KORDAFLEKS

Active material: Nifedipine
When ATH: C08CA05
CCF: Kalьcievыh channel blocker
ICD-10 codes (testimony): I10, i20, I20.1, I73.0
When CSF: 01.03.02
Manufacturer: EGIS PHARMACEUTICALS Plc (Hungary)

PHARMACEUTICAL FORM, COMPOSITION AND PACKAGING

Pills, coated yellow color, matte or slightly shiny, round, lenticular, with a faint characteristic odor.

Excipients: polyvinyl butyral, magnesium stearate, talc, hydroksypropyltsellyuloza, sodium croscarmellose, lactose monohydrate, microcrystalline cellulose, Titanium dioxide, iron oxide yellow, gipromelloza.

100 PC. – vials of dark glass (1) – packs cardboard.

Sustained-release tablets, coated brownish purple, round, lenticular, with a matte or slightly shiny surface, odorless or with a faint characteristic odor; of presentations – yellow with a narrow stripe of brownish-lilac along the edges.

Excipients: microcrystalline cellulose, lactose monohydrate, sodium croscarmellose, hydroksypropyltsellyuloza, polyvinyl butyral B 30 T, talc, magnesium stearate.

The composition of the shell: gipromelloza, Titanium dioxide, iron oxide red, magnesium stearate.

30 PC. – jars of dark glass (1) – cardboard boxes.
60 PC. – jars of dark glass (1) – cardboard boxes.

Pharmacological action

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, especially 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 practically does not affect the sinoatrial and AV nodes and has no effect on, 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 Cordaflex^® in the form of prolonged-release tablets, the clinical effect develops through 20 m, duration of clinical effect – 12-24 no.

Pharmacokinetics

Absorption

When taken by mouth quickly and almost completely (more 90%) absorbed from the gastrointestinal tract. Bioavailability – 40-70%.

After oral administration of Cordaflex^® tablet form 10 mg C_max blood achieved through 0.5-1 h after administration.

Once inside 1 tab. long-acting 20 mg the therapeutic concentration of nifedipine in blood plasma is achieved through 1 h and remains constant up to 6 no (prolonged-release plateau), and in subsequent 30-36 h is gradually reduced.

Distribution

The binding to plasma proteins (albumin) is 94-97%. Unbound nifedipine is distributed in all organs and tissues.

It penetrates through the BBB (less 5%), the placental barrier, excreted in breast milk.

Not accumulates.

Metabolism

Nifedipine is extensively metabolized in the liver to form 3 metabolites, non-pharmacological.

Deduction

After oral administration of Cordaflex^® tablet form 10 mg T_1/2 nifedipine is 2 no, after taking a long-acting tablet 20 mg – about 3.8-16.9 no.

60-80% of an oral dose is excreted in the urine as inactive metabolites, the remaining part – with bile and feces.

Pharmacokinetics in special clinical situations

In elderly patients, the metabolism of nifedipine in the liver is reduced.

In patients with hepatic impairment, the total clearance decreases and the T1 / 2 increases_1/2 Nifedipine.

Chronic renal failure, hemodialysis and peritoneal dialysis do not affect the pharmacokinetics of nifedipine.

Testimony

- arterial hypertension of various origins, including hypertensive crises (Pill 10 mg);

- CHD: for the prevention of attacks with various forms of angina, incl. angiospastic (Prinzmetal angina);

- Raynaud's syndrome (for extended-release tablets).

Dosage regimen

The mode set individually, depending on the severity of the disease and the patient's response to the therapy.

Adults Kordafleks^® in the form of tablets, coated, appoint 10 mg (1 tab.) 3 times / day. If necessary, the dose of the drug can be increased to 20 mg (2 tab.) 1-2 times / day. The maximum daily dose – 40 mg. The interval between doses of the drug – no less 2 no.

To accelerate the action of the drug at the beginning of the development of an attack of angina pectoris or hypertensive crisis, the tablet should be chewed, hold in your mouth for a while, and then swallow with a little water.

If necessary, increase the dose to 80-120 mg / 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 prolonged-release tablets.

When carrying out a course therapy, it is recommended to use Cordaflex^® in the form of prolonged-release tablets. The initial dose – 20 mg (1 tab.) 2 times / day at intervals 12 no. If necessary, the dose of the drug is gradually increased until the optimal clinical effect is achieved.. For long-term maintenance therapy, usually, it is enough to take 20-40 mg (1-2 tab.) 2 times / day. The maximum daily dose – 120 mg.

In elderly patients pharmacokinetics of nifedipine changes, in connection with which the initial dose of the drug is reduced in 2 times and to maintain the therapeutic effect, lower doses may be required.

At moderate impairment of liver or kidney function correction dosing regime is not required. At severe liver dysfunction the maximum daily dose should not exceed 40 mg.

Drug in tablet form, containing 10 mg nifedipine, taken orally before meals, in the form of prolonged-release tablets – regardless of the meal, without chewing, with a little water.

Side effect

Cardio-vascular system: facial flushing, severe hypotension, peripheral edema, tachycardia; rarely – increasing angina attacks (It requires removal of the drug), increased heart failure, swoon.

From the central and peripheral nervous system: headache, dizziness, fatigue, sleep disorders (drowsiness or insomnia); in a few cases – mood lability, visual impairment; long-term use in high doses – paresthesias in extremities, tremor.

From the digestive system: diarrhea, constipation, nausea, heartburn; rarely (with prolonged use of the drug) – dry mouth, flatulence, intrahepatic cholestasis, increase in liver transaminases; in some cases – giperplaziya right, gingivitis, anorexia.

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; in a few cases – arthritis.

On the part of the endocrine system: in a few cases – gynecomastia, giperglikemiâ (completely disappear after drug withdrawal), weight change, galactorrhea.

