Lercanidipine-SZ pills 10mg, 30pcs

Composition

1 film-coated tablet contains:

dosage 10 mg

Active ingredient:

lercanidipine hydrochloride-10 mg;

excipients (core):

lactose monohydrate (milk sugar) – 31.5 mg;

microcrystalline cellulose-38.5 mg;

sodium starch glycolate-15.5 mg;

hypromellose (hydroxypropylmethylcellulose) – 3.5 mg;

magnesium stearate-1.0 mg;

excipients (shell):

 Opadray 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 yellow dye E 172 – 0.06825 mg; iron oxide red dye E 172-0.00096 mg; iron oxide black dye E 172-0.00081 mg).

Pharmacological action

Slow calcium channel blocker. Pharmacodynamics :

Slow calcium channel blocker. Lercanidipine is a racemic mixture of right- (R) and left-rotating ones (S) stereoisomers, a derivative of 1,4-dihydropyridine, can selectively block the flow of calcium ions into the cells of the vascular wall, heart cells and smooth muscle cells. The mechanism of antihypertensive action is due to the direct relaxing effect on vascular smooth muscle cells. It has a prolonged antihypertensive effect. The therapeutic effect is achieved 5-7 hours after ingestion and its duration is maintained for a day (24 hours). Due to its high selectivity to vascular smooth muscle cells, there is no negative inotropic effect.

Lercanidipine is a metabolically neutral drug and does not significantly affect the content of lipoproteins and apolipoproteins in the blood serum, and also does not change the lipid profile in patients with arterial hypertension.

Pharmacokinetics:

Suction

Lercanidipine is completely absorbed after oral use. The maximum concentration (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 lercanidipine demonstrate similar pharmacokinetic profile have the same time to maximum concentration, the same T1/2. Cmax in plasma and area under the curve “concentration-time” (AUC) (-) S-enantiomer lercanidipine, on average,1.2 times higher than the (+) R-enantiomer. No interconversion of enantiomers was observed in the invivo experiments.

With the” primary passage ” 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 index after a meal. When lercanidipine is taken orally no later than 2 hours after a high-fat meal, its bioavailability increases 4-fold, 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 the ratio of 1: 3: 8, respectively, and AUC – in the ratio of 1: 4: 18, which suggests progressive saturation during the “primary passage” 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 plasma proteins exceeds 98%. 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.

Metabolism

Lercanidipine is metabolized by the CYP3A4 isoenzyme to form inactive metabolites.

Deduction

The elimination 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 value is 8-10 hours. Accumulation of lercanidipine with repeated oral use is not observed.

Pharmacokinetics in special patient groups

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

In patients with renal insufficiency (creatinine clearance 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 insufficiency, the systemic bioavailability of lercanidipine is likely to increase, since lercanidipine is mainly metabolized in the liver.

Indications

Arterial hypertension of 1-2 degrees.

Use during pregnancy and lactation

Pregnancy In animal studies, lercanidipine did not have a teratogenic effect, but teratogenic effects were observed with the use of other dihydropyridine derivatives. Therefore, the use of Lercanidipine-SZ during pregnancy and in women of childbearing age who do not use reliable contraception is contraindicated. Breast-feeding Due to the high lipophilicity of lercanidipine, its penetration into breast milk can be assumed, so the use of Lercanidipine-SZ during breastfeeding is contraindicated.

Recommendations for use

Inside. The drug Lercanidipine-SZ is prescribed 10 mg 1 time a day in the morning, at least 15 minutes before meals, without chewing, with a sufficient amount of water.

The dose can be increased to 20 mg (if taking 10 mg does not achieve the expected effect). The therapeutic dose is selected gradually, increasing the dose to 20 mg is carried out 2 weeks after the start of taking 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, at the same time, the risk of side effects increases.

Use in elderly patients

No dose adjustment is required, however, when taking the drug, constant monitoring of the patient’s condition is necessary.

Use in patients with impaired renal or hepatic function

In the presence of mild or moderate renal or hepatic insufficiency, as a rule, no dose adjustment is required, the initial dose is 10 mg, and an increase in the dose to 20 mg per day should be carried out with caution. If the antihypertensive effect is too pronounced, the dose should be reduced.

Contraindications

– Hypersensitivity to lercanidipine, other derivatives digidropiridinovmi series 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 myocardial infarction;

– severe liver failure;

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

– pregnancy and lactation;

– the use in women of childbearing age not using reliable contraception;

– age up to 18 years (efficacy and safety not established);

– lactose intolerance, lactase deficiency, a syndrome of glucose-galactose malabsorption;

– simultaneous use of inhibitors of CYP3A4 isoenzyme (ketoconazole, Itraconazole, erythromycin, ritonavir, troleandomycin);

– concomitant use with cyclosporine;

– simultaneous use with grapefruit juice.

With caution:

– Renal insufficiency (creatinine clearance more than 30 ml/min);

– violations of the liver function of mild and moderate severity;

old age;

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

– dysfunction of the left ventricle and coronary heart disease;

– chronic heart failure;

– simultaneous use with substrates of CYP3A4 (terfenadine, asmetal, antiarrhythmic drugs class III, for example, amiodarone, quinidine);- simultaneous use with inducers of the CYP3A4 isoenzyme, for example, anticonvulsants (phenytoin, carbamazepine) and rifampicin;

– simultaneous use with beta-blockers, digoxin.

