Pharmacological properties of the drug Cordipin
Nifedipine (2,6-dimethyl-4-(2'-nitrophenyl)-1,4-dihydropyridine-3,5-dihydrocarboxylic acid dimethyl ester) is a calcium antagonist of the dihydropyridine group; inhibits the flow of calcium ions into cardiomyocytes and smooth muscle cells of coronary and peripheral arteries through “slow” membrane channels. Reduces myocardial oxygen demand by reducing myocardial contractility and heart function, as well as by reducing afterload. It has a coronary and hypotensive effect, reduces pressure in the pulmonary vessels. The cardioprotective effect of nifedipine is associated with inhibition of the transmembrane entry and accumulation of calcium ions in cells, preventing the depletion of their energy resources. Nifedipine is quickly and completely absorbed from the digestive tract. In blood serum it is determined within 10 minutes after oral administration, the maximum concentration is reached 30–60 minutes after administration. It is absorbed faster if the tablet is pre-chewed or the drug is administered sublingually. The release of nifedipine from Cordipine XL tablets occurs very slowly, so taking it once a day is sufficient. Cordipine retard is released slowly from Cordipine tablets, the maximum concentration of the drug in the blood plasma is observed 2–4 hours after oral administration, and the duration of action is 10–12 hours. Nifedipine binds to blood plasma proteins. Metabolized in the liver to form inactive metabolites. About 80% of unchanged nifedipine and its metabolites are excreted in the urine. Renal failure, hemodialysis and peritoneal dialysis do not affect the pharmacokinetics of nifedipine.
Cordipin® retard
Nifedipine is metabolized by the CYP3A4 isoenzyme of the cytochrome P450 system, which is 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.
The severity of the decrease in blood pressure increases with the simultaneous use of other antihypertensive drugs, beta-blockers, nitrates, cimetidine (to a lesser extent ranitidine), inhalational anesthetics, diuretics and tricyclic antidepressants. 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.
Medicines from the BMCC group can further enhance the negative inotropic effect (lowering the force of heart contraction) of antiarrhythmic drugs such as amiodarone and 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 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. 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.
Increases plasma concentrations of digoxin and theophylline, and therefore the clinical effect and concentrations of digoxin and theophylline in the blood plasma should be monitored.
Inducers of microsomal liver enzymes (rifampicin and others) reduce the concentration of nifedipine. Therefore, the simultaneous use of nifedipine with rifampicin is contraindicated.
Clinical studies of the interaction of nifedipine with macrolide antibiotics have not been conducted. It is known that some macrolides are inhibitors of the CYP3A4 isoenzyme. As a result, the possibility of an increase in the concentration of nifedipine in the blood plasma cannot be excluded when these drugs are used simultaneously.
Azithromycin, a macrolide antibiotic, is not an inhibitor of the CYP3A4 isoenzyme.
When used simultaneously with nitrates, tachycardia increases. The antihypertensive effect is reduced by sympathomimetics, nonsteroidal anti-inflammatory drugs, estrogens, and calcium supplements.
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 .
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. Lithium preparations can increase toxic effects (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus).
Grapefruit juice suppresses the metabolism of nifedipine in the body, and therefore. their simultaneous use is contraindicated.
Nifedipine may cause a false increase in the concentration of vanillylmandelic acid in urine when determined by the spectrophotometric method, but does not affect the measurement results when using the high-performance liquid chromatography (HPLC) method.
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 inhibit the CYP3A4-mediated metabolism of nifedipine 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.
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. Clinical studies examining the interaction of nifedipine and fluoxetine have not been conducted. Fluoxetine is known in
vitro
. 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.
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.
Concomitant use of quinupristin/dalfopristin may lead to increased plasma concentrations of nifedipine.
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.
Concomitant use of cisapride and nifedipine may lead to increased plasma concentrations of nifedipine.
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 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 plasma concentration of nimodipine, which is structurally similar to BMCC. then we cannot exclude the possibility of a decrease in the concentration of nifedipine in the blood plasma and a decrease in its effectiveness.
Tacrolimus is metabolized with the participation of the CYP3A4 isoenzyme. Recently published data indicate the possibility of reducing the dose of tacrolimus in selected cases when used 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.
Use of the drug Cordipin
Cordipin. For hypertensive crisis, take 1 tablet sublingually. If necessary, repeat taking the drug in the same dose after 1 hour. Cordipin XL. Usually prescribed 1 tablet per day, the maximum dose is 2 tablets per day for 1 dose. Take the tablets whole with a glass of water during or after breakfast. Cordipine retard is usually prescribed 1 tablet 2 times a day; if necessary, the dose of the drug can be increased to 2 tablets 2 times a day.
