Cordaflex rd instructions for use, contraindications, side effects, reviews. One visitor reported the frequency of intake per day

Cordaflex rd - updated description of the medication, you can read contraindications, indications for use, Cordaflex rd. Reviews about Cordaflex rd -

Selective blocker of slow calcium channels, a 1,4-dihydropyridine derivative
Product: CORDAFFLEX® RD

Active substance of the drug: nifedipine
ATX coding: C08CA05
KFG: Calcium channel blocker
Registration number: LS-001219
Registration date: 12/29/06
Owner reg. cred.: SIEGFRIED Ltd. (Switzerland)

Controlled-release tablets, brown-red, round, biconvex, beveled, odorless, film-coated. 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 pieces. - blisters (1) - cardboard packs.
10 pieces. - blisters (3) - cardboard packs.

The description of the drug is based on the officially approved instructions for use and approved by the manufacturer.

Pharmacological action of Cordaflex rd

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 normalizes the transmembrane current of Ca2+ 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 inhibits the release of Ca2+ 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 of the drug.

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 release rate active substance. The relative bioavailability of Cordaflex RD is about 60%. Cmax in blood plasma is 29.4±12.0 mg/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. It was found that the concentration of nifedipine is 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.

Pharmacokinetics of the drug.

in special clinical settings
If kidney function is impaired

Pharmacokinetics of the drug.

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

Indications for use:

Arterial hypertension of various etiologies(primary or secondary);
- stable angina (angina pectoris);
- post-infarction angina;
- angiospastic angina (Prinzmetal's angina).

Dosage and method of administration of the drug.

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 coronary 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.
Cordaflex RD tablets should be taken with a meal (for example, breakfast), swallowed whole and washed down sufficient quantity 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 of Cordaflex rd:

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; at 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 hepatic 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 outside musculoskeletal system: myalgia; very rarely - arthritis, arthralgia.
Allergic reactions: rarely - urticaria, exanthema, itchy skin; 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 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.
The drug should be used with caution in 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 (in connections with the greatest likelihood of developing age-related disorders liver or kidney function).

Use during pregnancy and lactation.

The use of 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 released from breast milk, you should refrain from prescribing the drug during lactation, or stop breast-feeding during treatment.

Special instructions for use of Cordaflex rd.

After myocardial infarction, the drug should be started only after stabilization of hemodynamic parameters.
Patients with acute heart attack myocardium and for 30 days after it should not be used calcium channel blockers derivatives of 1,4-dihydropyridine short acting. 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 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 surgical intervention 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.
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 individual tolerance drug.

Drug overdose:

Symptoms: headache, arterial hypotension, and also (as under the influence of other vasodilators) violation of the energy supply of the myocardium (angina attack).
Treatment: Immediately after an overdose, first aid measures include washing the stomach and giving Activated carbon. If necessary, you can rinse thin section intestines, which is especially appropriate in case 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 the disorder heart rate Bradycardia can be treated with the administration of beta sympathomimetics. At life threatening bradycardia, temporary pacemakers should be used.
For severe arterial hypotension norepinephrine infusion is indicated standard doses. If symptoms of heart failure develop, intravenous administration of fast-acting digitalis glycosides is recommended.
Due to the lack of a specific antidote, it is indicated symptomatic therapy. Dopamine, isoprenaline and 10% calcium gluconate (10-20 ml IV) can be used as antidotes.

Interaction of Cordaflex rd 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 in the majority clinical situations safe and highly effective, because leads to summation and potentiation of effects, however, in some cases there is a risk of developing arterial hypotension and increased heart failure.
Gain hypotensive effect 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, and therefore should be monitored clinical effect and/or the content of digoxin and theophylline in the blood plasma.
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 QT interval 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, there is a transient increase in quinidine concentration (approximately 2 times), which reaches a maximum level on days 3-4, as well as a prolongation of the QT interval on the ECG. 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 (incl. indirect anticoagulants- coumarin and indanoine 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 concentration in the blood plasma of other calcium channel blockers; therefore, an increase in the concentration of nifedipine in the blood plasma cannot be excluded when simultaneous administration 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.

Terms of sale in pharmacies.

The drug is available with a prescription.

