Lercanidipine
Drug interactions
When used simultaneously with CYP3A4 inhibitors (including ketoconazole, intraconazole, erythromycin), drug interactions are possible (use combinations with caution).
When used together with CYP3A4 inducers (including antidepressants, rifampicin), the antihypertensive effect of lercanidipine may be reduced.
The hypotensive effect of lercanidipine may be enhanced by consuming grapefruit juice.
Ethanol may potentiate the action of lercanidipine.
When used simultaneously with metoprolol, the bioavailability of lercanidipine is reduced by 50%. This effect may also occur when used concomitantly with other beta-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.
The simultaneous use of cyclosporine and lercanidipine is not recommended, because There is an increase in the concentration of both substances in the blood plasma.
Caution should be exercised when lercanidipine is used concomitantly with other CYP3A4 substrates (terfenadine, astemizole, class III antiarrhythmic drugs, e.g. amiodarone, quinidine).
When lercanidipine 20 mg is co-administered with midazolam, the bioavailability of lercanidipine in elderly patients may increase by approximately 40%.
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.
When lercanidipine was co-administered at a dose of 20 mg in patients chronically taking beta-methyldigoxin, no pharmacokinetic interaction was observed, while healthy volunteers treated with digoxin experienced an average 33% increase in digoxin Cmax after dosing of 20 mg. lercanidipine in the fasted state, with AUC and renal clearance changing 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 - β-hydroxy acid - by 28%.
By taking drugs at different times of the day (lercanidipine in the morning, simvastatin in the evening) you can avoid unwanted interactions.
The antihypertensive effect may be enhanced by simultaneous administration of grapefruit juice and lercanidipine.
Ethanol may potentiate the antihypertensive effect of lercanidipine.
Lercanidipine-SZ 20 mg N30 (Northern Star)
The drug should not be used simultaneously with inhibitors of CYP3A4 (liver cytochrome P450 isoenzyme), such as ketoconazole, itraconazole, erythromycin (increase the concentration of lercanidipine in the blood and lead to potentiation of the antihypertensive effect). The simultaneous use of lercanidipine with cyclosporine is contraindicated as this leads to an increase in the content of both substances in the blood plasma. Lercanidipine should not be taken with grapefruit juice, as this leads to inhibition of lercanidipine metabolism and potentiation of the antihypertensive effect. Caution must be exercised when taken concomitantly with drugs such as terfenadine, astemizole, quinidine and class III antiarrhythmic drugs (for example, amiodarone). Concomitant use with anticonvulsants (for example, phenytoin, carbamazepine) and rifampicin may lead to a decrease in the plasma concentration of lercanidipine and, therefore, a decrease in the antihypertensive effect of lercanidipine. In patients chronically taking digoxin, no pharmacokinetic interaction was observed with concomitant use of lercanidipine at a dose of 20 mg. However, in healthy volunteers who took , there was an increase in the Cmax value of digoxin in blood plasma by an average of 33% after oral administration of 20 mg lercanidipine on an empty stomach, while the AUC and renal clearance of digoxin changed little. Patients receiving digoxin and lercanidipine concomitantly should be monitored for signs of digoxin toxicity. When lercanidipine 20 mg is co-administered with midazolam, the bioavailability of lercanidipine in elderly patients may increase by approximately 40%. Metoprolol reduces the bioavailability of lercanidipine by 50%, while the bioavailability of metoprolol remains unchanged. This effect may occur due to a decrease in hepatic blood flow, which is caused by beta-blockers, and may therefore also occur when used with other drugs in this group. Cimetidine at a dose of 800 mg per day does not lead to significant changes in the concentration of lercanidipine in the blood plasma, however, special caution is required, since at higher doses of cimetidine the bioavailability of lercanidipine, and therefore its antihypertensive effect, may increase. With simultaneous use of lercanidipine (20 mg) and simvastatin (40 mg), the AUC value for simvastatin increased by 56%, and for its active metabolite beta-hydroxy acid - by 28%. By taking medications at different times of the day (lercanidipine - in the morning, - in the evening), you can avoid unwanted interactions. When used simultaneously with fluoxetine (an inhibitor of CYP2D6 and CYP3A4 isoenzymes) in elderly patients, no clinically significant changes in the pharmacokinetics of lercanidipine were detected. Taking lercanidipine simultaneously with warfarin does not affect the pharmacokinetics of the latter. Lercanidipine can be used simultaneously with beta-blockers, diuretics, and angiotensin-converting enzyme (ACE) inhibitors. Ethanol may enhance the antihypertensive effect of lercanidipine.