Allergic reactions: rarely – hives, rash, itching; in some cases – autoimmune hepatitis.

Other: feeling the heat; in a few cases – weakness, Sweating, fever, chills, photodermatitis.

Contraindications

- acute stage of myocardial infarction;

- Cardiogenic shock;

- Severe hypotension (systolic BP below 90 mmHg.);

- severe aortic or mitral stenosis, idiopathic hypertrophic stenosis subaortalnыy;

- Severe heart failure;

- I trimester of pregnancy;

- Lactation (breast-feeding);

- Childhood and adolescence up 18 years;

- Hypersensitivity to nifedipine or other components of the drug.

FROM caution use Cordaflex^® in chronic heart failure, hypertrophic obstructive cardiomyopathy, severe violations of cerebral circulation, SSS, severe tachycardia, with severe impairment of liver and / or kidney function, malignant hypertension, patients, hemodialysis (due to the risk of severe arterial hypotension on the background of peripheral vasodilation), with lactose intolerance, and elderly patients.

Pregnancy and lactation

Kordafleks^® contraindicated for use in the I trimester of pregnancy.

Application of Cordaflex^® in pregnant women it is indicated only in those cases, when normalization of blood pressure is impossible with the use of other antihypertensive drugs.

Since nifedipine is excreted in breast milk, use of Cordaflex should be avoided^® during lactation or stop breastfeeding during drug treatment.

Cautions

Antihypertensive effect of Cordaflex^® increases with hypovolemia. Decreased pulmonary artery pressure and hypovolemia after dialysis may also enhance the drug's effects., therefore, it is recommended to reduce its dose.

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

With arterial hypertension or coronary artery disease, abrupt withdrawal of nifedipine can cause a hypertensive crisis or myocardial ischemia (phenomenon “Ricochet”).

If the patient requires surgery under general anesthesia during therapy, it is necessary to inform the anesthesiologist about the therapy with Cordaflex^®.

Elderly patients are more likely to decrease in cerebral blood flow due to the sharp peripheral vasodilatation.

During the course of treatment with Cordaflex^® drinking alcoholic beverages is not recommended due to the risk of excessive lowering of blood pressure.

Use in Pediatrics

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

Effects on ability to drive vehicles and management mechanisms

In the initial, individually determined period of application of Cordaflex^® It is not allowed to drive a vehicle and engaging in other potentially hazardous activities, requiring quickness of psychomotor reactions. During the further treatment of the degree of limitation is determined depending on the individual patient response to the drug.

Overdose

Symptoms: severe hypotension, tachycardia, chest pain (angina), headache, collapse, loss of consciousness, nodal or ventricular extrasystole due to inhibition of the sinus node, bradycardia, fainting. In severe cases, impairment of consciousness with a transition to a coma is possible, hyperkalemia, metabolic alkalosis, gipoksiya, cardiogenic shock with pulmonary edema.

Treatment: given the lack of a specific antidote, in cases of early detoxification, gastric lavage is performed with the appointment of activated carbon. If necessary, you can make washing the small intestine, which is more appropriate in the case of an overdose of controlled release drugs. When prescribing laxatives, consider, that taking slow calcium channel blockers suppresses intestinal motility to complete atony.

Since nifedipine is highly associated with blood plasma proteins, Hemodialysis is not effective, and plasmapheresis may be effective.

Symptomatic therapy. Symptoms of abnormal heart rhythm with bradycardia can be treated with beta-agonists and / or atropine. If life-threatening bradycardia should use an artificial pacemaker. With a pronounced decrease in blood pressure, infusion of usual doses of norepinephrine is indicated (noradrenalia) or epinephrine (adrenaline), dopamine can be used (the maximum dose 25 µg/kg body weight/min), doʙutamin (the maximum dose 15 µg/kg body weight/min), and isoprenaline 10% calcium gluconate solution (10-20 ml / in). With the development of symptoms of heart failure, intravenous administration of fast-acting cardiac glycosides is recommended.

Drug Interactions

Rational in terms of enhancing the antihypertensive and antianginal action is the combination of Cordaflex^® with beta-blockers, Diuretics, ACE inhibitors, nitratami. All of the above combinations are safe and effective in most clinical situations., t. to. lead to summation or potentiation of effects, however, in some cases there is a risk of a pronounced decrease in blood pressure and an increase in symptoms of heart failure.

Combination of Cordaflex^® with clonidine, methyldopa, octadine, prazosin according to indications is possible, however, may cause severe orthostatic hypotension.

Increased hypotensive effect is also observed in combination therapy with cimetidine, ranitidinom and triciklicheskimi antidepressantami.

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

Prokayn, quinidine and other drugs, causing prolongation of the QT interval, reinforce 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, what, apparently, due to a decrease in its bioavailability, as well as the induction of enzymes, inactivating quinidine. With the cancellation of nifedipine, a transient increase in the concentration of quinidine is observed (about 2 times), which reaches a maximum level at 3-4 day. Caution should be exercised when using such combinations., 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 indandiona, NSAIDs), as a result, it is possible to increase their concentrations in blood plasma.

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

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

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

Grapefruit juice, erythromycin and antifungal azoles (fluconazole, intraconazole, ketoconazole) can suppress the metabolism of nifedipine and therefore enhance its effects.

The same way, simultaneous use of Cordaflex^® and cimetidine increases the concentration of nifedipine in blood plasma, enhances its effects; however, the 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 can affect the metabolism of nifedipine. Cyclosporin is also a substrate of the CYP3A4 isoenzyme; therefore, when cyclosporine and nifedipine are used together, each can increase the duration of the effect of the other.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

List B. The drug should be stored in a dark and inaccessible to children at temperature from 15 ° to 25 ° C. Shelf life – 4 year.