Lerkamen® 10 (Lerkamen® 10)
Concomitant use is contraindicated
CYP3A4 inhibitors
It is known that lercanidipine is metabolized with the participation of the CYP3A4 isoenzyme. Therefore, inhibitors of this isoenzyme, when used simultaneously, may affect the metabolism and excretion of lercanidipine.
Concomitant use with the CYP3A4 inhibitor ketoconazole has been shown to increase plasma concentrations of lercanidipine (15-fold increase in AUC and 8-fold increase in Cmax for the S-enantiomer of lercanidipine).
Concomitant use of lercanidipine with CYP3A4 inhibitors (for example, ketoconazole, itraconazole, ritonavir, erythromycin, troleandomycin, clarithromycin) is contraindicated.
Cyclosporine
Increased plasma concentrations of both lercanidipine and cyclosporine were observed after concomitant use. A study in young healthy volunteers showed that when cyclosporine was administered 3 hours after lercanidipine dosing, plasma levels of lercanidipine were unchanged, while the AUC of cyclosporine increased by 27%. However, simultaneous administration of lercanidipine with cyclosporine caused a 3-fold increase in the concentration of lercanidipine in the blood plasma and an increase in the AUC of cyclosporine by 21%.
Cyclosporine and lercanidipine should not be used simultaneously (see section "Contraindications").
Grapefruit juice
Lercanidipine should not be taken at the same time as grapefruit or grapefruit juice. simultaneous use may lead to an increase in the systemic bioavailability of the drug and enhanced antihypertensive effect (see section “Contraindications”).
Concomitant use is not recommended
CYP3A4 inducers
Lercanidipine should be used with caution concomitantly with inducers of CYP3A4, such as anticonvulsants (phenytoin, phenobarbital, carbamazepine) and rifampicin, since the antihypertensive effect of the drug may be reduced. If co-administration is necessary, more frequent than usual blood pressure monitoring is required (see section "Precautions").
Ethanol (alcohol)
Ethanol may potentiate the antihypertensive effect of lercanidipine. When taking vasodilating antihypertensive drugs, alcohol should be avoided as it may enhance their effect (see section "Precautions").
Concomitant use requires caution (including dose adjustment)
CYP3A4 substrates
Caution should be exercised when lercanidipine is used concomitantly with other CYP3A4 substrates, such as terfenadine, astemizole, quinidine, class III antiarrhythmic drugs (amiodarone, sotalol) (see section "Caution").
Midazolam
When simultaneous oral administration of lercanidipine at a dose of 20 mg with midazolam (CYP3A4 substrate) in healthy elderly volunteers, the absorption of lercanidipine increases (by approximately 40%) and the rate of absorption slows down (increase in TCmax from 1.75 hours to 3 hours). The concentration of midazolam in my blood changed.
Metoprolol
When lercanidipine was co-administered with metoprolol (a beta blocker that is primarily metabolized in the liver [CYP2D6 substrate]), the bioavailability of metoprolol was not affected, whereas the bioavailability of lercanidipine was reduced by 50%. This effect may be due to a reduction in hepatic blood flow caused by beta-blockers and may occur when lercanidipine is used concomitantly with other drugs of this class. Therefore, lercanidipine can be safely used in combination with beta-blockers, but this combination may require dose adjustment of lercanidipine to achieve a therapeutic effect.
Digoxin
With simultaneous use of lercanidipine at a dose of 20 mg in patients chronically taking beta-methyldigoxin, no pharmacokinetic interaction was noted, while in healthy volunteers treated with digoxin, there was an increase in Cmax (maximum plasma concentration) for digoxin by an average of 33% after administration of 20 mg lercanidipine on an empty stomach, with little change in AUC and renal clearance. Patients taking digoxin and lercanidipine concomitantly should be monitored for signs of digitalis toxicity.
Other drug interactions
Fluoxetine
In a study, simultaneous use of lercanidipine with fluoxetine (an inhibitor of CYP2D6 and CYP3A4) in elderly volunteers (mean age 65 ± 7 years) did not lead to clinically significant changes in the pharmacokinetics of lercanidipine.
Cimetidine
The simultaneous use of lercanidipine with cimetidine (at a dose of 800 mg per day) did not cause significant changes in the concentration of lercanidipine in the blood plasma (increase in Cmax and AUC by an average of 11%). But at higher doses of cimetidine, caution must be exercised as the bioavailability and antihypertensive effect of lercanidipine may increase.
