Lercanorm - instructions for use, doses, side effects, contraindications

auxiliary substances: microcrystalline cellulose - 37.0 mg; lactose monohydrate 35.0 mg; carboxymethyl starch sodium (sodium starch glycolate, type A) - 10.0 mg; povidone K-30 - 4.5 mg; poloxamer 2.5 mg; magnesium stearate 1.0 mg; film sheath: [hypromellose - 1.5000 mg; giprolose (hydroxypropyl cellulose) - 0.5820 mg; talcum 0.5778 mg; titanium dioxide - 0.3161 mg; iron oxide yellow (iron oxide) 0.0141 mg] or [dry film coating mixture containing hypromellose (50%), giprolose (hydroxypropyl cellulose) (19.4%), talc (19.26%), titanium dioxide ( 10.87%) and iron oxide yellow (iron oxide) (0.47%)] - 3.0 mg.

Dosage of 20 mg

active substance: lercanidipine hydrochloride 20.0 mg;

Excipients: cellulose microcrystalline - 74.0 mg; lactose monohydrate - 70.0 mg; carboxymethyl starch sodium (sodium starch glycolate, type A) - 20,0 mg; povidone K-30 - 9.0 mg; poloxamer 5.0 mg; magnesium stearate - 2.0 mg; film sheath: [hypromellose - 3.0000 mg; giprolose (hydroxypropyl cellulose) - 1.1640 mg; talc - 1,1556 mg; titanium dioxide - 0,6522 mg; iron oxide yellow (iron oxide) - 0,0282 mg] or [dry film-coating mixture containing hypromellose (50%), giprolose (hydroxypropyl cellulose) (19.4%), talc (19.26%), titanium dioxide 10.87%) and iron oxide yellow (iron oxide) (0.47%)] - 6.0 mg.

Description:

Round biconvex tablets, covered with a film coating of yellow 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 derived from 1,4-dihydropyridine, inhibits the transmembrane flow of calcium ions into smooth muscle cells of the vessels. The mechanism of antihypertensive action of lercanidipine is due to a direct relaxing action on the smooth muscle cells of the vessels,as a result of which the total peripheral resistance of the vessels decreases. Despite a relatively short half-life (T_1/2) from the blood plasma, lercanidipine has a long-term antihypertensive effect due to the high membrane distribution coefficient. The therapeutic effect is achieved in 5-7 hours after taking the drug inside, and the duration of it persists throughout the day (24 hours). Due to the high selectivity to the smooth muscle cells of the vessels, lercanidipine does not have a negative inotropic effect.

A marked decrease in blood pressure (BP) with reflex tachycardia occurs rarely due to the gradual development of vasodilation with lercanidipine.

Lercanidipine is a racemic mixture (+) R- and (-) S-enantiomers. The antihypertensive effect of lercanidipine, as well as other asymmetric 1,4-dihydropyridine derivatives, is mainly determined S-enantiomer.

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 (-) S-enantiomers of lercanidipine show a similar pharmacokinetic profile: they have the same time to reach the maximum concentration, same T_1/2. C_max in the blood plasma and the area under the concentration-time curve (AUC) of the (-) S-enantiomer of lercanidipine is, on average, 1.2 times higher than the (+) R-enantiomer. Interconversions of enantiomers in experiments in vivo were 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 intestine. Average value T_1/2is 8-10 hours. Cumulation of lercanidipine with repeated ingestion is not observed.

Pharmacokinetics in special patient pears

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 insufficiency (QC more than 30 ml / min);

- hepatic insufficiency of mild and moderate degree;

- elderly age;

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

- cardiac ischemia;

- dysfunction of the left ventricle of the heart;

- 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 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 observed when other dihydropyridine derivatives were used. Therefore, the use of Lercanorm during pregnancy and in women of childbearing age who do not enjoy reliable contraception, it 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 Lercanorm during breastfeeding is contraindicated.

Dosing and Administration:

Inside.

The drug Lercanorm is taken 10 mg once a day in the morning, at least 15 minutes before meals, without chewing, squeezed with enough water.

Depending on the therapeutic effect and individual tolerance of the drug to the patient, the dose may be increased to 20 mg. 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 dose of more than 20 mg per day, while at the same time the risk of side effects increases.

Use in elderly patients

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

Use in patients with impaired renal or hepatic function

Care should be taken when using Lercanorm in patients with renal insufficiency (KC more than 30 ml / min) or with mild to moderate hepatic insufficiency. The initial dose is 10 mg per day. Increase the dose to 20 mg per day should be done with caution. If the antihypertensive effect is too severe, the dose should be lowered.

