degree of binding from protein binding (including indirect anticoagulants - derivatives of coumarin and indanedione, anticonvulsants, NSAIDs), as a result of which their concentrations in the blood plasma may increase. Because. It has been shown that carbamazepine and phenobarbital, by activating liver enzymes, reduce the plasma concentration of other calcium channel blockers; a similar decrease in the concentration of nifedipine in the blood plasma cannot be excluded. Valproic acid, inhibiting the activity of enzymes, led to an increase in the plasma concentration of other calcium channel blockers , therefore, an increase in the concentration of nifedipine in the blood plasma cannot be excluded when taken simultaneously with valproic acid. Nifedipine inhibits the elimination of vincristine from the body and may cause an increase in its side effects (if necessary, the dose of vincristine is reduced). Diltiazem suppresses the metabolism of nifedipine in the body, careful monitoring is necessary, if necessary, reduce the dose of nifedipine. Grapefruit juice suppresses the metabolism of nifedipine in the body, and therefore it is not recommended to use it with nifedipine.

Special instructions

After myocardial infarction, the drug should be started only after stabilization of hemodynamic parameters. Patients with acute myocardial infarction and for 30 days after it should not use short-acting calcium channel blockers derivatives of 1,4-dihydropyridine. When prescribing calcium channel blockers - 1,4-dihydropyridine controlled-release derivatives - to such patients, careful monitoring is necessary. It is more appropriate to prescribe these drugs in the absence of a tendency to tachycardia, as well as in patients in whom beta-blockers are ineffective or have contraindications to their use. In cases of insufficient effectiveness of Cordaflex RD monotherapy, it is advisable to continue treatment using effective combinations with other medicines.Patients with heart failure are recommended to undergo appropriate therapy with digitalis preparations before starting treatment with Cordaflex RD. If during therapy the patient requires surgery under general anesthesia, it is necessary to inform the anesthesiologist about the therapy being carried out. During the treatment period, alcohol consumption is not recommended due to the risk of an excessive decrease in blood pressure. Impact on the ability to drive vehicles and operate machinery. During the initial individually determined period of treatment, it is necessary to refrain from potentially dangerous species activities requiring quick mental and motor reactions. In progress further treatment the degree of restrictions is determined depending on the individual tolerability of the drug.

The drug should be stored at a temperature not exceeding 30°C, protected from direct sun rays and out of the reach of children.

Expiration date from date of manufacture

Product Description

Controlled-release tablets, brown-red, round, biconvex, beveled, odorless, film-coated.

Pharmacological action

Selective blocker of slow calcium channels, 1,4-dihydropyridine derivative. Has antihypertensive and antianginal effects.
Nifedipine reduces the flow of extracellular calcium ions into cardiomyocytes and smooth muscle cells of the coronary and peripheral arteries. In therapeutic doses, it normalizes the transmembrane current of calcium ions, which is disturbed in a number of pathological conditions, primarily arterial hypertension. Reduces spasm and dilates coronary and peripheral arterial vessels, reduces peripheral vascular resistance, reduces afterload and myocardial oxygen demand. At the same time, it improves blood supply to ischemic areas of the myocardium without the development of “steal” syndrome, and also increases the number of functioning collaterals.
Nifedipine has virtually no effect on the sinoatrial and AV node and does not have either pro- or antiarrhythmic effects. Does not affect the tone of the veins. Nifedipine increases renal blood flow, causing moderate natriuresis. In high doses, it inhibits the release of calcium ions from intracellular stores. Reduces the number of functioning calcium channels without affecting the time of their activation, inactivation and recovery.
After a single dose of Cordaflex® RD, the duration of the effect exceeds 24 hours.

Pharmacokinetics

Suction
After oral administration, the drug is quickly and almost completely (90%) absorbed from the gastrointestinal tract. When developing the dosage form of the drug Cordaflex® RD, zero-order release kinetics was chosen in order to ensure a constant rate of release of the active substance. The relative bioavailability of Cordaflex® RD is about 60%. Cmax in blood plasma is 29.4±12.0 ng/ml. The concentration of the drug in plasma reaches a plateau 7.4 ± 6.4 hours after taking each dose. Cmax of nifedipine in blood plasma is achieved when taking Cordaflex® RD in combination with food. However, at the end of the dosing interval, the concentration of the drug in the blood plasma does not change.
After taking Cordaflex® RD, after 24 hours, the concentration of nifedipine in the blood plasma reaches a minimum level of 12.0±6.5 ng/ml, which is twice the concentration achieved after taking Cordaflex 20 mg tablets (regular dosage form) 2 times a day.
Distribution
Binding to blood plasma proteins (albumin) is 94-97%. Studies with labeled nifedipine in animals have shown that unbound nifedipine is distributed in all organs and tissues. Nifedipine concentrations were found to be higher in the myocardium than in skeletal muscles. There is no cumulative effect.
Metabolism
Nifedipine is mainly metabolized in the liver to form inactive metabolites.
Removal
60-80% of the dose of the drug taken orally is excreted in the urine in the form of inactive metabolites, the remaining part is excreted in bile and feces. T1/2 of nifedipine from blood plasma is about 2 hours. However, after taking Cordaflex RD, excretion of nifedipine occurs over a longer period - up to 14.9± 6.0 h at steady state.

If renal function is impaired, the pharmacokinetics of nifedipine does not change.

Indications for use

Arterial hypertension; stable angina (angina pectoris); post-infarction angina; angiospastic angina (Prinzmetal's angina).

