Cordaflex tablets: instructions for use, price and reviews. Indications for use of the drug

Compound

Coated tablets contain 10 mg of nifedipine each as an active substance. Excipients: polyvinyl butyral in an amount of 0.7 mg; talc (1 mg); 0.3 mg magnesium stearate ; 4 mg hydroxypropylcellulose ; lactose monohydrate (15 mg); croscarmellose sodium (13 mg); microcellulose (46 mg). The shell consists of hypromellose - 2.63 mg; titanium dioxide CI 77891 - 0.82 mg; yellow iron oxide - 0.3 mg and magnesium stearate - 0.25 mg.
Long-acting film-coated tablets contain the same active substance, but in a dose of 20 mg. Each of them contains the following substances as auxiliary substances: microcellulose (99 mg); lactose monohydrate (30 mg); croscarmellose sodium (26 mg); copolymers of methyl methacrylate and ethyl methacrylate in a ratio of 1:2 (1.9 mg); talc (2 mg); magnesium stearate (0.6 mg); hyprolose (0.5 mg). The film shell is made of hypromellose - 5.26 mg; titanium dioxide - 1.64 mg; red iron oxide - 0.6 mg; magnesium stearate - 0.5 mg.

Release form

There are two options for the release form of the drug:

Coated tablets, weighing 10 mg. Every 100 tablets are placed in a brown glass bottle. The bottles are individually packaged in cardboard boxes.
Film-coated tablets with prolonged action. Each tablet weighs 20 mg. Place 30 or 60 tablets in brown glass bottles. Vials must be sealed with polyethylene caps that have a first-opening control. The bottle is packed in a cardboard box.

Pharmacodynamics and pharmacokinetics

Nifedipine is a selective blocker of slow calcium channels, one of the 1,4-dihydropyridine derivatives. Its effect is manifested in a decrease in the flow of extracellular calcium ions into cardiomyocytes and smooth muscle cells of the arteries. Nifedipine can also increase renal blood flow, causing moderate natriuresis .

After taking one tablet of Cordaflex, which has a prolonged action, the clinical effect usually develops after 20 minutes, the effect lasts from 12 to 24 hours.

After administration, it is quickly, almost completely (at least 90%) absorbed from the digestive tract. And the bioavailability of the drug is in the range of 40-70%.

The maximum concentration of the active substance in the blood is found 30-60 minutes after taking the drug.

After taking one tablet with a prolonged action, the therapeutic concentration in the blood plasma is achieved within an hour and remains at an equal level for up to 6 hours; over the next 30-36 hours, a gradual decrease in concentration is observed.

Nifedipine has the property of binding to blood plasma proteins, in particular albumins , penetrating the blood-brain barrier (in small quantities - no more than 5%), through the placenta , and can be excreted in breast milk.

The half-life is 2 hours for a 10 mg tablet; for a 20 mg extended-release tablet it is approximately 3.8-16.9 hours.

Cordaflex® RD

Pharmacokinetic interactions

Medicines that affect the metabolism of nifedipine

Nifedipine is metabolized by CYP3A4/5 isoenzymes, which are located in the intestinal mucosa and liver. Drugs that inhibit or induce this enzyme system may affect the first pass effect through the liver (after oral administration) or the clearance of nifedipine.

Inducers of the CYP3A4 isoenzyme

Rifampicin

Rifampin 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. Therefore, the simultaneous use of nifedipine with rifampicin is contraindicated.

Antiepileptic drugs that induce CYP3A4 (eg, phenytoin, carbamazepine, phenobarbital)

Phenytoin induces the CYP3A4 isoenzyme. With the simultaneous use of nifedipine and phenytoin, the bioavailability of nifedipine is reduced and its effectiveness is reduced. When using this combination simultaneously, it is necessary to monitor the clinical response to nifedipine therapy and, if necessary, increase its dose. If the dose of nifedipine is increased with simultaneous use of both drugs, the dose of nifedipine should be reduced after discontinuation of phenytoin. Clinical studies examining the potential interaction between nifedipine and carbamazepine or phenobarbital have not been conducted. Since both drugs reduce the concentration of nimodipine in the blood plasma, which is structurally similar to BMCC, the possibility of a decrease in the concentration of nifedipine in the blood plasma and a decrease in its effectiveness cannot be excluded.

CYP3A4 isoenzyme inhibitors

Macrolide antibiotics (for example, erythromycin)

Clinical studies on the interaction of nifedipine and macrolide antibiotics have not been conducted. Some macrolides are known to inhibit the CYP3A4 isoenzyme. As a result, the possibility of an increase in the concentration of nifedipine in the blood plasma cannot be excluded with the simultaneous use of nifedipine and macrolide antibiotics.

Azithromycin, a macrolide antibiotic, does not inhibit the CYP3A4 isoenzyme.

HIV protease inhibitors (eg, ritonavir)

When used simultaneously with nifedipine, a significant increase in the concentration of nifedipine in the blood plasma cannot be ruled out due to a decrease in the effect of “first pass” through the liver and slower elimination.

Azole antifungals (eg, ketoconazole)

Clinical studies examining the interaction of nifedipine and azole antifungals have not been conducted. It is known that drugs of this class inhibit the CYP3A4 isoenzyme. When used simultaneously with nifedipine, a significant increase in the systemic bioavailability of nifedipine is possible by reducing the effect of “first pass” through the liver.

Cimetidine and ranitidine

It has been established that cimetidine and ranitidine inhibit the CYP3A4 isoenzyme and cause an increase in the concentration of nifedipine in the blood plasma (by 80% and 70%, respectively), thereby enhancing its antihypertensive effect.

Diltiazem

Diltiazem reduces the clearance of nifedipine. This combination should be used with caution. A dose reduction of nifedipine may be required.

Fluoxetia

Clinical studies examining the interaction of nifedipine and fluoxetine have not been conducted. It is known that fluoxetine in vitro

suppresses the metabolism of nifedipine mediated by the action of the CYP3A4 isoenzyme. Therefore, the possibility of an increase in the concentration of nifedipine in the blood plasma cannot be excluded with the simultaneous use of nifedipine and fluoxetine.

Nefazodone

Clinical studies examining the interaction between nifedipine and nefazodone have not been conducted. Nefazodone is known to inhibit the metabolism of other drugs mediated by the CYP3A4 isoenzyme. Therefore, the possibility of an increase in the concentration of nifedipine in the blood plasma cannot be excluded with the simultaneous use of nifedipine and nefazodone.

Quinidine

Increased plasma concentrations of nifedipine have been reported when administered concomitantly with quinidine. Therefore, when using quinidine and nifedipine simultaneously, careful monitoring of blood pressure is necessary. If necessary, the dose of nifedipine should be reduced.

