Pharmacological properties

Pharmakodinamichesky parameters. lerkanidipin — a blocker of calcium channels, the representative of group of dihydropyridines. ca2 stream + through a cellular membrane in cardiomyocytes and cells of unstriated muscles of a wall of blood vessels oppresses. lerkanidipin renders hypotensive effect due to the direct relaxing influence on smooth muscles of a vascular wall, reducing opss. duration of hypotensive effect of a lerkanidipin is caused by high coefficient of its membrane distribution, contrary to insignificant t½ from blood plasma. the negative inotropic effect at reception of a lerkanidipin is absent in connection with its highly selective impact on vessels. as the vasodilatation caused by reception of a lerkanidipin is done gradually, at patients with ag sharp decrease hell with reflex increase chss is only in rare instances noted (90 ud. / mines). at regular daily reception, medicament causes uniform and steady decrease hell.

Pharmacokinetic parameters. Lerkanidipin is completely absorbed after use of per os of 10-20 mg of drug, With _max in blood plasma is reached in ≈1.5-3 h after introduction.

in case of oral introduction of a lerkanidipin after meal its absolute bioavailability is ≈10% because of high metabolism at the first passing through a liver. At reception of a lerkanidipin on an empty stomach by healthy volunteers of value of this indicator decrease by 3 times. In turn, the bioavailability of a lerkanidipin 4-multiply increases at its oral introduction to the period of ≤2 h after meal with a large amount of fats. Thus, reception of a lerkanidipin should be carried out before meal.

Lerkanidipin contacts proteins of blood plasma for 98% (at patients with renal or hepatic dysfunction of heavy degree the maintenance of free fraction of a lerkanidipin can increase) and is characterized by fast and extensive distribution in fabrics and bodies.

Metabolism of a lerkanidipin which is transformed to inactive metabolites happens extensively by means of CYP 3A4. With urine about a half of the entered dose is excreted. Biotransformation is the main way of elimination of a lerkanidipin. Average T _{½ values} = 8–10 h, however the therapeutic effect remains during 24 h because of high extent of linking of a lerkanidipin with lipids of cell membranes. At repeated use the cumulation is not observed.

ratio of values With _max in blood plasma makes

After reception of 10, 20 and 40 mg of a lerkanidipin, respectively, 1:3:8, and AUC — 1:4:18. It is an indicator of gradual saturation of metabolism at the first passing. Therefore, at increase in a dose the increase in bioavailability is observed.

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At elderly patients and patients with slight and medium-weight renal or hepatic dysfunction does not note differences in pharmacokinetics of a lerkanidipin in comparison with patients of the general group. Concentration of a lerkanidipin is higher (≈70%) at patients with a renal failure of heavy degree or being on dialysis. As metabolism of a lerkanidipin happens mainly in a liver, increase in its system bioavailability at patients with the moderate or profound hepatic dysfunction is probable.

Indication

Pervichnaya ag (severity — easy or average).

Use

Per os of 10 mg of 1 times a day in ≥15 min. prior to food (it is desirable in the morning). increase in a dose to 20 mg is possible (is defined by individual sensitivity of the patient).

Most significant hypotensive effect develops later ≥2 weeks of therapy therefore gradual selection of a dose is necessary.

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in the absence of achievement of adequate control of the ABP owing to use of a lerkanidipin as monomedicament allows its combination to blockers of β-adrenoceptors either diuretics (hydrochlorothiazide), or APF inhibitors (enalapril, captopril).

Contraindication

Hypersensitivity to active ingredient (or to other antagonists of calcium of a dihydropyridinic row) or any component of drug; the pathology causing disturbance of outflow of blood from a left ventricle; congestive hsn at the patients who were not receiving therapy concerning this state;

• instability of a coronary blood-groove;

• profound disorder of hepatic and renal functions (clearance of creatinine of 30 ml/min.);
• period after the postponed myocardial infarction (up to 1 month);
• combined use with grapefruit juice, cyclosporine, CYP inhibitors 3A4;
• woman at fertile age which plan pregnancy and do not apply effective contraceptives.