Use during pregnancy and lactation

Prescribing Cordaflex® RD during pregnancy may be recommended if it is impossible to use other drugs that do not have restrictions on their use.

Special instructions

After myocardial infarction, the drug should be started only after stabilization of hemodynamic parameters.
Patients with acute myocardial infarction and for 30 days after it should not use short-acting calcium channel blockers derived from 1,4-dihydropyridine. When prescribing calcium channel blockers - 1,4-dihydropyridine controlled-release derivatives - to such patients, careful monitoring is necessary. These drugs are more appropriate to prescribe in the absence of a tendency to tachycardia, as well as in patients in whom beta-blockers are ineffective or have contraindications to their use.
In cases of insufficient effectiveness of Cordaflex RD monotherapy, it is advisable to continue treatment using effective combinations with other drugs.
Patients with heart failure are recommended to undergo appropriate therapy with digitalis preparations before starting treatment with Cordaflex RD.
If during therapy the patient requires surgery under general anesthesia, it is necessary to inform the anesthesiologist about the therapy being performed.
During treatment, alcohol consumption is not recommended due to the risk of excessive reduction in blood pressure.

With caution (Precautions)

Contraindications

Unstable angina; myocardial infarction with left ventricular failure; severe arterial hypotension with a risk of collapse in cardiovascular shock with respiratory manifestations; hypersensitivity to nifedipine, other components of the drug, other 1,4-dihydropyridine derivatives.
The drug should be used with caution in acute myocardial infarction during the first 4 weeks, severe aortic stenosis, severe mitral valve stenosis, hypertrophic obstructive cardiomyopathy, severe bradycardia or tachycardia, SSSS, chronic heart failure, severe cerebrovascular accidents, renal or hepatic failure ( especially in patients on hemodialysis due to the high risk of excessive and unpredictable decrease in blood pressure), in patients under the age of 18 years (since safety and effectiveness have not been established), in elderly patients (due to the greatest likelihood of age-related renal dysfunction and liver).

Directions for use and doses

The dose should be selected individually, depending on the severity of the patient's condition and the effectiveness of treatment.
For arterial hypertension, Cordaflex® RD is prescribed 40 mg (1 tablet) 1 time/day. If necessary, the dose can be increased to 80 mg (2 tablets in 1-2 doses). Dose increases beyond 80 mg are not recommended.
For ischemic heart disease, 40 mg (1 tablet) is prescribed 1 time/day. If necessary, the dose can be increased to 80 mg (2 tablets in 1 or 2 doses). Doses greater than 80 mg may be given in exceptional cases under medical supervision. The daily dose should not exceed 120 mg.
The tablets should be taken with a meal (such as breakfast), swallowed whole and with plenty of water.
In case of impaired renal or liver function, the drug is recommended to be used with caution in the same doses as for normal renal or liver function. Tolerance may develop. If there is a significant decrease in liver function, the dose should not exceed 40 mg/day.

Overdose

Symptoms: headache, arterial hypotension, and also (as under the influence of other vasodilators) disruption of the energy supply to the myocardium (angina attack).
Treatment: Immediately after an overdose, first aid measures include gastric lavage and activated charcoal. If necessary, small intestinal lavage can be done, which is especially useful in cases of overdose of controlled-release drugs.
Because nifedipine is highly bound to plasma proteins, dialysis is not effective, but plasmapheresis may be effective.
Symptoms of heart rhythm disturbances with bradycardia can be eliminated by the administration of beta sympathomimetics. For life-threatening bradycardia, an artificial pacemaker should be used.
For severe hypotension, infusion of norepinephrine (norepinephrine) in standard doses is indicated. If symptoms of heart failure develop, intravenous administration of fast-acting digitalis glycosides is recommended.

Side effect

From the cardiovascular system: at the beginning of treatment - facial skin flushing, marked decrease in blood pressure, tachycardia; peripheral edema (ankles, feet, legs); rarely - increased frequency of angina attacks (which is typical for other vasoactive drugs and requires discontinuation of the drug), heart failure.
From the central nervous system and peripheral nervous system: headache, dizziness, increased fatigue, drowsiness; with long-term use in high doses - paresthesia in the limbs, tremor.
From the digestive system: nausea, heartburn, diarrhea or constipation; rarely with long-term use - intrahepatic cholestasis, increased activity of liver transaminases (disappears after discontinuation of the drug); in some cases - gum hyperplasia.
From the hematopoietic system: rarely - thrombocytopenia, thrombocytopenic purpura, leukopenia; in some cases - anemia.
From the urinary system: increased daily diuresis; rarely - deterioration of renal function in patients with chronic renal failure.
From the musculoskeletal system: myalgia; very rarely - arthritis, arthralgia.
Allergic reactions: rarely - urticaria, exanthema, itching; very rarely - photodermatitis.
Other: in some cases - visual impairment, gynecomastia, hyperglycemia (completely disappear after discontinuation of the drug), changes in body weight, galactorrhea.
In the vast majority of cases, Cordaflex® RD is well tolerated by patients.

Compound

Active substance: nifedipine 40 mg;

Shell composition: hypromellose 15 mPa.s - 2 mg, macrogol 6000 - 0.07 mg, macrogol 400 - 1.1 mg, red iron oxide (E172) - 0.9 mg, titanium dioxide (E171) - 2 mg, talc - 1 mg.

