Lercanidipine-cs tab p / 10 mg of the film 30 pc

Description

Composition
Active substance:
1 tablet contains: lercanidipine hydrochloride – 10 mg or 20 mg.
Excipients:
Lactose monohydrate (milk sugar); microcrystalline cellulose; sodium starch glycolate; Hypromellose (hydroxypropyl methylcellulose); magnesium stearate; adjuvants (shell):
Opadry II (polyvinyl alcohol, partially hydrolyzed; titanium dioxide E 171; talc; macrogol (polyethylene glycol) 3350; Yellow iron oxide coloring E 172; colorant red ferric oxide E 172, black iron oxide coloring E 172).
Description:
Tablets, film-coated from beige yellow to beige, round, biconvex. The cross-sectional core tablet pale yellow color (10 mg dosage).
Tablets, film-coated pinkish-orange, round, biconvex. The cross-sectional core tablet pale yellow color (20 mg dosage).
Product form:
Tablets, film-coated, 10 mg and 20 mg.
10 or 30 tablets in blisters. 30 tablets in a jar or vial polymeric resin. Each jar or vial, 3, 6 contour cell packs of 10 pills, or 1, 2 blisters of 30 tablets, together with instructions for use placed in a cardboard box.
Contraindications
– hypersensitivity to lercanidipine, other dihydropyridine derivatives or any component of the formulation; – untreated heart failure; – unstable angina; – obstruction of the outflow tract of the left ventricle; – the period within 1 month after myocardial infarction; – severe hepatic impairment; – severe renal impairment (creatinine clearance less than 30 mL / min); – Pregnancy and lactation; – the use in women of childbearing age who are not using reliable contraception; – the age of 18 years (effectiveness and safety have been established); – lactose intolerance, lactase deficiency, a syndrome of glucose-galactose malabsorption; – simultaneous with inhibitors isoenzyme CYP3A4 (ketoconazole, itraconazole, erythromycin, ritonavir, troleandomycin) (see “Interaction with other drugs.”); – simultaneous with cyclosporin (see “Interaction with other drugs.”); – simultaneous with grapefruit juice (see “Interaction with other drugs” section.).
Precautions – renal failure (creatinine clearance of 30 ml / min); – human liver mild and moderate severity; – elderly age; – sick sinus syndrome (without pacemaker); – dysfunction of the left ventricle of the heart and coronary heart disease; – Chronic heart failure; – simultaneous application with substrates isoenzyme CYP3A4 (terfenadine, asmetol, class III antiarrhythmic drugs, such as amiodarone, quinidine) (see “Interaction with other drugs.”); – simultaneous application isoenzyme inducers of CYP3A4, such as anticonvulsants (phenytoin, carbamazepine) and rifampicin (see “Interaction with other drugs.”); – simultaneous application of beta-blockers, digoxin (see “Interaction with other drugs.”).
Dosage
10 mg
Indications
Hypertension of 1-2 degrees.
Interaction with other drugs
The drug can not be used simultaneously with the CYP3A4 inhibitors (isozyme cytochrome P450 of the liver), such as ketoconazole, itraconazole, erythromycin (lercanidipine increase the concentration in the blood and lead to potentiation of the antihypertensive effect). Contraindicated in concomitant use of lercanidipine with cyclosporin as it 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 metabolism of lercanidipine and potentiation of the antihypertensive effect.
Care must be taken when concomitantly with drugs such as terfenadine, astemizole, quinidine and class III antiarrhythmics (e.g., amiodarone).
Simultaneous treatment with anticonvulsant (e.g., phenytoin, carbamazepine) and rifampicin can lead to a reduction in plasma concentration of lercanidipine and therefore, reduce the antihypertensive effect of lercanidipine.
In patients receiving digoxin continuously, while the use of lercanidipine 20mg no pharmacokinetic interaction was noted. However, in healthy volunteers who took digoxin Cmax values ​​was an increase of digoxin in plasma on average by 33% after oral administration of 20 mg lercanidipine fasting, the AUC and digoxin renal clearance changed slightly. It is necessary to control the presence of signs of digoxin toxicity in patients receiving both digoxin and lercanidipine.
With simultaneous use of lercanidipine 20 mg midazolam bioavailability of lercanidipine in elderly patients can be increased by approximately 40%.
Metoprolol reduces bioavailability of lercanidipine 50%, bioavailability of metoprolol thus remains unchanged. This effect may be due to reduction of hepatic blood flow, which is caused by beta-blockers, however can also be manifested when applied to other drugs of this group.