Quinupristin/dalfopristin

Concomitant use of quinupristin/dalfopristin may lead to increased plasma concentrations of nifedipine.

Valproic acid

Clinical studies examining the interaction of nifedipine and valproic acid have not been conducted. Since valproic acid increases the concentration of nimodipine in the blood plasma, which is structurally similar to BMCC, the possibility of increasing the concentration of nifedipine in the blood plasma and enhancing its effectiveness cannot be excluded.

Grapefruit juice

Grapefruit juice inhibits the CYP3A4 isoenzyme and suppresses the metabolism of nifedipine. The simultaneous use of nifedipine with grapefruit juice leads to an increase in the concentration of nifedipine in the blood plasma and a prolongation of its action due to a decrease in the effect of “primary passage” through the liver and a decrease in clearance. This may enhance the antihypertensive effect of nifedipine. With regular consumption of grapefruit juice, this effect can last for 3 days after the last consumption of the juice. The consumption of grapefruit/grapefruit juice during treatment with nifedipine is contraindicated (see section Contraindications).

CYP3A4 isoenzyme substrates

Substrates of the CYP3A4 isoenzyme (for example, cisapride, tacrolimus, benzodiazepines, imipramine, propafenone, terfenadine, warfarin), when used simultaneously with nifedipine, may act as CYP3A4 inhibitors and increase the concentration of nifedipine in the blood plasma.

Cisapride

Concomitant use of cisapride and nifedipine may lead to increased plasma concentrations of nifedipine.

Effect of nifedipine on other drugs

Quinidine

Nifedipine causes a decrease in the concentration of quinidine in the blood plasma. After discontinuation of nifedipine, a sharp increase in the concentration of quinidine in the blood plasma may occur. Therefore, when using nifedipine as additional therapy or discontinuing nifedipine, the concentration of quinidine in the blood plasma should be monitored and, if necessary, its dose should be adjusted.

Digoxin

The simultaneous use of nifedipine and digoxin may lead to a decrease in the clearance of digoxin and, consequently, to an increase in the concentration of digoxin in the blood plasma. The patient should be carefully monitored for symptoms of glycoside overdose and, if necessary, reduce the dose of digoxin, taking into account its concentration in the blood plasma.

Theophylline

Nifedipine increases plasma concentrations of theophylline, and therefore the concentration of theophylline in blood plasma should be monitored. The clinical effect of both drugs when used together does not change.

Tacrolimus

Tacrolimus is metabolized with the participation of the CYP3A4 isoenzyme. Recently published data indicate the possibility of increased tacrolimus concentrations in selected cases when administered concomitantly with nifedipine. When using tacrolimus and nifedipine simultaneously, the concentration of tacrolimus in the blood plasma should be monitored and, if necessary, its dose should be reduced.

Vincristine

Nifedipine slows down the elimination of vincristine from the body and may cause increased side effects of vincristine. If simultaneous use is necessary, reduce the dose of vincristine.

Drugs that bind to blood proteins

Nifedipine can displace drugs characterized by a high degree of binding from protein binding (including indirect anticoagulants - coumarin and indanedione derivatives, anticonvulsants, non-steroidal anti-inflammatory drugs (NSAIDs), quinine, salicylates, sulfinpyrazone), as a result of which their concentration may increase in blood plasma.

Cephalosporins

With the simultaneous administration of cephalosporins (for example, cefixime) and nifedipine in probands, the bioavailability of the cephalosporin increased by 70%.

Pharmacodynamic interactions

Medicines that lower blood pressure

The antihypertensive effect of nifedipine may be enhanced when used simultaneously with antihypertensive drugs, such as diuretics, beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists (ARA II), other BMCCs, alpha-blockers, phosphodiesterase-5 inhibitors, methyldopa.

When using nifedipine and beta-blockers simultaneously, it is necessary to carefully monitor the patient's condition, since in some cases the course of CHF may worsen.

The severity of the decrease in blood pressure increases with the simultaneous use of inhalational anesthetics and tricyclic antidepressants.

Nitrates

When used simultaneously with nitrates, tachycardia increases.

Antiarrhythmic drugs

BMCCs can enhance the negative inotropic effect of antiarrhythmic drugs such as amiodarone and quinidine. Nifedipine should be co-administered with disopyramide and flecainide with caution due to a possible increase in negative inotropic effect.

Magnesium sulfate

It is necessary to carefully monitor blood pressure in pregnant women while using nifedipine with intravenous magnesium sulfate due to the possibility of an excessive decrease in blood pressure, which is dangerous for both the mother and the fetus.

Fentanyl

The simultaneous use of nifedipine and fentanyl can lead to severe arterial hypotension. If possible, it is recommended that nifedipine be discontinued at least 36 hours before fentanyl-based anesthesia.

Calcium preparations

Reduced effectiveness of nifedipine.

NSAIDs

NSAIDs reduce the antihypertensive effect of nifedipine due to suppression of prostaglandin synthesis, sodium and fluid retention in the body.

Sympathomimetics

Sympathomimetics reduce the antihypertensive effect of nifedipine.

Estrogens

Estrogens reduce the antihypertensive effect of nifedipine due to fluid retention in the body.

Lithium preparations

When BMCC is used together with lithium drugs, it is possible to increase the manifestation of the neurotoxicity of the latter (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus).

Contraindications

Contraindications are:

intolerance to nifedipine , other 1,4-dihydropyridine , additional components included in the tablets;
arterial hypotension;
unstable angina;
the current or recent presence of acute myocardial infarction or severe aortic stenosis ;
idiopathic subaortic stenosis;
chronic heart failure during the period of decompensation;
childhood.

It is prescribed with special caution to elderly patients, those with impaired renal function, and patients with diabetes mellitus .

Cordaflex RD tab. with control release 40mg N30

Registration Certificate Holder

EGIS Pharmaceuticals (Hungary)

Dosage form

Medicine - Cordaflex® RD (Cordaflex® RD)

Description

Modified-release film-coated tablets

brownish-red in color, round, biconvex, chamfered, odorless.

1 tab.

nifedipine 40 mg

Excipients

: microcrystalline cellulose, cellulose*, lactose monohydrate*, hypromellose 4000, magnesium stearate, colloidal anhydrous silicon dioxide, film shell [hypromellose 15 (mPa.s)**, macrogol 6000, macrogol 400**, red iron oxide**, titanium dioxide**, talc**].

10 pieces. - blisters (1) - cardboard packs. 10 pieces. - blisters (3) - cardboard packs.

* 10 mg of cellulose and 30 mg of lactose monohydrate can be replaced with the commercially available Cellactose® product containing cellulose and lactose monohydrate of Euro quality. Pharm. ** Instead of these ingredients, Opadry® red 04B0003 can be used. The composition of the substance Opadry® red 04B0003 is qualitatively and quantitatively identical to the shell. Macrogol 6000 is used after the coating process as a polishing agent and is therefore not included in Opadry® Red 04B0003.

