Lerkamen 10, 28 pcs., 10 mg, film-coated tablets
Lercanidipine can be used simultaneously with β-blockers, diuretics, angiotensin-converting enzyme inhibitors (ACEIs).
When used simultaneously with metoprolol, the bioavailability of lercanidipine is reduced by 50%. This effect may also occur when used simultaneously 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, may affect 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 there is an increase in the concentration of both substances in the blood plasma (see section " Contraindications"
»).
Caution should be exercised when lercanidipine is used concomitantly with other CYP3A4 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%.
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 in healthy volunteers treated with digoxin, an increase in digoxin Cmax (maximum plasma concentration) was observed on average by 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 - β-hydroxy acid - by 28%. By taking medications at different times of the day (lercanidipine in the morning, simvastatin 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 to enhance the antihypertensive effect when taking grapefruit juice and lercanidipine simultaneously (see section " Contraindications"
»).
Ethanol may potentiate the antihypertensive effect of lercanidipine.
Impact on the ability to drive vehicles and operate machinery
Since dizziness, asthenia, increased fatigue and, in rare cases, drowsiness may occur during therapy with Lerkamen® 10, during the period of drug use, patients should be especially careful when driving vehicles and engaging in other potentially hazardous activities that require a high speed of psychomotor reactions.
Lerkamen 10 tablets on film 10 mg pack cont cell/pack of cards x28
Trade name: Lerkamen 10 International name: Lercanidipine
Pharmacological group: blocker of “slow” calcium channels. Pharmacological group for ATC: C08CA13. Lercanidipine Pharmacological action: BMKK selective, hypotensive Pharmacodynamics: BMKK, a derivative of the dihydropyridine series, inhibits the transmembrane Ca2+ current in cardiomyocytes and smooth muscle cells. The mechanism of the hypotensive effect is due to a direct relaxing effect on vascular smooth muscle cells, resulting in a decrease in peripheral vascular resistance. Has a long-term hypotensive effect. Due to its high selectivity for vascular smooth muscle cells, there is no negative inotropic effect. The duration of therapeutic action is 24 hours. Pharmacokinetics: Complete absorption. Cmax is 3.3 ng/ml and 7.66 ng/ml after taking 10 and 20 mg, respectively. TCmax - 1.5-3 hours. Distribution from blood plasma to tissues and organs occurs quickly. Protein binding - more than 98%. Against the background of hypoalbuminemia in patients with renal and hepatic insufficiency, the free fraction of lercanidipine may increase. Does not accumulate when taken repeatedly. Elimination occurs by metabolism involving the CYP3A4 isoenzyme; about 50% of the dose taken is excreted in the urine. T1/2 - 8-10 hours. Indications for use: Essential hypertension of mild to moderate severity. Contraindications: Hypersensitivity, decompensated CHF, unstable angina, aortic stenosis, recent myocardial infarction (within 1 month), severe liver dysfunction, renal dysfunction (creatinine clearance less than 12 ml/min), women of childbearing age who do not use reliable contraception, pregnancy, lactation, childhood and adolescence (up to 18 years). For dosage forms containing lactose (additionally): lactose intolerance, galactosemia, glucose/galactose malabsorption syndrome. Dosage regimen: Orally, in the morning, at least 15 minutes before meals, without chewing, with a sufficient amount of water, 10 mg 1 time per day. The dose can be increased to 20 mg (depending on the individual effect). The dose is increased to 20 mg 2 weeks after starting the drug. In case of mild or moderate renal or hepatic impairment, increasing the dose to 20 mg per day should be done with caution. Side effects: Peripheral edema, feeling of flushing of the face, palpitations, tachycardia, chest pain, decreased blood pressure, angina pectoris, myocardial infarction, asthenia, fatigue, headache, dizziness, gastrointestinal disorders (dyspepsia, nausea, vomiting, epigastric pain, diarrhea), increased activity of liver enzymes (reversible), polyuria, skin rash, drowsiness, myalgia, gingival hyperplasia.
