Corinfar retard 20 mg 30 pcs. extended-release film-coated tablets
pharmachologic effect
Selective blocker of slow calcium channels (SCBC), a derivative of 1,4-dihydropyridine.
Has antianginal and hypotensive effects. Reduces the flow of extracellular Ca2+ into cardiomyocytes and smooth muscle cells of the coronary and peripheral arteries; in high doses inhibits the release of Ca2+ from intracellular stores. In therapeutic doses, it normalizes the transmembrane Ca2+ current, which is disturbed in a number of pathological conditions, primarily in arterial hypertension. Does not affect the tone of the veins. Strengthens coronary blood flow, improves blood supply to ischemic areas of the myocardium without developing the “steal” phenomenon, and activates the functioning of collaterals.
By dilating peripheral arteries, it reduces peripheral vascular resistance, myocardial tone, afterload and myocardial oxygen demand. It has virtually no effect on the sinoatrial node and AV node, and has weak antiarrhythmic activity.
Increases renal blood flow, causes moderate natriuresis.
The negative chrono-, dromo- and inotropic effects are overlapped by reflex activation of the sympathoadrenal system and an increase in heart rate in response to peripheral vasodilation.
The onset of the clinical effect is 20 minutes and its duration is 4-6 hours.
With long-term use (2-3 months), tolerance to the action of the drug develops.
Composition and release form Corinfar retard 20 mg 30 pcs. extended-release film-coated tablets
Tablets - 1 tablet:
- Active substance: nifedipine 20 mg.
- Excipients: lactose monohydrate - 31.6 mg, potato starch - 31.4 mg, microcrystalline cellulose - 31 mg, povidone K25 - 5.4 mg, magnesium stearate - 0.6 mg.
- Film shell composition: hypromellose - 5.188 mg, macrogol 6000 - 0.861 mg, macrogol 35000 - 0.393 mg, quinoline yellow dye (E104) - 0.143 mg, titanium dioxide (E171) - 1.377 mg, talc - 1.038 mg.
30 pcs. - brown glass bottles (1) - cardboard packs.
Description of the dosage form
Extended-release tablets, yellow, round, biconvex, film-coated; at the fracture there is a homogeneous yellow mass.
Characteristic
Selective blocker of “slow” calcium channels, a 1,4-dihydropyridine derivative.
Directions for use and doses
Take orally after eating, without chewing and with a sufficient amount of liquid. The dose of the drug is selected by the doctor individually in accordance with the severity of the disease and the patient’s sensitivity to the drug. For patients with concomitant severe cerebrovascular diseases and in elderly patients, the dose of the drug should be reduced.
Simultaneous food intake delays, but does not reduce, the absorption of nifedipine from the gastrointestinal tract.
Chronic stable and vasospastic angina
The initial dose is 10 mg (1 tablet) 2-3 times a day. If the clinical effect is not sufficiently pronounced, the dose of the drug is gradually increased to 2 tablets. (20 mg) 1-2 times/day. The maximum daily dose is 40 mg (4 tablets/day).
Essential hypertension
The average daily dose is 10 mg (1 tablet) 2-3 times a day.
If the clinical effect is not sufficiently pronounced, it is possible to gradually increase the dose of the drug to 20 mg (2 tablets) 2 times a day. The maximum daily dose is 40 mg (4 tablets/day).
When prescribed twice, the minimum interval between doses of the drug should be at least 4 hours.
The duration of treatment is determined by the attending physician.
Pharmacodynamics
Strengthens coronary blood flow, improves blood supply to ischemic areas of the myocardium without developing the “steal” phenomenon, and activates the functioning of collaterals. By dilating peripheral arteries, it reduces peripheral vascular resistance, myocardial tone, afterload and oxygen demand. It has virtually no effect on the sinoatrial and AV nodes and has weak antiarrhythmic activity. Increases renal blood flow, causes moderate natriuresis. The negative chrono-, dromo- and inotropic effects are overlapped by reflex activation of the sympathoadrenal system and an increase in heart rate in response to peripheral vasodilation. Does not affect the tone of the veins. The onset of the clinical effect is 20 minutes, its duration is 4-6 hours.