With renal failure (QC less than 30 ml / min) and liver failure of severe degree, the use of Lercanorm is contraindicated (see section "Contraindications").

Side effects:

Classification of the incidence of adverse events according to recommendations World Health Organization (WHO):

very often ≥ 1/10;

often from ≥ 1/100 to <1/10;

infrequently from ≥ 1/1000 to <1/100;

rarely from ≥ 1/10000 to <1/1000;

very rarely <1/10000, including individual messages;

the frequency is unknown - it is not possible to establish the frequency of occurrence from the available data.

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

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

From the digestive system: rarely - nausea, indigestion, diarrhea, abdominal pain, vomiting.

From the skin: rarely - skin rash.

From the side of the musculoskeletal system: rarely - myalgia.

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

Allergic reactions: very rarely - hypersensitivity reactions.

Laboratory indicators: very rarely - a reversible increase in the activity of "liver" transaminases.

Other: infrequent peripheral edema; rarely - asthenia, increased fatigue; very rarely - gingival hyperplasia.

Overdose:

Symptoms

Presumably, in the case of an overdose of lercanidipine, symptoms will be observed,similar to those with an overdose of other dihydropyridine derivatives (peripheral vasodilation with pronounced lowering of 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:

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

With simultaneous application with metoprolol, the bioavailability of lercanidipine is reduced by 50%. This effect can also occur with simultaneous use 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 inhibitors and inducers of isoenzyme CYP3A4 with simultaneous application can affect the metabolism and excretion of lercanidipine. Contraindicated simultaneous use of lercanidipine with inhibitors of isoenzyme CYP3A4 (ketoconazole, itraconazole, ritonavir, erythromycin, troleandomycin) (see the section "Contraindications"). Contraindicated 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 isoenzyme substrates CYP3A4 (terfenadine, asmetol, antiarrhythmic drugs 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 used with caution at the same time as isozyme inducers CYP3A4, for example, anticonvulsants (phenytoin, carbamazepine) and rifampicin, since it is possible to reduce the antihypertensive effect of lercanidipine. Regular monitoring of blood pressure is necessary.

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 Cmax digoxin in 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. Simultaneous use of lercanidipine with cimetidine (up to 800 mg) does not cause significant changes in the concentration of lercanidipine in blood plasma. When high doses of cimetidine are used, the bioavailability of lercanidipine and its antihypertensive effect may increase.

With simultaneous application of lercanidipine (20 mg) and simvastatin (40 mg), the value AUC for simvastatin increased by 56%, and 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.

With simultaneous application with fluoxetine (inhibitor of isoenzymes CYP2D6 and CYP3A4) in elderly patients no clinically significant changes in the pharmacokinetics of lercanidipine were detected.

It is possible to enhance antihypertensive action while taking grapefruit juice and lercanidipine (see section "Contraindications").

Ethanol can potentiate the antihypertensive effect of lercanidipine.

Special instructions:

Care should be taken when using the drug in patients with impaired renal function, ischemic heart disease (there is a risk of increased episodes of angina pectoris). For chronic heart failure: it is necessary to compensate 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 hemodynamic studies have not revealed violations of left ventricular function, treatment with calcium channel blockers of 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 are a high-risk group 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 antihypertensive action.

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

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 with an increase in the dose of the drug (risk of drowsiness, asthenia, headache and dizziness).

Form release / dosage:

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

Packaging:

10, 15 or 30 tablets in a contoured cell pack of a polyvinylchloride film or a polyvinyl chloride opaque film and aluminum foil.

For 30, 60 or 90 tablets in a can of high-density polyethylene.

3, 6 or 9 contiguous cell packs of 10 tablets, 2, 4 or 6 contiguous cell packs of 15 tablets, 1, 2 or 3 contourcell packs of 30 tablets or one pot together with instructions for use in a pack of cardboard.

Storage conditions:

Store in a 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 expiry date.

Terms of leave from pharmacies:On prescription

Registration number:LP-003880

Date of registration:05.10.2016

Expiration Date:05.10.2021

The owner of the registration certificate:VERTEKS, AO VERTEKS, AO Russia

Manufacturer: & nbsp

VERTEKS, AO Russia

Information update date: & nbsp05.03.2018

Illustrated instructions

Instructions

Lercanorm (Lerkanorm)