Side effects of the drug Cordipin
The most common symptoms are arterial hypotension, dizziness, headache, facial skin flushing, weakness, increased fatigue, skin rash, heartburn, tachycardia, swelling of the feet and legs, nausea, and gum hyperplasia. Rarely observed diarrhea, constipation, flatulence, impaired joint mobility, muscle spasms, tremor, increased excitability, sleep disturbances, vision, balance, dermatitis, itching, urticaria, fever, sweating, chills, sexual dysfunction, loss of consciousness, thrombocytopenia, anemia, leukopenia, purpura, hepatitis, depression, paranoid syndrome, transient blindness at high plasma concentrations, erythromelalgia, arthritis, changes in liver function tests, which are usually not accompanied by clinical manifestations, but cases of cholestasis and jaundice have been reported.
Cordipin® XL (Cordipin® XL)
Pharmacokinetic interactions
Medicines affecting 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
Rifamycin 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 plasma concentration of nimodipine, 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. 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 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, when using quinidine and nifedipine simultaneously, careful monitoring of blood pressure is necessary. If necessary, the dose of nifedipine should be reduced.
Xinupristin/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 plasma concentration of nimodipine, which is structurally similar to BMCC, the possibility of an increase in the concentration of nifedipine in the blood plasma and an increase in 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. 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 inhibitors of the CYP3A4 isoenzyme 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 tsophylline, 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 reducing the dose of tacrolimus in selected cases when used 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 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
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 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 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).
Special instructions for the use of the drug Cordipin
At the beginning of treatment with the drug, especially with simultaneous use of beta-adrenergic receptor blockers, arterial hypotension may occur, which is poorly tolerated by patients; in such cases, careful medical supervision is necessary. In patients taking beta-adrenergic blockers, congestive heart failure may occur or worsen at the beginning of treatment. Patients with hypertrophic cardiomyopathy, unstable angina, diabetes mellitus, severe liver disease, pulmonary hypertension, as well as elderly patients should be under medical supervision when treated with nifedipine. In patients with severe forms of coronary artery disease, an increase in angina attacks may be observed at the beginning of treatment. Minor or moderate swelling of the lower extremities, which is observed in 10% of patients during use of the drug, is not associated with heart failure, but is caused by vasodilation. Nifedipine may affect the value of some laboratory tests (mainly liver function tests). These changes, as a rule, are not accompanied by clinical signs, although there are cases where an increase in the level of serum transaminases was accompanied by the appearance of cholestasis and jaundice. Nifedipine may have a moderate antiplatelet effect and increase bleeding time. Due to insufficient clinical experience, the drug should not be prescribed to children. During pregnancy, the use of the drug is possible only if the expected benefit for the expectant mother outweighs the potential risk to the fetus. In sensitive patients, mainly at the beginning of treatment or while taking alcohol, nifedipine impairs the ability to drive vehicles and operate potentially dangerous machinery.
Cordipin® xl (Cordipin xl)
It is recommended to discontinue treatment with Cordipin® CL gradually.
It should be borne in mind that at the beginning of treatment, the development of angina pectoris is possible, especially after the recent abrupt withdrawal of beta-blockers (the latter should be withdrawn gradually). The simultaneous administration of beta-blockers must be carried out under close medical supervision, since this may result in an excessive decrease in blood pressure, and in some cases, aggravation of symptoms of heart failure.
Diagnostic criteria for prescribing the drug for angiospastic 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 on hemodialysis with high blood pressure and irreversible renal failure with reduced blood volume, the drug should be used with caution, because A sharp drop in blood pressure may occur.
The condition of patients with impaired liver function should be carefully monitored and, if necessary, reduce the dose of the drug and/or use other dosage forms of nifedipine.
If during therapy the patient requires surgical intervention under general anesthesia, it is necessary to inform the anesthesiologist about the nature of the therapy being performed.
During treatment, positive results are possible with direct Coombs test and laboratory tests for antinuclear antibodies.
The drug should be prescribed with caution simultaneously with disopyramide and flecainamide.
Impact on the ability to drive vehicles and operate machinery
In some patients, especially at the beginning of treatment, the drug may cause dizziness, which reduces the ability to drive a car or use other machinery. In the future, the degree of restrictions is determined depending on the individual tolerability of the drug.
