Cordaflex 20 mg 60 pcs. extended-release film-coated tablets in Perm
Drugs that affect nifedipine
- Nifedipine is metabolized with the participation of the CYP3A4 isoenzyme of cytochrome P450 of the liver and intestinal mucosa. Drugs that induce or block this enzyme may interfere with the first-pass effect (when taken orally) or alter the clearance of nifedipine.
- The extent and duration of these interactions should be considered if nifedipine is co-administered with the following drugs.
Rifampicin
significantly induces the CYP3A4 isoenzyme. When used together with rifampicin, the bioavailability of nifedipine is sharply reduced, thus reducing the effectiveness of the drug. Therefore, the combined use of nifedipine with rifampicin is contraindicated.
- When used together with the following weak/moderate inhibitors of the CYP3A4 isoenzyme, blood pressure control is necessary and it may be necessary to reduce the dose of nifedipine.
Drugs that increase the concentration of nifedipine in the blood:
Macrolides (eg, erythromycin)
The interaction of macrolides with nifepidin has not been studied. It is known that some macrolide antibiotics inhibit the metabolism of other drugs involving the CYP3A4 isoenzyme. Therefore, when used together, a possible increase in the concentration of nifedipine in the blood plasma cannot be excluded.
Despite the fact that azithromycin belongs to the class of macrolides in its structure, it is not an inhibitor of the CYP3A4 isoenzyme.
HIV protease inhibitors (eg, ritonavir)
There have been no clinical studies of the interaction of HIV protease inhibitors with nifedipine. Drugs belonging to this group are known to inhibit the CYP3A4 isoenzyme of cytochrome P450. In addition, it was found that drugs of this group in vitro inhibit the metabolism of nifedipine mediated by the CYP3A4 isoenzyme. Therefore, when used together with nifedipine, it cannot be excluded that its concentration in the blood plasma will increase significantly as a result of a slowdown in the “first pass” effect. In addition, a slower elimination of the drug cannot be ruled out.
Antifungals, azoles (eg, ketoconazole)
There have been no clinical studies of the interaction of azole antifungals with nifedipine. It is known that some drugs in this group inhibit the CYP3A4 isoenzyme of cytochrome P450. In addition, it was found that drugs of this group in vitro inhibit the metabolism of nifedipine mediated by the CYP3A4 isoenzyme. Therefore, when used together with nifedipine, it cannot be excluded that its concentration in the blood plasma will increase significantly as a result of a slowdown in the “first pass” effect; In addition, a slower elimination of the drug cannot be ruled out.
Fluoxetine
There have been no clinical studies of the interaction of fluoxetine with nifedipine. It is known that fluoxetine in vitro inhibits the metabolism of nifedipine mediated by the cytochrome P450 isoenzyme CYP3A4. Therefore, when used together with nifedipine, an increase in its concentration in the blood plasma cannot be ruled out.
Nefazodone
There have been no clinical studies of the interaction of nefazodone with nifedipine. It is known that nefazodone in vitro inhibits the metabolism of nifedipine mediated by the cytochrome P450 isoenzyme CYP3A4. Therefore, when used together with nifedipine, an increase in its concentration in the blood plasma cannot be ruled out.
Quinupristin/dalfopristin
When quinupristin/dalfopristin is co-administered with nifedipine, the plasma concentration of nifedipine may increase.
Valproic acid
There have been no clinical studies of the interaction of valproic acid with nifedipine. Since valproic acid, by inhibiting the enzyme, increases the concentration of another calcium channel inhibitor, nimodipine, in the blood plasma, an increase in the effect in this case cannot be ruled out.
Cimetidine
Since cimetidine inhibits the cytochrome P450 isoenzyme CYP3A4, it increases the concentration of nifedipine in the blood plasma, enhancing its hypotensive effect.
Diltiazem
Increases the exposure (AUC) of nifedipine.
Other types of interaction
Cisapride
The combined use of cisapride with nifedipine leads to an increase in the concentration of nifedipine in the blood plasma.