Pharmacodynamics and pharmacokinetics
Lercanidipine is a typical calcium channel blocker that reduces the active transport of calcium ions through a semi-permeable membrane into cardiomyocytes of vascular smooth muscle cells. Under the influence of this substance, total peripheral vascular resistance and blood pressure . The hypotensive effect of taking the drug is quite long-lasting and lasts throughout the day. The medicine does not have a negative inotropic effect.
The substance is completely adsorbed from the gastrointestinal tract. The maximum concentration is observed one and a half to three hours after administration. The product is quickly distributed throughout all tissues and organs. The degree of binding to proteins in the blood is up to 98%. With hypoalbunemia , liver and kidney failure, the free fraction tends to increase. Repeated administration of the drug does not lead to its accumulation. Metabolized in the liver using the CYP3A4 , half of the drug taken is excreted through the kidneys in the urine. The half-life is from 7 to 10 hours.
Side effects
Side effects from taking Lercanidipine are quite rare.
May appear:
- peripheral edema , flushing of the face;
- palpitations, chest pain;
- angina pectoris , asthenia , headache , tachycardia ;
- myocardial infarction , dizziness , nausea;
- indigestion, vomiting, stomach pain;
- diarrhea , gum hyperplasia;
- increased activity of liver enzymes (reversible), decreased blood pressure ;
- skin rashes, myalgia , polyuria , drowsiness .
Efficacy of lercanidipine in elderly patients
An additional indication for the choice of CCBs as antihypertensive drugs is the elderly age of patients. Lercanidipine demonstrated good efficacy for patients with hypertension of different age groups. One study compared its effectiveness in different age groups. 375 patients under the age of 65 years and 315 patients over 65 years of age were included. Lercanidipine was prescribed at a dose of 10–20 mg/day. The effectiveness of lercanidipine, its dose at the end of treatment, and the need for combination therapy did not differ significantly in different age groups. The incidence of edema was small (3%) and did not differ between the two groups [14].
In a placebo-controlled, randomized trial, 144 elderly (60–85 years) patients were prescribed lercanidipine at a dose of 10 mg/day. Patients receiving lercanidipine had a significantly more pronounced decrease in systolic (15 and 7 mm Hg, respectively) and diastolic (10 and 6 mm Hg) blood pressure compared to the placebo group. The proportion of patients with normalization of blood pressure also turned out to be significantly higher: 59% in the lercanidipine group and 38% in the placebo group [15].
Lercanidipine is not inferior in effectiveness to other dihydropyridine CCBs in elderly patients. In elderly patients with isolated systolic hypertension, lercanidipine at a dose of 10–20 mg/day showed comparable antihypertensive efficacy to lacidipine at a dose of 2–4 mg/day [16]. In a similar comparison with nifedipine GITS at a dose of 30-60 mg, the antihypertensive effectiveness was similar, and the incidence of side effects in treatment with lercanidipine was significantly lower (19.4%) compared with treatment with nifedipine (28.4%). Edema developed significantly less frequently: 2.8% in the lercanidipine group and 10.1% in the nifedipine group [17].
Therapy with lercanidipine can lead to an improvement in mnestic-intellectual functions, which is especially important for patients in older age groups. This was shown in an open-label study where 467 patients over 40 years of age with grade 1 and 2 hypertension received lercanidipine for 6 months. Lercanidipine was prescribed at a dose of 10 mg/day. At the end of treatment, 98% of patients continued taking lercanidipine. Adequate blood pressure control was achieved in 68% of patients. Blood pressure decreased from 154.4/95.3 to 134.8/80.7 mm Hg. Art. According to testing data, by the end of treatment there was a significant improvement in mental functions, more significant for those patients for whom lercanidipine provided sufficient blood pressure control [18].
Nonsteroidal anti-inflammatory drugs (NSAIDs) cause an increase in blood pressure and reduce the effectiveness of selected antihypertensive therapy in patients with hypertension. Taking NSAIDs, often uncontrolled, is one of the reasons for hypertension resistance to therapy. This is especially significant for elderly patients, who have a high incidence of concomitant diseases of the musculoskeletal system. It is known that taking NSAIDs has the greatest effect on the effectiveness of angiotensin-converting enzyme inhibitors (ACEIs). For lercanidipine, a special study examined the effectiveness of the drug in patients with hypertension over 60 years of age taking NSAIDs. A total of 334 patients were included in the study, 280 completed the study. Blood pressure control was carried out according to 24-hour blood pressure monitoring data. First, patients received therapy with lercanidipine at a dose of 10 mg/day for 8 weeks. At the same time, a significant decrease in blood pressure was noted, which reached a level of 139/82 mm Hg. Art. Blood pressure control was achieved in 156 (55.7%) patients. Then a course of NSAID therapy (mainly diclofenac and naproxen) was started. Good blood pressure control was maintained in 128 patients. The blood pressure level of 28 patients slightly exceeded 140/90 mmHg. Art. There were no significant changes in blood pressure in the group as a whole. Thus, taking NSAIDs has little effect on the effectiveness of lercanidipine therapy [19].