Side effects

Reaction of hypersensitivity it is (very rare); heartbeat strengthening, increase chss (90 ud. / mines), rushes of blood (infrequently), angina pectoris (rarely); epigastralgias, nausea, vomiting, dyspepsia, diarrhea (seldom); muscle pain (seldom); rash (seldom); increase in amount of the emitted urine (1800 ml/days); peripheral hypostases (infrequently), weakness, increased fatigue (seldom); a cephalalgia, dizziness (infrequently), drowsiness (seldom), loss of consciousness it is (very rare).

development of a hypertrophic ulitis, tranzitorny increase in activity of aminotransferases of a liver, decrease in the ABP is In some cases possible

(90 mm Hg.), pollakiuria, thoracalgia.

In some cases at introduction of some antagonists of calcium of a dihydropyridinic row the developing of pain in heart or stenocardia as an exception — at patients with stenocardia can note tachycardia, increase in duration or weight of attacks is possible

, single episodes of development of a myocardial infarction are possible.

Special instructions to

discretion at use of a lerkanidipin for elderly patients in a treatment debut Is necessary for

.

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Needs discretion in therapy of patients with easy or moderate degree of insufficiency of function of kidneys or a liver. It is necessary to raise with care a dose of a lerkanidipin to 20 mg at such patients, despite good tolerance of titration of a dose.

Hepatic dysfunction can cause strengthening of hypotensive action of a lerkanidipin demanding dose adjustment.

alcohol their combination is forbidden to

In view of strengthening of vasodilating action of a lerkanidipin.

specified medicament is not recommended to

Because of presence of lactose (1 tablet Zanidipa of 10 mg contains 30 mg of lactose, 1 tablet Zanidipa of 20 mg — 60 mg of lactose) for use for patients with a syndrome of disturbance of absorption of glucose and a galactose, a galactosemia, insufficiency of Lappa lactase.

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Needs discretion in therapy of patients with Short's syndrome without implantation of an electrocardiostimulator, from patients with left ventricular dysfunction, an ischemic heart disease.

should inform the anesthesiologist Of use by the patient of a lerkanidipin.

is not applied during pregnancy and feeding by a breast, at children's age.

At emergence against the background of use of medicament of weakness, increased fatigue, dizziness or, in rare instances, drowsiness, it is forbidden to run vehicles or to work with other mechanisms.

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care at the combined use with other CYP substrates 3a4 Is necessary for

Interaction

(terfenadiny, astemizoly, quinidine, Amiodaronum).

Midazolam increases absorption of a lerkanidipin (20 mg) in a GIT.

Maintenance of a lerkanidipin in blood plasma (and, respectively, hypotensive effect) are reduced by inductors CYP 3A4 (rifampicin, Phenytoinum, carbamazepine). Their combined use demands frequent monitoring of the ABP level from the patient.

Combined use with metoprololy causes half decrease in bioavailability of a lerkanidipin, demanding correction of its dose. The specified effect is possible in case of use and with other blockers of β-adrenoceptors. Respectively, the combined use with medicaments of this group assumes dose adjustment of a lerkanidipin.

scrupulous control of development of symptoms of digoksinovy intoxication is necessary for

At the combined use with digoxin.

Lerkanidipin does not change

pharmacokinetic parameters of warfarin.

Perhaps combined use of a lerkanidipin with APF inhibitors and diuretics.

Pharmacokinetics of a lerkanidipin does not change significantly in clinical aspect at the combined use with such means as fluoxetine (patients of advanced age) and Cimetidinum (800 mg/days, at higher doses the increase in expressiveness of hypotensive effect is possible).

in the morning and a simvastatina in the evening interaction between them is not expected by

in case of the combined use of a lerkanidipin.

Overdose

development of an excess peripheral vazodilatation and the significant decrease hell with reflex increase chss Is probable

.

in case of the significant decrease in the ABP, ChSS and losses of consciousness is required introduction of cardiovascular means; ChSS demands the significant decrease in/in administrations of atropine. Monitoring of hemodynamic parameters of the patient is necessary for ≥1 days. Efficiency of dialysis at overdose of a lerkanidipin, presumably, insignificant.

Storage conditions

At a temperature of ≤30 °C in original packing out of children's reach.