Lernicor tablets p / o 10mg, No. 28
Expiration Date: 05/2027
Russian Pharmacy name:
Лерникор таблетки п/о 10мг, №28
arterial hypertension of 1-2 degrees.
Inside, at least 15 minutes before meals, preferably in the morning, without chewing, drinking plenty of water.
The recommended dose of the drug is 10 mg 1 time / day. Depending on the individual patient's tolerance of the drug, the dose may be increased to 20 mg. If necessary, an increase in the daily dose to 20 mg is carried out 2 weeks after the start of taking the drug.
The therapeutic dose is selected gradually, because the maximum antihypertensive effect develops approximately 2 weeks after the start of the drug.
It is unlikely that the effectiveness of the drug will increase with increasing doses of more than 20 mg / day, at the same time, the risk of side effects increases.
The pharmacokinetic profile and data from clinical studies show that dose adjustment of lercanidipine is not required in elderly patients . However, caution should be exercised at the initial stage of treatment in this group of patients.
In the presence of renal failure (CC more than 30 ml / min) or mild or moderate hepatic insufficiency, the initial dose is 10 mg, then the dose is increased with caution to 20 mg / day. The antihypertensive effect may be enhanced in patients with mild to moderate hepatic impairment and dose adjustment (reduction) may be required.
Lercanidipine hydrochloride
hypersensitivity to lercanidipine, other dihydropyridine derivatives or any component of the drug;
untreated chronic heart failure;
unstable angina;
obstruction of the outflow tract of the left ventricle;
period within 1 month after suffering myocardial infarction;
severe liver failure;
severe renal failure (CC less than 30 ml / min);
simultaneous use with powerful inhibitors of CYP3A4 (ketoconazole, itraconazole, erythromycin, ritonavir, troleandomycin);
simultaneous use with cyclosporine;
simultaneous reception with grapefruit juice;
lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome;
pregnancy;
breastfeeding period;
use in women of childbearing age who do not use reliable methods of contraception;
age up to 18 years (efficacy and safety have not been studied).
With care: renal failure (CC more than 30 ml / min) and / or hepatic failure of mild and moderate severity, old age, sick sinus syndrome (without a pacemaker), ischemic heart disease, left ventricular dysfunction.
Clinical and pharmacological group: Selective calcium channel blocker class II
Pharmaco-therapeutic group: Blocker of 'slow' calcium channels
pharmachologic effect
Lercanidipine is a selective blocker of slow calcium channels, a derivative of 1,4-dihydropyridine, inhibits the transmembrane flow of calcium ions into vascular smooth muscle cells.
Lercanidipine is a racemic mixture of the (+) - R- and (-) S- enantiomers. The antihypertensive effect of lercanidipine is primarily due to the S-enantiomer. The mechanism of the antihypertensive action of lercanidipine is due to a direct relaxing effect on vascular smooth muscle cells, as a result of which the total peripheral resistance decreases. Despite a relatively short half-life from blood plasma, lercanidipine has a prolonged antihypertensive effect due to a high coefficient of membrane distribution. Due to its high vascular selectivity, it does not have a negative inotropic effect. Acute arterial hypotension with reflex tachycardia rarely occurs due to the gradual development of vasodilation when taking lercanidipine.
Lercanidipine is metabolically neutral and does not significantly affect serum lipoproteins and apolipoproteins, and does not alter the lipid profile in hypertensive patients.
Pharmacokinetics
Suction
Lercanidipine is completely absorbed after oral administration. The maximum plasma concentration (Cmax) is reached 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 show a similar pharmacokinetic profile: they have the same time to reach the maximum concentration (TCmax), the same half-life (T1 / 2); Cmax and area under the concentration-time curve (AUC) are 1.2 times higher for the (-) S-enantiomer. No interconversion of enatetiomers was observed in experiments in vivo.
At the 'first pass' 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 ingestion of fatty foods, its bioavailability increases 4 times, therefore, lercanidipine should not be taken after meals. With oral administration of lercanidipine, its plasma concentration is not directly proportional to the dose taken (nonlinear kinetics). The saturation of the presystemic metabolism occurs gradually. Thus, bioavailability increases with increasing dose.
Distribution
Distribution from blood plasma to tissues and organs is rapid and extensive. The connection with blood plasma proteins exceeds 98%.
Metabolism and excretion
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. The duration of the therapeutic effect is 24 hours.
Cumulation of lercanidipine with repeated oral administration is not observed.
Pharmacokinetics in special clinical situations
It has been shown that the pharmacokinetics of lercanidipine in elderly patients, patients with renal insufficiency (creatinine clearance (CC) more than 30 ml / min) and in patients with mild to moderate hepatic insufficiency is similar to the pharmacokinetics that is observed in the general population of patients.
In patients with severe renal and / or hepatic insufficiency due to a decrease in the concentration of protein in the blood plasma, the free fraction of lercanidipine may increase.
In patients with renal insufficiency (CC less than 30 ml / min) and in patients on hemodialysis, plasma concentrations of lercanidipine were higher (approximately 70%).
