Active material: Nifedipine
When ATH: C08CA05
CCF: Kalьcievыh channel blocker
ICD-10 codes (testimony): I10, i20, I20.1
When CSF: 01.03.02
Manufacturer: EGIS PHARMACEUTICALS Plc (Hungary)
PHARMACEUTICAL FORM, COMPOSITION AND PACKAGING
Controlled release tablets, coated red-brown, round, lenticular, chamfered, without smell.
Excipients: cellulose, microcrystalline cellulose, lactose, gipromelloza 4000, magnesium stearate, Colloidal anhydrous silica.
The composition of the shell: gipromelloza 15, macrogol 6000, macrogol 400, iron oxide red (E172), Titanium dioxide (E171), talc.
10 PC. – blisters (1) – packs cardboard.
10 PC. – blisters (3) – packs cardboard.
Selective calcium channel blockers slow, 1,4-dihydropyridine derivative. It has antihypertensive and antianginal.
Nifedipine reduces the current extracellular calcium ions into cardiomyocytes and smooth muscle cells of coronary and peripheral arteries. At therapeutic doses, current normalizes transmembrane calcium ions, violations in a number of pathological conditions, primarily, with hypertension. It reduces spasms and dilates coronary and peripheral arterial vessels, reduces peripheral vascular resistance, reduces afterload and myocardial oxygen demand. This improves blood flow to ischemic areas of the myocardium without the syndrome “steal”, and also increases the number of functioning collaterals.
Nifedipine is almost no effect on sinoatrial and AV-node and has both pro-, and antiarrhythmic action. It does not affect tone of veins. Nifedipine increases renal blood flow, causing moderate natriuresis. In high doses inhibits the release of calcium ions from intracellular stores. It reduces the number of functioning of calcium channels, without exerting influence on the time they are activated, of inactivation and recovery.
After a single dose of the drug Kordafleks® RD exceeds the duration of the effect 24 no.
After oral administration, the drug is rapidly and almost completely (90%) absorbed from the gastrointestinal tract. In developing the dosage form of the drug Kordafleks® RD is selected zero-order release kinetics to achieve a constant rate of release of active substance. Relative bioavailability Kordafleks® RD is about 60%. Cmax in plasma is 29.4 ± 12.0 mg / ml. The concentration of drug in plasma reaches a plateau after 7.4 ± 6.4 hours after each dose. Cmax nifedipine plasma levels are achieved by combining the drug Kordafleks® RD with food. However, at the end of the dosing interval of the drug concentration in the blood plasma remains unchanged.
After receiving Kordafleksa® By RD 24 h nifedipine concentrations in plasma reaches a minimum level of 12.0 ± 6.5 ng / ml, twice the concentration, achieved after taking the pills Kordafleksa® 20 mg (conventional dosage form) 2 times / day.
The binding to plasma proteins (albumin) is 94-97%. Studies with labeled nifedipine animals showed, that unbound nifedipine is distributed in all organs and tissues. Detected, higher concentration of nifedipine in the myocardium, than in skeletal muscle. The cumulative effect is absent.
Nifedipine is mainly metabolized by the liver into inactive metabolites.
60-80% of an oral dose is excreted in the urine as inactive metabolites, the remaining part – Bile kalom.T1/2 nifedipine from plasma is about 2 no. However, after receiving Kordafleksa® RD elimination of nifedipine is more long lasting – to 14.9 ± 6.0 hours at steady state.
Pharmacokinetics in special clinical conditions
If the kidney function does not change the pharmacokinetics of nifedipine.
With a significant decrease in liver function decreases the clearance of nifedipine, so do not exceed the recommended daily dose.
- Arterial hypertension;
- Stable angina (angina);
- Postinfarktnaya angina;
- Angiospastic angina (Prinzmetal angina).
The dose should be selected individually, depending on the severity of the patient's condition and the effectiveness of treatment.