Storage conditions for the drug Cordaflex rd.

The drug should be stored at a temperature not exceeding 30°C, protected from direct sun rays and out of the reach of children. Shelf life – 4 years.

The page contains instructions for use Cordaflexa. It is available in various dosage forms of the drug (tablets 10 mg, 20 mg retard, 40 mg RD), and also has a number of analogues. This abstract has been verified by experts. Leave your feedback on using Cordaflex, which will help other site visitors. The drug is used for various diseases(arterial hypertension or low blood pressure, angina pectoris, Raynaud's syndrome). The product has a number of side effects and interactions with other substances. Doses of the drug differ for adults and children. There are restrictions on the use of the medicine during pregnancy and breastfeeding. Treatment with Cordaflex can only be prescribed by a qualified doctor. The duration of therapy may vary and depends on specific disease. Composition of the drug.

Instructions for use and dosage regimen

The dosage regimen is set individually, depending on the severity of the disease and the patient’s response to the therapy.

For adults, Cordaflex in the form of film-coated tablets is prescribed 10 mg (1 tablet) 3 times a day. If necessary, the dose of the drug can be increased to 20 mg (2 tablets) 1-2 times a day. The maximum daily dose is 40 mg. The interval between doses of the drug is at least 2 hours.

To speed up the action of the drug at the beginning of an attack of angina or hypertensive crisis, the tablet should be chewed, held in the mouth for a while, and then swallowed with a small amount of water.

If it is necessary to increase the dose to 80-120 mg per day for the treatment of angina pectoris or arterial hypertension, it is recommended to transfer the patient to taking the drug in the form of extended-release tablets.

When carrying out a course of therapy, it is recommended to use Cordaflex in the form of prolonged-release tablets. The initial dose is 20 mg (1 tablet) 2 times a day with an interval of 12 hours. If necessary, the dose of the drug is gradually increased until the optimal clinical effect is achieved. For long-term maintenance therapy, as a rule, it is enough to take 20-40 mg (1-2 tablets) 2 times a day. The maximum daily dose is 120 mg.

For moderate impairment of liver or kidney function, no dosage adjustment is required. In case of severe liver dysfunction, the maximum daily dose should not exceed 40 mg.

The drug in the form of tablets containing 10 mg of nifedipine is taken orally before meals, in the form of prolonged-release tablets - regardless of meals, without chewing, with a small amount of water.

Cordaflex RD

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 per 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 once a 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 per day.

Compound

Nifedipine + Excipients.

Release forms

Film-coated tablets 10 mg.

Extended-release, film-coated tablets 20 mg (retard).

Controlled-release film-coated tablets 40 mg (Cordaflex RD).

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

Nifedipine (the active ingredient of the drug Cordaflex) 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 in 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 developing the “steal” syndrome, and also increases the number of functioning collaterals.

Cordaflex has virtually no effect on the sinoatrial and AV 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.

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

Pharmacokinetics

When taken orally, it is quickly and almost completely (more than 90%) absorbed from the gastrointestinal tract. Bioavailability - 40-70%. After oral administration of 1 tablet of prolonged action 20 mg (retard), the therapeutic concentration of nifedipine in the blood plasma is achieved after 1 hour and remains at a constant level for up to 6 hours (plateau of prolonged action), and gradually decreases in the next 30-36 hours. Binding to blood plasma proteins (albumin) is 94-97%. Unbound nifedipine is distributed in all organs and tissues. Penetrates through the blood-brain barrier (BBB) (less than 5%), through the placental barrier, and is excreted in breast milk. Does not accumulate. Nifedipine is extensively metabolized in the liver with the formation of 3 metabolites that do not have pharmacological activity. 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. In elderly patients, the metabolism of nifedipine in the liver is reduced.

Indications

arterial hypertension of various origins, including hypertensive crises (for tablets 10 mg);
IHD: to prevent attacks during various forms angina pectoris (stable and post-infarction), incl. angiospastic (Prinzmetal's angina);
Raynaud's syndrome (for extended-release tablets).