Interaction with other drugs

Cordaflex® RD can be successfully used as part of combination therapy.
The combination of Cordaflex RD with beta-blockers, diuretics, ACE inhibitors, and nitrates is rational from the point of view of antihypertensive and antianginal effects.
The combined use of Cordaflex RD with beta-blockers is safe and highly effective in most clinical situations, because leads to summation and potentiation of effects, however, in some cases there is a risk of developing arterial hypotension and increased heart failure.
An increase in the hypotensive effect is also observed during combination therapy with cimetidine, ranitidine and tricyclic antidepressants.
During treatment with corticosteroids and NSAIDs, the effectiveness of Cordaflex RD does not decrease.
Cordaflex® RD increases the concentration of digoxin and theophylline; therefore, the clinical effect and/or the content of digoxin and theophylline in the blood plasma should be monitored.
When administered simultaneously with rifampicin and calcium preparations, the effect of Cordaflex RD is weakened.
Procaine, quinidine and other drugs that cause QT prolongation enhance the negative inotropic effect and increase the risk of QT prolongation. Under the influence of Cordaflex RD, the concentration of quinidine in the blood serum is significantly reduced, which is apparently due to a decrease in its bioavailability, as well as the induction of enzymes involved in the metabolism of quinidine. When Cordaflex RD is discontinued, a transient increase in quinidine concentration is observed (approximately 2 times), which reaches a maximum level on days 3-4. The use of this combination requires caution, especially in patients with impaired left ventricular function.
Nifedipine can displace drugs characterized by a high degree of binding from protein binding (including indirect anticoagulants - coumarin and indanedione derivatives, anticonvulsants, NSAIDs), as a result of which their concentrations in the blood plasma may increase.
Because It has been shown that carbamazepine and phenobarbital, by activating liver enzymes, reduce the plasma concentrations of other calcium channel blockers; a similar decrease in the plasma concentrations of nifedipine cannot be excluded.
Valproic acid, inhibiting the activity of enzymes, led to an increase in the plasma concentration of other calcium channel blockers, so an increase in the concentration of nifedipine in the blood plasma cannot be excluded when taken simultaneously with valproic acid.
Nifedipine inhibits the elimination of vincristine from the body and may cause an increase in its side effects (if necessary, reduce the dose of vincristine).
Diltiazem inhibits the metabolism of nifedipine in the body; careful monitoring is necessary; if necessary, reduce the dose of nifedipine.
Grapefruit juice inhibits the metabolism of nifedipine in the body, and therefore it is not recommended to use it with nifedipine.

Release form

Controlled-release tablets, brown-red, round, biconvex, beveled, odorless, film-coated.
1 tab. Active substance: nifedipine 40 mg;
Excipients: cellulose - 10 mg, microcrystalline cellulose - 48.5 mg, lactose - 30 mg, hypromellose 4000 mPa.s - 20 mg, magnesium stearate - 1.5 mg, colloidal anhydrous silicon dioxide - 0.75 mg.
Shell composition: hypromellose 15 mPa.s - 2 mg, macrogol 6000 - 0.07 mg, macrogol 400 - 1.1 mg, red iron oxide (E172) - 0.9 mg, titanium dioxide (E171) - 2 mg, talc - 1 mg.
10 pcs. - blisters (1) - cardboard packs.

Release form, composition and packaging

Controlled-release film-coated tablets brownish-red in color, round, biconvex, chamfered, odorless.

	1 tab.
nifedipine	40 mg

Excipients: cellulose, microcrystalline cellulose, lactose, hypromellose 4000, magnesium stearate, colloidal anhydrous silicon dioxide.

Shell composition: hypromellose 15, macrogol 6000, macrogol 400, red iron oxide (E172), titanium dioxide (E171), talc.

10 pcs. - blisters (1) - cardboard packs.
10 pcs. - blisters (3) - cardboard packs.

Clinical and pharmacological group

Calcium channel blocker

Pharmacological action

Selective blocker of slow calcium channels, 1,4-dihydropyridine derivative. Has antihypertensive and antianginal effects.

Nifedipine reduces the flow of extracellular calcium ions into cardiomyocytes and smooth muscle cells of the coronary and peripheral arteries. In therapeutic doses, it normalizes the transmembrane current of calcium ions, which is disturbed in a number of pathological conditions, primarily arterial hypertension. Reduces spasm and dilates coronary and peripheral arterial vessels, reduces peripheral vascular resistance, reduces afterload and myocardial oxygen demand. At the same time, it improves blood supply to ischemic areas of the myocardium without the development of “steal” syndrome, and also increases the number of functioning collaterals.

Nifedipine has virtually no effect on the sinoatrial and AV node and does not have either pro- or antiarrhythmic effects. Does not affect the tone of the veins. Nifedipine increases renal blood flow, causing moderate natriuresis. In high doses, it inhibits the release of calcium ions from intracellular stores. Reduces the number of functioning calcium channels without affecting the time of their activation, inactivation and recovery.

After a single dose of Cordaflex ® RD, the duration of the effect exceeds 24 hours.

Pharmacokinetics

Suction

After oral administration, the drug is quickly and almost completely (90%) absorbed from the gastrointestinal tract. When developing the dosage form of the drug Cordaflex ® RD, zero-order release kinetics was chosen in order to ensure a constant rate of release of the active substance. The relative bioavailability of the drug Cordaflex ® RD is about 60%. Cmax in blood plasma is 29.4±12.0 ng/ml. The concentration of the drug in plasma reaches a plateau 7.4±6.4 hours after taking each dose. Cmax of nifedipine in blood plasma is achieved when taking Cordaflex ® RD in combination with food. However, at the end of the dosing interval, the concentration of the drug in the blood plasma does not change.

