Lercanorm tablets p / o 10mg, No. 30

• arterial hypertension of 1-2 degrees.

The drug is taken orally, in the morning, at least 15 minutes before a meal. The tablets should be swallowed without chewing and drinking plenty of water.

The recommended dose is 10 mg 1 time / day. Depending on the therapeutic effect and individual patient tolerance of the drug, the dose may be increased to 20 mg. 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 an increase in the dose of more than 20 mg / day, at the same time, the risk of side effects increases.

When using the drug Lercanorm in elderly patients, dose adjustment is not required, however, when taking the drug, care should be taken, especially at the initial stage of treatment.

When using the drug Lercanorm in patients with renal insufficiency (CC more than 30 ml / min) or mild or moderate hepatic insufficiency, caution should be exercised. The initial dose is 10 mg / day. Increasing the dose to 20 mg / day should be done with caution. If the antihypertensive effect is too pronounced, the dose should be reduced. In renal failure (CC less than 30 ml / min) and severe hepatic failure, the use of the drug Lercanorm is contraindicated.

Lercanidipine hydrochloride

• untreated 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);

• pregnancy;

• lactation period (breastfeeding);

• use in women of childbearing age who do not use reliable contraception;

• age up to 18 years (efficacy and safety have not been established);

• lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome;

• simultaneous administration with inhibitors of the isoenzyme CYP3A4 (ketoconazole, itraconazole, erythromycin, ritonavir, troleandomycin);

• simultaneous reception with cyclosporine;

• simultaneous reception with grapefruit juice;

• hypersensitivity to lercanidipine, other dihydropyridine derivatives or any component of the drug.

With care: renal failure (CC more than 30 ml / min); mild to moderate hepatic impairment; SSSU (without a pacemaker); Ischemic heart disease; dysfunction of the left ventricle of the heart; chronic heart failure; simultaneous use with substrates of the isoenzyme CYP3A4 (terfenadine, asmethol, class III antiarrhythmic drugs, for example, amiodarone, quinidine); simultaneous use with inducers of the isoenzyme CYP3A4, for example, anticonvulsants (phenytoin, carbamazepine) and rifampicin; simultaneous use with digoxin; elderly age.

Clinical and pharmacological group: Calcium channel blocker. Antihypertensive drug

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, like other asymmetric derivatives of 1,4-dihydropyridine, is mainly determined by 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 systemic vascular resistance decreases. Despite the relatively short T1 / 2 from blood plasma, lercanidipine has a long-term antihypertensive effect due to the high coefficient of membrane distribution.

The therapeutic effect is achieved 5-7 hours after taking the drug inside, it lasts for a day (24 hours). Due to its high selectivity for vascular smooth muscle cells, lercanidipine does not have a negative inotropic effect.

A pronounced decrease in blood pressure with reflex tachycardia occurs rarely due to the gradual development of vasodilation when taking lercanidipine.

Pharmacokinetics

Suction

Lercanidipine is completely absorbed after oral administration. Cmax in blood plasma 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 mg and 20 mg of lercanidipine, respectively.

(+) R- and (-) S-enantiomers of lercanidipine show a similar pharmacokinetic profile: they have the same time to reach Cmax, the same T1 / 2. Cmax in blood plasma and AUC of the (-) S-enantiomer of lercanidipine are, on average, 1.2 times higher than the (+) R-enantiomer. No interconversion of enantiomers was observed in in vivo experiments.

At the 'first pass' through the liver, the absolute bioavailability of lercanidipine when taken orally after a meal is about 10%. When taken orally on an empty stomach, the bioavailability is 1/3 of the bioavailability after a meal. When lercanidipine is taken orally no later than 2 hours after a meal with a high fat content, its bioavailability increases by 4 times, so lercanidipine should not be taken after a meal.

The pharmacokinetics of lercanidipine in the therapeutic dose range is non-linear. When taking lercanidipine in doses of 10 mg, 20 mg and 40 mg, Cmax in blood plasma was determined in a ratio of 1: 3: 8, respectively, and AUC - in a ratio of 1: 4: 18, which suggests progressive saturation during the 'first pass' through the liver. Thus, bioavailability increases with increasing dose.

Distribution

The distribution of lercanidipine from blood plasma to tissues and organs is rapid. The degree of binding to blood plasma proteins exceeds 98%. Cumulation of lercanidipine with repeated oral administration is not observed.

Metabolism

Lercanidipine is metabolized with the participation of the CYP3A4 isoenzyme to form inactive metabolites.

Withdrawal

Excretion of lercanidipine occurs mainly by biotransformation. About 50% of the dose taken is excreted by the kidneys, about 50% through the intestines. The average T1 / 2 is 8-10 hours.

Pharmacokinetics in special patient groups

The pharmacokinetics of lercanidipine in elderly patients, patients with renal insufficiency (CC more than 30 ml / min) and patients with mild to moderate hepatic insufficiency is similar to the pharmacokinetics in healthy volunteers.

In patients with severe renal and hepatic impairment, the free fraction of lercanidipine may increase due to a decrease in the concentration of proteins in the blood plasma.

