Lernikor - instructions for use, dose, side effects, contraindications

Excipients: cellulose microcrystalline 39 mg / 78 mg, lactose monohydrate 30 mg / 60 mg, carboxymethyl starch sodium (sodium starch glycolate) 15.5 mg / 31 mg, povidone K30 4.5 mg / 9 mg, magnesium stearate 1 mg / 2 mg;

excipients for the shell:

for a dosage of 10 mg: Opadrai II 85F38107 yellow [polyvinyl alcohol 1.2 mg, titanium dioxide 0.6664 mg, macrogol (polyethylene glycol) 0.606 mg, talc 0.444 mg, aluminum lacquer based on quinoline yellow dye 0.0807 mg, iron oxide red 0.0009 mg];

for dosage of 20 mg: Opadrai II 85F34555 pink [alcohol polyvinyl 2,4 mg, titanium dioxide 1,4046 mg, macrogol (polyethylene glycol) 1,212 mg, talc 0,888 mg, aluminum lacquer based on the dye charming red 0,0348 mg, aluminum lacquer based on the dye sunset yellow 0, 0336 mg, aluminum varnish based on azorubin dye 0,027 mg].

Description:

Dosage of 10 mg: round, biconvex tablets, covered with a film coating of yellow color.

Dosage of 20 mg: round, biconcave tablets, covered with a film shell of pink color.

On the cross section, the core is light yellow in color.

Pharmacotherapeutic group:The blocker of "slow" calcium channels

ATX: & nbsp

C.08.C.A Dihydropyridine derivatives

C.08.C.A.13 Lercanidipine

Pharmacodynamics:

Lercanidipine is a selective blocker of "slow" calcium channels, a derivative of 1,4-dihydropyridine, inhibits the transmembrane current of calcium ions into the cells of the smooth muscles of the vessels.

Lercanidipine is a racemic mixture of (+) -R- and (-)S- enantiomers. The antihypertensive effect of lercanidipine is primarily due to S-enantiomer. The mechanism of antihypertensive action of lercanidipine is due to a direct relaxing action on the smooth muscle cells of the vessels, resulting in a decrease in the total peripheral resistance. Despite a relatively short half-life from plasma, lercanidipine has a prolonged antihypertensive effect due to the high membrane factordistribution. Due to high vascular selectivity does not have a negative inotropic effect. Acute arterial hypotension with reflex tachycardia occurs rarely due to the gradual development of vasodilation with lercanidipine.

Lercanidipine is metabolically neutral and has no significant effect on the lipoprotein and apolipoprotein content in the blood serum, nor does it alter the lipid profile in patients with hypertension.

Pharmacokinetics:

Suction

Lercanidipine is completely absorbed after ingestion. The maximum concentration in the blood plasma (C_mOh) 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 show a similar pharmacokinetic profile: they have the same time to reach the maximum concentration (TC_max), the same half-life (T_1/2); the C_max and the area under the concentration-time curve (AUC) is 1.2 times higher for (-)Senantiomer. Interconversions of enantiomers in experiments in vivo were not observed.

At the "primary passage" through the liver, the absolute bioavailability of lercanidipine for oral administration after eating is approximately 10%, when taken on an empty stomach, the bioavailability is reduced by 1/3. When lercanidipine is taken no later than 2 hours after the intake of fatty foods, its bioavailability is increased 4-fold, therefore lercanidipine should not be taken after meals. When oral lercanidipine is used, its concentration in the blood plasma is not directly proportional to the dose taken (nonlinear kinetics). Saturation of presystemic metabolism occurs gradually. Thus, bioavailability increases with increasing doses.

Distribution

The distribution of blood plasma into tissues and organs occurs quickly and extensively. The connection with blood plasma proteins exceeds 98%.

Metabolism and excretion

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

About 50% of the accepted dose is excreted by the kidneys (about 50% is excreted by the intestine). Elimination occurs mainly through biotransformation. The mean value of T_1/2is 8-10 hours. The duration of therapeutic action is 24 hours.

Cumulation of lercanidipine with repeated ingestion is not observed.

Pharmacokinetics in special clinical cases

It was shown that the pharmacokinetics of lercanidipine in elderly patients, patients with renal insufficiency (creatinine clearance (CK) more than 30 ml / min) and in patients with liver failure and moderate severity It is similar to the pharmacokinetics observed in the general population of patients.

In patients with severe renal and / or hepatic impairment due to a decrease in protein concentration 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, lercanidipine concentrations in the blood plasma were higher (approximately 70%).