Indications

arterial hypertension;
stable angina (angina pectoris);
post-infarction angina;
angiospastic angina (Prinzmetal's angina).

Contraindications for use

unstable angina;
myocardial infarction with left ventricular failure;
severe arterial hypotension with a risk of collapse in cardiovascular shock with respiratory manifestations;
hypersensitivity to nifedipine, other components of the drug, other 1,4-dihydropyridine derivatives.

Carefully _

the drug should be used for acute myocardial infarction during the first 4 weeks, severe aortic stenosis, severe mitral valve stenosis, hypertrophic obstructive cardiomyopathy, severe bradycardia or tachycardia, SSSS, chronic heart failure, severe cerebrovascular accidents, renal or hepatic failure (especially in patients on hemodialysis due to the high risk of excessive and unpredictable decrease in blood pressure), in patients under the age of 18 years (since safety and effectiveness have not been established), in elderly patients (due to the greatest likelihood of age-related impairment of kidney and liver function ).

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. 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 node and does not have either pro- or antiarrhythmic effects. 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.

After a single dose of Cordaflex® RD, the duration of the effect exceeds 24 hours.

Drug interactions

Cordaflex® RD can be successfully used as part of combination therapy.

The combination of Cordaflex RD with beta-blockers, diuretics, ACE inhibitors, and nitrates is rational from the point of view of antihypertensive and antianginal effects.

The combined use of Cordaflex RD with beta-blockers is safe and highly effective in most clinical situations, because leads to summation and potentiation of effects, however, in some cases there is a risk of developing arterial hypotension and increased heart failure.

An increase in the hypotensive effect is also observed with combination therapy with cimetidine, ranitidine and tricyclic antidepressants.

During treatment with corticosteroids and NSAIDs, the effectiveness of Cordaflex RD does not decrease.

Cordaflex® RD increases the concentration of digoxin and theophylline; therefore, the clinical effect and/or the content of digoxin and theophylline in the blood plasma should be monitored.

When administered simultaneously with rifampicin and calcium preparations, the effect of Cordaflex RD is weakened.

Procaine, quinidine and other drugs that cause QT prolongation enhance the negative inotropic effect and increase the risk of QT prolongation. Under the influence of Cordaflex RD, the concentration of quinidine in the blood serum is significantly reduced, which is apparently due to a decrease in its bioavailability, as well as the induction of enzymes involved in the metabolism of quinidine. When Cordaflex RD is discontinued, a transient increase in quinidine concentration is observed (approximately 2 times), which reaches a maximum level on days 3-4. The use of this combination requires caution, especially in patients with impaired left ventricular function.

Nifedipine can displace drugs characterized by a high degree of binding from protein binding (including indirect anticoagulants - coumarin and indanedione derivatives, anticonvulsants, NSAIDs), as a result of which their concentrations in the blood plasma may increase.

Because It has been shown that carbamazepine and phenobarbital, by activating liver enzymes, reduce the plasma concentrations of other calcium channel blockers; a similar decrease in the plasma concentrations of nifedipine cannot be excluded.

Valproic acid, inhibiting the activity of enzymes, led to an increase in the plasma concentration of other calcium channel blockers, so an increase in the concentration of nifedipine in the blood plasma cannot be excluded when taken simultaneously with valproic acid.

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

Diltiazem inhibits 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.

Dosage regimen

The dose should be selected individually, depending on the severity of the patient's condition and the effectiveness of treatment.

For arterial hypertension

Cordaflex® RD is prescribed 40 mg (1 tablet) 1 time/day. If necessary, the dose can be increased to 80 mg (2 tablets in 1-2 doses). Dose increases beyond 80 mg are not recommended.

With ischemic heart disease

prescribed 40 mg (1 tablet) 1 time/day.
If necessary, the dose can be increased to 80 mg (2 tablets in 1 or 2 doses). Doses greater than 80 mg may be given in exceptional cases under medical supervision. The daily dose should not exceed 120 mg. The tablets should be taken with a meal (such as breakfast), swallowed whole and with plenty of water.
If you have impaired renal or liver function

The drug is recommended to be used with caution in the same doses as for normal renal or hepatic function.
Tolerance may develop. If there is a significant decrease in liver function,
the dose should not exceed 40 mg/day.

Overdose

Symptoms:

headache, arterial hypotension, and also (as under the influence of other vasodilators) disruption of the energy supply of the myocardium (angina attack).

Treatment:

Immediately after an overdose, you can rinse the stomach and give activated charcoal as first aid. If necessary, small intestinal lavage can be done, which is especially useful in cases of overdose of controlled-release drugs.

Because nifedipine is highly bound to plasma proteins, dialysis is not effective, but plasmapheresis may be effective.

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

For severe hypotension, infusion of norepinephrine (norepinephrine) in standard doses is indicated. If symptoms of heart failure develop, intravenous administration of fast-acting digitalis glycosides is recommended.

Due to the lack of a specific antidote, symptomatic therapy is indicated. Dopamine, isoprenaline and 10% calcium gluconate (10-20 ml IV) can be used as antidotes.

Side effect

From the cardiovascular system:

at the beginning of treatment - facial skin flushing, marked decrease in blood pressure, tachycardia; peripheral edema (ankles, feet, legs); rarely - increased frequency of angina attacks (which is typical for other vasoactive drugs and requires discontinuation of the drug), heart failure.

From the central nervous system and peripheral nervous system:

headache, dizziness, increased fatigue, drowsiness; with long-term use in high doses - paresthesia in the limbs, tremor.

From the digestive system:

nausea, heartburn, diarrhea, or constipation; rarely with long-term use - intrahepatic cholestasis, increased activity of liver transaminases (disappears after discontinuation of the drug); in some cases - gum hyperplasia.

From the hematopoietic system:

rarely - thrombocytopenia, thrombocytopenic purpura, leukopenia; in some cases - anemia.

From the urinary system:

increased daily diuresis; rarely - deterioration of renal function in patients with chronic renal failure.

From the musculoskeletal system:

myalgia; very rarely - arthritis, arthralgia.

Allergic reactions:

rarely - urticaria, exanthema, itching;
very rarely - photodermatitis. Other:
in some cases - visual impairment, gynecomastia, hyperglycemia (completely disappear after discontinuation of the drug), changes in body weight, galactorrhea.

In the vast majority of cases, Cordaflex® RD is well tolerated by patients.

special instructions

After myocardial infarction, the drug should be started only after stabilization of hemodynamic parameters.

Patients with acute myocardial infarction and for 30 days after it should not use short-acting calcium channel blockers derived from 1,4-dihydropyridine. When prescribing calcium channel blockers - 1,4-dihydropyridine controlled-release derivatives - to such patients, careful monitoring is necessary. These drugs are more appropriate to prescribe in the absence of a tendency to tachycardia, as well as in patients in whom beta-blockers are ineffective or have contraindications to their use.