After taking Cordaflex ® RD, after 24 hours, the concentration of nifedipine in the blood plasma reaches a minimum level of 12.0±6.5 ng/ml, which is twice the concentration achieved after taking Cordaflex 20 mg tablets (usual dosage form) 2 times a day.

Distribution

Binding to blood plasma proteins (albumin) is 94-97%. Studies with labeled nifedipine in animals have shown that unbound nifedipine is distributed in all organs and tissues. Nifedipine concentrations were found to be higher in the myocardium than in skeletal muscles. There is no cumulative effect.

Metabolism

Nifedipine is mainly metabolized in the liver to form inactive metabolites.

Removal

60-80% of the dose of the drug taken orally is excreted in the urine in the form of inactive metabolites, the remaining part is excreted in bile and feces. T1/2 of nifedipine from the blood plasma is about 2 hours. However, after taking Cordaflex RD, excretion of nifedipine occurs over a longer period - up to 14.9 ±6.0 h at steady state.

Pharmacokinetics in special clinical conditions

If renal function is impaired, the pharmacokinetics of nifedipine does not change.

With a significant decrease in liver function, the clearance of nifedipine is reduced, so it is not recommended to exceed the daily dose.

Indications for use of the drug

- arterial hypertension;

- stable angina (angina pectoris);

- post-infarction angina;

- angiospastic angina (Prinzmetal's angina).

Dosage regimen

The dose should be selected individually, depending on the severity of the patient's condition and the effectiveness of treatment.

At arterial hypertension Cordaflex ® RD is prescribed 40 mg (1 tablet) 1 time/day. If necessary, the dose can be increased to 80 mg (2 tablets in 1-2 doses). Dose increases beyond 80 mg are not recommended.

At IHD prescribed 40 mg (1 tablet) 1 time/day. If necessary, the dose can be increased to 80 mg (2 tablets in 1 or 2 doses). Doses greater than 80 mg may be given in exceptional cases under medical supervision. The daily dose should not exceed 120 mg.

Cordaflex RD tablets should be taken with a meal (for example, breakfast), swallowed whole and with plenty of water.

At impaired renal or liver function The drug is recommended to be used with caution in the same doses as for normal renal or hepatic function. Tolerance may develop. If there is a significant decrease in liver function, the dose should not exceed 40 mg/day.

Side effect

From the cardiovascular system: at the beginning of treatment - facial skin hyperemia, marked decrease in blood pressure, tachycardia; peripheral edema (ankles, feet, legs); rarely - increased frequency of angina attacks (which is typical for other vasoactive drugs and requires discontinuation of the drug), heart failure.

From the central nervous system and peripheral nervous system: headache, dizziness, increased fatigue, drowsiness; with long-term use in high doses - paresthesia in the limbs, tremor.

From the digestive system: nausea, heartburn, diarrhea, or constipation; rarely with long-term use - intrahepatic cholestasis, increased activity of liver transaminases (disappears after discontinuation of the drug); in some cases - gum hyperplasia.

From the hematopoietic system: rarely - thrombocytopenia, thrombocytopenic purpura, leukopenia; in some cases - anemia.

From the urinary system: increased daily diuresis; rarely - deterioration of renal function in patients with chronic renal failure.

From the musculoskeletal system: myalgia; very rarely - arthritis, arthralgia.

Allergic reactions: rarely - urticaria, exanthema, itching; very rarely - photodermatitis.

Other: in some cases - visual impairment, gynecomastia, hyperglycemia (completely disappear after discontinuation of the drug), changes in body weight, galactorrhea.

In the vast majority of cases, Cordaflex ® RD is well tolerated by patients.

Contraindications to the use of the drug

- unstable angina;

— myocardial infarction with left ventricular failure;

- severe arterial hypotension with a risk of collapse in cardiovascular shock with respiratory manifestations;

- hypersensitivity to nifedipine, other components of the drug, other 1,4-dihydropyridine derivatives.

WITH caution the drug should be used for acute myocardial infarction during the first 4 weeks, severe aortic stenosis, severe mitral valve stenosis, hypertrophic obstructive cardiomyopathy, severe bradycardia or tachycardia, SSSS, chronic heart failure, severe cerebrovascular accidents, renal or hepatic failure (especially in patients on hemodialysis due to the high risk of excessive and unpredictable decrease in blood pressure), in patients under the age of 18 years (since safety and effectiveness have not been established), in elderly patients (due to the greatest likelihood of age-related impairment of kidney and liver function ).

Use of the drug during pregnancy and lactation

Prescribing Cordaflex ® RD during pregnancy may be recommended if it is impossible to use other drugs that do not have restrictions on their use.

Since nifedipine is excreted in breast milk, you should refrain from prescribing the drug during lactation, or stop breastfeeding during treatment.

Use for liver dysfunction

WITH caution the drug should be used for liver failure (especially in patients on hemodialysis due to the high risk of excessive and unpredictable decrease in blood pressure).

Use for renal impairment

WITH caution the drug should be used for renal failure (especially in patients on hemodialysis due to the high risk of excessive and unpredictable decrease in blood pressure).

Special instructions

After myocardial infarction, the drug should be started only after stabilization of hemodynamic parameters.

Patients with acute myocardial infarction and for 30 days after it should not use short-acting calcium channel blockers derived from 1,4-dihydropyridine. When prescribing calcium channel blockers - 1,4-dihydropyridine controlled-release derivatives - to such patients, careful monitoring is necessary. These drugs are more appropriate to prescribe in the absence of a tendency to tachycardia, as well as in patients in whom beta-blockers are ineffective or have contraindications to their use.