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

Indications:

Hypertension of 1-2 degrees.

Contraindications:

Hypersensitivity to lercanidipine,other derivatives of the dihydropyridine series or any component of the preparation.

Untreated chronic heart failure.

Unstable angina.

Obstruction of the outflow tract of the left ventricle.

Period for 1 month after myocardial infarction.

Severe hepatic insufficiency.

Severe renal failure (CC less than 30 ml / min).

Simultaneous application with powerful inhibitors CYP3A4 (ketoconazole, itraconazole, erythromycin, ritonavir, troleandomycin).

Simultaneous use with cyclosporine.

Simultaneous reception with grapefruit juice.

Lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome.

Pregnancy and the period of breastfeeding.

The use of women of childbearing age who do not use reliable methods of contraception.

Age under 18 years (effectiveness and safety not studied).

Carefully:Renal failure (QC more than 30 ml / min) and / or hepatic insufficiency of mild and moderate severity, elderly age, sinus node weakness syndrome (without a pacemaker), coronary heart disease, left ventricular dysfunction.

Pregnancy and lactation:

The use of lercanidipine in pregnancy and during breastfeeding, as well as in women of childbearing age in the absence of reliable contraception is contraindicated.

Pre-clinical studies showed no teratogenic effect of lercanidipine in rats and rabbits, and the reproductive function of rats was unchanged.

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

Due to the high lipophilicity of lercanidipine, it can be assumed that it penetrates into breast milk, so lercanidipine it is not recommended to apply during breastfeeding.

Dosing and Administration:

Dosing and Administration Inside, at least 15 minutes before meals, preferably in the morning, without chewing, squeezed enough water.

The recommended dose of the drug is 10 mg once a day. Depending on the individual tolerance of the drug to the patient, 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 the drug.

The therapeutic dose is selected gradually, since 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 per day, while the risk of side effects increases.

Application in elderly patients

The pharmacokinetic profile and clinical trial data show that in older patients no correction of the dose of lercanidipine is required. However, care should be taken at the initial stage of treatment in this group of patients.

Use in patients with impaired renal or hepatic function

In the presence of renal failure (QC more than 30 ml / min) or liver failure of mild or moderate severity, the initial dose is 10 mg, then with caution increase the dose to 20 mg per day.

Antihypertensive effect can be increased in patients with mild or moderate hepatic insufficiency and dose correction may be required.

Side effects:

Possible adverse reactions are shown below in the descending frequency of occurrence: often (<1/10, ≥1 / 100), infrequently (<1/100, ≥1 / 1000), rarely (<1/1000, ≥1 / 10000), very rarely (<1/10000), including individual messages.

From the nervous system: infrequently - headache, dizziness; rarely - drowsiness.

From the side of the cardiovascular system: infrequently - a feeling of palpitation, tachycardia, "hot flashes" of blood to the skin of the face; rarely - angina, chest pain; very rarely - fainting, myocardial infarction, marked decrease in blood pressure (BP), patients with angina may increase the frequency, duration and severity of attacks.

From the gastrointestinal tract: rarely - nausea, dyspepsia, diarrhea, epigastric pain, vomiting; very rarely - a reversible increase in the activity of "liver" transaminases, gingival hyperplasia.

On the part of the respiratory system, the organs of the thorax and the mediastinum: very rarely - pain in the chest.

From 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 site of administration: infrequently - peripheral edema; rarely - asthenia, increased fatigue.

Overdose:

Symptoms:

Presumably, in the case of an overdose of lercanidipine, symptoms similar to those seen with an overdose of other dihydropyridine derivatives will be observed: peripheral vasodilation with marked lowering of blood pressure and reflex tachycardia.

Treatment:

Treatment is symptomatic. In the case of a marked decrease in blood pressure, loss of consciousness shows cardiovascular therapy, with bradycardia - intravenous atropine.

There are data on 3 cases of overdose when taking lercanidipine at doses of 150 mg, 280 mg and 800 mg for the purpose of suicide.

In the case of taking 150 mg of lercanidipine + alcohol (an unspecified amount), drowsiness was observed. Treatment: gastric lavage, reception of activated carbon.

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: reception of activated carbon and laxative, intravenously - dopamine.

In all cases of overdose, all patients remained alive. Information on the effectiveness of dialysis for lercanidipine is absent. It is most likely that due to the high lercanidipine binding to plasma proteins, dialysis may be ineffective.