At hypertension Kordafleks® RD appoint 40 mg (1 tab.) 1 time / day. If necessary, the dose can be increased to 80 mg (2 tab. in 1-2 admission). Increasing the dose more 80 mg is not recommended.
At CHD appoint 40 mg (1 tab.) 1 time / day. If necessary, the dose can be increased to 80 mg (2 tab. in 1 or 2 admission). Doses more 80 mg may be given in exceptional cases, under medical supervision. The daily dose should not exceed 120 mg.
Tablets Kordafleksa® RD should be taken with food (eg, breakfast), swallowed whole and drink enough water.
At renal impairment or hepatic the drug is recommended with caution in the same doses, and that in normal kidney or liver. Perhaps the development of tolerance. With a significant decrease in liver function should not exceed the dose 40 mg / day.
Cardio-vascular system: at the beginning of treatment – facial flushing, marked reduction in blood pressure, tachycardia; peripheral edema (ankles, stop, goleneй); rarely – increased frequency of angina attacks (which is typical of other vasoactive drugs and requires discontinuation of the drug), heart failure.
From the central and peripheral nervous system: headache, dizziness, fatigue, drowsiness; long-term use in high doses – paresthesias in extremities, tremor.
From the digestive system: nausea, heartburn, diarrhea or constipation; rarely Propafenone – intrahepatic cholestasis, increase in liver transaminases (go after drug withdrawal); in some cases – giperplaziya right.
From the hematopoietic system: rarely – thrombocytopenia, trombotsitopenicheskaya purpura, leukopenia; in some cases – anemia.
From the urinary system: increase in daily diuresis; rarely – worsening renal function in patients with chronic renal failure.
On the part of the musculoskeletal system: mialgii; rarely – arthritis, artralgii.
Allergic reactions: rarely – hives, rash, itching; rarely – photodermatitis.
Other: in some cases – visual impairment, gynecomastia, giperglikemiâ (completely disappear after drug withdrawal), weight change, galactorrhea.
In most cases, the drug Kordafleks® RD was well tolerated.
- Unstable angina;
- Myocardial infarction with left ventricular failure;
- Severe hypotension with the risk of a collapse in cardiovascular shock with respiratory symptoms;
- Hypersensitivity to nifedipine, other ingredients, other derivatives of 1,4-dihydropyridine.
FROM caution use in patients with acute myocardial infarction within the first 4 weeks, severe aortic stenosis, significant stenosis of the mitral valve, hypertrophic obstructive cardiomyopathy, bradycardia or tachycardia, SSS, in chronic heart failure, severe violations of cerebral circulation, kidney or liver failure (especially in patients, on hemodialysis because of the high risk of excessive blood pressure lowering and unpredictable), patients aged 18 years (tk. Safety and efficacy have not been established), in elderly patients (due to the age of highest probability of disorders of the kidney and liver).
Pregnancy and lactation
The appointment of the drug Kordafleks® RD during pregnancy may be recommended if you can not use other medicines, no restrictions on the use of.
Since nifedipine is excreted in breast milk, should refrain from prescribing during lactation, or to stop breastfeeding during treatment.
After myocardial infarction the drug should be started only after the stabilization of hemodynamic parameters.
Patients with acute myocardial infarction and during 30 days after no use of calcium channel blockers, derivatives of 1,4-dihydropyridine short-acting. When appointing such patients calcium channel blockers – 1,4-dihydropyridine derivatives with controlled release careful observation. These drugs are more appropriate to designate the absence of tendency to tachycardia, and patients, in which beta-blockers are ineffective or there are contraindications to their use.
In cases of lack of effectiveness of monotherapy Kordafleksom® RD appropriate to continue treatment with effective combinations with other drugs.
Patients with heart failure before treatment Kordafleksom® RD recommend carrying out a proper therapy with digitalis.
If during therapy the patient requires surgery under general anesthesia, you must inform the anesthesiologist about the therapy.
During treatment, alcohol is not recommended because of the risk of excessive blood pressure lowering.
