Lercanidipine-SZ - instructions for use, doses, side effects, contraindications

auxiliary substances (core): lactose monohydrate (sugar milk) - 31.5 mg; cellulose microcrystalline - 38.5 mg; sodium starch glycolate - 15.5 mg; hypromellose (hydroxypropylmethylcellulose) 3.5 mg; magnesium stearate 1.0 mg;

auxiliary substances (shell): Opadrai II (polyvinyl alcohol, partially hydrolyzed - 1.2 mg, titanium dioxide E 171 - 0.67998 mg, talc - 0.444 mg, macrogol (polyethylene glycol) 3350 - 0.606 mg, iron oxide oxide yellow E 172 - 0.06825 mg; iron dye oxide red E 172 - 0.00096 mg, iron oxide oxide black E 172 - 0.00081 mg).

dosage of 20 mg

active substance: lercanidipine hydrochloride - 20 mg;

auxiliary substances (core): lactose monohydrate (sugar milk) - 63.0 mg; cellulose microcrystalline - 77.0 mg; sodium starch glycolate - 31.0 mg; hypromellose (hydroxypropylmethylcellulose) - 7.0 mg; magnesium stearate - 2.0 mg;

auxiliary substances (shell): Opadrai II (polyvinyl alcohol, partially hydrolyzed - 2,4 mg, titanium dioxide E 171 - 1,3416 mg, talc - 0,888 mg macrogol (polyethylene glycol) 3350 - 1.212 mg; ferric oxide yellow E 172 - 0.0885 mg; iron dye oxide red E 172 - 0.0726 mg).

Description:

The tablets covered with a film cover from beige-yellow to beige color, round, biconcave. On the cross-section the nucleus of the tablet is light yellow (dosage 10 mg).

Tablets covered with a film membrane pinkish-orange color, round, biconcave. On the cross section, the core of the tablet is a light yellow color (dosage of 20 mg).

Pharmacotherapeutic group:The blocker of "slow" calcium channels

ATX: & nbsp

C.08.C.A Dihydropyridine derivatives

C.08.C.A.13 Lercanidipine

Pharmacodynamics:

The blocker of "slow" calcium channels. Lercanidipine is a racemic mixture of the right- (R) and levorotatory (S) stereoisomers, 1,4-dihydropyridine derivative, is able to selectively block the current of calcium ions inside the cells of the vascular wall, cardiac cells and smooth muscle cells.The mechanism of hypotensive action is caused by a direct relaxing action on the smooth muscle cells of the vessels. Has a prolonged antihypertensive effect. The therapeutic effect is achieved 5-7 hours after ingestion and the duration is maintained for 24 hours. Due to the high selectivity to the smooth muscle cells of the vessels, a negative inotropic effect is absent.

Lercanidipine is a metabolically neutral drug and does not significantly affect the content of lipoproteins and apolipoproteins in blood serum, nor does it alter the lipid profile in patients with hypertension.

Pharmacokinetics:

Suction

Lercanidipine is completely absorbed after ingestion. The maximum concentration (C_m_Oh) 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 mg and 20 mg of lercanidipine, respectively.

(+) R- and (-) SThe enantiomers of lercanidipine show a similar pharmacokinetic profile: they have the same time to reach maximum concentration, the same T₁_/2. C_max in the blood plasma and the area under the curve "concentration-time" (AUC) (-) S-enantiomer lercanidipine, on average, 1.2 times higher than (+) Renantiomer. Interconversion of enantiomers in experiments in vivo not observed.

In the "primary passage" through the liver, the absolute bioavailability of lercanidipine for oral administration after ingestion is about 10%. When administered on an empty stomach bioavailability is 1/3 of the bioavailability after eating. When lercanidipine is taken orally within 2 hours after a high-fat diet, its bioavailability increases 4-fold, so lercanidipine should not be taken after meals. The pharmacokinetics of lercanidipine in the range of therapeutic doses is non-linear. When taking lercanidipine in doses of 10 mg, 20 mg and 40 mg of C_m_Oh in blood plasma was determined in a ratio of 1: 3: 8, respectively, and AUC - in a ratio of 1: 4: 18, which suggests a progressive saturation in the "primary passage" through the liver. Thus, bioavailability increases with increasing dose.

Distribution

The distribution of lercanidipine from plasma to tissues and organs is rapid. The degree of binding to plasma proteins exceeds 98%.In patients with impaired renal and hepatic function due to a decrease in plasma protein concentration, the free fraction of lercanidipine may increase.

Metabolism

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

Excretion

Excretion of lercanidipine occurs predominantly by biotransformation. About 50 % of the accepted dose is excreted by the kidneys, about 50 % - through the intestines. Average value T₁_/2 is 8-10 hours. Cumulation of lercanidipine with repeated ingestion is not observed.