Interaction:

Lercanidipine can simultaneously be used with beta-blockers, diuretics, angiotensin-converting enzyme (ACE inhibitors) inhibitors.

When used simultaneously with metoprolol, the bioavailability of lercanidipine is reduced by 50%. This effect can occur and with simultaneous application with other beta-blockers, so a correction of the dose of lercanidipine may be required to achieve a therapeutic effect in this combination.

Lercanidipine metabolized with the participation of isoenzyme CYP3A4, therefore, the inhibitors and inducers of this isoenzyme, with simultaneous application, can influence the metabolism and excretion of lercanidipine.The simultaneous use of lercanidipine with potent inhibitors is not recommended CYP3A4 (ketoconazole, itraconazole, ritonavir, erythromycin, troleandomycin).

It is not recommended simultaneous use of cyclosporine and lercanidipine, since an increase in the concentration of both substances in the blood plasma is observed.

Care should be taken when lercanidipine is used together with other substrates CYP3A4 (terfenadine. astemizole, antiarrhythmic drugs of the III class, for example, amiodarone, quinidine).

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

Lercanidipine should be administered with caution at the same time as inducers CYP3A4, for example, anticonvulsants (phenytoin, carbamazepine) and rifampicin, since it is possible to reduce the antihypertensive effect. Regular monitoring of blood pressure is necessary.

With the simultaneous use of lercanidipine in a dose of 20 mg in patients who constantly take beta-methyl-digoxin, no pharmacokinetic interaction was observed, while in healthy volunteers who were treated with digoxin. an increase in the value of C_max for digoxin on average by 33% after taking 20 mg of lercanidipine on an empty stomach, while the AUC (area under the curve - "concentration-time") and renal clearance changed insignificantly. It is necessary to monitor the presence of signs of intoxication with digoxin in patients taking both digoxin and lercanidipine.

Simultaneous use of lercanidipine with cimetidine (up to 800 mg) does not cause significant changes in the concentration of lercanidipine in blood plasma. At high doses of cimetidine, the bioavailability and antihypertensive effects of lercanidipine may increase.

With the simultaneous use of lercanidipine (20 mg) and simvastatin (40 mg), the value AUC for simvastatin increased by 56%, and the same value for its active metabolite - 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.

With the simultaneous use of 20 mg lercanidipine and warfarin in healthy volunteers, there was no change in the pharmacokinetics of warfarin.

Simultaneous use with fluoxetine (inhibitor CYP2D6 and CYP3A4) in elderly patients did not have clinically significant changes in the pharmacokinetics of lercanidipine.

It is possible to increase the antihypertensive effect while taking the juice of grapefruit and lercanidipine.

Ethanol can potentiate the antihypertensive effect of lercanidipine.

Special instructions:

Particular care should be taken when administering lercanidipine to patients with sinus node weakness syndrome (without a pacemaker). Despite the fact that studies with hemodynamic control have not revealed a deterioration in ventricular function when taking lercanidipine, caution should be exercised in prescribing lercanidipine in patients with left ventricular dysfunction. It has been suggested that the intake of certain dihydropyridines may be associated with a risk of increased episodes of angina in patients with coronary heart disease. Therefore, in such patients therapy with lercanidipine should be carried out with extreme caution.

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

Since the drug may cause dizziness, asthenia, increased fatigue and, in rare cases, drowsiness,During the period of application of the drug, patients should be very careful to drive vehicles and engage in other potentially hazardous activities requiring high rates of psychomotor reactions.

Form release / dosage:

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

Packaging:

By 7, 10, 14, 28 tablets in a contoured cell pack of a polyvinylchloride film and aluminum foil printed lacquered.

By 1, 2, 3, 4 contour mesh packs together with instructions for use are placed in a pack of cardboard.

Storage conditions:

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-003807

Date of registration:23.08.2016

Expiration Date:23.08.2021

The owner of the registration certificate:OBOLENSKOE PHARMACEUTICAL ENTERPRISE, CJSC OBOLENSKOE PHARMACEUTICAL ENTERPRISE, CJSC Russia

Manufacturer: & nbsp

OBOLENSKOE PHARMACEUTICAL ENTERPRISE, CJSC Russia

Representation: & nbspOBOLENSKOE PHARMACEUTICAL ENTERPRISE, CJSCOBOLENSKOE PHARMACEUTICAL ENTERPRISE, CJSCRussia

Information update date: & nbsp05.03.2018

Illustrated instructions

Instructions

Lernikor® (Lernicor®)