In patients with renal insufficiency (CC less than 30 ml / min) and in patients on hemodialysis, the concentration of lercanidipine in the blood plasma increases by about 70%.

In patients with moderate to severe hepatic impairment, the systemic bioavailability of lercanidipine is likely to increase as lercanidipine is metabolized primarily in the liver.

Indications

• arterial hypertension of 1-2 degrees.

Dosage regimen

The drug is taken orally, in the morning, at least 15 minutes before a meal. The tablets should be swallowed without chewing and drinking plenty of water.

The recommended dose is 10 mg 1 time / day. Depending on the therapeutic effect and individual patient tolerance of the drug, the dose may be increased to 20 mg. 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 an increase in the dose of more than 20 mg / day, at the same time, the risk of side effects increases.

When using the drug Lercanorm in elderly patients, dose adjustment is not required, however, when taking the drug, care should be taken, especially at the initial stage of treatment.

When using the drug Lercanorm in patients with renal insufficiency (CC more than 30 ml / min) or mild or moderate hepatic insufficiency, caution should be exercised. The initial dose is 10 mg / day. Increasing the dose to 20 mg / day should be done with caution. If the antihypertensive effect is too pronounced, the dose should be reduced. In renal failure (CC less than 30 ml / min) and severe hepatic failure, the use of the drug Lercanorm is contraindicated.

Side effect

Classification of the incidence of side effects according to the WHO recommendations: very often (? 1/10); often (from? 1/100 to <1/10); infrequently (from? 1/1000 to <1/100); rarely (from? 1/10 000 to <1/1000); very rare (<1/10 000, including isolated messages); the frequency is unknown (according to available data, it is not possible to establish the frequency of occurrence).

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, marked decrease in blood pressure, myocardial infarction, in patients with angina pectoris, an increase in the frequency, duration and severity of attacks is possible.

From the digestive system: rarely - nausea, dyspepsia, diarrhea, abdominal pain, vomiting; very rarely - gingival hyperplasia.

From the side of the skin: rarely - skin rash.

From the musculoskeletal system: rarely - myalgia.

From the urinary system: rarely - polyuria; very rarely - pollakiuria (increased frequency of urination).

Allergic reactions: very rarely - hypersensitivity reactions.

On the part of laboratory parameters: very rarely - a reversible increase in the activity of hepatic transaminases.

Others: infrequently - peripheral edema; rarely - asthenia, increased fatigue.

Contraindications for use

• untreated 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);

• pregnancy;

• lactation period (breastfeeding);

• use in women of childbearing age who do not use reliable contraception;

• age up to 18 years (efficacy and safety have not been established);

• lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome;

• simultaneous administration with inhibitors of the isoenzyme CYP3A4 (ketoconazole, itraconazole, erythromycin, ritonavir, troleandomycin);

• simultaneous reception with cyclosporine;

• simultaneous reception with grapefruit juice;

• hypersensitivity to lercanidipine, other dihydropyridine derivatives or any component of the drug.

With care: renal failure (CC more than 30 ml / min); mild to moderate hepatic impairment; SSSU (without a pacemaker); Ischemic heart disease; dysfunction of the left ventricle of the heart; chronic heart failure; simultaneous use with substrates of the isoenzyme CYP3A4 (terfenadine, asmethol, class III antiarrhythmic drugs, for example, amiodarone, quinidine); simultaneous use with inducers of the isoenzyme CYP3A4, for example, anticonvulsants (phenytoin, carbamazepine) and rifampicin; simultaneous use with digoxin; elderly age.

Application during pregnancy and lactation

In animal studies, lercanidipine did not have a teratogenic effect, however, teratogenic effects were observed with the use of other dihydropyridine derivatives. Therefore, the use of the drug Lercanorm during pregnancy and in women of childbearing age who do not use reliable contraception is contraindicated.

Due to the high lipophilicity of lercanidipine, it can be assumed that it is excreted in breast milk, therefore, the use of the drug Lercanorm during breastfeeding is contraindicated.

Application for violations of liver function

The use of the drug is contraindicated in severe hepatic insufficiency.

With caution, the drug should be prescribed for mild and moderate hepatic insufficiency.

Application for impaired renal function

The use of the drug is contraindicated in severe renal failure (CC less than 30 ml / min).

The drug should be prescribed with caution in case of 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 established).

Use in elderly patients

The drug should be prescribed with caution to elderly patients.

special instructions

Caution should be exercised when using the drug in patients with impaired renal function, coronary artery disease (there is a risk of increased frequency of angina attacks). In chronic heart failure, the drug is prescribed after reaching a state of compensation.

The drug should be used with extreme caution in patients with SSSS (without a pacemaker).

Despite the fact that controlled hemodynamic studies have not revealed any abnormalities in the function of the left ventricle, treatment with calcium channel blockers in patients with signs of left ventricular dysfunction should be carried out with extreme caution. There is also an opinion that patients with coronary artery disease receiving short-acting dihydropyridines are at high risk for diseases of the cardiovascular system.

