Lerkamen 10 tab.p.p.o.10mg No. 60 Berlin-Chemie/Menarini

Lerkamen 10 tab.pp.p.o.10mg No. 60

Indications

essential hypertension of I-II severity.

pharmachologic effect

Selective blocker of slow calcium channels with a predominant effect on blood vessels, a dihydropyridine derivative. Inhibits the transmembrane flow of calcium ions into vascular smooth muscle cells. The mechanism of the antihypertensive effect of lercanidipine is due to a direct relaxing effect on vascular smooth muscle cells, resulting in a decrease in peripheral vascular resistance.

Despite the relatively short T1/2 from blood plasma, lercanidipine has a prolonged antihypertensive effect due to its high membrane distribution coefficient. Due to its high vascular selectivity, it does not have a negative inotropic effect. Acute arterial hypotension with reflex tachycardia occurs rarely due to the gradual development of vasodilation when taking lercanidipine.

Lercanidipine is a racemic mixture of (+)R- and (-)S-enantiomers. The antihypertensive effect of lercanidipine is primarily due to the S-enantiomer.

The duration of therapeutic action is 24 hours.

Drug interactions

Lercanidipine can be used simultaneously with beta-blockers, diuretics, and 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 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 coadministered 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 co-administered with lercanidipine 20 mg in patients chronically taking beta-methyldigoxin, no pharmacokinetic interaction was observed, whereas healthy volunteers treated with digoxin experienced an average 33% increase in digoxin Cmax after administration of 20 mg lercanidipine. on an empty stomach, while AUC 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 of simvastatin increased by 56%, and the same value of 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.

With simultaneous use of lercanidipine at a dose of 20 mg 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 cause clinically significant changes in the pharmacokinetics of lercanidipine.

The antihypertensive effect may be enhanced by simultaneous administration of grapefruit juice and lercanidipine.

Ethanol may potentiate the antihypertensive effect of lercanidipine.

Dosage regimen

Take orally at least 15 minutes before meals, preferably in the morning. Prescribe 10 mg 1 time/day. Depending on the patient’s individual tolerance of the drug, the dose can be increased to 20 mg.

The therapeutic dose is selected gradually, because The maximum antihypertensive effect develops approximately 2 weeks after starting the drug. It is unlikely that the effectiveness of the drug will increase with increasing doses above 20 mg/day, and at the same time the risk of side effects increases.

Pharmacokinetic profile and clinical trial data indicate that in elderly patients

no dose adjustment is required. However, caution should be exercised at the initial stage of treatment with the drug in this group of patients.

When used in patients with mild to moderate renal and hepatic impairment

caution should be exercised.

In case of renal failure (creatinine clearance more than 30 ml/min) or mild or moderate liver failure

The initial dose is 10 mg, then increase the dose with caution to 20 mg/day.
The antihypertensive effect may be enhanced in patients with mild or moderate hepatic impairment
and dose adjustment (reduction) may be required.

In case of renal failure (creatinine clearance less than 30 ml/min) and severe liver failure

severity, the use of the drug is contraindicated.

Contraindications for use

untreated heart failure;
unstable angina;
obstruction of blood vessels originating from the left ventricle of the heart;
period within 1 month after myocardial infarction;
severe liver failure;
severe renal failure (creatinine clearance less than 30 ml/min);
simultaneous use with CYP3A4 inhibitors (ketoconazole, itraconazole, erythromycin, ritonavir, troleandomycin);
simultaneous use with cyclosporine;
simultaneous use with grapefruit juice;
lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome;
pregnancy;
lactation period (breastfeeding);
use in women of childbearing age who do not use reliable methods of contraception;
children and adolescents under 18 years of age (efficacy and safety have not been studied);
hypersensitivity to the components of the drug;
hypersensitivity to other dihydropyridine derivatives.

Carefully

should be used for renal (creatinine clearance more than 30 ml/min) and/or liver failure of mild to moderate severity, in elderly patients, with CVS (without a pacemaker), coronary artery disease, left ventricular dysfunction.

Use in children

The drug is contraindicated in children and adolescents under 18 years of age.

Restrictions for children

Contraindicated

Use in elderly patients

Use with caution in elderly patients.

Restrictions for elderly patients

Use with caution

Use for liver dysfunction

Use with caution in mild to moderate liver failure.

Use is contraindicated in severe liver failure.

Restrictions for liver dysfunction

Use with caution

Use during pregnancy and breastfeeding

Preclinical studies did not reveal a teratogenic effect of lercanidipine in rats and rabbits; the reproductive function of rats was unchanged.

Due to the lack of clinical experience with the use of lercanidipine during pregnancy and breastfeeding, and since other dihydropyridine derivatives are known to have a teratogenic effect in animals, lercanidipine is not recommended for use during pregnancy or in women of childbearing age who do not use reliable methods of contraception.

Due to the high lipophilicity of lercanidipine, it can be expected to pass into breast milk, so the drug is not recommended for use during breastfeeding.

Restrictions when breastfeeding

Contraindicated

Restrictions during pregnancy

Contraindicated

Use for renal impairment

Should be used with caution in case of renal failure (creatinine clearance more than 30 ml/min).

Use is contraindicated in severe renal failure (creatinine clearance less than 30 ml/min).

Restrictions for impaired renal function

Use with caution

special instructions

Impact on the ability to drive vehicles and machinery

Since dizziness, asthenia, fatigue and, in rare cases, drowsiness may occur during therapy with lercanidipine, patients should be especially careful while using the drug to drive vehicles and engage in other potentially hazardous activities that require a high speed of psychomotor reactions.

Side effect

Possible side effects are listed below in descending order of frequency: common (

From the nervous system:

infrequently - headache, dizziness; rarely - drowsiness.

From the cardiovascular system:

infrequently - palpitations, tachycardia, “flushes” of blood to the skin of the face; rarely - angina pectoris, chest pain; very rarely - fainting; in patients with angina pectoris, the frequency, duration and severity of attacks may increase.

From the digestive system:

rarely - nausea, dyspepsia, diarrhea, epigastric pain, vomiting.

For the skin and subcutaneous tissues:

rarely - skin rash.

From the musculoskeletal system:

rarely - myalgia.

From the urinary system:

rarely - polyuria.

From the immune system:

very rarely
-
hypersensitivity reactions.

From the body as a whole:

uncommon - peripheral edema;
rarely -
asthenia, increased fatigue.

There are reports of the following very rare side effects (myocardial infarction, gum hyperplasia, reversible increase in the activity of liver transaminases, marked decrease in blood pressure, pollakiuria (increased frequency of urination), chest pain.

Possible product names

Lerkamen 10 tablets p.p.o. 10 mg. No. 60
LERKAMEN-10 10 MG TAB. No. 60
LERKAMEN 10 0.01 N60 TABLE P/O
LERKAMEN 10 TABLE. P/O PLEN 10 MG X60
LERKAMEN 10 TAB. P/O PLEEN. 10MG No. 60
LERKAMEN 10 10MG TAB. P/PL/OB. X60
(Lerkamen 10) Lerkamen 10 tab. p.p.o. 10 mg. No. 60

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.