Contraindications

acute stage of myocardial infarction;
cardiogenic shock;
severe arterial hypotension (systolic blood pressure below 90 mm Hg);
pronounced aortic or mitral stenosis, idiopathic hypertrophic sub aortic stenosis;
severe heart failure;
1st trimester of pregnancy;
lactation period (breastfeeding);
children's and adolescence up to 18 years old;
hypersensitivity to nifedipine and other components of the drug.

special instructions

The antihypertensive effect of Cordaflex is enhanced by hypovolemia. Reduced pressure in pulmonary artery and hypovolemia after dialysis can also enhance the effects of the drug, and therefore a dose reduction is recommended.

IN in rare cases at the beginning of a course of treatment with Cordaflex or when its dose is increased, chest pain (angina due to paradoxical ischemia) may occur soon after taking the drug. If a causal relationship is found between taking the drug and angina pectoris, treatment should be discontinued.

For hypertension or illness coronary vessels Abrupt withdrawal of nifedipine may cause hypertensive crisis or myocardial ischemia (rebound phenomenon).

If during therapy the patient requires surgical intervention under general anesthesia, it is necessary to inform the anesthesiologist about the Cordaflex therapy being carried out.

Elderly patients are more likely to have decreased cerebral blood flow due to acute peripheral vasodilation.

During course treatment Cordaflex is not recommended for use alcoholic drinks due to the risk of excessive reduction in blood pressure.

Impact on the ability to drive vehicles and operate machinery

Driving is not permitted during the initial, individually determined period of Cordaflex use. Vehicle and engaging in other potentially hazardous activities that require rapid psychomotor reactions. In the process of further treatment, the degree of restrictions is determined depending on individual reaction patient for the drug.

Side effect

facial skin hyperemia;
severe arterial hypotension;
peripheral edema;
tachycardia;
increased angina attacks (requires discontinuation of the drug);
increased heart failure;
fainting;
headache;
dizziness;
increased fatigue;
sleep disorders (drowsiness or insomnia);
visual impairment;
paresthesia in the limbs;
tremor;
diarrhea;
constipation;
nausea;
heartburn;
dry mouth;
flatulence;
gingivitis;
anorexia;
thrombocytopenia, thrombocytopenic purpura, leukopenia, anemia;
increased daily diuresis;
deterioration of kidney function in patients with chronic renal failure;
myalgia;
gynecomastia;
hyperglycemia (completely disappear after discontinuation of the drug);
change in body weight;
galactorrhea;
hives;
exanthema;
skin itching;
autoimmune hepatitis;
feeling of heat;
weakness;
sweating;
fever;
chills;
photodermatitis.

Drug interactions

From the point of view of enhancing the antihypertensive and antianginal effect, the combination of Cordaflex with beta-blockers, diuretics, ACE inhibitors, and nitrates is rational. All of the above combinations are safe and effective in most clinical situations, since they lead to summation or potentiation of effects, however, in some cases there is a risk of a pronounced decrease in blood pressure and increased symptoms of heart failure.

The combination of Cordaflex with clonidine, methyldopa, octadine, prazosin is possible according to indications, but can cause severe orthostatic hypotension.

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

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

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 (NSAIDs)), as a result of which their concentrations in the blood plasma may increase.

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

Nifedipine inhibits the elimination of vincristine from the body and may cause increased side effects of vincristine; if necessary, the dose of vincristine is reduced.

Diltiazem inhibits the metabolism of nifedipine in the body; if necessary, reduce the dose of nifedipine.

Grapefruit juice, erythromycin and antifungal drugs azole groups (fluconazole, itraconazole, ketoconazole) can suppress the metabolism of nifedipine and therefore enhance its effects.

Alcohol enhances the hypotensive effect of Nifedipine.

The same way, simultaneous use Cordaflex and cimetidine increases the concentration of nifedipine in the blood plasma and enhances its effects; however, simultaneous use with ranitidine does not lead to a significant increase in the concentration of nifedipine in the blood plasma.

Since nifedipine is metabolized by the CYP3A4 isoenzyme, any inhibitor or inducer of this enzyme may affect the metabolism of nifedipine. Cyclosporine is also a CYP3A4 substrate; therefore when joint use cyclosporine and nifedipine may each prolong the duration of the effect of the other.