Cimetidine at 800 mg per day did not lead to significant changes lercanidipine plasma concentrations, however, requires special care, since at higher doses cimetidine bioavailability of lercanidipine and therefore its antihypertensive effect, can be increased.
With simultaneous use of lercanidipine (20 mg) and simvastatin (40 mg) AUC value for simvastatin increased by 56% and its active metabolite beta-hydroxy – 28%. When receiving the drugs at different times of the day (lercanidipine – morning, simvastatin – in the evening), you can avoid unwanted interaction. While the use of fluoxetine (an inhibitor of isozyme CYP2D6 and CYP3A4) elderly patients clinically significant changes in the pharmacokinetics of lercanidipine not revealed.
Lercanidipine concurrently with warfarin did not affect the pharmacokinetics of the latter.
Lercanidipine may be applied simultaneously with beta-blockers, diuretics, angiotensin-converting enzyme (ACE). Ethanol may enhance the antihypertensive effect of lercanidipine.
Overdose
symptoms
Presumably, in the case of an overdose of lercanidipine be observed symptoms similar to those of overdosing of other dihydropyridine derivatives (peripheral vasodilation with marked decrease in blood pressure and reflex tachycardia), and nausea.
Treatment
Symptomatic. In case of significant decrease in blood pressure, loss of consciousness is a cardiovascular therapy bradycardia – intravenous atropine. Information about the effectiveness of hemodialysis absent. Given the high degree of association with plasma proteins, dialysis can be inefficient. There is evidence of three cases of overdosage by lercanidipine in doses of 150 mg, 280 mg and 800 mg. In all cases of overdose, patients survived. In the case of simultaneously receiving 150 mg lercanidipine ethanol (unknown number) somnolence observed.
Treatment: gastric lavage, administration of activated charcoal.
In the case of simultaneously receiving 280 mg lercanidipine from 5.6 mg moxonidine were observed following symptoms: cardiogenic shock, severe myocardial ischemia, renal failure mild.
Treatment: cardiac glycosides, diuretics (furosemide), high doses of catecholamine plasma expanders.
In case of receiving 800 mg lercanidipine observed: nausea, marked reduction in blood pressure. Treatment: Ingestion of activated charcoal and laxatives, IV – dopamine.
pharmachologic effect
Pharmacodynamics:
Blocker “slow” calcium channels. Lercanidipine is a racemic mixture of dextro- (R) and levorotatory (S) stereoisomers of 1,4-dihydropyridine derivative, capable of selectively blocking current of calcium ions into cells of the vascular wall, cardiac cells and smooth muscle cells. Mechanism hypotensive action is due to a direct relaxant effect on vascular smooth muscle cells.
It has a prolonged antihypertensive effect. The therapeutic effect is achieved within 5-7 hours after ingestion, and its duration is stored for one day (24 hours). Due to their high selectivity for vascular smooth muscle cells is not the negative inotropic effect.
Lercanidipine is metabolically neutral drug and has no significant impact on the content of lipoproteins and apolipoproteins in the blood serum, and does not alter the lipid profile in hypertensive patients.
Pharmacokinetics:
Suction
Lercanidipine is completely absorbed after ingestion. The maximum concentration (Cmax) in plasma reached in 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 lercanidipine respectively. (+) R- and (-) S-enantiomers of lercanidipine demonstrate similar pharmacokinetic profile: have the same time to reach maximum concentration equal T1 / 2. Cmax in plasma and area under the curve “concentration-time» (AUC) (-) S-enantiomers of lercanidipine on average 1.2 times higher than the (+) R-enantiomer. Interconversion of the enantiomers in the experiments in vivo was not observed. By “primary pass” through the liver absolute bioavailability of lercanidipine when administered after a meal is about 10%. The ingestion fasting bioavailability of 1/3 of the index of bioavailability after eating. When lercanidipine inwardly within 2 hours after eating a high-fat bioavailability increased 4 times, lercanidipine therefore not to be taken after meals.
Pharmacokinetics of lercanidipine in the therapeutic dose range is nonlinear. When lercanidipine at doses of 10 mg, 20 mg and 40 mg Cmax in plasma was determined in a ratio of 1: 3: 8, respectively, and AUC – in a ratio of 1: 4: 18, suggesting a progressive saturation with “primary pass” through the liver. Thus, bioavailability increases with the dose.
Distribution
The distribution of lercanidipine from plasma into tissues and organs is rapid. The degree of binding to plasma proteins exceeds 98%. Patients with impaired renal function and liver, severe because of lower concentration of proteins in blood plasma of lercanidipine free fraction can be increased.