In cases of insufficient effectiveness of Cordaflex RD monotherapy, it is advisable to continue treatment using effective combinations with other drugs.

Patients with heart failure are recommended to undergo appropriate therapy with digitalis preparations before starting treatment with Cordaflex RD.

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

During treatment, alcohol consumption is not recommended due to the risk of excessive reduction in blood pressure.
Effect on the ability to drive vehicles and operate machinery.
During the initial individually determined period of treatment, it is necessary to refrain from potentially hazardous activities that require a quick mental and motor reaction. In the process of further treatment, the degree of restrictions is determined depending on the individual tolerability of the drug.

Storage conditions

The drug should be stored at a temperature not exceeding 30°C, protected from direct sunlight and out of the reach of children.

Best before date

Shelf life – 5 years.

Use during pregnancy and breastfeeding

Restrictions during pregnancy - With caution. Restrictions when breastfeeding - Contraindicated.

The use of Cordaflex® RD during pregnancy may be recommended if it is impossible to use other drugs that do not have restrictions on their use.

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

Use for renal impairment

Restrictions for impaired renal function - With caution.

Carefully _

the drug should be used for renal failure (especially in patients on hemodialysis due to the high risk of excessive and unpredictable decrease in blood pressure).

Use for liver dysfunction

Restrictions for liver dysfunction - With caution. With caution

the drug should be used for liver failure (especially in patients on hemodialysis due to the high risk of excessive and unpredictable decrease in blood pressure).

Use in elderly patients

Restrictions for elderly patients - Use with caution.

Carefully _

the drug should be used in elderly patients (due to the greatest likelihood of age-related impairment of kidney and liver function).

Use in children

Restrictions for children - With caution.

Carefully _

the drug should be used in patients under 18 years of age (since safety and effectiveness have not been established).

Terms of sale

The drug is available with a prescription.

Contacts for inquiries

EGIS pharmaceutical plant JSC (Hungary)

CJSC "Pharmaceutical EGIS-RUS" 121108 Moscow, Ivana Franko st. 8 Tel.; Fax

Side effects

Cordaflex is usually well tolerated. Side effects appear rarely, more often at the beginning of treatment (then they may become weaker or disappear).

There are such side effects:

On the heart and blood vessels: decreased blood pressure, flushing of the face and torso, swelling in the extremities , accelerated heart rate, paradoxical attack of angina , development of acute heart failure .
On the nervous system: increased fatigue , dizziness , weakness , emotional lability , sleep disturbances, headache, tremor , paresthesia .
On the gastrointestinal tract: the occurrence of heartburn , nausea , vomiting , flatulence , stool disorders, dryness or inflammation of the oral mucosa, intrahepatic cholestasis , as well as increased activity of certain liver enzymes.
On the circulatory system: thrombocytopenia , leukopenia , anemia .
On the urinary system: increased daily diuresis, night urination , decreased renal function.

Allergic reactions may occur in the form of urticaria , exanthema , and skin itching .

Cordaflex rd 40 mg 30 pcs. modified-release film-coated tablets

pharmachologic effect

Blocker of “slow” calcium channels.

Composition and release form Cordaflex RD 40 mg 30 pcs. modified-release film-coated tablets

Tablets - 1 tablet:

active substance: nifedipine - 40 mg;
excipients: cellulose, microcrystalline cellulose, lactose, hypromellose 4000, magnesium stearate, colloidal anhydrous silicon dioxide;
Shell: hypromellose 15, macrogol 6000, macrogol 400, red iron oxide E 172, titanium dioxide E 171, talc.

10 tablets in a blister made of PVC/PVDC/alfoil. 1 or 3 blisters in a cardboard box along with instructions for use.

Description of the dosage form

Round, biconvex, film-coated tablets, brown-red in color, chamfered, odorless.

Characteristic

Nifedipine is a selective CCB, a 1,4-dihydropyridine derivative.

Directions for use and doses

Cordaflex® RD 40 mg should be taken in the morning, during a meal (for example, breakfast), not chewed and washed down with a sufficient amount of water.

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

Arterial hypertension

1 tablet of Cordaflex® RD 40 mg 1 time per day.

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

Cardiac ischemia

1 tablet of Cordaflex® RD 40 mg 1 time per day.

If necessary, the dose can be increased to 80 mg (2 tablets of Cordaflex® RD 40 mg in one or two doses). Doses above 80 mg can be given in exceptional cases under medical supervision. The daily dose should not exceed 120 mg.

Dosage for decreased renal or hepatic function

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 exceed the daily dose of 40 mg.

Pharmacodynamics

The active ingredient of the drug Cordaflex® RD is nifedipine. Nifedipine is a selective blocker of “slow” calcium channels, a 1,4-dihydropyridine derivative. Has antihypertensive and antianginal effects. Reduces the flow of extracellular calcium ions into cardiomyocytes and smooth muscle cells of the coronary and peripheral arteries. 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 total peripheral resistance, reduces afterload and myocardial oxygen demand. At the same time, it improves blood supply to ischemic areas of the myocardium without developing the “steal” syndrome, and also activates the functioning of collaterals. It has virtually no effect on the sinoatrial and atrioventricular nodes and does not have either pro- or antiarrhythmic effects. 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.

Pharmacokinetics

Suction

Nifedipine is rapidly and almost completely (90%) absorbed from the gastrointestinal tract after oral administration. The duration of the effect after a single oral dose exceeds 24 hours. When developing the active substance of the drug Cordaflex® RD, zero-order release kinetics was chosen in order to ensure a constant release rate. The relative bioavailability of the drug is about 60%. The maximum concentration (Cmax) in blood plasma is 29.4 ± 12.0 mg/ml (x ± SD); the concentration of the drug in the blood plasma reaches a plateau 7.4 ± 6.4 hours after taking each dose. Maximum levels of the drug in blood plasma are achieved when it is taken in combination 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 (albumin) is 94-97%. Studies with labeled nifedipine in animals have shown that unbound nifedipine is distributed in all organs and tissues. Nifedipine concentrations were found to be higher in the myocardium than in skeletal muscles. There is no cumulative effect.

Metabolism

Nifedipine is mainly metabolized in the liver to inactive metabolites.

Removal

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. The half-life of nifedipine from blood plasma is approximately 2 hours. However, the release of the drug Cordaflex® RD is longer - up to 14.9 ± 6.0 hours in the equilibrium concentration phase.

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

If renal function is impaired, the pharmacokinetics of nifedipine does not change (nifedipine is excreted in the urine in small quantities). With a significant decrease in liver function, the clearance of nifedipine is reduced, so it is not recommended to exceed the daily dose.

