Cordaflex RD controlled release tablets, po 40mg, No. 30

Arterial hypertension
Stable angina (exertional angina), postinfarction angina, as well as vasospastic angina (Prinzmetal's angina).

CordaflexЃ RD 40 mg should be taken in the morning, with meals (for example, breakfast), not chewed and washed down with plenty of water.
The dose should be selected individually, depending on the severity of the patient's condition and the response to therapy. The following doses can be recommended:
Arterial hypertension
1 tablet of CordaflexЃ RD 40 mg 1 time per day.
If necessary, the dose can be increased to 80 mg (2 tablets of CordaflexЃ RD 40 mg in one or two doses). Dose increases over 80 mg are not recommended.
Ischemic heart disease
1 tablet of CordaflexЃ RD 40 mg 1 time per day.
If necessary, the dose can be increased to 80 mg (2 tablets of CordaflexЃ RD 40 mg in one or two doses). Doses over 80 mg can be given in exceptional cases under medical supervision. The daily dose should not exceed 120 mg.
Dosage with a decrease in renal or hepatic function
It is recommended to use the same doses with caution as with normal renal or hepatic function (tolerance may develop). With a significant decrease in liver function, it is not recommended to exceed a daily dose of 40 mg.

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

Hypersensitivity to nifedipine or any other component of the drug, other 1,4-dihydropyridine derivatives Severe arterial hypotension with risk of collapse in cardiovascular shock with respiratory manifestations Unstable angina Myocardial infarction with left ventricular failure Precautions: severe aortic stenosis myocardial infarction (within the first 4 weeks), severe mitral stenosis, hypertrophic obstructive cardiomyopathy, severe bradycardia or tachycardia, sick sinus syndrome, chronic heart failure, severe cerebrovascular accident, age up to 18 years (efficacy and safety have not been established ), old age, renal and hepatic insufficiency (especially patients,who are on hemodialysis - a high risk of excessive and unpredictable lowering of blood pressure).

Trade name: Cordaflex RD

International non-proprietary name:

nifedipine

Dosage form:

controlled release coated tablets

Composition:

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

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

Pharmacotherapeutic group:

slow calcium channel blocker

PHARMACOLOGICAL PROPERTIES
Pharmacodynamics
The active ingredient of CordaflexЃ RD is nifedipine.
Nifedipine is a selective blocker of 'slow' calcium channels, a derivative of 1,4-dihydropyridine. It has antihypertensive and antianginal effects. Reduces the flow of extracellular calcium ions into cardiomyocytes and smooth muscle cells of coronary and peripheral arteries. In therapeutic doses, it normalizes the transmembrane current of calcium ions, impaired 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 the blood supply to the ischemic zones of the myocardium without the development of the 'steal' syndrome, and also activates the functioning of collaterals.
It practically does not affect the sinoatrial and atrioventricular nodes and does not have both pro and antiarrhythmic effects. Does not affect the tone of the veins. Nifedipine increases renal blood flow, causing mild 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
Absorption
Nifedipine is rapidly and almost completely (90%) absorbed from the gastrointestinal tract after oral administration. The duration of the effect after a single oral administration of the drug exceeds 24 hours. When developing the active substance of the drug CordaflexЃ RD, the kinetics of release of the zero order was chosen in order to ensure a constant rate of release. 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. The maximum levels of the drug in blood plasma are achieved when it is combined 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 94Ц97%. Studies with labeled nifedipine in animals have shown that unbound nifedipine is distributed in all organs and tissues. 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 inactive metabolites.
Excretion
60-80% of the dose taken orally is excreted in the urine in the form of inactive metabolites, the rest - with bile and feces. The plasma half-life of nifedipine is approximately 2 hours. However, the release of the drug CordaflexЃ RD is more prolonged - up to 14.9 ± 6.0 hours in the phase of equilibrium concentration.
The concentration of the drug in 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.
In case of impaired renal function, the pharmacokinetics of nifedipine does not change (nifedipine is excreted in the urine in small amounts). With a significant decrease in liver function, the clearance of nifedipine decreases, therefore it is not recommended to exceed the daily dose.