In cases of insufficient effectiveness of Cordaflex RD monotherapy, it is advisable to continue treatment using effective combinations with other drugs.

Patients with heart failure are recommended to undergo appropriate therapy with digitalis preparations before starting treatment with Cordaflex RD.

If during therapy the patient requires surgery under general anesthesia, it is necessary to inform the anesthesiologist about the therapy being performed.

Impact on the ability to drive vehicles and operate machinery

During the initial individually determined period of treatment, it is necessary to refrain from potentially dangerous activities that require a quick mental and motor reaction. In the process of further treatment, the degree of restrictions is determined depending on the individual tolerability of the drug.

Overdose

Symptoms: headache, arterial hypotension, and also (as under the influence of other vasodilators) disruption of the energy supply of the myocardium (angina attack).

Treatment: Immediately after an overdose, you can rinse the stomach and give activated charcoal as first aid. If necessary, small intestinal lavage can be done, which is especially useful in cases of overdose of controlled-release drugs.

Because nifedipine is highly bound to plasma proteins, dialysis is not effective, but plasmapheresis may be effective.

Symptoms of heart rhythm disturbances with bradycardia can be eliminated by the administration of beta sympathomimetics. For life-threatening bradycardia, an artificial pacemaker should be used.

For severe hypotension, infusion of norepinephrine (norepinephrine) in standard doses is indicated. If symptoms of heart failure develop, intravenous administration of fast-acting digitalis glycosides is recommended.

Due to the lack of a specific antidote, symptomatic therapy is indicated. Dopamine, isoprenaline and 10% calcium gluconate (10-20 ml IV) can be used as antidotes.

Drug interactions

Cordaflex ® RD can be successfully used as part of combination therapy.

Catad_pgroup Calcium channel blockers

Cordaflex RD - instructions for use

Registration number:

LS-001219

Trade name: Cordaflex RD

International nonproprietary name:

nifedipine

Dosage form:

controlled-release film-coated tablets

Compound:

1 tablet contains 40 mg of the active substance - nifedipine, as well as excipients: cellulose, microcrystalline cellulose, lactose, hypromellose 4000, magnesium stearate, colloidal anhydrous silicon dioxide. The tablet shell contains: hypromellose 15, macrogol 6000, macrogol 400, red iron oxide E 172, titanium dioxide E 171, talc.

Description: round, biconvex, film-coated tablets, brown-red in color, beveled, odorless.

Pharmacotherapeutic group:

blocker of "slow" calcium channels

ATX Code: C08 CA05

PHARMACOLOGICAL PROPERTIES
Pharmacodynamics
The active ingredient of the drug Cordaflex ® RD is nifedipine.
Nifedipine is a selective blocker of “slow” calcium channels, a 1,4-dihydropyridine derivative. Has antihypertensive and antianginal effects. Reduces the flow of extracellular calcium ions into cardiomyocytes and smooth muscle cells of the coronary and peripheral arteries. In therapeutic doses, it normalizes the transmembrane current of calcium ions, which is disturbed in a number of pathological conditions, primarily arterial hypertension. Reduces spasm and dilates coronary and peripheral arterial vessels, reduces total peripheral resistance, reduces afterload and myocardial oxygen demand. At the same time, it improves blood supply to ischemic areas of the myocardium without developing the “steal” syndrome, and also activates the functioning of collaterals.
It has virtually no effect on the sinoatrial and atrioventricular nodes and does not have either pro- or antiarrhythmic effects. Does not affect the tone of the veins. Nifedipine increases renal blood flow, causing moderate natriuresis. In high doses, it inhibits the release of calcium ions from intracellular stores. Reduces the number of functioning calcium channels without affecting the time of their activation, inactivation and recovery.

Pharmacokinetics
Suction
Nifedipine is rapidly and almost completely (90%) absorbed from gastrointestinal tract after ingestion. The duration of the effect after a single oral dose exceeds 24 hours. When developing the active substance of the drug Cordaflex ® RD, zero-order release kinetics was chosen in order to ensure a constant release rate. The relative bioavailability of the drug is about 60%. The maximum concentration (Cmax) in blood plasma is 29.4±12.0 mg/ml (x±SD); the concentration of the drug in the blood plasma reaches a plateau 7.4 ± 6.4 hours after taking each dose. Maximum levels of the drug in blood plasma are achieved when it is taken in combination with food. However, at the end of the dosing interval, the concentration of the drug in the blood plasma does not change.
Distribution
The connection with blood plasma proteins (albumin) is 94–97%. Studies with labeled nifedipine in animals have shown that unbound nifedipine is distributed in all organs and tissues. Nifedipine concentrations were found to be higher in the myocardium than in skeletal muscles. There is no cumulative effect.
Metabolism
Nifedipine is mainly metabolized in the liver to inactive metabolites.
Removal
60–80% of the drug dose taken orally is excreted in the urine in the form of inactive metabolites, the remaining part is excreted in bile and feces. The half-life of nifedipine from blood plasma is approximately 2 hours. However, the release of the drug Cordaflex ® RD is longer - up to 14.9±6.0 hours in the phase of equilibrium concentration.
The concentration of the drug in the blood plasma reaches a minimum of 12.0±6.5 ng/ml 24 hours after administration, which is twice the concentration achieved after taking 20 mg of nifedipine 2 times a day.
If renal function is impaired, the pharmacokinetics of nifedipine does not change (nifedipine is excreted in the urine in small quantities). With a significant decrease in liver function, the clearance of nifedipine is reduced, so it is not recommended to exceed the daily dose.

