Cordaflex RD - instructions for use, dose, side effects, contraindications

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

Description:Round biconvex tablets coated with a coat, brownish-red, with a bevel, odorless.

Pharmacotherapeutic group:The blocker of "slow" calcium channels

ATX: & nbsp

C.08.C.A.05 Nifedipine

Pharmacodynamics:The active ingredient of the drug Kordaflex® RD is nifedipine. Nifedipine - selective blocker of "slow" calcium channels, 1,4-dihydropyridine derivative. Has antihypertensive and antianginal action.Reduces the current of extracellular calcium ions inside cardiomyocytes and smooth muscle cells of the coronary and peripheral arteries. In therapeutic doses normalizes the transmembrane current of calcium ions, disrupted in a number of pathological conditions, especially in hypertension. Reduces spasm and dilates coronary and peripheral arterial vessels, reduces overall peripheral resistance, reduces afterload and myocardial oxygen demand. At the same time it improves the blood supply of ischemic zones of the myocardium without the development of the syndrome of "stealing", and also activates the functioning of collaterals. Virtually 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 strengthens the renal blood flow, causing a moderate sodium naresis. 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 quickly and almost completely (90%) is absorbed from the gastrointestinal tract after ingestion. The duration of the effect after a single intake of the drug exceeds 24 hours. When developing the active substance Kordaflex ® RD, the kinetics of zero-order release is chosen to ensure a constant release rate. The relative bioavailability of the drug is about 60%. The maximum concentration (Сmах) in blood plasma is equal to 29,4 ± 12,0 mg / ml (x ± SD); the concentration of the drug in the blood plasma reaches a plateau after 7.4 ± 6.4 hours after each dose. Maximum levels of the drug in blood plasma are achieved by combining its reception 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 (albumins) is 94-97%. Studies with labeled nifedipine in animals have shown that unrelated nifedipine distributed in all organs and tissues. It was found that the concentration of nifedipine is higher in the myocardium than in the 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 internally is excreted in the urine in the form of inactive metabolites, the rest - with bile and feces. The half-life of nifedipine from plasma is approximately 2 hours. However, the release of Kordaflex® RD is more prolonged - up to 14.9 ± 6.0 h in the phase of equilibrium concentration.

The concentration of the drug in the blood plasma reaches a minimum of 12.0 ± 6.5 mg / ml 24 hours after ingestion, which is twice the concentration achieved after taking 20 mg of nifedipine 2 times a day.

When the renal function is impaired, the pharmacokinetics of nifedipine does not change (nifedipine with urine is excreted in small amounts). 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 (stress angina), postinfarction angina, as well as vasospastic angina (Prinzmetal angina).

Contraindications:

Hypersensitivity to nifedipine or any other component of the preparation, other 1,4-dihydropyridine derivatives.

Pronounced arterial hypotension with 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, sinus node weakness syndrome, chronic heart failure, severe cerebral circulation disorders, age under 18 years ( efficacy and safety are not established), advanced age, renal and hepatic insufficiency (especially patients on hemodialysis - a high risk of excessive and unpredictable lowering blood pressure).

Pregnancy and lactation:

The use of nifedipine in pregnant women is recommended when it is not possible to use other drugs that do not have limitations.

Because the nifedipine excreted in breast milk, should refrain from prescribing during lactation, or stop breastfeeding during treatment.

Dosing and Administration:

Cordaflex® RD 40 mg should be taken in the morning, during meals (eg, breakfast), not chew and drink with sufficient water.

The dose should be selected individually, depending on the severity of the patient's condition and the response to ongoing therapy. The following doses may be recommended:

Arterial hypertension

For 1 tablet Kordafleksa RD 40 mg once a day.

If necessary, the dose can be increased to 80 mg (2 tablets Kordaflexa RD 40 mg for one or two doses). Increasing the dose above 80 mg is not recommended.

Cardiac ischemia

For 1 tablet Kordafleksa RD 40 mg once a day.

If necessary, the dose can be increased to 80 mg (2 tablets Kordaflexa RD 40 mg for 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 reduced renal or hepatic function

It is recommended to use with caution the same doses as with normal kidney or liver function (tolerance is possible). With a significant decrease in liver function, it is not recommended to exceed the daily dose of 40 mg.

Side effects:

In the overwhelming In most cases, Cordaflex® RD 40 mg is tolerated well by patients.

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

The cardiovascular system: at the beginning of treatment - hyperemia of the facial skin, marked decrease in arterial pressure, tachycardia; peripheral edema (ankles, feet, tibia); rarely - the appearance of attacks of angina (which is typical for other vasodilators and requires the withdrawal of the drug), heart failure.

Central nervous system: headache, dizziness, fatigue, drowsiness. With prolonged use in high doses - paresthesia in the extremities, tremor. Digestive system: nausea, heartburn, diarrhea, or constipation; rarely with prolonged use of the drug, intrahepatic cholestasis, increased activity of "liver" enzymes, which occur after drug discontinuation; very rarely - gingival hyperplasia.

The system of hematopoiesis: rarely - thrombocytopenia, thrombocytopenic purpura, leukopenia; very rarely anemia.

Urinary system: an increase in daily diuresis; rarely - impaired renal function (in patients with renal insufficiency).

Musculoskeletal system: myalgia; very rarely - arthritis, arthralgia.

