Lerkamen 20 - instructions for use, dosage, adverse effects, contraindications

Excipients: lactose monohydrate 60.0 mg, microcrystalline cellulose 78.0 mg, sodium carboxymethyl starch (type A) 31.0 mg, povidone (K = 30) 9.0 mg, magnesium stearate 2.0 mg.

Shell

Opadry 02F25077 - 6.0 mg, consisting of: hypromellose - 3.825 mg, talcum - 0.300 mg, titanium dioxide -1.200 mg, macrogol 6000 - 0.600 mg, iron oxide (III) - 0.075 mg.

Description:

Round biconvex tablets, film-coated, reddish-pink color with a risk on one side.

View of the break: light yellow color.

Pharmacotherapeutic group:Selective calcium channel blockers with a predominant effect on blood vessels

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 dihydropyridine, inhibits the transmembrane current of calcium ions into the cells of the smooth muscles of the vessels. The mechanism of antihypertensive action due lercanidipine direct relaxant effect on vascular smooth-muscle cells, thereby reducing the total peripheral resistance.

Despite a relatively short half-life from plasma, lercanidipine has a prolonged antihypertensive effect due to the high membrane distribution coefficient. 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 during admission lercanidipine. Lercanidipine is a racemic mixture (+)-R- and (-)S- enantiomers. The antihypertensive effect of lercanidipine, primarily due to S-enantiomer.

Pharmacokinetics:

Lercanidipine is completely absorbed after ingestion. The maximum concentration in the blood plasma (C_m_Oh) 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- the enantiomers of lercanidipine show a similar pharmacokinetic profile: they have the same time to reach the maximum concentration (TC_m_Oh), the same half-life (T_1/2); the C_m_Oh and the area under the curve - "concentration-time" (AUC) is 1.2 times higher for the (-) - S enantiomer. 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 ingestion of fatty foods, its bioavailability is increased 4-fold, so the drug Lercamen® 20 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.The distribution of blood plasma into tissues and organs occurs quickly and extensively. The connection with blood plasma proteins exceeds 98 %. In patients with severe renal and / or liver failure, due to a decrease in protein concentration in the blood plasma, the free fraction of lercanidipine may increase.

Lercanidipine is metabolized with the participation of isoenzyme CYP3A4 with the formation of inactive metabolites. About 50% of the dose is excreted by the kidneys (about 50% % is displayed intestines). Elimination occurs mainly through biotransformation.

Average value T_1/2 is 8-10 hours. The duration of the therapeutic action is 24 hours. Cumulation of lercanidipine with repeated ingestion is not observed. It has been shown that the pharmacokinetics of lercanidipine, in elderly patients, patients with renal insufficiency (creatinine clearance more than 30 ml / min) and in patients with mild to moderate hepatic insufficiency is similar to the pharmacokinetics observed in the general population of patients. 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 moderate and severe hepatic insufficiency, the systemic bioavailability of lercanidipine is likely to increase, since lercanidipine it is metabolized mainly in the liver.

Indications:

Essential hypertension I - II severity.

Contraindications:

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

- untreated heart failure;

- unstable angina;

- obstruction of vessels emanating from the left ventricle of the heart;

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

- severe hepatic impairment;

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

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

- pregnancy and the period of breastfeeding;

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

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

- simultaneous use with drugs:

-inhibitors CYP3A4 (ketoconazole, itraconazole, erythromycin, ritonavir, troleandomycin); cyclosporine;

- simultaneous reception of the drug Lercamen® 20 with grapefruit juice.

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 of the heart.

Pregnancy and lactation:

The use of Lercamen® 20 during 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, 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 for use in pregnancy and in women of childbearing age who are not using reliable methods of contraception. Due to the high lipophilicity of lercanidipine, it can be assumed that it penetrates into breast milk,so the drug is not recommended for use during breastfeeding.

Dosing and Administration:

For 10 mg (1/2 tablets of the preparation Lercamen® 20) orally 1 time per day at least 15 minutes before meals, preferably in the morning, without chewing, squeezed with enough water.

Depending on the individual tolerance of the drug to the patient, the dose may be increased to 20 mg (1 tablet of Lercamen® 20).

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 a dose increase of more than 20 mg / day, while the risk of side effects increases.

Application in elderly patients

The pharmacokinetic profile and clinical trial data show that in elderly patients, dose adjustment of Lercamen® 20 is not required. However, care should be taken at the initial stage of treatment with Lercamen® 20 in this group of patients.