INDICATIONS FOR USE
Arterial hypertension
Stable angina (angina pectoris), post-infarction angina, as well as vasospastic angina (Prinzmetal angina).

CONTRAINDICATIONS
Increased sensitivity to nifedipine or any other component of the drug, other 1,4-dihydropyridine derivatives.
Severe arterial hypotension with a risk of collapse in cardiovascular shock with respiratory manifestations.
Unstable angina.
Myocardial infarction with left ventricular failure.

With caution: severe aortic stenosis, acute heart attack myocardium (during the first 4 weeks), severe mitral valve stenosis, hypertrophic obstructive cardiomyopathy, severe bradycardia or tachycardia, sick sinus syndrome, chronic heart failure, severe violations cerebral circulation, age up to 18 years (efficacy and safety have not been established), old age, renal and liver failure (especially patients on hemodialysis - high risk excessive and unpredictable decrease in blood pressure).

PREGNANCY AND LACTATION
The use of nifedipine in pregnant women is recommended if it is impossible to use other drugs without restrictions.
Since nifedipine is excreted in breast milk, you should refrain from prescribing the drug during lactation, or stop breastfeeding during treatment.

METHOD OF APPLICATION AND DOSES
Cordaflex ® RD 40 mg should be taken in the morning, during a meal (for example, breakfast), not chewed and washed down with a sufficient amount of water.
The dose should be selected individually, depending on the severity of the patient's condition and response to therapy. The following doses can be recommended:
Arterial hypertension
If necessary, the dose can be increased to 80 mg (2 tablets of Cordaflex ® RD 40 mg in one or two doses). Increasing the dose above 80 mg is not recommended.
Ischemic disease hearts
1 tablet of Cordaflex ® RD 40 mg 1 time per day.
If necessary, the dose can be increased to 80 mg (2 tablets of Cordaflex ® RD 40 mg in one or two doses). Doses above 80 mg can be given in exceptional cases under medical supervision. The daily dose should not exceed 120 mg.
Dosage for decreased renal or liver function
It is recommended to use with caution the same doses as for normal renal or hepatic function (tolerance may develop). If there is a significant decrease in liver function, it is not recommended to exceed the daily dose of 40 mg.

SIDE EFFECTS
In the vast majority of cases, Cordaflex ® RD 40 mg is well tolerated by patients.
In some cases, especially in initial period treatment, the following transient adverse events may occur:
Cardiovascular system: at the beginning of treatment - facial skin hyperemia, marked decrease in blood pressure, tachycardia; peripheral edema (ankles, feet, legs); rarely - the appearance of angina attacks (which is also typical for other vasodilators and requires discontinuation of the drug), heart failure.
Central nervous system: headache, dizziness, increased fatigue, drowsiness. With long-term use in high doses - paresthesia in the limbs, tremor.
Digestive system: nausea, heartburn, diarrhea, or constipation; rarely with long-term use of the drug - intrahepatic cholestasis, increased activity of liver enzymes, which disappear after discontinuation of the drug; very rarely - gum hyperplasia.
Hematopoietic system: rarely - thrombocytopenia, thrombocytopenic purpura, leukopenia; very rarely - anemia.
Urinary system: increase in daily diuresis; rarely - deterioration of renal function (in patients with renal failure).
Musculoskeletal system: myalgia; very rarely - arthritis, arthralgia.
Allergic reactions: rarely - urticaria, exanthema, itching; very rarely - photodermatitis.
Other: very rarely - visual impairment, gynecomastia, hyperglycemia, which completely disappear after discontinuation of the drug; change in body weight, galactorrhea.

Overdose
Symptoms
In case of acute overdose, headache, a pronounced decrease in blood pressure, as well as a violation of the energy supply of the myocardium (an attack of angina) occur.
Treatment
In the early stages after an overdose is detected, first aid can be to rinse the stomach and give activated charcoal. If necessary, you can rinse small intestine, which is especially useful in cases of overdose of controlled-release drugs.
Since nifedipine is highly bound to plasma proteins, hemodialysis is not effective, but plasmapheresis may be effective.
Symptoms of heart rhythm disturbances with bradycardia can be eliminated by the administration of beta sympathomimetics. For life-threatening bradycardia, an artificial pacemaker should be used.
If there is a significant decrease in blood pressure, an infusion of usual doses of norepinephrine (norepinephrine) is indicated. If symptoms of heart failure develop, it is recommended intravenous administration fast-acting digitalis glycosides.
Due to the lack of a specific antidote, symptomatic therapy is indicated. Dopamine, isoprenaline and 10% calcium gluconate solution (10–20 ml IV) can be used as antidotes.

