Cordaflex, 60 pcs., 20 mg, extended-release film-coated tablets

Compound

Directions for use and doses

Inside.

10 mg film-coated tablets should be swallowed whole before meals, without chewing, with a little water.

The dosage regimen is set individually, depending on the severity of the disease and the patient’s response to the therapy. The initial dose is 1 tablet. (10 mg) 3 times a day. If necessary, the dose can be increased to 2 tablets. (20 mg) - 1-2 times a day. At least 2 hours should pass between two doses of the drug. The maximum daily dose is 40 mg.

If it is necessary to increase the dose to 80–120 mg for the treatment of angina pectoris or arterial hypertension, it is recommended to transfer the patient to Cordaflex® extended-release film-coated tablets, 20 mg.

To speed up the action of the drug at the beginning of an attack of angina or hypertensive crisis, the tablet should be chewed, held in the mouth for some time, and then swallowed with a small amount of water.

In elderly patients, the pharmacokinetics of nifedipine changes, and therefore lower doses may be required to maintain sufficient therapeutic effect.

If renal or hepatic function decreases, it is recommended to use with caution the same doses as for normal renal or hepatic function (tolerance may develop). If there is a significant decrease in liver function, it is not recommended to take a dose of more than 40 mg per day.

20 mg extended-release film-coated tablets should be swallowed whole, without chewing, with a small amount of water.

The recommended starting dose is 1 tablet. 2 times a day (2 × 20 mg). If necessary, the daily dose can be increased up to 2 times 2 tablets. The maximum daily dose of nifedipine should not exceed 120 mg. It is recommended to divide the daily dose into 2 doses at 12-hour intervals.

In patients with impaired liver function, the drug is used with caution under the monitoring of liver function; in case of severe impairment of liver function, the dose must be reduced. In patients with impaired renal function, no dose adjustment is required.

In elderly patients, the metabolism of nifedipine during the initial passage through the liver is reduced, and there is also a higher likelihood of deterioration of cerebral blood flow due to possible sharp peripheral vasodilation, therefore, at the beginning of treatment, the dose of Cordaflex® is reduced by approximately 2 times.

The drug should be discontinued gradually, especially after taking high doses.

Cordaflex 10 mg 100 pcs. film-coated tablets

pharmachologic effect

Selective blocker of slow calcium channels, 1.4-dihydropyridine derivative.
Has antihypertensive and antianginal effects. Nifedipine reduces the flow of extracellular calcium ions into cardiomyocytes and smooth muscle cells of the coronary and peripheral arteries. Uncouples the processes of excitation and contraction in vascular smooth muscles mediated by calmodulin. In therapeutic doses, it normalizes the transmembrane current of calcium ions, which is disturbed in a number of pathological conditions, primarily in arterial hypertension. Reduces spasm and dilates coronary and peripheral arterial vessels, reduces peripheral vascular resistance, reduces afterload and myocardial oxygen demand. At the same time, it improves blood supply to ischemic areas of the myocardium without the development of “steal” syndrome, and also increases the number of functioning collaterals.

Nifedipine has virtually no effect on the sinoatrial and AV nodes and does not have an antiarrhythmic effect. Does not affect the tone of the veins. Nifedipine increases renal blood flow, causing moderate 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.

Composition and release form Cordaflex 10 mg 100 pcs. film-coated tablets

Tablets - 1 tablet:

• Active substance: nifedipine 10 mg.
• Excipients: microcrystalline cellulose, lactose monohydrate, croscarmellose sodium, copolymer of methyl methacrylate and ethyl acrylate [1:2], talc, magnesium stearate, hyprolose.
• Shell composition: hypromellose, titanium dioxide, red iron oxide dye (E172), black iron oxide dye (E172), magnesium stearate.

100 pieces. - dark glass jars (1) - cardboard packs.

Description of the dosage form

Extended-release tablets, film-coated, brownish-violet, round, biconvex, with a matte or slightly shiny surface, odorless or with a slight characteristic odor; on the fracture - yellow with a narrow strip of brownish-violet color along the edges.

Directions for use and doses

The drug is taken orally. The tablets should be swallowed whole, without chewing, with a small amount of water.

The recommended initial dose of the drug is 1 tablet. (20 mg) 2 times/day. If necessary, the daily dose can be increased to 2 tablets. 2 times/day. The maximum daily dose of nifedipine should not exceed 120 mg. It is recommended to divide the daily dose into 2 doses at 12-hour intervals.

In patients with impaired liver function, the drug is used with caution under the monitoring of liver function; in case of severe impairment of liver function, the dose must be reduced.

In patients with impaired renal function, no dose adjustment is required.