Indications for use Cordaflex RD 40 mg 30 pcs. modified-release film-coated tablets

Arterial hypertension

Stable angina (angina pectoris), post-infarction angina, as well as vasospastic angina (Prinzmetal angina).

Contraindications

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

Severe arterial hypotension with a risk of collapse in cardiovascular shock with respiratory manifestations.

Unstable angina.

Myocardial infarction with left ventricular failure.

With caution: severe aortic stenosis, acute myocardial infarction (within the first 4 weeks), severe mitral valve stenosis, hypertrophic obstructive cardiomyopathy, severe bradycardia or tachycardia, sick sinus syndrome, chronic heart failure, severe cerebrovascular accidents, age up to 18 years (efficacy and safety have not been established), elderly age, renal and liver failure (especially patients on hemodialysis - high risk of excessive and unpredictable decrease in blood pressure).

Application of Cordaflex rd 40 mg 30 pcs. modified-release film-coated tablets during pregnancy and lactation

The use of nifedipine in pregnant women is recommended if it is impossible to use other drugs without restrictions.

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

special instructions

After myocardial infarction, the drug should be started only after stabilization of hemodynamic parameters.

Patients with acute myocardial infarction and for 30 days after it should not use short-acting calcium channel blockers such as 1,4-dihydropyridine. When treating such patients with controlled-release BMCCs such as 1,4-dihydropyridine, careful monitoring is necessary. It is more advisable to prescribe in the absence of a tendency to tachycardia, as well as in patients in whom beta-blockers are ineffective or have contraindications to their use.

In cases of insufficient effectiveness of monotherapy with Cordaflex® RD 40 mg, it is advisable to continue treatment using effective combinations with other drugs.

During treatment, drinking alcohol is not recommended due to the risk of excessively lowering blood pressure.

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

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

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

Impact on the ability to drive vehicles and operate machinery

During the initial individually determined period of treatment, it is necessary to refrain from potentially hazardous activities that require rapid psychomotor reactions. In the process of further treatment, the degree of restrictions is determined depending on the individual tolerability of the drug.

Overdose

Symptoms

In case of acute overdose, headache, a pronounced decrease in blood pressure, as well as a violation of the energy supply of the myocardium (an attack of angina) occur.

Treatment

In the early stages after an overdose is detected, first aid can be to rinse the stomach and give activated charcoal. If necessary, small intestinal lavage can be done, which is especially useful in cases of overdose of controlled-release drugs.

Since nifedipine is highly bound to plasma proteins, hemodialysis is ineffective, but plasmapheresis may be effective.

Symptoms of cardiac arrhythmias with bradycardia can be eliminated by administering beta sympathomimetics. For life-threatening bradycardia, an artificial pacemaker should be used.

If there is a significant decrease in blood pressure, an infusion of usual doses of norepinephrine (norepinephrine) is indicated. If symptoms of heart failure develop, intravenous administration of fast-acting digitalis glycosides is recommended.

Due to the lack of a specific antidote, symptomatic therapy is indicated. Dopamine, isoprenaline and 10% calcium gluconate solution (10 - 20 ml IV) can be used as antidotes.

Side effects of Cordaflex rd 40 mg 30 pcs. modified-release film-coated tablets

In the vast majority of cases, Cordaflex® RD 40 mg is well tolerated by patients.

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

Cardiovascular system: at the beginning of treatment - facial skin flushing, marked decrease in blood pressure, tachycardia; peripheral edema (ankles, feet, legs); rarely - the appearance of angina attacks (which is also typical for other vasodilators and requires discontinuation of the drug), heart failure.

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

Hematopoietic system: rarely - thrombocytopenia, thrombocytopenic purpura, leukopenia; very rarely - anemia.

Urinary system: increased daily diuresis; rarely - deterioration of renal function (in patients with renal failure).

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

Allergic reactions: rarely - urticaria, exanthema, itching; very rarely - photodermatitis.

Other: very rarely - visual impairment, gynecomastia, hyperglycemia, which completely disappear after discontinuation of the drug; change in body weight, galactorrhea.

Drug interactions

The drug Cordaflex® RD 40 mg with controlled release of the active substance has wide possibilities for highly effective combination therapy. Rational from the point of view of antihypertensive and antianginal effects is the combination of Cordaflex® RD 40 mg with beta-blockers, diuretics, angiotensin-converting enzyme (ACE) inhibitors, and nitrates.

The combined use of Cordaflex® RD 40 mg with beta-blockers is safe and effective in most clinical situations, as 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.

An increase in the hypotensive effect is also observed with combination therapy with cimetidine, ranitidine and tricyclic antidepressants.

Cordaflex® RD 40 mg does not reduce its effectiveness during treatment with steroidal 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.

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

Procaine, quinidine and other drugs that cause QT prolongation enhance 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, which is apparently due to a decrease in its bioavailability, as well as the induction of enzymes that inactivate quinidine. When nifedipine is discontinued, a transient increase in quinidine concentration is observed (approximately 2 times), which reaches a maximum level on days 3-4. Caution should be exercised when using such combinations, especially in patients with impaired left ventricular function.

Nifedipine can displace drugs characterized by a high degree of binding from protein binding (including indirect anticoagulants - coumarin and indanedione derivatives, non-steroidal anti-inflammatory drugs), as a result of which their concentration in the blood plasma may increase.

Since it has been shown that carbamazepine and phenobarbital, by activating liver enzymes, reduce the plasma concentrations of other slow calcium channel blockers (SCBCs), a similar decrease in the plasma concentrations of nifedipine cannot be excluded. Valproic acid, inhibiting the activity of enzymes, led to an increase in the concentration in the blood plasma of other blockers of “slow” calcium channels, so an increase in the concentration of nifedipine in the blood plasma cannot be excluded when taken simultaneously with valproic acid.

Nifedipine inhibits the elimination of vincristine from the body and may cause increased side effects of vincristine; if necessary, the dose of vincristine is reduced.

Diltiazem inhibits 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.

Instructions for use of Cordaflex (Method and dosage)

The drug is taken orally. 10 mg film-coated tablets are swallowed whole before meals with water.

The dosage is set individually, as it very much depends on the severity of the disease, the type of disease and the body’s response to the therapy. Start with 1 tablet (10 mg) 3 times a day. There should be at least 2 hours between doses of the drug. The maximum dose per day is 40 mg.

Long-acting film-coated tablets are swallowed whole and washed down with water. In this case, the initial dose is 1 tablet 2 times a day. In any case, the daily dose is divided into 2 doses, between which a 12-hour interval must be observed.

According to the instructions for use of Cordaflex, discontinuation of the drug should be carried out gradually.