INTERACTION WITH OTHER MEDICINES
Drug Cordaflex ® RD 40 mg controlled release active substance has wide potential for highly effective combination therapy.
Rational from the point of view of antihypertensive and antianginal effects is the combination of Cordaflex ® RD 40 mg with beta-blockers, diuretics, angiotensin-converting enzyme (ACE) inhibitors, and nitrates.
The combined use of Cordaflex ® RD 40 mg with beta-blockers is safe and effective in most clinical situations, as it leads to summation and potentiation of effects; however, in some cases there is a risk of arterial hypotension and increased symptoms of heart failure.
An increase in the hypotensive effect is also observed during combination therapy with cimetidine, ranitidine and tricyclic antidepressants.
Cordaflex ® RD 40 mg does not reduce its effectiveness during treatment with steroidal and non-steroidal anti-inflammatory drugs.
Nifedipine increases the concentration of digoxin and theophylline, and therefore the clinical effect and/or the content of digoxin and theophylline in the blood plasma should be monitored.
When administered simultaneously with rifampicin and calcium preparations, the effect of nifedipine is weakened.
Procaine, quinidine and other drugs that cause QT prolongation enhance the negative inotropic effect and increase the risk of QT prolongation. Under the influence of nifedipine, the concentration of quinidine in the blood serum is significantly reduced, which is apparently due to a decrease in its bioavailability, as well as the induction of enzymes that inactivate quinidine. When nifedipine is discontinued, a transient increase in quinidine concentration is observed (approximately 2 times), which reaches a maximum level on days 3–4. Caution should be exercised when using such combinations, especially in patients with impaired left ventricular function.
Nifedipine can displace drugs characterized by a high degree of binding from protein binding (including indirect anticoagulants - coumarin and indanedione derivatives, non-steroidal anti-inflammatory drugs), as a result of which their concentration in the blood plasma may increase.
Since it has been shown that carbamazepine and phenobarbital, by activating liver enzymes, reduce the plasma concentrations of other slow calcium channel blockers (SCBCs), a similar decrease in the plasma concentrations of nifedipine cannot be excluded.
Valproic acid, inhibiting the activity of enzymes, led to an increase in the concentration in the blood plasma of other blockers of “slow” calcium channels, so an increase in the concentration of nifedipine in the blood plasma cannot be excluded when taken simultaneously with valproic acid.
Nifedipine inhibits the elimination of vincristine from the body and may cause increased side effects vincristine, if necessary, reduce the dose of vincristine.
Diltiazem inhibits the metabolism of nifedipine in the body; careful monitoring is necessary; if necessary, reduce the dose of nifedipine.
Grapefruit juice inhibits the metabolism of nifedipine in the body, and therefore it is not recommended to use it with nifedipine.

SPECIAL INSTRUCTIONS
After myocardial infarction, the drug should be started only after stabilization of hemodynamic parameters.
Patients with acute myocardial infarction and for 30 days after it should not use short-acting calcium channel blockers such as 1,4-dihydropyridine. When treating such patients with controlled-release BMCCs such as 1,4-dihydropyridine, careful monitoring is necessary. It is more advisable to prescribe in the absence of a tendency to tachycardia, as well as in patients in whom beta-blockers are ineffective or have contraindications to their use.
During the initial individually determined period of treatment, it is necessary to refrain from potentially hazardous activities that require rapid psychomotor reactions. In the process of further treatment, the degree of restrictions is determined depending on the individual tolerability of the drug.
In cases of insufficient effectiveness of monotherapy with Cordaflex ® RD 40 mg, it is advisable to continue treatment using effective combinations with other drugs (see Interactions with other drugs).
During treatment, drinking alcohol is not recommended due to the risk of excessively lowering blood pressure.
In patients with heart failure, appropriate therapy with digitalis preparations is recommended before starting treatment with Cordaflex ® RD 40 mg.
If during therapy the patient requires surgical intervention under general anesthesia, it is necessary to inform the anesthesiologist about the therapy being performed.
Caution should be exercised in elderly patients due to the greater likelihood of age-related impairment of renal and hepatic function.

RELEASE FORM
Controlled-release film-coated tablets, 40 mg. 10 tablets in a blister made of PVC/PVDC/alfoil. 1 or 3 blisters in a cardboard box along with instructions for use.

STORAGE CONDITIONS
At a temperature not exceeding 30 ° C, in a place protected from direct sunlight.
Keep out of reach of children.

BEST BEFORE DATE
5 years. Do not use after the date indicated on the package.

CONDITIONS OF VACATION FROM PHARMACIES
By doctor's prescription.

MANUFACTURER
JSC Pharmaceutical Plant EGIS 1106 Budapest, st. Keresturi, 30–38 HUNGARY
Tablet production: Arena Pharmaceuticals GmbH, Switzerland
Representative office of JSC "EGIS Pharmaceutical Plant" (Hungary) Moscow 121108, Moscow, st. Ivana Franko, no. 8.

Calcium channel blockers

INN

Nifedipine

10 pcs in blister; in a cardboard pack 1 or 3 blisters.

The drug Cordaflex ® RD with controlled release of the active substance has broad potential for highly effective combination therapy. Rational, from the point of view of antihypertensive and antianginal effects, is the combination of Cordaflex ® RD 40 mg with beta-blockers, diuretics, ACE inhibitors, and nitrates.

The combined use of Cordaflex ® RD with beta-blockers is safe and effective in most clinical situations, because leads to summation and potentiation of effects, however, in some cases there is a risk of arterial hypotension and increased heart failure.

An increase in the hypotensive effect is also observed during combination therapy with cimetidine, ranitidine and tricyclic antidepressants.

Cordaflex ® RD 40 mg does not reduce its effectiveness during treatment steroid drugs and NSAIDs.

Nifedipine increases the concentration of digoxin and theophylline, and therefore the clinical effect and/or the content of digoxin and theophylline in the blood plasma should be monitored.

When administered simultaneously with rifampicin and calcium preparations, the effect of nifedipine is weakened.

Procaine, quinidine and other drugs that cause prolongation of the QT interval enhance the negative inotropic effect and increase the risk of prolongation of the QT interval. Under the influence of nifedipine, the concentration of quinidine in the blood serum is significantly reduced, which is apparently due to a decrease in its bioavailability, as well as the induction of enzymes that inactivate quinidine. When nifedipine is discontinued, a transient increase in quinidine concentration is observed (approximately 2 times), which reaches its maximum level on the 3rd–4th day. Caution should be exercised when using such combinations, especially in patients with impaired left ventricular function.