Use in patients with impaired kidney or liver function

Care should be taken when using Lercamen® 20 in patients with mild and moderate renal and hepatic insufficiency. 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 strengthen in patients with hepatic insufficiency of mild or moderate severity, and dosage correction (reduction) may be required.

With renal failure (KC less than 30 ml / min) and liver failure of severe severity, the use of Lercamen® 20 is contraindicated (see section "Contraindications").

Side effects:

Possible side effects are shown below in the descending frequency of occurrence:

often (<1/10, ≥ 1/100),

infrequently (<1/100, ≥1 / 1000),

rarely (<1/1000, ≥1/10000),

rarely (<1/10000), including individual message.

Disturbances from the nervous system

Infrequently: headache, dizziness;

Rarely: drowsiness.

Disorders from the cardiovascular system

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

Rarely: stenocardia, chest pain;

Rarely: fainting, in patients with angina pectoris may increase the frequency, duration and severity of attacks.

Disorders from the gastrointestinal tract

Rarely: nausea, dyspepsia, diarrhea, epigastric pain, vomiting.

Disturbances from the skin and subcutaneous tissue

Rarely: skin rash.

Disturbances from musculoskeletal and connective tissue

Rarely: myalgia.

Infringements from kidneys and urinary tract

Rarely: polyuria.

Common Disorders

Infrequently: peripheral edema;

Rarely: asthenia, increased fatigue.

Disorders from the immune system systems

Rarely: reaction sensitivity.

There are reports of the following secondary very rare (<1/10000) phenomena: myocardial infarction, gum hyperplasia, reversible an increase in the activity of "hepatic" transaminases, a pronounced decrease in blood pressure pollakiuria (increased frequency of urination), pain in the chest.

Overdose:

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

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, intake 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, renal failure of the lung degree.

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 β-adrenoblockers, 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 use with other β-blockers, so dose adjustment may be required lercanidipine to achieve a therapeutic effect with this combination. Lercanidipine is metabolized with the participation of the CYP3A4 isoenzyme, so the inhibitors and inducers of this isoenzyme, when used at the same time, can affect the metabolism and excretion of lercanidipine. It is not recommended simultaneous application of lercanidipine with inhibitors of CYP3A4 (ketoconazole, itraconazole, ritonavir, erythromycin, troleandomycin) (see section "Contraindications").

It is not recommended simultaneous use of cyclosporine and lercanidipine, as there is an increase in the concentration of both substances in the blood plasma (see section "Contraindications").

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 at 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 inductors CYP3A4, for example, anticonvulsants (phenytoin, carbamazepine) and rifampicinbecause it is possible to reduce the antihypertensive action of the drug. 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 as in healthy volunteers who were treated digoxin, an increase in the value of C_max (maximum concentration in blood plasma) for digoxin on average by 33% after taking 20 mg of lercanidipine on an empty stomach, while AUC (the area under the curve is "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 AUC value for simvastatin increased by 56%, and the same value for its active metabolite - β-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 intensify antihypertensive action with simultaneous while taking the juice of grapefruit and lercanidipine (see section "Contraindications").

Ethanol can potentiate the antihypertensive effect of lercanidipine.

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

Since the appearance of dizziness, asthenia, increased fatigue and, in rare cases, drowsiness, during the treatment with Lercamen® 20, during the period of application of the drug, patients should be very careful to drive and engage in other vehiclespotentially dangerous activities that require a high rate of psychomotor reactions.

Form release / dosage:

The tablets covered with a film cover of 20 mg.

Packaging:

By 7, 10 or 14 tablets per blister [opaque PVC film / aluminum foil].

1 (7 or 14 tablets), 2 (14 tablets), 3 (14 tablets), 4 (14 tablets), 5 (7 or 10 tablets), 6 (10 tablets), 7 14 tablets), 9 (10 tablets) or 10 (10 tablets) blisters together with the instructions for use are placed in a cardboard box.

Storage conditions:

At a temperature of no higher than 30 ° C. Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-006976/08

Date of registration:01.09.2008 / 06.12.2017

Expiration Date:Unlimited

The owner of the registration certificate:Berlin-Chemie / A. Menarini, LLCBerlin-Chemie / A. Menarini, LLC Russia

Manufacturer: & nbsp

BERLIN-CHEMIE, AG Germany

Representation: & nbspBERLIN-CHEMI / MENARINI PHARMA GmbH BERLIN-CHEMI / MENARINI PHARMA GmbH Germany

Information update date: & nbsp05.03.2018

Illustrated instructions

Instructions

Lercamen® 20 (Lerkamen® 20)