INDICATIONS FOR USE
Arterial hypertension
Stable angina pectoris (exertional angina), postinfarction angina pectoris, as well as vasospastic angina pectoris (Prinzmetal's angina pectoris).

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

With care: severe aortic stenosis, acute myocardial infarction (during the first 4 weeks), severe mitral stenosis, hypertrophic obstructive cardiomyopathy, severe bradycardia or tachycardia, sick sinus syndrome, chronic heart failure, severe cerebrovascular accident, age up to 18 years (efficacy and safety have not been established), advanced age, renal and hepatic failure (especially patients on hemodialysis - a high risk of excessive and unpredictable lowering of blood pressure).

PREGNANCY AND LACTATION PERIOD
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.

DOSAGE AND METHOD OF APPLICATION CordaflexЃ RD 40 mg should be taken in the morning with meals (eg breakfast), do not chew and drink plenty of water.
The dose should be selected individually, depending on the severity of the patient's condition and the response to therapy. The following doses can be recommended:
Arterial hypertension
1 tablet of CordaflexЃ RD 40 mg 1 time per day.
If necessary, the dose can be increased to 80 mg (2 tablets of CordaflexЃ RD 40 mg in one or two doses). Dose increases over 80 mg are not recommended.
Ischemic heart disease
1 tablet of CordaflexЃ RD 40 mg 1 time per day.
If necessary, the dose can be increased to 80 mg (2 tablets of CordaflexЃ RD 40 mg in one or two doses). Doses over 80 mg can be given in exceptional cases under medical supervision. The daily dose should not exceed 120 mg.
Dosage with a decrease in renal or hepatic function
It is recommended to use the same doses with caution as with normal renal or hepatic function (tolerance may develop). With a significant decrease in liver function, it is not recommended to exceed a daily dose of 40 mg.

SIDE EFFECTS
In the overwhelming majority of cases, CordaflexЃ RD 40 mg is well tolerated by patients.
In some cases, especially in the initial period of treatment, the following transient adverse events may occur:
Cardiovascular system: at the beginning of treatment - hyperemia of the skin of the face, a marked decrease in blood pressure, tachycardia; peripheral edema (ankles, feet, legs); rarely - the appearance of angina attacks (which is typical for other vasodilators and requires discontinuation of the drug), heart failure.
Central nervous system: headache, dizziness, fatigue, drowsiness. With prolonged use in high doses - paresthesia in the extremities, tremors.
Digestive system:nausea, heartburn, diarrhea, or constipation; rarely with prolonged use of the drug - intrahepatic cholestasis, increased activity of 'hepatic' enzymes, passing after drug withdrawal; very rarely - gingival hyperplasia.
Hematopoietic system: rarely - thrombocytopenia, thrombocytopenic purpura, leukopenia; very rarely - anemia.
Urinary system: increased daily urine output; rarely - deterioration of renal function (in patients with renal failure).
Musculoskeletal system: myalgia; very rarely - arthritis, arthralgia.
Allergic reactions: rarely - urticaria, exanthema, pruritus; very rarely - photodermatitis.
Others:very rarely - visual impairment, gynecomastia, hyperglycemia, completely disappearing after discontinuation of the drug; change in body weight, galactorrhea.

Overdose
Symptoms
In acute overdose, there is a headache, a marked decrease in blood pressure, as well as a violation of the energy supply of the myocardium (an attack of angina pectoris).
Treatment
In the early stages after detecting an overdose, as a first aid, you can wash the stomach and give activated charcoal. If necessary, you can wash the small intestine, which is especially advisable in case of overdose of drugs with controlled release.
Since nifedipine is largely associated with blood plasma proteins, hemodialysis is not effective, and plasmapheresis may be effective.
Symptoms of abnormal heart rhythms with bradycardia can be treated with beta-sympathomimetics. With life-threatening bradycardia, an artificial pacemaker should be used.
With a pronounced decrease in blood pressure, infusion of usual doses of norepinephrine (norepinephrine) is indicated. With the development of symptoms of heart failure, intravenous administration of fast-acting digitalis glycosides is recommended.
In the absence of a specific antidote, symptomatic therapy is indicated. Dopamine, isoprenaline and 10% calcium gluconate solution (10Ц20 ml IV) can be used as antidotes.

