Cordipine XL extended release tablets 40 mg 20 pcs. in Elektrougli
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 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.
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 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 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 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).