Cordaflex retard

Full name: Cordaflex retard film-coated tablets 20 mg No. 60

Product code: 7GMID8 Price: 91

Release form:
film-coated tablets
Packaging:
60 tablets
Dosage:
20mg

Description:

Indications

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

— IHD: for the prevention of attacks in various forms of angina, incl. angiospastic (Prinzmetal's angina);

- Raynaud's syndrome (for extended-release 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. 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 either pro- or antiarrhythmic effects. 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.

After a single dose of Cordaflex in the form of extended-release tablets, the clinical effect develops within 20 minutes, the duration of the clinical effect is 12-24 hours.

Pharmacokinetics

Suction

When taken orally, it is quickly and almost completely (more than 90%) absorbed from the gastrointestinal tract. Bioavailability - 40-70%.

After oral administration of Cordaflex in tablet form, 10 mg Cmax in the blood is achieved 0.5-1 hour after administration.

After oral administration of 1 tablet of 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%. Unbound nifedipine is distributed in all organs and tissues.

Penetrates through the BBB (less than 5%), through the placental barrier, and is 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

After oral administration of Cordaflex in the form of a 10 mg tablet, T1/2 of nifedipine is 2 hours, after taking a prolonged-release tablet 20 mg - about 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 clinical situations

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

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.

Instructions for use / dosage

Instructions for use/dosage are determined individually, depending on the severity of the disease and the patient’s response to the therapy.

For adults
, Cordaflex in the form of film-coated tablets is prescribed 10 mg (1 tablet) 3 times a day.
If necessary, the dose of the drug can be increased to 20 mg (2 tablets) 1-2 times a day. The maximum daily dose is 40 mg. The interval between doses of the drug is at least 2 hours. 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.

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 extended-release tablets.

When carrying out a course of therapy, it is recommended to use Cordaflex in the form of prolonged-release tablets. The initial dose is 20 mg (1 tablet) 2 times a day. with an interval of 12 hours. If necessary, the dose of the drug is gradually increased until the optimal clinical effect is achieved. For long-term maintenance therapy, as a rule, it is enough to take 20-40 mg (1-2 tablets) 2 times a day. The maximum daily dose is 120 mg.

In elderly patients

The pharmacokinetics of nifedipine changes, and therefore the initial dose of the drug is reduced by 2 times and lower doses may be required to maintain the therapeutic effect.

For moderate liver or kidney dysfunction

no dosage regimen adjustment is required.
In case of severe liver dysfunction,
the maximum daily dose should not exceed 40 mg.

The drug in the form of tablets containing 10 mg of nifedipine is taken orally before meals, in the form of prolonged-release tablets - regardless of meals, without chewing, with a small amount of water.

Side effect

From the cardiovascular system:

facial skin flushing, severe arterial hypotension, peripheral edema, tachycardia; rarely - increased angina attacks (drug discontinuation required), increased heart failure, fainting.

From the central nervous system and peripheral nervous system:

headache, dizziness, increased fatigue, sleep disturbances (drowsiness or insomnia); in isolated cases - mood lability, visual impairment; with long-term use in high doses - paresthesia in the limbs, tremor.

From the digestive system:

diarrhea, constipation, nausea, heartburn; rarely (with long-term use of the drug) - dry mouth, flatulence, intrahepatic cholestasis, increased activity of liver transaminases; in some cases - gum hyperplasia, gingivitis, anorexia.

From the hematopoietic system:

rarely - thrombocytopenia, thrombocytopenic purpura, leukopenia; in some cases - anemia.

From the urinary system:

increased daily diuresis; rarely - deterioration of renal function in patients with chronic renal failure.

From the musculoskeletal system:

myalgia; in isolated cases - arthritis.

From the endocrine system:

in isolated cases - gynecomastia, hyperglycemia (completely disappear after discontinuation of the drug), changes in body weight, galactorrhea.

Allergic reactions:

rarely - urticaria, exanthema, itching; in some cases - autoimmune hepatitis.

Other:

feeling of heat; in isolated cases - weakness, sweating, fever, chills, photodermatitis.

Contraindications

— acute stage of myocardial infarction;

- cardiogenic shock;

— severe arterial hypotension (systolic blood pressure below 90 mm Hg);

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

- severe heart failure;

— I trimester of pregnancy;

- lactation period (breastfeeding);

- children and adolescents up to 18 years of age;

- hypersensitivity to nifedipine and other components of the drug.

Carefully _

Cordaflex should be used for chronic heart failure, hypertrophic obstructive cardiomyopathy, severe cerebrovascular accidents, CVS, severe tachycardia, severe liver and/or kidney dysfunction, malignant arterial hypertension, in patients on hemodialysis (due to the risk of severe arterial hypotension due to peripheral vasodilation), with lactose intolerance, as well as in elderly patients

Use during pregnancy and breastfeeding

Cordaflex is contraindicated for use in the first trimester of pregnancy.

The use of Cordaflex in pregnant women is indicated only in cases where normalization of blood pressure is impossible with the use of other antihypertensive drugs.

Since nifedipine is excreted in breast milk, you should avoid using Cordaflex during lactation or stop breastfeeding during treatment with the drug.

Use for liver dysfunction

Carefully _

Cordaflex should be used in case of severe impairment of liver and/or kidney function.
In case of severe impairment of liver function.

the maximum daily dose should not exceed 40 mg.

Use for renal impairment

Carefully _

Cordaflex should be used in cases of severe impairment of liver and/or kidney function

special instructions

The antihypertensive effect of Cordaflex is enhanced by hypovolemia. A decrease in pulmonary artery pressure and hypovolemia after dialysis may also enhance the effects of the drug, and therefore a dose reduction is recommended.

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

In case of arterial hypertension or coronary vascular disease, abrupt withdrawal of nifedipine can cause a hypertensive crisis or myocardial ischemia (the “rebound” phenomenon).

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

Elderly patients are more likely to have decreased cerebral blood flow due to acute peripheral vasodilation.

During a course of treatment with Cordaflex, the consumption of alcoholic beverages is not recommended due to the risk of an excessive decrease in 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 18 years of age.

Impact on the ability to drive vehicles and operate machinery

During the initial, individually determined period of use of Cordaflex, driving vehicles and engaging in other potentially hazardous activities that require rapid psychomotor reactions are not allowed. In the process of further treatment, the degree of restrictions is determined depending on the patient’s individual response to the drug.

Overdose

Symptoms:

severe arterial 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, disturbances of consciousness leading to coma, hyperkalemia, metabolic alkalosis, hypoxia, cardiogenic shock with pulmonary edema are possible.

Treatment:

Given the lack of a specific antidote, in cases of early detoxification, gastric lavage is performed with the administration of activated charcoal. If necessary, small intestinal lavage can be done, which is more appropriate in case of overdose of controlled-release drugs. When prescribing laxatives, it should be taken into account that taking slow calcium channel blockers suppresses intestinal motility to the point of complete atony.