Side effects

The following is a list of adverse reactions distributed by organ system and frequency of occurrence (World Health Organization classification): :

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.

Nervous system disorders

Infrequently:  headache, dizziness;

Rarely:  drowsiness.

Disorders of the cardiovascular system

Infrequently:  palpitation, tachycardia, “hot flashes” of blood to the skin of the face;

Rarely:  angina pectoris;

Very rare:  fainting, a marked decrease in blood pressure, chest pain, myocardial infarction, in patients with angina, an increase in the frequency, duration and severity of attacks is possible.

Disorders of the gastrointestinal tract

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

Very rare: increased activity of “liver” enzymes (reversible).

Skin and subcutaneous tissue disorders

Rarely:  skin rash.

Musculoskeletal and connective tissue disorders

Rarely:  myalgia.

Kidney and urinary tract disorders

Rarely: pollakiuria (increased frequency of urination).

General violations

Infrequently: peripheral edema;

Rarely: asthenia, increased fatigue;

Very rarely: gum hyperplasia.

Immune system disorders:

Very rarely: hypersensitivity reactions.

Interaction

The drug can not be used simultaneously with inhibitors of CYP3A4 (liver cytochrome p450 isoenzyme), such as ketoconazole, itraconazole, erythromycin (increase the concentration of lercanidipine in the blood and lead to potentiation of the antihypertensive effect). Concomitant use of lercanidipine with cyclosporine is contraindicated, as this leads to an increase in the content of both substances in the blood plasma.

Lercanidipine should not be taken together with grapefruit juice, as this leads to inhibition of lercanidipine metabolism and potentiation of the antihypertensive effect.

Caution should be exercised when taking concomitant medications such as terfenadine, astemizole, quinidine and Class III antiarrhythmic drugs (for example, amiodarone). Concomitant use with anticonvulsants (e. g., phenytoin, carbamazepine) and rifampicin may lead to a decrease in the concentration of lercanidipine in blood plasma and, therefore, to a decrease in the antihypertensive effect of lercanidipine. No pharmacokinetic interaction was observed in patients taking digoxin continuously when lercanidipine was co-administered at a dose of 20 mg. However, in healthy volunteers who took digoxin, there was an increase in the Cmax of digoxin in blood plasma, on average, by 33% after ingestion of 20 mg of lercanidipine on an empty stomach, while AUC and renal clearance of digoxin changed slightly. It is necessary to monitor the presence of signs of digoxin intoxication in patients taking digoxin and lercanidipine simultaneously.

When lercanidipine 20 mg is co-administered with midazolam, the bioavailability of lercanidipine in elderly patients may increase by approximately 40%.

Metoprolol reduces the bioavailability of lercanidipine by 50%, while 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 occur when used with other drugs of this group.

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

When lercanidipine (20 mg) and simvastatin (40 mg) were co-administered, the AUC value for simvastatin increased by 56%, and for its active metabolite beta-hydroxy acid-by 28%. When taking medications at different times of the day (lercanidipine in the morning, simvastatin in the evening), undesirable interactions can be avoided.

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

Taking 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 may enhance the antihypertensive effect of lercanidipine.

Overdose

Symptoms

Presumably, in the 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

Symptomatic. In the case of a marked decrease in blood pressure, loss of consciousness, cardiovascular therapy is indicated, with bradycardia – intravenous use of atropine. There is no information on the effectiveness of hemodialysis. Given the high degree of binding to plasma proteins, dialysis may not be effective.

Three cases of overdose have been reported with lercanidipine 150 mg,280 mg and 800 mg. In all cases of overdose, patients remained alive.

In the case of simultaneous use of 150 mg of lercanidipine with ethanol (unknown amount), drowsiness was observed. Treatment: gastric lavage, ingestion of activated charcoal.

In the case of simultaneous use 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-dose catecholamines, plasma substitutes. In the case of taking 800 mg of lercanidipine, the following cases were observed:: nausea, marked decrease in blood pressure. Treatment: ingestion of activated charcoal and laxatives, intravenous dopamine.

Special instructions

Caution should be exercised when prescribing to patients with impaired renal function, coronary heart disease (there is a risk of increased angina attacks), in relation to chronic heart failure: it is necessary to compensate before starting 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 any abnormalities in left ventricular function, patients with signs of left ventricular dysfunction should be treated with calcium channel blockers with extreme caution. There is also an opinion that patients with coronary heart disease receiving short-acting dihydropyridines are a high-risk group for diseases of the cardiovascular system.

Special care should be taken in the initial stages of treatment of patients with mild to moderate hepatic insufficiency.

Influence on the ability to drive vehicles and mechanisms:

During treatment, care should be taken when performing work that requires increased attention, when driving vehicles, especially at the beginning of treatment and when increasing the dose of the drug (risk of drowsiness, headache and dizziness).

Form of production

Tablets, film-coated from beige-yellow to beige in color, round, biconvex. On the cross-section, the core of the tablet is light yellow (dosage of 10 mg).

Storage conditions

Keep out of the reach of children in a dark place, at a temperature not exceeding 25 °C.

Shelf

life is 3 years. Do not use after the expiration date indicated on the package.

Active ingredient

Lercanidipine

Conditions of release from pharmacies

By prescription

Dosage form

Tablets