Pharmacokinetics
Suction
Absorption is high (more than 90%). Bioavailability - 50-70%. Eating increases bioavailability. Has a “first pass” effect through the liver. The Cmax of nifedipine in blood plasma after a single oral dose of 2 tablets (corresponding to 20 mg of nifedipine) is achieved after 1-3 hours and its value averages 28.3 ng/ml.
Distribution
Binding to blood plasma proteins (albumin) - 95%.
Penetrates through the BBB and placental barrier, excreted in breast milk.
There is no cumulative effect.
Metabolism and excretion
Completely metabolized in the liver.
T1/2 is 2-5 hours. It is excreted by the kidneys in the form of an inactive metabolite (60-80% of the dose taken), 20% with bile.
Pharmacokinetics in special clinical situations
Chronic renal failure, hemodialysis and peritoneal dialysis do not affect pharmacokinetics.
In patients with liver failure, total clearance decreases and T1/2 increases.
Indications for use Corinfar retard 20 mg 30 pcs. extended-release film-coated tablets
- Chronic stable angina (angina pectoris);
- Prinzmetal's angina (variant angina);
- arterial hypertension.
Contraindications
- Arterial hypotension (systolic blood pressure below 90 mm Hg);
- cardiogenic shock, collapse;
- chronic heart failure in the stage of decompensation;
- severe aortic stenosis;
- unstable angina;
- acute myocardial infarction (first 4 weeks);
- combined use with rifampicin;
- I trimester of pregnancy;
- lactation period (breastfeeding);
- hypersensitivity to nifedipine and other 1,4-dihydropyridine derivatives or other components of the drug.
With caution: mitral valve stenosis, hypertrophic obstructive cardiomyopathy, severe bradycardia or tachycardia, SSSS, malignant arterial hypertension, hypovolemia, severe cerebrovascular accidents, myocardial infarction with left ventricular failure, gastrointestinal obstruction, renal and hepatic failure, hemodialysis (due to the risk of arterial hypotension), II and III trimesters of pregnancy, childhood and adolescence up to 18 years (efficacy and safety have not been established), simultaneous use of beta-blockers, digoxin.
Application of Corinfar retard 20 mg 30 pcs. extended-release film-coated tablets during pregnancy and lactation
The drug is contraindicated in the first trimester of pregnancy and lactation.
With caution: the drug should be prescribed in the second and third trimesters of pregnancy.
Use in children
With caution: under 18 years of age (efficacy and safety have not been established).
special instructions
During the treatment period it is necessary to refrain from taking ethanol. It is recommended to stop treatment with the drug gradually.
It should be borne in mind that angina pectoris may occur at the beginning of treatment, especially after recent abrupt withdrawal of beta-blockers (the latter should be withdrawn gradually).
The simultaneous administration of beta-blockers must be carried out under conditions of careful medical supervision, as this may cause an excessive decrease in blood pressure, and in some cases, aggravation of symptoms of heart failure.
In case of severe heart failure, the drug is dosed with great caution.
The diagnostic criteria for prescribing the drug for vasospastic angina are: the classic clinical picture, accompanied by an increase in the ST segment, the occurrence of ergonovine-induced angina or coronary artery spasm, the detection of coronary spasm during angiography or the identification of an angiospastic component without confirmation (for example, with a different voltage threshold or with unstable angina, when ECG data indicate transient vasospasm).
For patients with severe obstructive cardiomyopathy, there is a risk of increased frequency, severity and duration of angina attacks after taking nifedipine; in this case, discontinuation of the drug is necessary.
In patients with irreversible renal failure who are on hemodialysis, have high blood pressure and reduced blood volume, the drug should be used with caution, because a sharp drop in blood pressure is possible. Patients with impaired liver function are closely monitored; if necessary, reduce the dose of the drug and/or use other dosage forms of nifedipine.