Pharmacokinetics in specific patient groups

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

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

In patients with moderate and severe hepatic insufficiency, the systemic bioavailability of lercanidipine is likely to increase, since lercanidipine it is metabolized mainly in the liver.

Indications:

Hypertension of 1-2 degrees.

Contraindications:

- Hypersensitivity to lercanidipine, other dihydropyridine derivatives or any component of the drug;

- untreated heart failure;

- unstable angina;

- obstruction of the outflow tract of the left ventricle;

- the period within 1 month after the transferred myocardial infarction;

- severe hepatic impairment;

- severe renal failure (CC less than 30 ml / min);

- pregnancy and the period of breastfeeding;

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

- age under 18 years (effectiveness and safety not established);

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

- simultaneous administration with inhibitors of isoenzyme CYP3A4 (ketoconazole, itraconazole, erythromycin, ritonavir, troleandomycin) (see section "Interaction with other drugs");

- simultaneous administration with cyclosporine (see section "Interaction with other drugs");

- simultaneous reception with grapefruit juice (see section "Interaction with other drugs").

Carefully:

- Renal failure (creatinine clearance more than 30 ml / min);

- violations of liver function of mild and moderate severity;

- elderly age;

- syndrome of weakness of the sinus node (without a pacemaker);

- left ventricular dysfunction of the heart and ischemic heart disease;

- chronic heart failure;

- simultaneous application with isoenzyme substrates CYP3A4 (terfenadine, asmetol, antiarrhythmic drugs of III class, for example, amiodarone, quinidine) (see the section "Interaction with other drugs");

- simultaneous application with isoenzyme inducers CYP3A4, for example, anticonvulsants (phenytoin, carbamazepine) and rifampicin (see section "Interaction with other drugs");

- simultaneous use with beta-blockers, digoxin (see section "Interaction with other drugs").

Pregnancy and lactation:

Pregnancy

In animal studies lercanidipine did not have a teratogenic effect, however, teratogenic effects were noted with the use of other dihydropyridine derivatives. Therefore, the use of the drug Lercanidipine-SZ in pregnancy and in women of childbearingage, not using reliable contraception, is contraindicated.

Breastfeeding period

Due to the high lipophilicity of lercanidipine, it can be assumed that it penetrates into breast milk, therefore the use of Lercanidipine-C3 during breastfeeding is contraindicated.

Dosing and Administration:

Inside. The drug Lercanidipine-SZ is prescribed 10 mg once a day in the morning, at least 15 minutes before meals, without chewing, squeezed with enough water.

The dose may be increased to 20 mg (in the event that the expected effect is not achieved with 10 mg administration). The therapeutic dose is selected gradually, increasing the dose to 20 mg is carried out 2 weeks after the start of the drug.

It is unlikely that the effectiveness of the drug will increase with an increase in dose of more than 20 mg per day, while at the same time the risk of side effects increases.

Application in elderly patients

Correction of the dose is not required, however, when taking the drug requires constant monitoring of patients.

Use in patients with impaired renal or hepatic function

In the presence of renal or hepatic insufficiency of mild or moderate severity,as a rule, dose adjustment is not required, the initial dose is 10 mg, increasing the dose to 20 mg per day should be done with caution. If the antihypertensive effect is too severe, the dose should be lowered.

Side effects:

Below is a list of undesirable reactions distributed over systems of organs and frequency of occurrence (classification of the World organization of health):

often from more than 1/100 to less than 1/10,

infrequently - from more than 1/1000 to less than 1/100,

rarely from more than 1/10000 to less than 1/1000,

very rarely - less than 1/10000, including individual messages.

Disturbances from the nervous system

Infrequently: headache, dizziness;

Rarely: drowsiness.

Disorders from the cardiovascular system

Infrequently: heart palpitations, tachycardia, "tides" of blood to the skin of the face;

Rarely: angina pectoris;

Rarely: syncope, marked decrease in blood pressure, chest pain, myocardial infarction, patients with angina may increase the frequency, duration and severity of attacks.

Disorders from the gastrointestinal tract

Rarely: nausea, vomiting, diarrhea, abdominal pain, indigestion;

Rarely: increased activity of "liver" enzymes (reversible).

Disturbances from the skin and subcutaneous tissues

Rarely: skin rash.

Disturbances from musculoskeletal and connective tissue

Rarely: myalgia.

Disorders from the kidneys and urinary tract

Rarely: pollakiuria (increased frequency of urination).

Common Disorders

Infrequently: peripheral edema;

Rarely: asthenia, increased fatigue;

Rarely: gingival hyperplasia.

Immune system disorders:

Rarely: hypersensitivity reactions.

Overdose:

Symptoms

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

Treatment

Symptomatic. In the case of a marked decrease in blood pressure, loss of consciousness shows cardiovascular therapy, with bradycardia - intravenous atropine. Information on the effectiveness of hemodialysis is absent. Given the high degree of association with plasma proteins, dialysis may be ineffective.

