Кордафлекс RD

General characteristics. Structure:

Tablets with controlled release, coated 1 table.
nifedipine of 40 mg
excipients: cellulose; MKTs; lactose; gipromelloza 4000; magnesium stearate; silicon dioxide colloid anhydrous  
tablet cover: gipromelloza 15; macrogoal 6000; macrogoal 400; ferrous oxide red E172; titanium E171 dioxide; talc  
in the blister of 10 pieces; in a pack cardboard the 1 or 3 blister.
Description of a dosage form

Round, biconvex tablets, coated, brown-red color, inodorous.

Pharmacological properties:

Pharmacological action - hypotensive, anti-anginal.

Pharmacokinetics. Absorption
Nifedipine quickly and almost completely (90%) is soaked up from a GIT after intake. Effect duration after a single dose of drug of Kordafleks of RD exceeds 24 h. When developing active agent of drug of Kordafleks of RD the kinetics of release of a zero order for the purpose of ensuring constant speed of release is chosen. Relative bioavailability — about 60%. Cmax is equal in a blood plasma (29,4±12,0) mg/ml (x±SD); concentration of drug in plasma reaches the plateau in (7,4±6,4) h after reception of each dose. The maximum levels of drug in a blood plasma are reached at a combination of its reception to food. However at the end of a dosing interval concentration of drug in plasma does not change.
Distribution
Linkng with proteins of a blood plasma (albumine) makes 94–97%. Researches with marked nifedipine at animals showed that untied nifedipine is distributed in all bodies and fabrics. It is revealed that concentration of nifedipine is higher in a myocardium, than in skeletal muscles. The cumulative effect is absent.
Metabolism
Nifedipine is completely transformed to inactive metabolites.
Removal
In the form of inactive metabolites with urine 60–80% of the dose accepted inside, the rest — with bile and a stake are removed. Nifedipine T1/2 makes about 2 h of a blood plasma. However release of drug of Kordafleks of RD is more long — to (14,9±6,0) h in a phase of equilibrium concentration. Concentration of drug in a blood plasma reaches a minimum (12,0±6,5) ng/ml in 24 h after reception that twice exceeds the concentration reached after reception of tablets of Kordafleks of 20 mg 2 times a day.
At a renal failure the pharmacokinetics of nifedipine does not change (nifedipine with urine is removed in insignificant quantities). At considerable depression of function of a liver the clearance of nifedipine therefore it is not recommended to exceed a daily dose decreases.

Pharmacodynamics. Active active ingredient of drug of Kordafleks of RD is nifedipine. Has anti-hypertensive and anti-anginal effect. Reduces current of extracellular calcium ions in cardiomyocytes and smooth muscle cells of coronary and peripheral arteries. In therapeutic doses normalizes the transmembrane current of Sa2+ broken at a number of morbid conditions, first of all at arterial hypertension. Reduces a spasm and expands coronary and peripheral arterial vessels, reduces OPSS, reduces an afterload and the need of a myocardium for oxygen. At the same time improves blood supply of ischemic zones of a myocardium without development of a syndrome of "burglarizing", and also activates functioning of collaterals. Nifedipine practically does not influence on sinuatrial and AV nodes and does not render both proaritmogenny, and antiarrhytmic action. Does not influence a tone of veins. Nifedipine strengthens a renal blood stream, causing a moderate natriuresis. In high doses inhibits release of calcium ions from intracellular depots. Reduces quantity of the functioning calcium channels, without making at the same time impact on time of their activation, an inactivation and recovery.

Indications to use:

- arterial hypertension;
- stable stenocardia (angina of exertion), postinfarction stenocardia, and also vasospastic stenocardia (Printsmetal's stenocardia).