Particular care should be taken in the initial stages of treatment of patients with mild to moderate hepatic insufficiency due to the possible increase in the antihypertensive effect.

Influence on the ability to drive vehicles and use mechanisms

During the period of treatment, care must be taken when driving vehicles and mechanisms and when performing work that requires concentration of attention and speed of psychomotor reactions, especially at the beginning of treatment and when the dose of the drug is increased (the risk of drowsiness, asthenia, headache and dizziness).

Overdose

Symptoms: Presumably, in case of an overdose of lercanidipine, symptoms similar to those of an overdose of other dihydropyridine derivatives (peripheral vasodilation with a pronounced decrease in blood pressure and reflex tachycardia), nausea will be observed.

Treatment

Conducting symptomatic therapy. In the case of a pronounced decrease in blood pressure, loss of consciousness, cardiovascular therapy is indicated, with bradycardia - intravenous administration of atropine. There is no information on the effectiveness of hemodialysis. Given the high binding to plasma proteins, dialysis may be ineffective.

There are data on three cases of overdose when taking lercanidipine at doses of 150 mg, 280 mg and 800 mg. In all cases of overdose, the patients survived.

In the case of the simultaneous administration of lercanidipine at a dose of 150 mg with ethanol (unknown amount), drowsiness was observed. Treatment: gastric lavage, ingestion of activated carbon.

In the case of simultaneous administration of lercanidipine at a dose of 280 mg with moxonidine at a dose of 5.6 mg, the following symptoms were observed: cardiogenic shock, severe myocardial ischemia, mild renal failure. Treatment: cardiac glycosides, diuretics (furosemide), catecholamines in high doses, plasma substitutes.

In the case of taking lercanidipine at a dose of 800 mg, the following were observed: nausea, a marked decrease in blood pressure. Treatment: ingestion of activated charcoal and laxatives, iv - dopamine.

Drug interactions

Lercanidipine can be used simultaneously with beta-blockers, diuretics, ACE inhibitors.

ѕри одновременном применении с метопрололом биодоступность лерканидипина уменьшаетс¤ на 50%. Ётот эффект может про¤вл¤тьс¤ и при одновременном применении с другими бета-адреноблокаторами, поэтому может потребоватьс¤ коррекци¤ дозы лерканидипина дл¤ достижени¤ терапевтического эффекта в данной комбинации.

Ћерканидипин метаболизируетс¤ при участии изофермента CYP3A4, поэтому ингибиторы и индукторы изофермента CYP3A4 при одновременном применении могут вли¤ть на метаболизм и выведение лерканидипина. ѕротивопоказано одновременное применение лерканидипина с ингибиторами изофермента CYP3A4 (кетоконазол, итраконазол, ритонавир, эритромицин, тролеандомицин).

ѕротивопоказано одновременное применение циклоспорина и лерканидипина, т.к. наблюдаетс¤ увеличение концентрации обоих веществ в плазме крови.

—ледует соблюдать осторожность при одновременном применении лерканидипина с другими субстратами изофермента CYP3A4 (терфенадин, асметол, антиаритмические препараты III класса, например, амиодарон, хинидин).

ѕри одновременном применении лерканидипина в дозе 20 мг с мидазоламом биодоступность лерканидипина у пациентов пожилого возраста может увеличиватьс¤ приблизительно на 40%.

Ћерканидипин следует примен¤ть с осторожностью одновременно с индукторами изофермента CYP3A4, например, противосудорожными средствами (фенитоин, карбамазепин) и рифампицином, поскольку возможно снижение антгипертензивного действи¤ лерканидипина. Ќеобходим регул¤рный контроль ј?.

” пациентов, посто¤нно принимающих дигоксин, при одновременном применении лерканидипина в дозе 20 мг не было отмечено фармакокинетического взаимодействи¤. ќднако у здоровых добровольцев, которые принимали дигоксин, отмечалось увеличение значени¤ —mах дигоксина в плазме крови, в среднем, на 33% после приема внутрь натощак лерканидипина в дозе 20 мг, при этом AUC и почечный клиренс дигоксина 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 применении циметидина в высоких дозах может увеличиватьс¤ биодоступность лерканидипина и его антигипертензивное действие.

ѕри одновременном применении лерканидипина (20 мг) и симвастатина (40 мг) значение AUC дл¤ симвастатина увеличивалось на 56%, а 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 лерканидипина в дозе 20 мг и варфарина у здоровых добровольцев изменений фармакокинетики варфарина не наблюдалось.

ѕри одновременном применении с флуоксетином (ингибитором изоферментов CYP2D6 и CYP3A4) у пациентов пожилого возраста клинически значимых изменений фармакокинетики лерканидипина не вы¤влено.

¬озможно усиление антигипертензивного действи¤ при одновременном приеме грейпфрутового сока и лерканидипина.

Ётанол может потенцировать антигипертензивное действие лерканидипина.

”слови¤ хранени¤

The drug should be stored out of the reach of children, protected from light at a temperature not exceeding 25 ? C.

Shelf life

Shelf life is 3 years. Do not use after the expiration date.

Terms of sale

The drug is available with a prescription.