Since nifedipine is highly bound to plasma proteins, hemodialysis is not effective, but plasmapheresis may be effective.

Symptomatic therapy is indicated. Symptoms of cardiac arrhythmias with bradycardia can be eliminated by administering beta-agonists and/or atropine. For life-threatening bradycardia, an artificial pacemaker should be used. With a pronounced decrease in blood pressure, an infusion of usual doses of norepinephrine (norepinephrine) or epinephrine (adrenaline) is indicated; dopamine (maximum dose 25 mcg/kg body weight/min), dobutamine (maximum dose 15 mcg/kg body weight/min), isoprenaline and 10% calcium gluconate solution (10-20 ml i.v.). If symptoms of heart failure develop, intravenous administration of fast-acting cardiac glycosides is recommended.

Drug interactions

From the point of view of enhancing the antihypertensive and antianginal effect, the combination of Cordaflex with beta-blockers, diuretics, ACE inhibitors, and nitrates is rational. All of the above combinations are safe and effective in most clinical situations, since they lead to summation or potentiation of effects, however, in some cases there is a risk of a pronounced decrease in blood pressure and increased symptoms of heart failure.

The combination of Cordaflex with clonidine, methyldopa, octadine, prazosin is possible according to indications, but can cause severe orthostatic hypotension.

An increase in the hypotensive effect is also observed with combination therapy with cimetidine, ranitidine and tricyclic antidepressants.

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

Nifedipine can displace drugs characterized by a high degree of binding from protein binding (including indirect anticoagulants - coumarin and indanedione derivatives, NSAIDs), as a result of which their concentration in the blood plasma may increase.

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

Nifedipine inhibits the elimination of vincristine from the body and may cause increased side effects of vincristine; if necessary, the dose of vincristine is reduced.

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

Grapefruit juice, erythromycin and azole antifungals (fluconazole, intraconazole, ketoconazole) may inhibit the metabolism of nifedipine and therefore enhance its effects.

Similarly, the simultaneous use of Cordaflex and cimetidine increases the level of nifedipine in the blood plasma and enhances its effects; however, simultaneous administration with ranitidine does not lead to a significant increase in plasma levels of nifedipine.

Since nifedipine is metabolized by the CYP3A4 enzyme, any inhibitor or inducer of this enzyme may affect the metabolism of nifedipine. Cyclosporine is also a substrate of the CYP3A4 enzyme; therefore, when cyclosporine and nifedipine are administered together, each may increase the duration of the effect of the other.

Conditions for dispensing from pharmacies

The drug is available with a prescription.

Storage conditions and periods

List B. The drug should be stored in a place protected from light and out of reach of children at a temperature of 15° to 25°C. Shelf life: 4 years.

Pharmacies where the goods are available: Pharmacy on the street.
40 Let Pobedy, 33/1 Pharmacy on the street. Atarbekova, 9 Pharmacy on the street. Severnaya, 305 Pharmacy on the street. Kommunarov, 71 Pharmacy on the street. Vishnyakova, 126 Pharmacy on the street. Sadovaya, 2 Pharmacy on the street. Kommunarov, 69 *For accurate information about product availability, please contact the phone numbers listed on the Contacts page

Similar products:

There are no similar products.

Overdose

An overdose of nifedipine may cause the following consequences:

arterial hypotension;
chest pain (similar to an angina );
tachycardia;
loss of consciousness;
collapse;
ventricular or nodal extrasystole ;
bradycardia.

In severe cases, the development of metabolic alkalosis , cardiogenic shock with pulmonary edema, hypoxia , hyperkalemia , as well as disturbances of consciousness, which can progress to coma .

Interaction

Cordaflex should not be administered with alcohol-containing medications.

Orthostatic hypotension may develop when used with methyldopa , clonidine , as well as prazosin and octadine .

Cimetidine , ranitidine and tricyclic antidepressants will potentiate the antihypertensive effect .

When Cordaflex is combined with theophylline and digoxin , it is necessary to monitor the plasma concentrations of these drugs, as they may increase.

Phenytoin , calcium supplements and rifampicin reduce the effect of nifedipine .

Cordaflex reduces the rate of elimination of vincristine , which increases the risk of side effects. Therefore, dose adjustment is necessary.

Erythromycin , diltiazem , grapefruit juice in large quantities, azole antimicrobial drugs when taken with nifedipine significantly slow down its metabolism.

CORDAFLEKS RD TAB. P/P/O MODIF.HIGH. 40MG No. 30

Interaction

Pharmacokinetic interactions • Drugs that affect the metabolism of nifedipine. Nifedipine is metabolized by CYP3A4/5 isoenzymes, which are found in the intestinal mucosa and liver. Drugs that inhibit or induce this enzyme system may affect the first pass effect through the liver (after oral administration) or the clearance of nifedipine.

Inducers of the CYP3A4 isoenzyme

Rifampicin

Rifampicin is a powerful inducer of the CYP3A4 isoenzyme. When used simultaneously with rifampicin, the bioavailability of nifedipine is significantly reduced and, accordingly, its effectiveness is reduced. Therefore, the simultaneous use of nifedipine with rifampicin is contraindicated.

Antiepileptic drugs that induce the CYP3A4 isoenzyme (for example, phenytoin, carbamazepine, phenobarbital) Phenytoin induces the CYP3A4 isoenzyme. With the simultaneous use of nifedipine and phenytoin, the bioavailability of nifedipine decreases and its effectiveness decreases. When using this combination simultaneously, it is necessary to monitor the clinical response to nifedipine therapy and, if necessary, increase its dose. If the dose of nifedipine is increased with simultaneous use of both drugs, the dose of nifedipine should be reduced after discontinuation of phenytoin. Clinical studies examining the potential interaction between nifedipine and carbamazepine or phenobarbital have not been conducted. Since both drugs reduce the concentration of nimodipine in the blood plasma, which is structurally similar to BMCC, the possibility of a decrease in the concentration of nifedipine in the blood plasma and a decrease in its effectiveness cannot be excluded.

CYP3A4 isoenzyme inhibitors

Macrolide antibiotics (for example, erythromycin) Clinical studies on the interaction of nifedipine and macrolide antibiotics have not been conducted. It is known that some macrolides inhibit the CYP3A4 isoenzyme. As a result, the possibility of an increase in the concentration of nifedipine in the blood plasma cannot be excluded with the simultaneous use of nifedipine and macrolide antibiotics. Azithromycin, which belongs to the macrolide group of antibiotics, does not inhibit the CYP3A4 isoenzyme.