INTERACTION WITH OTHER MEDICINAL PRODUCTS
CordaflexЃ RD 40 mg with controlled release of the active substance has ample opportunities for highly effective combination therapy.
Rational in terms of antihypertensive and antianginal effects is the combination of CordaflexЃ RD 40 mg with beta-blockers, diuretics, angiotensin-converting enzyme (ACE) inhibitors, nitrates.
The combined use of CordaflexЃ RD 40 mg with beta-blockers in most clinical situations is safe and effective, as it leads to the summation and potentiation of the 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 in combination therapy with cimetidine, ranitidine and tricyclic antidepressants.
CordaflexЃ RD 40 mg does not reduce its effectiveness during treatment with steroid 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 prolongation of the QT interval increase 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, apparently, is due to a decrease in its bioavailability, as well as the induction of enzymes that inactivate quinidine. With the cancellation of nifedipine, a transient increase in the concentration of quinidine (approximately 2 times) is observed, which reaches its 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 with a high degree of binding from the connection with proteins (including indirect anticoagulants - coumarin and indandione derivatives, non-steroidal anti-inflammatory drugs), as a result of which their concentration in blood plasma may increase.
Since it has been shown that carbamazepine and phenobarbital, by activating liver enzymes, reduce the plasma concentration of other slow calcium channel blockers (BMCC), a similar decrease in the concentration of nifedipine in the blood plasma cannot be ruled out.
Valproic acid, inhibiting the activity of enzymes, led to an increase in the plasma concentration of other blockers of 'slow' calcium channels, therefore, an increase in the concentration of nifedipine in the blood plasma cannot be ruled out while taking it with valproic acid.
Nifedipine inhibits the excretion of vincristine from the body and can cause an increase in the side effects of vincristine; if necessary, the dose of vincristine is reduced.
Diltiazem suppresses the metabolism of nifedipine in the body, careful observation is necessary, if necessary, the dose of nifedipine should be reduced.
Grapefruit juice inhibits the metabolism of nifedipine in the body, therefore, it is not recommended to use it with nifedipine.

SPECIAL INSTRUCTIONS
After myocardial infarction, the drug should be taken only after stabilization of hemodynamic parameters.
Patients with acute myocardial infarction and within 30 days after it should not use blockers of 'slow' short-acting calcium channels such as 1,4-dihydropyridine. Careful monitoring is necessary when treating such patients with controlled-release BMCC such as 1,4-dihydropyridine. It is more advisable to prescribe in the absence of a tendency to tachycardia, as well as to patients in whom beta-blockagors are ineffective or have contraindications to their use.
In the initial individually determined period of treatment, it is necessary to refrain from potentially hazardous activities that require rapid psychomotor reactions. In the course of further treatment, the degree of restrictions is determined depending on the individual tolerance of the drug.
In cases of insufficient effectiveness of monotherapy with CordaflexЃ RD 40 mg, it is advisable to continue treatment using effective combinations with other drugs (see Interaction with other drugs).
Drinking alcohol is not recommended during treatment because of the risk of an excessive decrease in blood pressure.
In patients with heart failure, before starting treatment with CordaflexЃ RD 40 mg, appropriate therapy with digitalis drugs is recommended.
If during therapy the patient requires surgery under general anesthesia, it is necessary to inform the anesthesiologist about the therapy.
Caution should be exercised in elderly patients due to the greatest likelihood of age-related renal and liver dysfunction.

FORM OF RELEASE
40 mg film-coated controlled release tablets. 10 tablets in a PVC / PVDC / aluminum foil blister. 1 or 3 blisters in a cardboard box along with instructions for use.

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

SHELF LIFE
5 years. Do not use after the date indicated on the package.

TERMS OF RELEASE FROM PHARMACIES
On prescription.