Interactions of the drug Cordipin
With the simultaneous administration of antihypertensive drugs, diuretics, nitroglycerin, long-acting nitrates, fentanyl and tricyclic antidepressants, the hypotensive effect of Cordipine is enhanced. When combined with beta-adrenergic receptor blockers, the development of arterial hypotension and heart failure is possible. Nifedipine, when used simultaneously with magnesium sulfate, can cause neuromuscular blockade (impetuous movements, difficulty swallowing, paradoxical breathing and muscle weakness). This combination is life-threatening and should not be prescribed. Nifedipine increases the concentration of digoxin, carbamazepine, phenytoin, theophylline and tacrolimus in the blood plasma and enhances their effect. When nifedipine is combined with quinidine, the concentration of the latter in the blood plasma decreases. Rifampicin induces liver enzymes and accelerates the metabolism of nifedipine, which may lead to a weakening of the effects of the latter. Prescribing nifedipine simultaneously with cimetidine, triazole antifungals (itraconazole, fluconazole), imidazoles (ketoconazole), cyclosporine, ritonavir or saquinavir may cause an increase in the concentration of nifedipine in the blood serum and enhance its effect. During treatment with nifedipine, it is not recommended to consume large amounts of grapefruit juice, since it increases the level of nifedipine in the blood serum and enhances its effect. Nifedipine may interfere with the results of the methacholine breath challenge test; therefore, if possible, treatment with nifedipine should be discontinued before performing the methacholine test.
Instructions for use CORDIPIN® RETARD
If drugs that lower blood pressure, beta-blockers, diuretics, nitroglycerin or sustained-release isosorbide are taken simultaneously with nifedipine, their synergistic effect should be taken into account.
In patients taking nifedipine, fentanyl may also lower blood pressure. Treatment with nifedipine should be discontinued at least 36 hours before planned surgery if the patient is to be anesthetized with fentanyl.
The simultaneous use of cimetidine and nifedipine may lead to an increase in the concentration of the latter in the blood serum and, thus, an increase in its antihypertensive effect. Nifedipine should be used with caution in patients already taking cimetidine, and the dose of nifedipine in such patients should be increased gradually.
Serum levels of carbamazepine and phenytoin may be increased when co-administered with nifedipine. During concomitant therapy with these drugs, the doctor needs to monitor the patient's condition more often than usual. If signs of toxicity are observed or serum levels of phenytoin or carbamazepine increase, the doses of these drugs should be reduced.
Concomitant use of nifedipine and quinidine may cause a decrease in quinidine concentrations and increase the sensitivity of patients to the effects of nifedipine. When prescribing nifedipine to patients already taking quinidine, the physician should carefully monitor possible side effects of the drug. It is necessary to monitor the concentration of quinidine in the blood serum, and additionally, when stopping nifedipine, adjust its dose.
Nifedipine can significantly increase the toxicity of magnesium sulfate and cause neuromuscular blockade. The simultaneous use of these drugs is not recommended, since such a combination is dangerous and can threaten the patient's life.
When nifedipine is co-administered with theophylline or digoxin, the concentration of theophylline or digoxin in the blood serum may increase. It is recommended to monitor the concentration of these drugs in the blood serum and, if necessary, adjust their doses. The simultaneous administration of rifampicin and nifedipine may cause a decrease in the concentration of the latter in the blood serum, which leads to a weakening of its therapeutic effect. If angina attacks occur or blood pressure increases during concomitant use of nifedipine and rifampicin, the dose of nifedipine should be increased.
With the simultaneous administration of nifedipine and itraconazole (probably also other triazole antifungal drugs, as well as erythromycin and clarithromycin, which have an inhibitory effect on the cytochrome isoenzyme CYP3A4), the concentration of nifedipine in the blood serum, its effect and the frequency of side effects may increase. If side effects of nifedipine occur, the dose of the drug should be reduced (if possible) or treatment with antifungal agents should be discontinued.
Serum concentrations of nifedipine may be increased and its effects may be enhanced when co-administered with cyclosporine, indinavir or saquinavir (CYP3A4 inhibitors). If side effects of nifedipine occur, its dose should be reduced.
When nifedipine and tacrolimus are used together, the serum concentration of the latter may increase (this drug is metabolized by CYP3A4). It is necessary to monitor the concentration of tacrolimus in the blood serum and, if necessary, reduce its dose.
Patients taking coumarin anticoagulants may experience an increase in prothrombin time after taking nifedipine. The interactions between these drugs have not been fully studied.
Nifedipine may affect the interpretation of the results of bronchial tests with methacholine. If possible, nifedipine should be interrupted before testing with methacholine.
Drinking grapefruit juice during treatment with nifedipine may lead to an increase in the serum concentration of the latter and, thus, an increase in its effect.
Overdose of the drug Cordipin, symptoms and treatment
May cause peripheral vasodilation with severe and prolonged arterial hypotension, which is manifested by nausea, reflex tachycardia, dizziness or collapse. Manifestations of overdose can develop only 3–4 hours after administration. Gastric lavage is performed, activated charcoal is prescribed, and symptomatic treatment is carried out. In case of severe hypotension, calcium preparations (calcium chloride or gluconate) are administered; if they are insufficiently effective, it is advisable to use sympathomimetics (dopamine, norepinephrine).
