Corinfar retard, 20 mg, extended-release film-coated tablets, 50 pcs.
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occur at the beginning of treatment, especially after recent abrupt withdrawal of beta-blockers (the latter should be withdrawn gradually).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.
Diagnostic criteria for prescribing the drug for vasospastic angina are: a classic clinical picture, accompanied by an increase in the ST segment, the occurrence of ergonovine-induced angina or coronary artery spasm, detection of coronary spasm during angiography or 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 a reduced total 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 general anesthesia is necessary, it is necessary to inform the anesthesiologist about the patient's treatment with nifedipine.
During in vitro fertilization, in some cases, BCC caused changes in the head of the sperm, which can lead to dysfunction of the sperm. In cases in which repeat in vitro fertilization has failed for an unclear reason, the use of CCBs, 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 vanillylmandelic acid in urine, nifedipine may cause a falsely elevated result, however, nifedipine does not affect the results of tests performed using HPLC.
Caution should be exercised during simultaneous treatment with nifedipine, disopyramide and flecainamide due to a possible increase in inotropic effect.
Influence on the ability to drive a car and other mechanisms.
During the treatment period, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.
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).