Simvastatin
With repeated co-administration of lercanidipine 20 mg and simvastatin 40 mg, the AUC of lercanidipine did not change significantly, while the AUC of simvastatin increased by 56% and the AUC of its active metabolite (β-hydroxy acid) by 28%. . It is unlikely that such changes are clinically significant. When taking the drug at different times of the day (lercanidipine in the morning, simvastatin in the evening), no unwanted interaction is expected.
Warfarin
With simultaneous use of 20 mg of lercanidipine and warfarin in healthy volunteers, no changes in the pharmacokinetics of warfarin were observed.
Diuretics and ACE inhibitors
Lercanidipine can be used simultaneously with diuretics and ACE inhibitors.
Other drugs that affect blood pressure
An increase in the antihypertensive effect can be observed when lercanidipine is taken simultaneously with alpha-blockers, tricyclic antidepressants, and antipsychotics.
On the contrary, a decrease in the antihypertensive effect may be observed when used simultaneously with glucocorticosteroids.
Instructions for use LERKAMEN 10
Since lercanidipine is metabolized by the CYP3A4 isoenzyme, inhibitors and inducers of the CYP3A4 isoenzyme taken together with the drug may affect the metabolism and elimination of lercanidipine.
The simultaneous administration of lercanidipine hydrochloride with inhibitors of the CYP3A4 isoenzyme (including ketoconazole, itraconazole, ritonavir, erythromycin, troleandomycin) should be avoided.
An interaction study with the strong CYP3A4 inhibitor ketoconazole showed that plasma concentrations of lercanidipine were markedly increased (15-fold increase in AUC and 8-fold increase in Cmax for the S-lercanidipine eutomer).
Cyclosporine and lercanidipine should not be co-administered. Increased plasma concentrations were observed for both lercanidipine and cyclosporine following coadministration. A study in young healthy volunteers showed that when cyclosporine was administered 3 hours after lercanidipine, the plasma concentration of lercanidipine was unchanged, whereas the AUC of cyclosporine increased by 27%. However, coadministration of lercanidipine hydrochloride with cyclosporine resulted in a 3-fold increase in lercanidipine plasma concentrations and a 21% increase in cyclosporine AUC.
When lercanidipine was administered orally at a dose of 20 mg to elderly volunteers together with midazolam, the absorption of lercanidipine increased (by approximately 40%) and the rate of absorption decreased (Tmax slowed down and was 3 hours instead of 1.75 hours). Midazolam concentrations did not change.
Caution should be exercised when using lercanidipine hydrochloride simultaneously with other substrates of the CYP3A4 isoenzyme (terfenadine, astemizole), antiarrhythmic drugs (amiodarone, quinidine).
Inducers of the CYP3A4 isoenzyme (anticonvulsants - phenytoin, carbamazepine) and rifampicin can reduce the concentration of lercanidipine in plasma, reducing the effectiveness of lercanidipine. Because the hypotensive effect may be reduced, blood pressure should be monitored more frequently.
When lercanidipine hydrochloride was administered concomitantly with metoprolol (which is metabolized primarily in the liver), the bioavailability of metoprolol did not change, while the bioavailability of lercanidipine was reduced by 50%. This effect is likely due to the reduction in hepatic blood flow caused by beta-blockers and may therefore also occur with other drugs in this class. Therefore, lercanidipine can be prescribed concomitantly with beta-blockers, but dosage adjustment may be required.
An interaction study with fluoxetine (an inhibitor of CYP2D6 and CYP3A4 isoenzymes), conducted on volunteers aged 65±7 years, indicates the absence of clinically significant changes in the pharmacokinetics of lercanidipine.
Co-administration of cimetidine 800 mg/day does not cause significant changes in plasma concentrations of lercanidipine, but caution is required at higher doses as the bioavailability and hypotensive effect of lercanidipine may be increased.
Co-administration of 20 mg lercanidipine to patients chronically taking β-methyldigoxin showed no pharmacokinetic interaction. In healthy volunteers using digoxin, digoxin Cmax increased by an average of 33% after taking 20 mg lercanidipine in the fasted state, while AUC and renal clearance were not significantly affected. Patients receiving digoxin concomitantly with lercanidipine should be closely monitored (frequent clinical monitoring) for digoxin toxicity.