Overdose. Symptoms: peripheral vasodilation with a pronounced decrease in blood pressure and reflex tachycardia, increased frequency and duration of angina attacks, myocardial infarction. Treatment: symptomatic therapy. Interaction: Compatible with beta-blockers, diuretics, ACE inhibitors. When used concomitantly with cardiac glycosides, it is necessary to monitor the symptoms and signs of digoxin intoxication. Concomitant use with cimetidine does not cause significant changes in the plasma concentration of lercanidipine; at high doses of cimetidine, the bioavailability and, accordingly, the hypotensive effect of lercanidipine increases. Use with caution with CYP3A4 inhibitors (including ketoconazole, itraconazole, erythromycin). Inducers of the CYP3A4 isoenzyme (antidepressants, rifampicin) may reduce the hypotensive effect of the drug. Grapefruit juice and ethanol may enhance the hypotensive effect of lecarnidipine. Special instructions: During the treatment period, care must be taken when driving vehicles and engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions.
Carefully. Renal and/or liver failure, CVS (without a pacemaker), coronary artery disease, LV dysfunction, old age.
Manufacturer: Berlin-Chemie AG/Menarini Group, Germany Registration certificate holder: Berlin-Chemie AG/Menarini Group, Germany Release form: film-coated tablets 10 mg (blisters) Composition: lercanidipine hydrochloride 10 mg Shelf life: 3 years Registration data : LSR-007057/09 dated 09/07/2009 Registration certificate status: valid HS codes: 3004 90 190 9
Lerkamen 10 tablets p/o 10 mg No. 15x4
Name
Lerkamen 10 tablets p/o 10 mg in blister pack No. 15x4
Description
Film-coated tablets from pale yellow to light yellow, round, biconvex, scored on one side; on the fracture - light yellow.
Main active ingredient
Lercanidipine
Release form
Film-coated tablets from pale yellow to light yellow, round, biconvex, scored on one side; on the fracture - light yellow. 1 tab. lercanidipine hydrochloride 10 mg Excipients: lactose monohydrate - 30 mg, microcrystalline cellulose - 39 mg, sodium carboxymethyl starch (type A) - 15.5 mg, povidone K30 - 4.5 mg, magnesium stearate - 1 mg. Shell composition: opadry OY-SR-6497 - 3 mg (hypromellose - 1.913 mg, macrogol 6000 - 0.3 mg, talc - 0.15 mg, titanium dioxide - 0.6 mg, iron dye yellow oxide - 0.037 mg). 15 pcs. - blisters (4) - cardboard packs.
special instructions
Effect on the ability to drive vehicles and operate machinery Since dizziness, asthenia, fatigue and, in rare cases, drowsiness may occur during therapy with Lerkamen®, during the period of use of the drug, patients should be especially careful when driving vehicles and engaging in other potentially hazardous activities that require high speed of psychomotor reactions.
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 plasma half-life, 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.
Pharmacokinetics
Absorption Lercanidipine is completely absorbed after oral administration. Cmax in blood plasma is achieved after 1.5-3 hours and is 3.3±2.09 ng/ml and 7.66±5.90 ng/ml after taking 10 and 20 mg of lercanidipine, respectively. (+)R- and (-)S-enantiomers of lercanidipine demonstrate a similar pharmacokinetic profile: they have the same time to reach Cmax, the same T1/2; the Cmax and AUC values are 1.2 times higher for the (-)S-enantiomer. Interconversion of enantiomers was not observed in in vivo experiments. Due to the “first pass” effect through the liver, the absolute bioavailability of lercanidipine when taken orally after meals is approximately 10%; when taken on an empty stomach, the bioavailability value decreases by 1/3. When taking lercanidipine no later than 2 hours after eating a fatty meal, its bioavailability increases 4 times, so Lerkamen® should not be taken after meals. When lercanidipine is administered orally, its plasma concentration is not directly proportional to the dose taken (nonlinear kinetics). Saturation of presystemic metabolism occurs gradually. Thus, bioavailability increases with increasing dose. Distribution Distribution from blood plasma to tissues and organs occurs quickly and widely. Plasma protein binding exceeds 98%. Metabolism and elimination Lercanidipine is metabolized with the participation of the CYP3A4 isoenzyme to form inactive metabolites. About 50% of the dose taken is excreted by the kidneys (about 50% is excreted by the intestines). Elimination occurs mainly through biotransformation. The average T1/2 is 8-10 hours. Cumulation of lercanidipine is not observed upon repeated oral administration. Pharmacokinetics in special clinical situations The pharmacokinetics of lercanidipine in elderly patients, patients with renal impairment (creatinine clearance greater than 30 ml/min) and patients with mild to moderate hepatic impairment have been shown to be similar to the pharmacokinetics observed in the general patient population. In patients with renal insufficiency (creatinine clearance less than 30 ml/min) and in patients on hemodialysis, plasma concentrations of lercanidipine were higher (approximately 70%). In patients with severe renal and/or hepatic impairment due to decreased plasma protein concentrations, the free fraction of lercanidipine may increase. In patients with moderate to severe hepatic impairment, the systemic bioavailability of lercanidipine is likely to be increased since lercanidipine is metabolized primarily in the liver.