In patients with moderate to severe hepatic impairment, the systemic bioavailability of lercanidipine is likely to increase, since lercanidipine is metabolized primarily in the liver.
Indications
arterial hypertension of 1-2 degrees.
Dosage regimen
Inside, at least 15 minutes before meals, preferably in the morning, without chewing, drinking plenty of water.
The recommended dose of the drug is 10 mg 1 time / day. Depending on the individual patient's tolerance of the drug, the dose may be increased to 20 mg. If necessary, an increase in the daily dose to 20 mg is carried out 2 weeks after the start of taking the drug.
The therapeutic dose is selected gradually, because the maximum antihypertensive effect develops approximately 2 weeks after the start of the drug.
It is unlikely that the effectiveness of the drug will increase with increasing doses of more than 20 mg / day, at the same time, the risk of side effects increases.
The pharmacokinetic profile and data from clinical studies show that dose adjustment of lercanidipine is not required in elderly patients . However, caution should be exercised at the initial stage of treatment in this group of patients.
In the presence of renal failure (CC more than 30 ml / min) or mild or moderate hepatic insufficiency, the initial dose is 10 mg, then the dose is increased with caution to 20 mg / day. The antihypertensive effect may be enhanced in patients with mild to moderate hepatic impairment and dose adjustment (reduction) may be required.
Side effect
Possible adverse reactions are listed below in descending frequency of occurrence: often (<1/10,> 1/100), infrequently (<1/100,> 1/1000), rarely (<1/1000,> 1/10 000), very rare (<1/10 000), including isolated reports.
From the nervous system: infrequently - headache, dizziness; rarely, drowsiness.
From the side of the cardiovascular system: infrequently - a feeling of palpitations, tachycardia, 'hot flushes' of blood to the skin of the face; rarely - angina pectoris, chest pain; very rarely - fainting, myocardial infarction, a marked decrease in blood pressure, in patients with angina pectoris, an increase in the frequency, duration and severity of attacks is possible.
From the gastrointestinal tract: rarely - nausea, dyspepsia, diarrhea, epigastric pain, vomiting; very rarely - a reversible increase in the activity of hepatic transaminases, gingival hyperplasia.
From the respiratory system, chest and mediastinal organs: very rarely - chest pain.
On the part of the skin and subcutaneous tissues: rarely - skin rash.
From the side of the musculoskeletal system: rarely - myalgia.
From the side of the kidneys and urinary tract: rarely - polyuria; very rarely - pollakiuria (increased frequency of urination).
From the immune system: very rarely - hypersensitivity reactions.
General disorders and disorders at the injection site: infrequently - peripheral edema; rarely - asthenia, increased fatigue.
Contraindications for use
hypersensitivity to lercanidipine, other dihydropyridine derivatives or any component of the drug;
untreated chronic heart failure;
unstable angina;
obstruction of the outflow tract of the left ventricle;
period within 1 month after suffering myocardial infarction;
severe liver failure;
severe renal failure (CC less than 30 ml / min);
simultaneous use with powerful inhibitors of CYP3A4 (ketoconazole, itraconazole, erythromycin, ritonavir, troleandomycin);
simultaneous use with cyclosporine;
simultaneous reception with grapefruit juice;
lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome;
pregnancy;
breastfeeding period;
use in women of childbearing age who do not use reliable methods of contraception;
age up to 18 years (efficacy and safety have not been studied).
With care: renal failure (CC more than 30 ml / min) and / or hepatic failure of mild and moderate severity, old age, sick sinus syndrome (without a pacemaker), ischemic heart disease, left ventricular dysfunction.
Application during pregnancy and lactation
The use of lercanidipine during pregnancy and during breastfeeding, as well as in women of childbearing age in the absence of reliable contraception, is contraindicated.
In the course of preclinical studies, no teratogenic effect of lercanidipine in rats and rabbits was revealed, the reproductive function of rats was unchanged.
Due to the lack of clinical experience with the use of lercanidipine during pregnancy and during breastfeeding, and since it is known that other dihydropyridine derivatives have a teratogenic effect in animals, lercanidipine is not recommended for use during pregnancy and in women of childbearing age who do not use reliable methods of contraception.
Due to the high lipophilicity of lercanidipine, its penetration into breast milk can be assumed; therefore, lercanidipine is not recommended for use during breastfeeding.
Application for violations of liver function
The use of the drug is contraindicated in severe hepatic insufficiency.
With care: mild to moderate hepatic impairment.
Application for impaired renal function
The use of the drug is contraindicated in severe renal failure (CC less than 30 ml / min).
With caution: renal failure (CC more than 30 ml / min).
Application in children
The use of the drug under the age of 18 is contraindicated (efficacy and safety have not been studied).