When lercanidipine hydrochloride was administered repeatedly at a dose of 20 mg concomitantly with 40 mg simvastatin, the AUC value for lercanidipine changed little, while the AUC value for simvastatin increased by 56%, the AUC value for its active β-hydroxy acid metabolite increased by 28%. It is unlikely that such changes are clinically significant. It is recommended to use lercanidipine in the morning and simvastatin in the evening.
When 20 mg of lercanidipine was taken on an empty stomach concomitantly with warfarin, no changes in the pharmacokinetics of warfarin were observed in healthy volunteers.
Lercanidipine hydrochloride can be used simultaneously with diuretics and ACE inhibitors.
Lerkamen 10 should not be taken with grapefruit juice, since due to the increase in systemic bioavailability, the hypotensive effect of the drug also increases.
During therapy with Lerkamen 10, alcohol should be avoided, since ethanol may potentiate the effect of vasodilating antihypertensive drugs.
There were no cases of pharmaceutical incompatibility.
Lerkamen 20, 28 pcs., 20 mg, film-coated tablets
Lercanidipine can be used simultaneously with β-blockers, diuretics, angiotensin-converting enzyme inhibitors (ACE inhibitors). When used simultaneously with metoprolol, the bioavailability of lercanidipine is reduced by 50%. This effect may also occur when used concomitantly with other β-blockers, so dose adjustment of lercanidipine may be required to achieve a therapeutic effect with this combination. Lercanidipine is metabolized with the participation of the CYP3A4 isoenzyme, therefore inhibitors and inducers of this isoenzyme, when used simultaneously, can affect the metabolism and excretion of lercanidipine. Concomitant use of lercanidipine with CYP3A4 inhibitors (ketoconazole, itraconazole, ritonavir, erythromycin, troleandomycin) is not recommended (see section "Contraindications").
The simultaneous use of cyclosporine and lercanidipine is not recommended, as an increase in the concentration of both substances in the blood plasma is observed (see section “Contraindications”).
Caution should be exercised when lercanidipine is used simultaneously with other CYP3 A4 substrates (terfenadine, astemizole, class III antiarrhythmic drugs, for example, amiodarone, quinidine).
When lercanidipine 20 mg is coadministered with midazolam, the bioavailability of lercanidipine in elderly patients may increase by approximately 40 mg. %.
Lercanidipine should be administered with caution concomitantly with inducers of CYP3A4, such as anticonvulsants (phenytoin, carbamazepine) and rifampicin, as the antihypertensive effect of the drug may be reduced. Regular blood pressure monitoring is necessary.
With simultaneous use of lercanidipine at a dose of 20 mg in patients chronically taking betamethyldigoxin, no pharmacokinetic interaction was noted, while in healthy volunteers treated with digoxin, an increase in the Cmax value (maximum plasma concentration) for digoxin was observed by an average of 33 % after taking 20 mg of lercanidipine on an empty stomach, while AUC (area under the concentration-time curve) and renal clearance changed slightly. Patients receiving digoxin and lercanidipine concomitantly should be monitored for signs of digoxin toxicity. The simultaneous use of lercanidipine with cimetidine (up to 800 mg) does not cause significant changes in the concentration of lercanidipine in the blood plasma. At high doses of cimetidine, the bioavailability and antihypertensive effect of lercanidipine may be increased.
With simultaneous use of lercanidipine (20 mg) and simvastatin (40 mg), the AUC value for simvastatin increased by 56%,
and the same value for its active metabolite - P-hydroxy acid - by 28
%.
By taking medications at different times of the day (lercanidipine in the morning, simvaetatin in the evening), unwanted interactions can be avoided.
With simultaneous use of 20 mg of lercanidipine and warfarin in healthy volunteers, no changes in the pharmacokinetics of warfarin were observed. Concomitant use with fluoxetine (an inhibitor of CYP2D6 and CYP3A4) in elderly patients did not have clinically significant changes in the pharmacokinetics of lercanidipine.
It is possible that the antihypertensive effect may be enhanced when grapefruit juice and lercanidipine are taken concomitantly (see section "Contraindications"
»).
Ethanol may potentiate the antihypertensive effect of lercanidipine.