Drugs that induce the cytochrome P450 isoenzyme CYP3A4:
Antiepileptic drugs (phenobarbital, phenytoin, carbamazepine)
Phenytoin
induces the CYP3A4 isoenzyme of cytochrome P450. With simultaneous use of phenytoin with nifedipine, the bioavailability and, accordingly, the effectiveness of the latter decreases. When using these drugs together, clinical efficacy should be monitored and the dose of nifedipine should be increased if necessary. In this case, upon completion of treatment with phenytoin, it may be necessary to increase the dose of nifedipine. If the dose of nifedipine was increased when the two drugs were used together, then after discontinuation of treatment with phenytoin, the possibility of lowering the dose of nifedipine should be considered.
No clinical studies have been conducted on the interaction of carbamazepine or phenobarbital
with nifedipine. Due to the fact that carbamazepine, as an inducer of the cytochrome P450 isoenzyme CYP3A4, reduces the blood concentration of nimodipine, a calcium channel blocker similar in structure, the possibility of a decrease in the concentration of nifedipine in the blood plasma and a deterioration in its effectiveness cannot be ruled out.
Effect of nifedipine on other drugs:
Antihypertensive drugs
When prescribed together with the following antihypertensive drugs, additive antihypertensive effects are possible:
- diuretics;
- β-blockers;
- angiotensin-converting enzyme inhibitors (ACE inhibitors);
- angiotensin receptor antagonists;
- other calcium channel blockers;
- alpha-blockers;
- phosphodiesterase-5 inhibitors;
- methyldopa;
- magnesium sulfate.
- β-blockers
- When nifedipine is used concomitantly with beta-blockers, careful monitoring is necessary, as worsening of HF has been reported in some cases.
Digoxin
Co-administration with digoxin may lead to an increase in the plasma concentration of this drug due to a decrease in its clearance. Due to the danger of digoxin overdose, patients' condition should be monitored and, if necessary, the dose of the glycoside should be reduced.
Quinidine
When quinidine is used together with nifedipine, the concentration of quinidine in the blood plasma may decrease, and after discontinuation of nifedipine, in some cases an increase in the concentration of quinidine in the blood is observed. According to some literature data, when the two drugs were used together, an increase in the concentration of nifedipine in the blood plasma was observed; other authors did not observe changes in the pharmacokinetics of nifedipine. Thus, if quinidine is necessary during therapy with nifedipine, blood pressure should be carefully monitored and, if necessary, the dose of nifedipine should be reduced.
Tacrolimus
Tacrolimus is metabolized with the participation of the cytochrome P450 isoenzyme CYP3A4. According to the published literature, co-administration of tacrolimus with nifedipine may increase the plasma concentration of tacrolimus. Tacrolimus concentrations should be monitored and the dose reduced if necessary.
Vincristine
When used simultaneously with nifedipine, the excretion of vincristine is reduced, which may require a reduction in its dose.
Cephalosporins
When used simultaneously with nifedipine, the concentration of cephalosporins in the blood plasma increases.
Nitrates
It is necessary to take into account the synergistic effect when using nifedipine and nitrates simultaneously.
Theophylline
Nifedipine increases the concentration of theophylline in blood plasma when used simultaneously.
Fentanyl
The simultaneous use of fentanyl and nifedipine can lead to a significant decrease in blood pressure, therefore, if possible, it is recommended to discontinue nifedipine at least 36 hours before anesthesia with fentanyl.
Indirect anticoagulants
In rare cases, prolongation of prothrombin time has been reported with simultaneous use of indirect anticoagulants (for example, warfarin) with nifedipine. The clinical significance of this effect is unknown.
Interaction with food and drink
Grapefruit juice
inhibits the cytochrome P450 isoenzyme system CYP3A4. Due to a decrease in first-pass metabolism and delayed elimination, the concentration of nifedipine in the blood plasma may increase and the duration of the effect may be prolonged, that is, the antihypertensive effect may become more pronounced. After the last consumption of grapefruit juice, this effect can be observed for three days. Therefore, concomitant use of nifedipine with grapefruit juice should be avoided.
Cordaflex®
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.
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 - derivatives of coumarin and indanedione, NSAIDs), as a result of which their concentrations 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 concentration of nifedipine in the blood plasma and enhances its effects; however, simultaneous use with ranitidine does not lead to a significant increase in the concentration of nifedipine in the blood plasma.
Since nifedipine is metabolized by the CYP3A4 isoenzyme, any inhibitor or inducer of this enzyme may affect the metabolism of nifedipine. Cyclosporine is also a CYP3A4 substrate; therefore, when cyclosporine and nifedipine are used together, each may increase the duration of the effect of the other.