Allergic reactions: rarely - hives, exanthema, itchy skin; very rarely - photodermatitis.

Other: very rarely - visual impairment, gynecomastia, hyperglycemia, completely passing after drug withdrawal; 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 myocardial energy supply (an attack of angina pectoris).

Treatment

In the early stages after detecting an overdose, as a first aid, you can wash your stomach and give Activated carbon. If necessary, it can be done to wash the small intestine, which is particularly useful in case of overdose of drugs with controlled release.

As nifedipine is largely associated with plasma proteins, hemodialysis is notis effective, and plasmapheresis can be effective.

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

With a marked decrease in blood pressure, infusion of usual doses of norepinephrine (norepinephrine) is indicated.When developing symptoms of heart failure, intravenous rapid-acting glycosides of digitalis are recommended.

In connection with the absence of a specific antidote, symptomatic therapy is indicated. As antidotes, dopamine, isoprenaline and 10% calcium gluconate solution (10-20 ml IV) can be used.

Interaction:

The drug Cordaflex® 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,The combination of Cordaflex® RD 40 mg with beta adrenoblockers, diuretics, angiotensin converting enzyme (ACE) inhibitors, nitrates.

CombiniThe application of Cordaflex® RD 40 mg with beta-blockers in most clinical situations is safe and effective, since 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.

Strengthening of the hypotensive effect is also observed with combined therapy with cimetidine, ranitidine and tricyclic antidepressants.

Cordaflex® RD 40 mg does not reduce its effectiveness against the background of 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.

With simultaneous administration with rifampicin and calcium preparations, the effect of nifedipine is weakened

Procaine, quinidine and other medicines, causing interval lengthening QT, increase the negative inotropic effect and increase the risk of lengthening the interval QT. 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 induction of enzymes that inactivate quinidine. With the withdrawal of nifedipine, there is a transient increase in the concentration of quinidine (approximately 2-fold), which reaches a maximum level of 3-4 days. Care should be taken when using such combinations, especially in patients with left ventricular dysfunction.

Nifedipine can displace from the bond with proteins preparations characterized by a high degree of binding (incl.indirect anticoagulants - derivatives of coumarin and indanedione, non-steroidal anti-inflammatory drugs), so that their concentration in the blood plasma can increase.

Since it was shown that carbamazepine and phenobarbital, activating liver enzymes, reduce the concentration in the blood plasma of other slow calcium channel blockers (BCCI), it is impossible to exclude a similar decrease in the concentration of nifedipine in blood plasma. Valproic acid, suppressing the activity of enzymes, led to an increase in the concentration in the blood plasma of other blockers of the "slow" calcium channels, so one can not exclude the increase in the concentration of nifedipine in blood plasma with simultaneous administration with valproic acid.

Nifedipine inhibits the excretion of vincristine from the body and may cause an increase in side effects of vincristine, if necessary, reduce the dose of vincristine.

Diltiazem suppresses 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 taken only after stabilization of hemodynamic parameters.

Patients with acute myocardial infarction and within 30 days after it should not use blockers of "slow" calcium channels short-acting type 1,4-dihydropyridine. In the treatment of these patients with controlled release of 1,4-dihydropyridine type, careful monitoring is necessary. It is more advisable to appoint in the absence of a tendency to tachycardia, as well as patients who have ineffective beta-blockers or have contraindications to their use.

In cases of insufficient effectiveness of monotherapy Kordaflexom RD 40 mg it is advisable to continue treatment with effective combinations with other drugs (see Interaction with other drugs).

During treatment, the use of alcoholic beverages is not recommended because of the risk of excessive lowering of blood pressure.

In patients with heart failure, before treatment with Cordaflex ® RD 40 mg, appropriate therapy with digitalis preparations is recommended.

If during the therapy the patient requires surgical intervention under general anesthesia, it is necessary to inform the anesthetist about the therapy.

Caution should be exercised in elderly patients due to the greatest likelihood of age-related renal and hepatic impairment.

Effect on the ability to drive transp. cf. and fur:In the initial individually defined period of treatment, it is necessary to refrain from potentially dangerous activities requiring rapid psychomotor reactions. In the process of further treatment, the degree of restriction is determined depending on the individual tolerability of the drug.

Form release / dosage:

Controlled-release tablets coated with a coating, 40 mg.

Packaging:For 10 tablets in a blister of PVC / PVDC / alfolga. 1 or 3 blisters in a cardboard box together with instructions for use.

Storage conditions:

At a temperature not higher than 30 ° C, in a place protected from direct sunlight.

Keep out of the reach of children.

Shelf life:

5 years.

Do not use after the date shown on the package.

Terms of leave from pharmacies:On prescription

Registration number:LS-001219

Date of registration:23.07.2010 / 13.10.2014

Expiration Date:Unlimited

The owner of the registration certificate:EGIS ZAO Pharmaceutical Plant EGIS ZAO Pharmaceutical Plant Hungary

Manufacturer: & nbsp

ARENA PHARMACEUTICALS, GmbH Switzerland

Representation: & nbspEGIS ZAO Pharmaceutical Plant EGIS ZAO Pharmaceutical Plant Hungary

Information update date: & nbsp04.02.2018

Illustrated instructions

Instructions

Cordaflex® RD (Cordaflex® RD)