If surgical intervention under anesthesia is necessary, it is necessary to inform the anesthesiologist about the patient's treatment with nifedipine.
During in vitro fertilization, in some cases, BMCC caused changes in the head part of the sperm, which can lead to dysfunction of the sperm. In cases in which repeated in vitro fertilization has not been carried out for an unclear reason, the use of BMCC, including nifedipine, can be considered a possible reason for failure.
During treatment, it is possible to obtain a false positive result from the direct Coombs test and laboratory tests for antinuclear antibodies.
In the spectophotometric determination of vanillyl-mandelic acid in urine, nifedipine may cause a falsely high result, however, nifedipine does not affect the results of tests carried out using HPLC.
Caution should be exercised during simultaneous treatment with nifedipine, disopyramide and flecainide due to a possible increase in inotropic effect.
Impact on the ability to drive vehicles and operate machinery
During the treatment period, patients must be careful when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.
Overdose
Symptoms: headache, facial flushing, prolonged pronounced decrease in blood pressure, depression of sinus node function, bradycardia/tachycardia, bradyarrhythmia. In case of severe poisoning - loss of consciousness, coma.
Treatment: symptomatic therapy. In case of severe poisoning (collapse, suppression of the sinus node), the stomach is washed (if necessary, the small intestine), and activated charcoal is prescribed. The antidote is calcium preparations; intravenous administration of 10% calcium chloride or calcium gluconate is indicated, followed by transfer to a long-term infusion. With a pronounced decrease in blood pressure, slow intravenous administration of dopamine, dobutamine, adrenaline or norepinephrine is indicated. It is recommended to monitor glucose levels (insulin release may decrease) and electrolytes in the blood (K+, Ca2+). With the development of heart failure - intravenous administration of strophanthin. For conduction disorders - atropine, isoprenaline or an artificial pacemaker. Hemodialysis is not effective; plasmapheresis is recommended.
Side effects Corinfar retard 20 mg 30 pcs. extended-release film-coated tablets
From the cardiovascular system: tachycardia, palpitations, arrhythmias, peripheral edema (ankles, feet, legs), manifestations of excessive vasodilation (asymptomatic decrease in blood pressure, development or worsening of heart failure, “flushes” of blood to the facial skin, hyperemia of the facial skin, feeling of heat), marked decrease in blood pressure (rare), syncope. In some patients, especially at the beginning of treatment or when the dose is increased, angina attacks and, in isolated cases, myocardial infarction may occur, which requires discontinuation of the drug.
From the nervous system: headache, dizziness, general weakness, increased fatigue, drowsiness. With long-term use of the drug in high doses - paresthesia of the limbs, tremor, extrapyramidal (parkinsonian) disorders (ataxia, “mask-like” face, shuffling gait, tremor of the hands and fingers, difficulty swallowing), depression.
From the digestive system: dyspepsia (nausea, diarrhea or constipation), dry mouth, flatulence, increased appetite; rarely - gum hyperplasia, which completely disappears after discontinuation of the drug; with long-term use - liver dysfunction (intrahepatic cholestasis, increased activity of liver transaminases).
From the musculoskeletal system: arthritis, myalgia, swelling of the joints, cramps of the upper and lower extremities.
Allergic reactions: rarely - skin itching, urticaria, exanthema, autoimmune hepatitis, exfoliative dermatitis, photodermatitis, anaphylactic reactions.
From the hematopoietic system: anemia, leukopenia, thrombocytopenia, thrombocytopenic purpura, agranulocytosis.
From the urinary system: increased daily diuresis, deterioration of renal function (in patients with renal failure).
Other: rarely - visual impairment (including transient blindness at the maximum concentration of nifedipine in the blood plasma), gynecomastia (in elderly patients, completely disappearing after discontinuation of the drug), galactorrhea, hyperglycemia, pulmonary edema, bronchospasm, weight gain.