Effects on ability to drive vehicles and management mechanisms
In the initial individually defined period of treatment should refrain from potentially hazardous activities, require rapid mental and motor responses. In the course of further treatment is determined by the degree of restrictions depending on the individual tolerability.
Symptoms: headache, hypotension, and (as well as under the influence of other vasodilators) violation of the energy supply of the myocardium (angina).
Treatment: immediately after the overdose as first aid can wash out the stomach and give activated charcoal. If necessary, you can make washing the small intestine, which is especially useful in the event of an overdose of controlled-release preparations.
Since nifedipine is highly bound to plasma proteins, Dialysis is not effective, and plasmapheresis may be effective.
Symptoms of cardiac arrhythmias with bradycardia can be eliminated by introducing a beta-sympathomimetic. If life-threatening bradycardia should use an artificial pacemaker.
In severe hypotension shows infusion norepinefriena (noradrenaline) at standard doses. With the development of heart failure symptoms is recommended / in a fast digitalis glycosides.
In the absence of a specific antidote is a symptomatic therapy. As an antidote can be used dopamine, and isoprenaline 10% kalytsiya gluconate (10-20 ml / in).
Kordafleks® RD can be successfully used in a combination therapy.
Rational from the perspective of an anti-hypertensive and anti-anginal effects of a combination of Kordafleksa® RD with beta-blockers, Diuretics, ACE inhibitors, nitratami.
Combined use Kordafleksa® RD with beta-blockers in most clinical situations, safe and highly effective, tk. It leads to summation and potentiation of effects, however, in some cases, there is the risk of hypotension and cardiac insufficiency gain.
Increased hypotensive effect is also observed in combination therapy with cimetidine, ranitidinom and triciklicheskimi antidepressantami.
The treatment with corticosteroids and NSAIDs efficiency Kordafleksa® RD is not reduced.
Kordafleks® FH increases the concentration of digoxin and theophylline, concerning clinical effect should be monitored and / or the content of Digoxin and theophylline in plasma.
When concomitant administration with rifampicin and calcium supplementation action Kordafleksa® RD is weakened.
Prokayn, quinidine and other drugs, causing prolongation of the QT interval, reinforce the negative inotropic effect and increase the risk of QT prolongation. Influenced Kordafleksa® RD quinidine concentration in serum is significantly reduced, what, apparently, due to a decrease in its bioavailability, as well as the induction of enzymes, involved in the metabolism of quinidine. If you cancel Kordafleksa® RD observed transient increase in the concentration of quinidine (about 2 times), which reaches a maximum level at 3-4 day. The use of such combinations requires caution, particularly in patients with left ventricular dysfunction.
Nifedipine can displace from its association with protein drugs, characterized by a high degree of binding (incl. indirect anticoagulants – coumarin and derivatives indanoina, anticonvulsants, NSAIDs), whereby they may increase plasma concentrations.
Unnecessarily. It was shown, Chto carbamazepine and phenobarbital, activating enzymes of the liver, reduce the plasma concentration of other calcium channel blockers, can not exclude a similar decrease in the concentration of nifedipine in the blood plasma.
Valproic Acid, inhibiting the activity of enzymes, It led to an increase in plasma concentrations of other calcium channel blockers, so we can not rule out an increase in the concentration of nifedipine in blood plasma while taking valproic acid.
Nifedipine inhibits the excretion of vincristine from the body and may cause an increase of its side effects (if necessary, reduce the dose of vincristine).
Diltiazem Nifedipine inhibits the metabolism in the body, should be closely monitored, if necessary, reduce the dose of nifedipine.
Grapefruit juice inhibits the metabolism in the body of nifedipine, and therefore it is not recommended to use it with nifedipine.
Conditions of supply of pharmacies
The drug is released under the prescription.
Conditions and terms
The drug should be stored at a temperature no higher than 30 ° C, protected from direct sunlight and away from children. Shelf life - 4 year.