There are three cases of overdose with lercanidipine at doses of 150 mg, 280 mg and 800 mg. In all cases of overdose, patients remained alive.

In the case of concurrent administration of 150 mg of lercanidipine with ethanol (an unspecified amount), drowsiness was observed. Treatment: gastric lavage, ingestion of activated charcoal.

In the case of simultaneous administration of 280 mg of lercanidipine with 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: ingestion of activated carbon and laxatives, intravenously - dopamine.

Interaction:

The drug should not be used concomitantly with inhibitors CYP3A4 (isoenzyme of cytochrome P450 of the liver), such as ketoconazole, itraconazole, erythromycin (increase the concentration of lercanidipine in the blood and lead to a potentiation of the antihypertensive effect). Contraindicated simultaneous reception of lercanidipine with cyclosporin since 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.

Care should be taken when taking drugs with terfenadine, astemizole, quinidine and antiarrhythmic drugs of III class (for example, amiodarone).

Simultaneous reception with anticonvulsants (for example, phenytoin, carbamazepine) and rifampicin can lead to a decrease in the concentration of lercanidipine in the blood plasma and, in this connection, to reduce the antihypertensive effect of lercanidipine.

In patients who are constantly taking digoxin, with the simultaneous use of lercanidipine at a dose of 20 mg, there was no pharmacokinetic interaction. However, in healthy volunteers who took digoxin, there was an increase in the value of C_maxdigoxin in the blood plasma, on average, by 33% after ingestion of 20 mg of lercanidipine, while AUC and renal clearance of digoxin changed insignificantly.It is necessary to monitor the presence of signs of intoxication with digoxin in patients taking both digoxin and lercanidipine.

With the simultaneous use of lercanidipine at a dose of 20 mg s midazolam The bioavailability of lercanidipine in elderly patients may increase by approximately 40%.

Metoprolol reduces the bioavailability of lercanidipine by 50%, the bioavailability of metoprolol remains unchanged. This effect can occur due to a decrease in hepatic blood flow, which is caused by beta-blockers, so it can also appear when used with other drugs in this group.

Cimetidine in a dose of 800 mg per day does not lead to significant changes in the concentration of lercanidipine in the blood plasma, however, special care is required, since with higher doses of cimetidine, the bioavailability of lercanidipine, and hence its antihypertensive effect, may increase.

With the simultaneous use of lercanidipine (20 mg) and simvastatin (40 mg) value AUC for simvastatin increased by 56%, and for it the active metabolite of beta-hydroxy acid - by 28%. When taking drugs at different times of the day (lercanidipine - In the morning, simvastatin - in the evening) you can avoid unwanted interaction.

When used simultaneously with fluoxetine (inhibitor of isoenzymes CYP2D6 and CYP3A4) in elderly patients no clinically significant changes in the pharmacokinetics of lercanidipine were detected.

Acceptance of lercanidipine concomitantly with warfarin does not affect the pharmacokinetics of the latter.

Lercanidipine can be used simultaneously with beta-blockers, diuretics, angiotensin-converting enzyme (ACE) inhibitors. Ethanol can enhance the antihypertensive effect of lercanidipine.

Special instructions:

Caution should be exercised in appointing patients with impaired renal function, ischemic heart disease (there is a risk of increased episodes of angina pectoris), with respect to chronic heart failure: it must be compensated before starting the use of the drug.

With extreme caution, the drug should be used in patients with sinus node weakness syndrome (without a pacemaker).

Despite the fact that controlled studies of hemodynamics did not reveal violations of left ventricular function,treatment of calcium channel blockers in patients with signs of left ventricular dysfunction should be carried out with extreme caution. There is also the view that patients with ischemic heart disease who receive short-acting dihydropyridines represent a high risk group for cardiovascular disease.

Particular care should be taken in the initial stages of treatment of patients with mild to moderate degree of liver function deficiency.

Effect on the ability to drive transp. cf. and fur:

During the period of treatment, care should be taken when carrying out work requiring increased attention when driving vehicles, especially at the beginning of treatment and with an increase in the dose of the drug (risk of drowsiness, headache and dizziness).

Form release / dosage:

Tablets, film-coated, 10 mg and 20 mg.

Packaging:

For 10 or 30 tablets in a contour cell package.

For 30 tablets in a can of polymer or a bottle of polymer.

Each jar or vial, 3, 6 contour cell packs of 10 tablets or 1, 2 contourcell packs of 30 tablets,together with the instructions for use are placed in a cardboard box.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-004444

Date of registration:01.09.2017

Expiration Date:01.09.2022

The owner of the registration certificate:NORTH STAR, CJSC NORTH STAR, CJSC Russia

Manufacturer: & nbsp

NORTH STAR, CJSC Russia

Information update date: & nbsp28.09.2017

Illustrated instructions

Instructions

Lercanidipine-SZ (Lercanidipine-SZ)