Metabolism
Lercanidipine metabolized involving CYP3A4 isozyme to inactive metabolites.
breeding
Lercanidipine excretion occurs mainly by biotransformation. About 50% of the dose is excreted by the kidneys, about 50% – through the intestines. The average value of T1 / 2 is 8-10 hours.
Cumulation of lercanidipine with repeated ingestion is not observed.
Pharmacokinetics in special patient groups
Pharmacokinetics of lercanidipine in elderly patients, patients with renal failure (creatinine clearance (CC) of more than 30 ml / min) and patients with liver failure mild to moderate similar to the pharmacokinetics in healthy volunteers. In patients with renal impairment (creatinine clearance less than 30 mL / min) and in patients on hemodialysis, the concentration in plasma of lercanidipine increases by about 70%.
In patients with liver failure secondary to severe systemic bioavailability of lercanidipine is probably increased because the lercanidipine is metabolized primarily in the liver.
Pregnancy and breast-feeding
Pregnancy
In animal studies, lercanidipine not teratogenic, but teratogenic effects were observed when other dihydropyridine derivatives. Therefore, the use of the drug lercanidipine NW during pregnancy and in women of childbearing age who are not using adequate contraception, contraindicated.
Breastfeeding
Due to the high lipophilicity of lercanidipine may assume its penetration into breast milk, so the use of Lercanidipine NW drug during breast feeding is contraindicated.
Conditions of supply of pharmacies
Prescription.
side effects
Below is a list of adverse reactions distributed systems of organs and frequency of occurrence (World Health Organization): often – from more than 1/100 to less than 1/10, rarely – from more to less than 1/100 to 1/1000, rarely – from the more 1/10000 and less than 1/1000, very rare – less than 1/10000, including isolated reports.
Disorders of the nervous system
Uncommon: headache, dizziness;
Rare: drowsiness.
Violations of the cardiovascular system
Uncommon: palpitations, tachycardia, “tides” of blood to the facial skin;
Rare: angina pectoris;
Very rare: syncope, marked reduction in blood pressure, chest pain, heart attack, in patients with angina may increase the frequency, duration and severity of attacks.
Disorders of the gastrointestinal tract
Rare: nausea, vomiting, diarrhea, abdominal pain, dyspepsia;
Very rare: increased activity of “liver” enzymes (reversible).
Violations of the skin and subcutaneous tissue
Rare: skin rash.
Violations by musculoskeletal and connective tissue
Rare: myalgia.
Violations of the kidneys and the urinary tract
Rare: pollakiuria (increased urination frequency).
Violation of a general nature
Uncommon: peripheral edema;
Rare: asthenia, fatigue;
Very rarely: gingival hyperplasia.
Violations by the immune system:
Very rare: hypersensitivity reactions.
special instructions
Caution should be exercised when administered to patients with impaired renal function, coronary heart disease (the risk of increased frequency of angina attacks), in relation to chronic heart failure: need to be compensated before starting the drug.
With extreme caution should be used on patients with sick sinus syndrome (without a pacemaker). Despite the fact that the hemodynamic controlled studies revealed no violations on the part of the left ventricular function, treatment with calcium channel blockers in patients with signs of left ventricular dysfunction should be administered with extreme caution. There is also a belief that patients with coronary heart disease who receive short-dihydropyridines, are the high-risk group of diseases of the cardiovascular system.
Particular caution should be observed in the initial stages of treatment of patients with mild to moderate severity of liver failure.
The effect on the ability to operate vehicles, machinery
During treatment, care must be taken when performing tasks that require attention when driving, especially at the beginning of treatment and at higher doses of the drug (the risk of drowsiness, headache and dizziness).
Storage conditions
In the dark place at a temperature not higher than 25 C.
Keep out of the reach of children.
Dosing and Administration
Inside. Lercanidipine drug-NW appoint 10 mg 1 time per day in the morning, at least 15 minutes before eating, without chewing, with a sufficient amount of water.
The dose may be increased to 20 mg (in case when receiving 10 mg of the expected effect is not achieved). The therapeutic dose is selected gradually increasing the dose to 20 mg is carried out through 2 weeks after the start of treatment.
It is unlikely that the effectiveness of the drug will increase with increasing doses of 20 mg per day, at the same time increases the risk of side effects.
Use in elderly patients
No dose adjustment is required, however, while taking the drug requires constant monitoring of patients.
The use in patients with impaired renal or hepatic function
In the presence of renal or hepatic insufficiency, mild to moderate, usually dose adjustment is required, the initial dose – 10 mg, increasing the dose to 20 mg per day should be done with caution. If the antihypertensive effect is too pronounced, should reduce the dose.
Information
Appearance may differ from that depicted in the picture. There are contraindications. You need to read the manual or consult with a specialist