Drugs containing (Lercanidipine analogues)
Level 4 ATC code matches:
Lacipil
Cordafen
Azomex
Nimodipine
Felodipin
Nifedipine
Farmadipin
Amlotop
Nimotop
Tenox
Nifecard HL
Cordipin
Felodip
Normodipine
Phenigidine
Norvask
Cordaflex
Lerkamen
Corinfar
Vero-Amlodipine
Analogues of lek. products: Zanidip-Recordati , Lercanidipine hydrochloride , Lernikor , Lerkamen 10 and 20 mg, Lercanorm , Coripren (multicomponent product), Enal L Combi (with enalapril ).
Lercanidipine, instructions for use (Method and dosage)
The tablets are taken orally. In the morning, on an empty stomach. Not earlier than a quarter of an hour before meals. It is not recommended to chew the medicine. Take the tablets with plenty of water.
On average, the daily dosage is 10 mg, but it can be doubled. The daily dose can be increased in the second week of treatment.
For mild to moderate liver and kidney diseases, it is better not to increase the dosage, but to take the minimum active dose of 10 mg.
Lercanidipine and the condition of the vascular wall
An essential component that determines the advantages of CCBs in influencing the prognosis of patients with hypertension over other classes of antihypertensive drugs is the ability to influence the condition of the vascular wall and influence central pressure. The significance of these effects was demonstrated in the CAFE (Conduit Artery Function Evaluation) study conducted as part of the ASCOT (Anglo-Scandinavian Cardiac Outcomes Trial) project. The combination of amlodipine and perindopril has been shown to reduce central aortic pressure to a greater extent than treatment with atenolol and bendroflumethiazide. As is known, central blood pressure is closely related to the stiffness/elasticity of the vascular wall and pulse wave speed, which in turn can affect the occurrence of cardiovascular events, especially stroke. Lercanidipine has been shown to have angioprotective properties in several studies.
Treatment with lercanidipine may affect the state of endothelium-dependent vasodilation and endothelial NO production. This was shown in a study where the endothelial function of 15 healthy individuals and 15 patients with hypertension was assessed by the degree of vasodilation in response to bradykinin infusion. Therapy with lercanidipine at a dose of 10 mg/day for 3 months significantly increased the response of the brachial artery to bradykinin infusion. The blocking effect of NO inhibitors decreased, as well as plasma concentrations of malonaldehyde and isoprostanoids, and the antioxidant activity of blood plasma increased [24].
The effects of lercanidipine and hydrochlorothiazide on vascular health were compared in a study involving 26 previously untreated hypertensive patients. The effects of drugs on blood pressure, blood flow assessed by plethysmography, vascular resistance, and changes in blood flow in response to ischemia were assessed. Treatment continued for 12 months with assessment of blood flow parameters at 6 and 12 months. It turned out that lercanidipine causes a more significant decrease in vascular resistance in the arteries of the upper and lower extremities (-46.1 and -40.9% versus 22.5 and -19.9%, respectively; p < 0.01 in both cases). However, the state of blood flow did not reach the levels characteristic of healthy individuals [25].
In a relatively small study (59 patients over the age of 60 years with isolated systolic hypertension), the effect of drugs of different groups (perindopril, atenolol, lercanidipine and bendrofluthiazide) on central pressure, pulse wave velocity and augmentation index was studied. Therapy continued for 10 weeks. The levels of systolic and pulse blood pressure did not differ significantly either before or during treatment. Central pressure decreased during treatment with all drugs except atenolol. Lercanidipine was the only drug that reduced the augmentation index. No reliable dynamics of pulse wave propagation speed was achieved in any of the treatment groups [26].
Contraindications
The substance is contraindicated:
- for chronic heart failure in the stage of decompensation;
- for aortic stenosis and unstable angina ;
- if less than a month ago the patient suffered a myocardial infarction ;
- with severe liver failure;
- if the CK reaches less than 10 ml per minute;
- with galactosemia ;
- patients with lactose intolerance, with malabsorption syndrome of galactose , glucose ;
- pregnant women;
- children and teenagers;
- when breastfeeding;
- patients with allergies to the components of the drug and other dihydropyridine derivatives.