HIV protease inhibitors (eg, ritonavir)

Clinical studies examining the interaction of nifedipine and HIV protease inhibitors have not been conducted. It is known that drugs of this class inhibit the CYP3A4 isoenzyme. In addition, it has been shown that drugs of this class suppress the metabolism of nifedipine mediated by the CYP3A4 isoenzyme in vitro. When used simultaneously with nifedipine, a significant increase in the concentration of nifedipine in the blood plasma cannot be ruled out due to a decrease in the effect of “first pass” through the liver and slower elimination.

Azole antifungals (for example, ketoconazole) Clinical studies examining the interaction of nifedipine and azole antifungals have not been conducted. It is known that drugs of this class inhibit the CYP3A4 isoenzyme. When used simultaneously with nifedipine, a significant increase in the systemic bioavailability of nifedipine is possible by reducing the effect of “first pass” through the liver.

Cimetidine and ranitidine

Diltiazem

Diltiazem reduces the clearance of nifedipine. This combination should be used with caution. A dose reduction of nifedipine may be required.

Fluoxetine

Clinical studies examining the interaction of nifedipine and fluoxetine have not been conducted. It is known that fluoxetine in vitro suppresses the metabolism of nifedipine, mediated by the action of the CYP3A4 isoenzyme. Therefore, the possibility of an increase in the concentration of nifedipine in the blood plasma cannot be excluded with the simultaneous use of nifedipine and fluoxetine.

Nefazodone

Clinical studies examining the interaction between nifedipine and nefazodone have not been conducted. Nefazodone is known to suppress the metabolism of other drugs mediated by the action of the CYP3A4 isoenzyme. Therefore, the possibility of an increase in the concentration of nifedipine in the blood plasma cannot be excluded with the simultaneous use of nifedipine and nefazodone.

Quinidine

Quinupristin/dalfopristin Concomitant use of quinupristin/dalfopristin may lead to increased plasma concentrations of nifedipine.

Valproic acid

Grapefruit juice

Substrates of the CYP3A4 isoenzyme

CYP3A4 isoenzyme substrates (for example, cisapride, tacrolimus, benzodiazepines, imipramine, propafenone, terfenadine, warfarin), when used simultaneously with nifedipine, can act as CYP3A4 inhibitors and increase the concentration of nifedipine in the blood plasma.

Cisapride

Concomitant use of cisapride and nifedipine may lead to increased plasma concentrations of nifedipine.

• Effect of nifedipine on other drugs

Quinidine

Digoxin. The simultaneous use of nifedipine and digoxin may lead to a decrease in the clearance of digoxin and, consequently, to an increase in the concentration of digoxin in the blood plasma. The patient should be carefully monitored for symptoms of glycoside overdose and, if necessary, reduce the dose of digoxin, taking into account its concentration in the blood plasma.

Theophylline. Nifedipine increases plasma concentrations of theophylline, and therefore the concentration of theophylline in blood plasma should be monitored. The clinical effect of both drugs when used together does not change.

Tacrolimus. Tacrolimus is metabolized with the participation of the CYP3A4 isoenzyme. Recently published data indicate the possibility of increased tacrolimus concentrations in selected cases when administered concomitantly with nifedipine. When using tacrolimus and nifedipine simultaneously, the concentration of tacrolimus in the blood plasma should be monitored and, if necessary, its dose should be reduced.

Vincristine. Nifedipine slows down the elimination of vincristine from the body and may cause increased side effects of vincristine. If simultaneous use is necessary, reduce the dose of vincristine.

Drugs that bind to blood proteins

Cephalosporins. With the simultaneous administration of cephalosporins (for example, cefixime) and nifedipine in probands, the bioavailability of the cephalosporin increased by 70%.

Pharmacodynamic interactions

Medicines that lower blood pressure. The antihypertensive effect of nifedipine may be enhanced when used simultaneously with antihypertensive drugs, such as diuretics, beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists (ARA II), other BMCCs, alpha-blockers, phosphodiesterase-5 inhibitors, methyldopa. When using nifedipine and beta-blockers simultaneously, it is necessary to carefully monitor the patient's condition, since in some cases the course of CHF may worsen. The severity of the decrease in blood pressure increases with the simultaneous use of inhalational anesthetics and tricyclic antidepressants.

Nitrates. When used simultaneously with nitrates, tachycardia increases. Antiarrhythmic drugs BMCC can enhance the negative inotropic effect of antiarrhythmic drugs such as amiodarone and quinidine. Nifedipine should be co-administered with disopyramide and flecainide with caution due to a possible increase in negative inotropic effect.

Magnesium sulfate It is necessary to carefully monitor blood pressure in pregnant women while using nifedipine with intravenous administration of magnesium sulfate due to the possibility of an excessive decrease in blood pressure, which poses a danger to both the mother and the fetus.

Fentanyl. The simultaneous use of nifedipine and fentanyl can lead to severe arterial hypotension. If possible, it is recommended that nifedipine be discontinued at least 36 hours before fentanyl-based anesthesia. Calcium preparations Reduced effectiveness of nifedipine. NSAIDs NSAIDs reduce the antihypertensive effect of nifedipine due to suppression of prostaglandin synthesis, sodium and fluid retention in the body. Sympathomimetics Sympathomimetics reduce the antihypertensive effect of nifedipine.

Estrogens. Estrogens reduce the antihypertensive effect of nifedipine due to fluid retention in the body.

Lithium preparations. When BMCC is used together with lithium drugs, it is possible to increase the manifestation of the neurotoxicity of the latter (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus).

Cordaflex analogues (drugs that have a similar effect)

Level 4 ATC code matches:
Lacipil

Cordafen

Azomex

Nimodipine

Felodipin

Nifedipine

Farmadipin

Amlotop

Nimotop

Tenox

Nifecard HL

Cordipin

Felodip

Normodipine

Phenigidine

Norvask

Lerkamen

Corinfar

Vero-Amlodipine

Amlodipine

Analogs are the following drugs: Adalat , Vero-Nifedipine , Calcigard Retard , Zanifed , Cordafen , Cordaflex Retard , Cordipin , Cordipin Retard , Cordipine XL Corinfar , Nifedicap , Nifedipine and some other drugs.

Cordaflex Retard has particularly similar pharmaceutical characteristics and therapeutic applications.

Cordaflex price, where to buy

The price for 10 mg tablets is 72-95 rubles for 10 pieces, for 20 mg tablets – 63-139 rubles for 30 pieces, 74-168 rubles for 60 pieces.

Online pharmacies in RussiaRussia

ZdravCity

Cordaflex tablets p.p.o.
prolonged action 20 mg 60 pcs. Egis 128 rub. order
Cordaflex tab. p.o 10 mg n100Egis
96 RUR order
Cordaflex RD tablets p.p.o. with control release 40 mg 30 pcs Arena Pharmaceuticals GmbH/Egis
190 rub. order
Cordaflex tablets p.p.o. prolonged action 20 mg 30 pcs. Egis
95 rub. order