Nifedipine can displace drugs characterized by a high degree of binding from protein binding (including indirect anticoagulants - coumarin and indanedione derivatives, NSAIDs), as a result of which their concentration in the blood plasma may increase.

Since it has been shown that carbamazepine and phenobarbital, by activating liver enzymes, reduce the plasma concentrations of other CCBs, a similar decrease in the plasma concentrations of nifedipine cannot be excluded.

Valproic acid, inhibiting the activity of enzymes, led to an increase in the plasma concentration of other CCBs; therefore, an increase in the concentration of nifedipine in the blood plasma cannot be excluded when taken simultaneously with valproic acid.

Nifedipine inhibits the elimination of vincristine from the body and may cause increased side effects of vincristine (if necessary, reduce the dose of vincristine).

Diltiazem inhibits the metabolism of nifedipine in the body, so careful monitoring is necessary (if necessary, reduce the dose of nifedipine).

Grapefruit juice inhibits the metabolism of nifedipine in the body, and therefore it is not recommended to use it with nifedipine.

arterial hypertension;

stable angina (angina pectoris), post-infarction angina, as well as vasospastic angina (Prinzmetal angina).

hypersensitivity to nifedipine or any other component of the drug, other 1,4-dihydropyridine derivatives;

severe arterial hypotension with a risk of collapse in cardiovascular shock with respiratory manifestations;

unstable angina;

myocardial infarction with left ventricular failure.

With caution: severe aortic stenosis, acute myocardial infarction (within the first 4 weeks), severe mitral valve stenosis, hypertrophic obstructive cardiomyopathy, severe bradycardia or tachycardia, sick sinus syndrome, chronic heart failure, severe cerebrovascular accidents, age under 18 years (efficacy and safety has not been established), older age, renal and liver failure (especially patients on hemodialysis have a high risk of excessive and unpredictable decrease in blood pressure).

Inside, in the morning, during a meal (for example, breakfast), without chewing and drinking plenty of water.

The dose should be selected individually, depending on the severity of the patient's condition and response to therapy.

Arterial hypertension. 1 table each Cordaflexa ® RD 40 mg once a day. If necessary, the dose can be increased to 80 mg (2 tablets of Cordaflex ® RD 40 mg in 1 or 2 doses). Increasing the dose above 80 mg is not recommended.

Coronary heart disease. 1 table each Cordaflexa ® RD 40 mg once a day. If necessary, the dose can be increased to 80 mg (2 tablets of Cordaflex ® RD 40 mg in 1 or 2 doses). Doses above 80 mg can be prescribed in exceptional cases under medical supervision. The daily dose should not exceed 120 mg.

Decreased renal or hepatic function. It is recommended to use with caution the same doses as for normal renal or hepatic function (tolerance may develop). If there is a significant decrease in liver function, it is not recommended to exceed the daily dose of 40 mg.

In the vast majority of cases, Cordaflex ® RD 40 mg is well tolerated by patients.

In some cases, especially during the initial period of treatment, the following transient adverse events may occur.

From the SSS side: at the beginning of treatment - facial skin hyperemia, marked decrease in blood pressure, tachycardia; peripheral edema (ankles, feet, legs); rarely - the appearance of angina attacks (which is also typical for other vasodilators and requires discontinuation of the drug), heart failure.

From the side of the central nervous system: headache, dizziness, increased fatigue, drowsiness. With long-term use in high doses - paresthesia in the limbs, tremor.

From the digestive system: nausea, heartburn, diarrhea, or constipation; rarely with long-term use - intrahepatic cholestasis, increased activity of liver enzymes, which occurs after discontinuation of the drug; very rarely - gum hyperplasia.

From the hematopoietic system: rarely - thrombocytopenia, thrombocytopenic purpura, leukopenia; very rarely - anemia.

From the urinary system: increase in daily diuresis; rarely - deterioration of renal function (in patients with renal failure).

From the musculoskeletal system: myalgia; very rarely - arthritis, arthralgia.

Allergic reactions: rarely - urticaria, exanthema, itching; very rarely - photodermatitis.

Other: very rarely - visual impairment, gynecomastia, hyperglycemia, which completely disappear after discontinuation of the drug; change in body weight, galactorrhea.

Symptoms acute overdose: headache, pronounced decrease in blood pressure, as well as a violation of the energy supply of the myocardium (angina attack).

Treatment: in the early stages after an overdose is detected, gastric lavage and activated charcoal are recommended as first aid. If necessary, lavage of the small intestine, which is especially advisable in case of overdose of controlled-release drugs.

Hemodialysis is ineffective because Nifedipine is highly bound to plasma proteins. Plasmapheresis may be effective.

Symptoms of heart rhythm disturbances with bradycardia can be eliminated by the administration of beta-agonists. For life-threatening bradycardia, an artificial pacemaker should be used.

With a pronounced decrease in blood pressure, an infusion of usual doses of norepinephrine (norepinephrine) is indicated. If symptoms of heart failure develop, intravenous administration of fast-acting digitalis glycosides is recommended.

Due to the lack of a specific antidote, symptomatic therapy is indicated. Dopamine, isoprenaline and 10% calcium gluconate (10–20 ml IV) can be used as antidotes.

Protected from direct sunlight place, at a temperature not exceeding 30 °C