Lercanidipine-SZ, 10 mg 30 pcs

Slow calcium channel blocker.

Pharmacodynamics:

.

Indications

Arterial hypertension 1-2 degrees.

Pharmacological effect

Blocker of “slow” calcium channels.

Pharmacodynamics:

Blocker of “slow” calcium channels. Lercanidipine is a racemic mixture of dextro- (R) and levorotatory (S) stereoisomers, a derivative of 1,4-dihydropyridine, capable of selectively blocking the flow of calcium ions into the cells of the vascular wall, cardiac cells and smooth muscle cells. The mechanism of hypotensive action is due to a direct relaxing effect on vascular smooth muscle cells. Has a prolonged antihypertensive effect.

The therapeutic effect is achieved 5-7 hours after oral administration and its duration persists throughout the day (24 hours). Due to its high selectivity for vascular smooth muscle cells, there is no negative inotropic effect.

Lercanidipine is a metabolically neutral drug and does not have a significant effect on the content of lipoproteins and apolipoproteins in the blood serum, and does not change the lipid profile in patients with arterial hypertension.

Pharmacokinetics:

Suction

Lercanidipine is completely absorbed after oral administration. The maximum concentration (Cmax) in the 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 of lercanidipine demonstrate a similar pharmacokinetic profile: they have the same time to reach maximum concentration, the same T1/2. The plasma Cmax and area under the concentration-time curve (AUC) of the (-) S-enantiomer of lercanidipine is on average 1.2 times higher than the (+) R-enantiomer. Interconversion of enantiomers was not observed in in vivo experiments.

During first pass through the liver, the absolute bioavailability of lercanidipine when taken orally after meals is about 10%. When taken orally on an empty stomach, the bioavailability is 1/3 of the bioavailability after a meal.

When lercanidipine is taken orally within 2 hours after a high-fat meal, its bioavailability increases 4-fold, so lercanidipine should not be taken after meals. The pharmacokinetics of lercanidipine over the therapeutic dose range is nonlinear. When taking lercanidipine in doses of 10 mg, 20 mg and 40 mg, Cmax in blood plasma was determined in a ratio of 1: 3: 8, respectively, and AUC in a ratio of 1: 4: 18, which suggests progressive saturation during the “primary passage” through the liver. Thus, bioavailability increases with increasing dose taken.

Distribution

Distribution of lercanidipine from blood plasma to tissues and organs occurs quickly. The degree of binding to blood plasma proteins exceeds 98%. In patients with severe renal and hepatic impairment, the free fraction of lercanidipine may increase due to a decrease in plasma protein concentrations.

Metabolism

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

Removal

Lercanidipine is excreted primarily through biotransformation. About 50% of the dose taken is excreted by the kidneys, about 50% through the intestines. The average T1/2 is 8-10 hours. There is no accumulation of lercanidipine upon repeated oral administration.

Pharmacokinetics in special groups of patients

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

In patients with renal failure (creatinine clearance less than 30 ml/min) and in patients on hemodialysis, the plasma concentration of lercanidipine increases by approximately 70%.

In patients with moderate to severe hepatic impairment, the systemic bioavailability of lercanidipine is likely to be increased since lercanidipine is metabolized primarily in the liver.

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), and chronic heart failure: it is necessary to compensate before starting to use the drug.

The drug should be used with extreme caution in patients with sick sinus syndrome (without a pacemaker).

Although controlled hemodynamic studies have not revealed any abnormalities in left ventricular function, treatment with calcium channel blockers in patients with signs of left ventricular dysfunction should be carried out with extreme caution. There is also an opinion that patients with coronary heart disease receiving short-acting dihydropyridines represent a high-risk group for cardiovascular diseases.

Particular caution should be observed in the initial stages of treatment in patients with mild to moderate liver failure.

Impact on the ability to drive vehicles. Wed and fur.:

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

Active ingredient

Lercanidipine

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 (hydroxypropyl methylcellulose) – 3.5 mg;

magnesium stearate – 1.0 mg;

excipients (shell):

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

Pregnancy

Pregnancy

Contraindications

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

– untreated heart failure;

– unstable angina;

– obstruction of the left ventricular outflow tract;

– period within 1 month after myocardial infarction;

– severe liver failure;

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

– pregnancy and breastfeeding;

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

– age under 18 years (efficacy and safety have not been established);

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

– simultaneous use with inhibitors of the CYP3A4 isoenzyme (ketoconazole, itraconazole, erythromycin, ritonavir, troleandomycin);

– simultaneous use with cyclosporine;

– simultaneous use with grapefruit juice.

With caution:

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

– mild to moderate liver dysfunction;

– old age;

– sick sinus syndrome (without pacemaker);

– dysfunction of the left ventricle of the heart and coronary heart disease;

– chronic heart failure;

– simultaneous use with substrates of the CYP3A4 isoenzyme (terfenadine, asmetol, class III antiarrhythmic drugs, 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

Below 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,

uncommon – 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

Uncommon: headache, dizziness;

Rarely: drowsiness.

Cardiovascular disorders

Uncommon: palpitations, tachycardia, flushes of blood to the skin of the face;

Rarely: angina pectoris;

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

Gastrointestinal disorders

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.

Renal and urinary tract disorders

Rarely: pollakiuria (increased frequency of urination).

General violations

Uncommon: peripheral edema;

Rarely: asthenia, increased fatigue;

Very rare: gingival hyperplasia.

Immune system disorders:

Very rare: hypersensitivity reactions.

Interaction

The drug should 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). The simultaneous 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 with grapefruit juice, as this leads to inhibition of lercanidipine metabolism and potentiation of the antihypertensive effect.

Caution must be exercised when taken concomitantly with drugs such as terfenadine, astemizole, quinidine and class III antiarrhythmic drugs (for example, amiodarone).

Concomitant use with anticonvulsants (for example, phenytoin, carbamazepine) and rifampicin may lead to a decrease in the plasma concentration of lercanidipine and, therefore, a decrease in the antihypertensive effect of lercanidipine.
In patients chronically taking digoxin, no pharmacokinetic interaction was observed with concomitant use of lercanidipine at a dose of 20 mg.

However, in healthy volunteers who took
digoxin, there was an increase in the Cmax value of digoxin in blood plasma by an average of 33% after oral administration of 20 mg lercanidipine on an empty stomach, while the AUC and renal clearance of digoxin changed slightly. Patients receiving digoxin and lercanidipine concomitantly should be monitored for signs of digoxin toxicity.

Overdose

Symptoms

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

Treatment

Symptomatic. In case of a pronounced decrease in blood pressure and loss of consciousness, cardiovascular therapy is indicated; in case of bradycardia, intravenous administration of atropine is indicated. There is no information on the effectiveness of hemodialysis. Given the high degree of binding to plasma proteins, dialysis may be ineffective.

There are reports of three cases of overdose when taking lercanidipine in doses of 150 mg, 280 mg and 800 mg. In all cases of overdose, the patients survived.

Drowsiness has been observed when lercanidipine 150 mg was coadministered with ethanol (unspecified amount). Treatment: gastric lavage, ingestion of activated carbon.

In 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 expanders.
When taking 800 mg of lercanidipine, the following were observed: nausea, a marked decrease in blood pressure. Treatment: oral administration of activated carbon and laxatives, intravenous dopamine.

Storage conditions

In a place protected from light, at a temperature not exceeding 25 ° C.

Keep out of the reach of children.

Shelf life

3 years.
Do not use after the expiration date stated on the package.

Manufacturer

North Star NAO, Russia