In elderly patients, the metabolism of nifedipine during the “first pass” through the liver is reduced, and there is also a higher likelihood of deterioration in cerebral blood flow due to possible sharp peripheral vasodilation, therefore, at the beginning of treatment, the dose of Cordaflex® is reduced by approximately 2 times.

The drug should be discontinued gradually, especially after use in high doses.

Pharmacokinetics

Suction

When taken orally, it is quickly and almost completely (90%) absorbed from the gastrointestinal tract. Bioavailability - 40-60%. Eating increases bioavailability. Subject to a first-pass effect through the liver.

After oral administration 1 tablet. prolonged action 20 mg, the therapeutic concentration of nifedipine in the blood plasma is achieved after 1 hour and remains at a constant level for up to 6 hours (prolonged action plateau), and gradually decreases in the next 30-36 hours.

Distribution

Binding to blood plasma proteins (albumin) is 94-97%. Penetrates through the BBB and placental barrier, excreted in breast milk. Does not accumulate.

Metabolism

Nifedipine is extensively metabolized in the liver with the formation of 3 metabolites that do not have pharmacological activity.

Removal

T1/2 - 3.8-16.9 hours.

60-80% of the drug dose taken orally is excreted in the urine in the form of inactive metabolites, the remaining part is excreted in bile and feces.

Pharmacokinetics in special groups of patients

In patients with liver failure, total clearance decreases and T1/2 of nifedipine increases.

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

Indications for use Cordaflex 10 mg 100 pcs. film-coated tablets

• Arterial hypertension;
• IHD: for the prevention of attacks in various forms of angina, incl. angiospastic (Prinzmetal's angina);
• Raynaud's syndrome.

Contraindications

• Acute myocardial infarction (in the first 4 weeks);
• SSSU;
• cardiogenic shock;
• severe arterial hypotension (systolic blood pressure below 90 mm Hg);
• severe aortic or mitral stenosis, hypertrophic obstructive cardiomyopathy (risk of a pronounced decrease in blood pressure);
• chronic heart failure functional class IV according to NYHA;
• simultaneous use of rifampicin;
• pregnancy up to 20 weeks;
• lactation period (breastfeeding);
• children and adolescents up to 18 years of age;
• lactase deficiency, lactose intolerance, glucose-galactose malabsorption syndrome (the drug contains lactose monohydrate);
• hypersensitivity to nifedipine and other components of the drug;
• hypersensitivity to other dihydropyridine derivatives.

The drug should not be used to relieve attacks of angina.

Cordaflex® should be used with caution in chronic heart failure, severe impairment of liver and/or kidney function, severe cerebrovascular accidents, diabetes mellitus, malignant arterial hypertension, bradycardia, in patients on hemodialysis (due to the risk of severe arterial hypotension) .

Application of Cordaflex 10 mg 100 pcs. film-coated tablets during pregnancy and breastfeeding

Cordaflex® extended-release tablets are contraindicated for use before the 20th week of pregnancy.

There have been no controlled studies of the use of Cordaflex® in pregnant women. Based on the available clinical data, specific prenatal risk cannot be judged. At the same time, there is evidence of an increased likelihood of perinatal asphyxia, cesarean section, premature birth and intrauterine growth retardation. It is unclear whether these cases are a consequence of the underlying disease (arterial hypertension), the treatment, or a specific effect of nifedipine. The available information is insufficient to exclude the possibility of side effects that pose a danger to the fetus and newborn. Therefore, the use of Cordaflex® after the 20th week of pregnancy requires a careful individual assessment of the risk-benefit ratio for the patient, fetus and/or newborn and can only be considered in cases where other methods of therapy are contraindicated or ineffective.

Careful monitoring of blood pressure in pregnant women should be carried out when using Cordaflex® simultaneously with intravenous administration of magnesium sulfate due to the possibility of an excessive decrease in blood pressure, which poses a danger for both the mother and the fetus and/or newborn.

Since nifedipine is excreted in breast milk, you should refrain from prescribing Cordaflex® during lactation, or stop breastfeeding during treatment with the drug.

Use in children

Due to the lack of sufficient clinical data, the drug is contraindicated for use in children and adolescents under the age of 18 years.

special instructions

Should not be used to relieve an attack of angina.

Particular caution is required when prescribing Cordaflex® to patients with significant arterial hypotension (systolic blood pressure below 90 mm Hg). The antihypertensive effect of Cordaflex® is enhanced by hypovolemia. In case of kidney disease, the dose of nifedipine does not need to be adjusted. A decrease in pulmonary artery pressure and hypovolemia after dialysis may enhance the effects of Cordaflex®, and therefore a dose reduction is recommended.

Despite the absence of withdrawal syndrome with Cordaflex®, a gradual dose reduction is recommended before stopping treatment.

Regularity of treatment is important, regardless of how you feel, since the patient may not feel the symptoms of arterial hypertension.