Indications for use
— essential hypertension of I-II severity.
Directions for use and doses
The drug is taken orally at least 15 minutes before meals, preferably in the morning, without chewing, with a sufficient amount of water. 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. The pharmacokinetic profile and clinical trial data show that no dose adjustment of Lerkamen® is required in elderly patients. However, caution should be exercised at the initial stage of treatment with Lerkamen® in this group of patients. When using the drug Lerkamen® in patients with mild to moderate renal and hepatic insufficiency, 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, use of the drug Lerkamen®
Use during pregnancy and lactation
The use of Lerkamen® during pregnancy and breastfeeding, as well as in women of childbearing age in the absence of reliable contraception, is contraindicated. 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
Precautionary measures
It should be used with caution in 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, and left ventricular dysfunction.
Interaction with other drugs
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 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. 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 have 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.
Contraindications
- 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.
Compound
1 tab. lercanidipine hydrochloride 10 mg Excipients: lactose monohydrate - 30 mg, microcrystalline cellulose - 39 mg, sodium carboxymethyl starch (type A) - 15.5 mg, povidone K30 - 4.5 mg, magnesium stearate - 1 mg. Shell composition: opadry OY-SR-6497 - 3 mg (hypromellose - 1.913 mg, macrogol 6000 - 0.3 mg, talc - 0.15 mg, titanium dioxide - 0.6 mg, iron dye yellow oxide - 0.037 mg).
Overdose
Presumably, in case of an overdose of lercanidipine, symptoms similar to those of an overdose of other dihydropyridine derivatives will be observed: peripheral vasodilation with a pronounced decrease in blood pressure and reflex tachycardia. Treatment: symptomatic therapy; in case of a pronounced decrease in blood pressure and loss of consciousness, cardiovascular therapy is indicated; in case of bradycardia, intravenous administration of atropine is indicated. There is evidence of 3 cases of overdose when taking lercanidipine in doses of 150 mg, 280 mg and 800 mg for the purpose of suicide. Drowsiness has been observed with lercanidipine 150 mg + alcohol (unspecified amount). Treatment: gastric lavage, taking activated charcoal. When taking 280 mg of lercanidipine + 5.6 mg of moxonidine, the following symptoms were observed: cardiogenic shock, severe myocardial ischemia, mild renal failure. Treatment: cardiac glycosides, diuretics (furosemide), high doses of catecholamines, plasma expanders. When taking 800 mg of lercanidipine, nausea and a marked decrease in blood pressure were observed. Treatment: taking activated carbon and a laxative, intravenous dopamine. In all cases of overdose, all patients survived. There is no information available on the effectiveness of dialysis for lercanidipine. It is most likely that due to the high binding of lercanidipine to plasma proteins, dialysis may be ineffective.
Side effect
Possible side effects are listed below in descending order of frequency: common (
Storage conditions
The drug should be stored out of the reach of children at a temperature not exceeding 30°C.