Analogues medicinal product Cordaflex

Structural analogues of the active substance:

Adalat;
Calcigard retard;
Cordafen;
Cordaflex RD;
Cordipin;
Cordipin retard;
Corinfar;
Corinfar retard;
Corinfar UNO;
Nicardia;
Nicardia SD retard;
Nifadil;
Nifebene;
Nifehexal;
Nifedex;
Nifedicap;
Nifedicor;
Nifedipine;
Nifecard;
Nifelat;
Nifesan;
Osmo Adalat;
Sanfidipin;
Sponif 10;
Phenigidine.

Use in elderly patients

In elderly patients, the pharmacokinetics of nifedipine changes, and therefore the initial dose of the drug is reduced by 2 times and to maintain therapeutic effect Lower doses may be required.

Use in children

Due to the lack of sufficient clinical data, the drug is not recommended for use in children and adolescents under 18 years of age.

Use during pregnancy and breastfeeding

Minimum age from.	18 years
Mode of application	Orally
Amount in a package	30 pcs
Best before date	60 months
Maximum permissible storage temperature, °C	30°C
Storage conditions	In a dry place
Release form	Film-coated tablets
Manufacturer country	Hungary
Leave procedure	On prescription
Active substance	Nifedipine
Scope of application	Cardiovascular diseases
Pharmacological group	C08CA Dihydropyridine derivatives

Instructions for use

Active ingredients

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, which is disturbed in a number of pathological conditions, primarily in 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 the drug Cordaflex RD, the duration of the effect exceeds 24 hours.

Pharmakinetics

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 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 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. 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 with the formation of inactive metabolites. Excretion 60-80% of the 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 conditionsIn case of impaired renal function, the pharmacokinetics of nifedipine does not change.With a significant decrease in liver function, the clearance of nifedipine decreases, 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 mitral valve stenosis, hypertrophic obstructive cardiomyopathy, severe bradycardia or tachycardia, SSSS, with 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 most likely age-related dysfunction of the kidneys and liver).

Precautionary measures

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 the supervision of a physician. 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. Influence 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 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.

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 sufficient 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 function 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 extremities, 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. 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 useful in cases of overdose of controlled-release drugs. Since nifedipine is highly bound to plasma proteins, dialysis is not effective, but plasmapheresis may be effective. Symptoms of cardiac arrhythmias with bradycardia can be eliminated by administering beta -sympathomimetics. For life-threatening bradycardia, an artificial pacemaker should be used. For severe hypotension, an 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 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 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, 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 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 - coumarin and indanedione derivatives, anticonvulsants, NSAIDs), as a result of which their concentrations in 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 advisable 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 drugs. For patients with heart disease insufficiency before starting treatment with Cordaflex RD, it is recommended to carry out appropriate therapy with digitalis preparations. If during therapy the patient requires surgery under general anesthesia, it is necessary to inform the anesthesiologist about the therapy being carried out. During treatment, 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 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.

Catad_pgroup Calcium channel blockers

Cordaflex RD - official* instructions for use

*registered by the Ministry of Health of the Russian Federation (according to grls.rosminzdrav.ru)

Registration number:

LS-001219

Tradename: 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 in 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.

Carefully: severe aortic stenosis, acute myocardial infarction (within the first 4 weeks), severe mitral valve stenosis, hypertrophic obstructive cardiomyopathy, severe bradycardia or tachycardia, weakness syndrome sinus node, chronic heart failure, severe violations cerebral circulation, age up to 18 years (efficacy and safety have not been established), elderly age, renal and liver failure(especially patients on hemodialysis - high risk excessive and unpredictable decline 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 EFFECT
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 symptoms may occur: adverse events:
The 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.
Others: very rarely - visual impairment, gynecomastia, hyperglycemia, which completely disappear after discontinuation of the drug; change in body weight, galactorrhea.

Overdose
Symptoms
At 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) occurs.
Treatment
On early stages after detecting an overdose, you can rinse the stomach and give activated charcoal as first aid. If necessary, you can rinse small intestine, which is especially useful in cases of overdose of controlled-release drugs.
Since nifedipine is to a large extent binds 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 is indicated usual doses norepinephrine (norepinephrine). 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 with 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 of vincristine; if necessary, the dose of vincristine is reduced.
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 surgery 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
Company Pharmaceutical factory 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.