Route of administration and doses:

Inside, in the morning, during food (for example a breakfast), without chewing and washing down with enough water.
The dose should be selected individually, depending on weight of a condition of the patient and reaction to the carried-out therapy. It is possible to recommend the following doses:
Arterial hypertension
According to 1 tab. of Kordafleks of RD of 1 times a day. If necessary the dose can be raised to 80 mg (2 tab. of Kordafleks of RD of 40 mg for 1 or 2 receptions). Increase in a dose over 80 mg is not recommended.
Coronary heart disease
According to 1 tab. of Kordafleks of RD of 1 times a day. If necessary the dose can be raised to 80 mg (2 tab. of Kordafleks of RD for 1 or 2 receptions). Doses over 80 mg can be given in exceptional cases under medical control. The daily dose should not exceed 120 mg.
At decrease in renal or hepatic function
It is recommended to apply with care the same doses, as at normal function of kidneys or a liver (tolerance development is possible). At considerable depression of function of a liver it is not recommended to exceed a daily dose of 40 mg.

Features of use:

After a myocardial infarction administration of drug should be begun only after stabilization of hemodynamic parameters.
Patients with an acute myocardial infarction and within 30 days after it should not use BKK of short action of type 1,4 of dihydropyridine. At treatment of such patients (BKK with controlled release of type 1,4 of dihydropyridine) needs careful observation. It is more reasonable to appoint in the absence of tendency to tachycardia, and also patients at whom beta adrenoblockers are inefficient or there are contraindications to their use.
In the initial individually defined stage of treatment it is necessary to abstain from potentially dangerous types of activity demanding a bystra psychomotor reactions. In the course of further treatment extent of restrictions is defined depending on individual portability of drug.
In cases of insufficient efficiency of monotherapy Kordafleksy RD it is reasonable to continue treatment with use of effective combinations with other HP (see. "Interaction").
During treatment the use of alcoholic drinks because of risk of excessive decrease in the ABP is not recommended.
At patients with heart failure before an initiation of treatment with Kordafleks to RD recommends appropriate therapy by foxglove drugs.
If during therapy the patient needs surgical intervention under the general anesthesia, it is necessary to inform the anesthesiologist on the carried-out therapy.
It is necessary to be careful at elderly patients owing to bigger probability of age renal failures and a liver.

Side effects:

In most cases Kordafleks of RD is transferred by patients well.
In some cases, especially in an initial stage of treatment, there can be passing undesirable phenomena:
From cardiovascular system: in an initiation of treatment — a dermahemia of the person, hypotonia, tachycardia; peripheral hypostases (anklebones, feet, shins); seldom — emergence of attacks of stenocardia (that is characteristic of other vazodilatator and demands drug withdrawal), heart failure.
From TsNS: headache, dizziness, increased fatigue, drowsiness. At prolonged use in high doses — paresthesias in extremities, a tremor.
From the alimentary system: nausea, heartburn, diarrhea or lock; seldom at long reception — an intra hepatic cholestasia, the increase in level of "hepatic" enzymes which is taking place after drug withdrawal; very seldom — a hyperplasia of gums.
From system of a hemopoiesis: seldom — thrombocytopenia, a Werlhof's disease, a leukopenia; very seldom — anemia.
From an urinary system: increase in a daily urine; seldom — deterioration in function of kidneys (at patients with a chronic renal failure).
From a musculoskeletal system: mialgiya; very seldom — arthritis, an arthralgia.
Allergic reactions: seldom — a small tortoiseshell, a dieback, a skin itch; very seldom — a photodermatitis.
Others: very seldom — the vision disorders, a gynecomastia, a hyperglycemia which are completely undergoing later drug withdrawals; change of body weight, galactorrhoea.

Interaction with other medicines:

Drug of Kordafleks of RD with controlled release of active ingredient has ample opportunities for a highly effective combination therapy. From the point of view of anti-hypertensive and anti-anginal effects, Kordafleks's combination of RD to beta adrenoblockers, diuretics, APF inhibitors, nitrates is rational.
The combined Kordafleks's use is safe and effective RD with beta adrenoblockers in the majority of clinical situations since leads to summation and potentiation of effects, however in some cases there is a risk of arterial hypotension and strengthening of heart failure.
Strengthening of hypotensive effect is observed also at a combination therapy with Cimetidinum, ranitidine and tricyclic antidepressants.
Does not reduce the efficiency against the background of treatment by steroid drugs and NPVS.
Nifedipine increases concentration of digoxin and theophylline in this connection it is necessary to control clinical effect and/or content of digoxin and theophylline in a blood plasma.
At co-administration with rifampicin and drugs of calcium effect of nifedipine is weakened.
Procainum, quinidine and other HP causing lengthening of an interval of QT strengthen a negative inotropic effect and increase risk of lengthening of an interval of QT. Under the influence of nifedipine concentration of quinidine in blood serum considerably decreases that, apparently, is caused by reduction of its bioavailability, and also induction of the enzymes inactivating quinidine. At cancellation of nifedipine tranzitorny increase in concentration of quinidine is observed (approximately twice) which reaches the maximum level for 3–4 day. When using such combinations it is necessary to be careful, especially at patients with dysfunction of a left ventricle.
Nifedipine can force out from linkng with proteins the drugs which are characterized by high extent of binding (including indirect anticoagulants — derivatives of coumarin and an indandion, NPVS) owing to what their concentration in a blood plasma can increase.
As it was shown that carbamazepine and phenobarbital, activating liver enzymes, reduce concentration in a blood plasma of other BKK, it is impossible to exclude similar decrease in concentration of nifedipine in a blood plasma.
Valproic acid, oppressing activity of enzymes, led to increase in concentration in a blood plasma of other BKK therefore it is impossible to exclude also increase in concentration of nifedipine in a blood plasma at a concomitant use with valproic acid.
Nifedipine slows down removal of Vincristinum from an organism and can cause strengthening of its side effects (if necessary the dose of Vincristinum is reduced).
Diltiazem suppresses metabolism of nifedipine in an organism therefore careful observation is necessary (if necessary reduce a nifedipine dose).
Grapefruit juice suppresses metabolism of nifedipine in an organism in this connection it is not recommended to apply it with nifedipine.

Contraindications:

- hypersensitivity to nifedipine or any other component of drug, other derivatives 1,4 dihydropyridines;
- the expressed arterial hypotension with risk of a collapse at cardiovascular shock with respiratory manifestations;
- unstable stenocardia;
- a myocardial infarction with a left ventricular failure.

With care:
the expressed aortal stenosis;
acute myocardial infarction (during the first 4 weeks);
the expressed stenosis of the mitral valve;
hypertrophic subaortic stenosis;
the expressed bradycardia or tachycardia;
syndrome of weakness of a sinus node;
chronic heart failure;
heavy disturbances of cerebral circulation;
age up to 18 years (efficiency and safety are not established);
advanced age;
renal and liver failure (especially the patients who are on a hemodialysis — high risk of the excessive and not predicted decrease in the ABP).

Use at pregnancy and feeding by a breast

Use of nifedipine for pregnant women is recommended at impossibility of use of other drugs which do not have restrictions. As nifedipine is emitted with breast milk, it is necessary to refrain from purpose of drug in the period of a lactation, or to stop breastfeeding during treatment.

Overdose:

Symptoms of acute overdose: a headache, the expressed decrease in the ABP, and also disturbance of power providing a myocardium (a stenocardia attack).
Treatment: at early stages after detection of overdose as means of first aid the gastric lavage and purpose of absorbent carbon is recommended. If necessary — washing of a small intestine which is especially reasonable in case of overdose of drugs with controlled release.
The hemodialysis is not effective since nifedipine substantially contacts proteins. The plasmapheresis can be effective.
Symptoms of disturbance of a cordial rhythm with bradycardia can be eliminated with administration of beta-adrenergic agonists. At life-threatening bradycardia it is necessary to apply an artificial pacemaker.
At the expressed decrease in the ABP infusion of usual doses of Norepinephrinum (noradrenaline) is shown. At development of symptoms of heart failure it is recommended in/in introduction of high-speed glycosides of a foxglove.
Due to the lack of a specific antidote symptomatic therapy is shown. As antidotes it is possible to use dopamine, изопреналин and 10% a calcium gluconate (10–20 ml in/in).

Storage conditions:

Period of validity 4 years. List B. In the place protected from a direct sunlight, at a temperature not above 30 °C.

Issue conditions:

According to the recipe

Packaging:

Tablets with controlled release, coated, 40 mg. According to 10 tab. in the blister from PVC/PVDH / aluminum foil. 1 or 3 blisters are packed into a cardboard pack.