The simultaneous administration of beta-blockers must be carried out under conditions of careful medical supervision, since this may cause an excessive decrease in blood pressure, and in some cases, aggravation of heart failure. It is not recommended to simultaneously administer IV therapy with β-adrenergic receptor blockers and intracoronary administration of nifedipine.

During treatment, positive results are possible with direct Coombs test and laboratory tests for antinuclear antibodies.

If during therapy the patient requires surgical intervention under general anesthesia, it is necessary to inform the anesthesiologist about the nature of the therapy being performed.

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

Caution is required when using Cordaflex® in patients with liver disease. For portal hypertension and liver cirrhosis, the dose should be reduced.

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

Patients with diabetes mellitus require careful medical supervision while using Cordaflex®.

During the course of treatment with the drug, you should avoid drinking alcohol.

Each tablet contains 30 mg of lactose monohydrate, so the drug should not be prescribed to patients with lactase deficiency, lactose intolerance, or glucose-galactose malabsorption.

Impact on the ability to drive vehicles and operate machinery

During the treatment period, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Overdose

Symptoms: depending on the severity of intoxication - a pronounced decrease in blood pressure, tachycardia, chest pain, fainting and loss of consciousness due to heart rhythm disturbances (sinus node depression, bradycardia, prolongation of AV conduction, ventricular extrasystole), inhibition of insulin secretion. In more severe cases, confusion leading to coma, hyperkalemia, metabolic acidosis, hypoxia, and cardiogenic shock with pulmonary edema may occur.

Treatment: there is no specific antidote, therefore, first of all, measures should be taken to remove nifedipine and maintain the function of the cardiovascular system. In case of overdose, the first therapeutic measure should be gastric lavage and activated charcoal; if necessary, with colon lavage.

Complete removal of unabsorbed nifedipine by gastric and colon lavage is especially important in cases of overdose with extended-release drugs to prevent further absorption. Laxatives can be prescribed, however, in the case of slow calcium channel blockers, inhibition of intestinal motility up to atony should be taken into account. Nifedipine is not excreted by dialysis, therefore, hemodialysis is ineffective, however, plasmapheresis is recommended (given the high percentage of nifedipine binding to plasma proteins and the relatively small Vd). Atropine and/or beta-agonists may be prescribed for symptomatic treatment of bradycardia. For life-threatening bradycardia, a temporary pacemaker should be installed. With a pronounced decrease in blood pressure due to cardiogenic shock and vasodilation of the arteries, calcium (1-2 g of calcium gluconate intravenously), dopamine (maximum 25 mcg/kg body weight/min), dobutamine (maximum 15 mcg/kg body weight/min) should be prescribed ) and epinephrine or norepinephrine. The dose of these drugs should be determined according to the patient's response. Serum calcium may be normal or slightly elevated. Additional fluid administration should be done with caution under the control of hemodynamic parameters to prevent cardiac overload.

Side effects Cordaflex 10 mg 100 pcs. film-coated tablets

The frequency of side effects is adjusted to the following categories: very common (≥1/10); often (≥1/100 -

From the nervous system: often - dizziness, headache, drowsiness; infrequently - insomnia, anxiety, paresthesia, dizziness; rarely - hypoesthesia, tremor, sleep disturbances, mood changes.

From the organ of vision: rarely - blurred vision, pain in the eyes.

From the cardiovascular system: often - palpitations, symptoms of vasodilation (redness of the facial skin, feeling of heat), swelling; uncommon - fainting, tachycardia, marked decrease in blood pressure, orthostatic hypotension; very rarely - in some cases myocardial infarction may develop, although this is most likely a consequence of the underlying disease.

From the respiratory system: infrequently - shortness of breath; rarely - nosebleeds; very rarely - allergic reactions with swelling of the vocal cords, in extreme cases bronchospasm with life-threatening shortness of breath, which appears after cessation of treatment.

From the gastrointestinal tract: infrequently - diarrhea, dry oral mucosa, bloating, nausea, constipation; rarely - vomiting, anorexia, belching, gingivitis, hypertrophic gingivitis; very rarely - esophagitis, intestinal obstruction, ulcerative lesions of the intestine.

From the liver and biliary tract: rarely - impaired liver function (increased GGT activity), very rarely - jaundice, hepatitis.

From the hematopoietic system: very rarely - anemia, leukopenia, thrombocytopenia or thrombocytopenic purpura, agranulocytosis.

From the endocrine system: very rarely - transient hyperglycemia.

From the genitourinary system: infrequently - nocturia, polyuria; rarely - dysuria, impotence; very rarely - a temporary deterioration in renal function is possible while taking nifedipine in patients with renal failure.