Use in elderly patients
The drug should be prescribed with caution to elderly patients.
special instructions
Particular care should be taken when prescribing lercanidipine to patients with sick sinus syndrome (without a pacemaker). Despite the fact that studies with hemodynamic control did not reveal deterioration of ventricular function when taking lercanidipine, caution should be exercised when prescribing lercanidipine in patients with left ventricular dysfunction. It has been suggested that taking certain dihydropyridines may be associated with the risk of increased angina attacks in patients with coronary artery disease. Therefore, in such patients, therapy with lercanidipine must be carried out with extreme caution.
Influence on the ability to drive vehicles and use mechanisms
Since dizziness, asthenia, increased fatigue and, in rare cases of drowsiness, may appear during drug therapy, during the period of drug use, patients should be especially careful to drive vehicles and engage in other potentially hazardous activities that require a high speed of psychomotor reactions.
Overdose
Symptoms: 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. In the case of a pronounced decrease in blood pressure, loss of consciousness, cardiovascular therapy is indicated, with bradycardia - intravenous administration of atropine.
There are data on 3 cases of overdose when taking lercanidipine in doses of 150 mg, 280 mg and 800 mg for the purpose of suicide.
In the case of taking 150 mg of lercanidipine + alcohol (unspecified amount), drowsiness was observed. Treatment: gastric lavage, intake of activated charcoal.
In the case of 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 substitutes.
In the case of taking 800 mg of lercanidipine, nausea and a marked decrease in blood pressure were observed. Treatment: intake of activated charcoal and laxative, intravenous - dopamine.
In all cases of overdose, all patients survived. There is no information on the effectiveness of dialysis for lercanidipine. It is most likely that due to the high binding of lercanidipine to blood plasma proteins, dialysis may be ineffective.
Drug interactions
Lercanidipine can be used simultaneously with beta-blockers, diuretics, angiotensin-converting enzyme (ACE) inhibitors.
With simultaneous use with metoprolol, the bioavailability of lercanidipine decreases by 50%. This effect can also occur with simultaneous use with other beta-blockers, therefore, a dose adjustment of lercanidipine may be required to achieve a therapeutic effect with this combination. Lercanidipine is metabolized with the participation of the isoenzyme CYP3A4, therefore inhibitors and inducers of this isoenzyme, when used simultaneously, can affect the metabolism and excretion of lercanidipine. The simultaneous use of lercanidipine with potent inhibitors of CYP3A4 (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.
—ледует про¤вл¤ть осторожность при одновременном применении лерканидипина с другими субстратами CYP3A4 (терфенадин, астемизол, антиаритмические препараты III класса, например, амиодарон, квинидин).
ѕри одновременном применении лерканидипина в дозе 20 мг с мидазоламом биодоступность лерканидипина у пожилых пациентов может увеличиватьс¤ приблизительно на 40%.
Ћерканидипин следует назначать с осторожностью одновременно с индукторами CYP3A4, например, противосудорожные средства (фенитоин, карбамазепин) и рифампицин, поскольку возможно снижение антигипертензивного действи¤. Ќеобходим регул¤рный контроль артериального давлени¤ (ј?).
ѕри одновременном применении лерканидипина в дозе 20 мг у пациентов, посто¤нно принимающих бета-метилдигоксин, не было отмечено фармакокинетического взаимодействи¤, в то врем¤ как у здоровых добровольцев, которых лечили дигоксином, отмечалось увеличение значени¤ —mах дл¤ дигоксина в среднем на 33% после приема 20 мг лерканидипина натощак, при этом AUC (площадь под кривой 'концентраци¤- врем¤') и почечный клиренс измен¤лись незначительно. Ќеобходимо контролировать наличие признаков интоксикации дигоксином у пациентов, принимающих одновременно дигоксин и лерканидипин.
ќдновременное применение лерканидипина с циметидином (до 800 мг) не вызывает значительных изменений концентрации лерканидипина в плазме крови. ѕри высоких дозах циметидина могут увеличиватьс¤ биодоступность и антигипертензивное действие лерканидипина.
ѕри одновременном применении лерканидипина (20 мг) и симвастатина (40 мг), значение AUC дл¤ симвастатина увеличивалось на 56%, а это же значение дл¤ его активного метаболита - бета-гидроксикислоты - на 28%. ѕри приеме препаратов в разное врем¤ суток (лерканидипин - утром, симвастатин - вечером) можно избежать нежелательного взаимодействи¤.
ѕри одновременном применении 20 мг лерканидипина и варфарина у здоровых добровольцев изменений фармакокинетики варфарина не наблюдалось.
ќдновременное применение с флуоксетином (ингибитором CYP2D6 и CYP3A4) у пациентов пожилого возраста не оказало клинически значимых изменений фармакокинетики лерканидипина.
¬озможно усиление антигипертензивного действи¤ при одновременном приеме сока грейпфрута и лерканидипина.
Ётанол может потенцировать антигипертензивное действие лерканидипина.
”слови¤ хранени¤
The drug should be stored out of the reach of children at a temperature not exceeding 25 ? C.
Shelf life
Shelf life is 3 years. Do not use after the expiration date printed on the package.
Terms of sale
The drug is available with a prescription.