Drug interactions
With the simultaneous use of other antihypertensive drugs, as well as tricyclic antidepressants, nitrates, cimetidine, inhalational anesthetics, diuretics, the hypotensive effect of nifedipine may be enhanced.
BMCCs may further enhance the negative inotropic effects of antiarrhythmic drugs such as amiodarone and quinidine.
When nifedipine is combined with nitrates, tachycardia increases.
Diltiazem inhibits the metabolism of nifedipine in the body, which may require a reduction in the dose of nifedipine when these drugs are prescribed simultaneously.
Reduces the concentration of quinidine in blood plasma.
Increases the concentration of digoxin and theophylline in the blood plasma.
Rifampicin accelerates the metabolism of nifedipine; co-administration is not recommended.
When administered concomitantly with cephalosporins (for example, cefixime), the concentration of cephalosporins in the blood may increase.
Sympathomimetics, NSAIDs (suppression of prostaglandin synthesis in the kidneys and retention of sodium ions and fluid in the body), estrogens (fluid retention in the body) reduce the hypotensive effect.
Nifedipine can displace drugs with a high degree of binding from protein binding (including indirect anticoagulants - coumarin and indanedione derivatives, anticonvulsants, NSAIDs, quinine, salicylates, sulfinpyrazone), as a result of which their concentrations in the blood plasma may increase.
Nifedipine inhibits the metabolism of prazosin and other alpha-blockers, which may lead to increased hypotensive effects.
If necessary, the dose of vincristine is reduced, because nifedipine inhibits its elimination from the body, which may cause increased side effects.
Lithium preparations may enhance toxic effects (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus).
When procainamide, quinidine and other drugs known to prolong the QT interval are co-administered, the risk of significant prolongation of the QT interval increases.
Grapefruit juice inhibits the metabolism of nifedipine in the body and is therefore contraindicated during treatment with nifedipine.
Nifedipine is metabolized by the CYP3A isoenzyme, and therefore the simultaneous use of drugs that inhibit this system can lead to interaction between this drug and nifedipine: for example, macrolides, antiviral drugs (for example, amprenavir, indinavir, nelfinavir, ritonavir or saquinavir), antifungal drugs of the group azoles (ketoconazole, itraconazole or fluconazole) cause an increase in the concentration of nifedipine in the blood plasma.
Taking into account the experience with the use of nimodipine BMCC, similar interactions with nifedipine cannot be excluded: carbamazepine, phenobarbital can cause a decrease in the concentration of nifedipine in the blood plasma, and valproic acid can cause an increase in the concentration of nifedipine in the blood plasma.
Corinfar® retard
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 nimodipine 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)
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, drugs of this class have been shown to 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 (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.
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 inhibit the metabolism of other drugs mediated by the CYP3A4 isoenzyme. Therefore, the possibility of increased plasma concentrations of nifedipine cannot be excluded with simultaneous use of nifedipine and nefazodone.
Quinidine
Increased plasma concentrations of nifedipine have been reported when administered concomitantly with quinidine. Therefore, careful monitoring of blood pressure is necessary when using quinidine and nifedipine simultaneously. If necessary, the dose of nifedipine should be reduced.
Quinupristin/dalfopristip
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 the drug 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 “first pass” effect 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. Consumption of grapefruit/grapefruit juice during treatment with nifedipine is contraindicated.
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 the concentration of theophylline in the blood plasma, and therefore the concentration of theophylline in the blood plasma should be monitored. The clinical effect of both drugs when used together does not change.
Tacrolimus
Tacrolimus is metabolized via 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, quinine, salicylates, sulfinpyrazone), as a result of which their concentration in the blood plasma may increase .
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 chronic heart failure 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
ICHCs may enhance the negative inotropic effects 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 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.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs reduce the antihypertensive effect of nifedipine due to suppression of prostaglandin synthesis, as well as sodium and fluid retention in the body.
Syptomimetics
Sympathomimetic agents 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).