From the skin and subcutaneous tissues: often - redness of the facial skin, accompanied by a feeling of heat; uncommon - itching, skin rash; rarely - angioedema, maculopapular, pustular, vesicular and bullous rash, edema, urticaria; very rarely - hypersensitivity reactions, exfoliative dermatitis may occur. Photodermatitis may occur when exposed to sunlight or ultraviolet light.

From the musculoskeletal system: myalgia, rarely - pain in joints and muscles, very rarely - arthritis.

Other: infrequently - pain (in the abdomen, chest, legs), weakness; rarely - allergic reactions, chest pain, chills, fever, gynecomastia (especially in elderly patients and during long-term use of the drug - the condition always normalizes after stopping treatment), cardiac sphincter insufficiency, swelling of the joints, muscle cramps.

Angina attacks may appear at the very beginning of therapy, or in patients with a history of angina attacks, the frequency, duration and severity of attacks may increase. In case of hypertension or coronary artery disease, sudden withdrawal of nifedipine can provoke a hypertensive crisis or myocardial ischemia (withdrawal syndrome).

Drug interactions

Rifampicin is a potent inducer of the CYP3A4 isoenzyme. When used simultaneously with rifampicin, the bioavailability of nifedipine is significantly reduced and, accordingly, its effectiveness is reduced. The use of nifedipine in combination with rifampicin is contraindicated.

Because Rifampicin and phenytoin, through enzyme induction, significantly reduce the concentration of nifedipine in plasma; a similar effect of barbiturates and carbamazepine cannot be excluded.

When taken simultaneously with other antihypertensive drugs (ACE inhibitors, diuretics, etc.), nitrates, psychotropic drugs and drugs containing magnesium, the hypotensive effect may be enhanced.

Simultaneous use with beta-blockers enhances the hypotensive and antianginal effects, which is generally beneficial; however, the use of such a combination of drugs requires special caution due to the possibility of an excessive decrease in blood pressure, the development of arterial hypotension and heart failure.

When used together with prazosin, severe orthostatic hypotension may occur.

Concomitant use of nifedipine with digoxin may lead to increased plasma concentrations of digoxin.

When used simultaneously with theophylline, the concentration of theophylline in plasma may increase.

The use of nifedipine simultaneously with quinidine requires special caution, since with simultaneous use, the concentration of quinidine in plasma may decrease, and when nifedipine is discontinued, it may increase. The simultaneous use of these drugs may lead to malignant ventricular arrhythmia (abnormal increase in the QT interval on the ECG).

Diltiazem increases plasma concentrations of nifedipine.

Nifedipine may increase the anticoagulant effect of coumarin derivatives.

Since nifedipine is metabolized with the participation of the CYP3A4 isoenzyme, any inhibitor or inducer of this enzyme can alter the metabolism of nifedipine: grapefruit juice, erythromycin, azole antifungals (for example, ketoconazole), some fluoroquinolones, norfloxacin, ciprofloxacin, oral contraceptives containing gestagen, and HIV protease inhibitors (for example, indinavir, ritonavir) can inhibit the metabolism of nifedipine and increase its effect. Similarly, coadministration of nifedipine and cimetidine increases its plasma concentration and thus the effect of nifedipine, but coadministration of ranitidine does not significantly increase plasma levels of nifedipine. Cyclosporine is also a substrate for the CYP3A4 isoenzyme, therefore, when taken simultaneously, the duration of action of both drugs may increase. Concomitant use of nifedipine with weak and moderate inhibitors of the CYP3A4 isoenzyme requires regular monitoring of blood pressure and, if necessary, a reduction in the dose of nifedipine. These drugs include macrolide antibiotics (azithromycin, which belongs to the macrolide group, is not an inhibitor of the CYP3A4 isoenzyme).

Nifedipine reduces the excretion of vincristine, thereby increasing its side effects. The need to reduce the dose of vincristine should be considered.

Concomitant use of cisapride and nifedipine may lead to an increase in the concentration of nifedipine in the blood plasma. Blood pressure should be monitored and, if necessary, the dose of nifedipine should be reduced.

Concomitant use of quinupristin/dalfopristin and nifedipine may lead to an increase in the concentration of nifedipine in the blood plasma. Blood pressure should be monitored and, if necessary, the dose of nifedipine should be reduced.

Clinical studies of the interaction of nifedipine with valproic acid have not been conducted. Since it has been shown that valproic acid increases the plasma concentration of nimodipine, a structurally similar BMCC to nifedipine, due to inhibition of microsomal liver enzymes, the possibility of an increase in the concentration of nifedipine in the blood plasma cannot be excluded.

The following drugs do not affect the pharmacokinetics of nifedipine: ajmaline, benazepril, debrisoquine, doxazosin, irbesartan, omeprazole, orlistat, pantoprazole, ranitidine, rosiglitazone, talinolol, triamterene/hydrochlorothiazide, acetylsalicylic acid and candesartan.