Zanidip

General characteristics. Structure:

Active ingredient: lerkanidipina hydrochloride of 10 mg or 20 mg;

Excipients: lactoses monohydrate of 30 mg / 60 mg, cellulose of microcrystallic 39 mg / 78 mg, carboxymethylstarch of sodium of 15,5 mg / 31 mg, povidon-K30 4,5 mg / 9 mg, magnesium stearate of 1 mg / 2 mg;

Structure of a cover: a dosage of 10 mg - опадрай yellow (OY-SR-6497) of 3 mg [a gipromelloza, talc, titanium dioxide (E171), a macrogoal-6000, dye ferrous oxide yellow (E172)]; a dosage of 20 mg - опадрай pink (02F25077) 6 mg [a gipromelloza, talc, titanium dioxide (E171), a macrogoal-6000, dye ferrous oxide red (E172)].

Pharmacological properties:

Pharmacodynamics. Blocker of "slow" calcium channels. Lerkanidipin is racemic mix of right-(R) and left rotating (S) of stereoisomers, derivative 1,4 dihydropyridines, is capable to block selectively current of calcium ions in cells of a vascular wall, cordial cells and cells of smooth muscles. The mechanism of hypotensive action is caused by the direct running-down action on smooth muscle cells of vessels. Possesses the prolonged anti-hypertensive action. The therapeutic effect is reached in 5-7 hours after intake and its duration remains within a day (24 hours). Thanks to high selectivity to smooth muscle cells of vessels negative inotropic effect is absent. Lerkanidipin is metabolic neutral drug and does not make essential impact on the maintenance of lipoproteins and apolipoproteins in blood serum, and also does not change a lipidic profile at patients with arterial hypertension.

Pharmacokinetics. Absorption: after intake лерканидипин it is soaked up from the digestive tract (DT) almost completely. The maximum concentration in a blood plasma is reached in 1,5-3 hours and makes 3,3 ng/ml and 7,66 ng/ml after reception of 10 and 20 mg respectively.

- distribution: distribution in fabrics and bodies comes from a blood plasma quickly. Communication with proteins of a blood plasma exceeds 98%. At patients with a renal and liver failure the content of proteins of plasma is reduced therefore the free fraction of a lerkanidipin can be increased.

- metabolism: it is metabolized at "primary passing" through a liver by biotransformation by a CYP3A4 system isoenzyme with formation of a number of metabolites which have no pharmacological activity.

- removal: occurs kidneys and intestines after biotransformation. Allocate 2 phases of allocation of a lerkanidipin: early (value of an indicator elimination half-life (T1/2): 2-5 h) and final (value of an indicator T1/2: 8-10 h). Drug in an invariable look is practically not found in urine and fecal masses. At repeated use does not kumulirut.

Indications to use:

Essential hypertensia of soft and moderate severity.

Route of administration and doses:

Inside.
The drug Zanidip®-Rekordati is appointed on 10 mg once a day in the morning, not less than in 15 min. prior to food, without chewing, washing down with enough water.
The dose can be increased to 20 mg (if at reception of 10 mg the expected effect is not reached). The therapeutic dose is selected gradually, increase in a dose up to 20 mg is carried out in 2 weeks after the beginning of administration of drug.

Use for elderly patients
Dose adjustment is not required, however, at administration of drug constant control of a condition of patients is necessary.

Use for patients with renal failures or a liver
In the presence of a renal or liver failure of dose adjustment easy or moderately severe, as a rule, it is not required, an initial dose - 10 mg, increase in a dose up to 20 mg a day it is necessary to carry out with care. If the anti-hypertensive effect is too strongly expressed, it is necessary to lower a dose.

Features of use:

It is necessary to be careful at appointment to patients with a renal failure, coronary heart disease (there is a risk of increase of attacks of stenocardia), concerning chronic heart failure: it is necessary to compensate, before drug use. Extra care should be observed at initial stages of treatment of patients with easy and average degree of manifestation of insufficiency of function of a liver.

Influence on ability to drive mechanisms and the car
During treatment it is necessary to be careful when working, requiring special attention, at control of vehicles, especially in an initiation of treatment and at increase in a dose of drug (risk of development of drowsiness, a headache and dizziness).

Side effects:

Statistics on WHO: very often - 1/10 appointments, are frequent - 1/100 appointments, is not frequent - 1/1000 appointments, is rare - 1/10000 appointments, is very rare - less than 1/10000 appointments.
From a nervous system: seldom - drowsiness; infrequently - a headache, dizziness;
From immune system: very seldom - hypersensitivity;
From cardiovascular system: not often - tachycardia, a heart consciousness; "inflows" of blood to face skin; seldom - stenocardia; very seldom - a faint, the expressed lowering of arterial pressure, stethalgias, a myocardial infarction;
From the alimentary system: seldom - nausea, vomiting, diarrhea, abdominal pains, dyspepsia, it is very rare - increase in activity of "hepatic" enzymes (reversible);
From skin: seldom - skin rash;
From a musculoskeletal system: seldom - a mialgiya;
From an urinary system: seldom - a polyuria;
General frustration and local reactions: not often - peripheral hypostases, it is rare - an adynamy, increased fatigue; very seldom - a hyperplasia of gums.

Interaction with other medicines:

Drug cannot be accepted along with CYP3A4 inhibitors (a liver P450 cytochrome isoenzyme), such as кетоконазол, интраконазол, erythromycin (increase concentration of a lerkanidipin in blood and bring in potentiation of anti-hypertensive effect). The concomitant use of a lerkanidipin with cyclosporine as it leads to increase in content of both substances in a blood plasma is contraindicated. Lerkanidipin it is impossible to accept together with grapefruit juice as it leads to oppression of metabolism of a lerkanidipin and potentiation of anti-hypertensive effect.

It is necessary to be careful at a concomitant use with such drugs as терфенадин, астемизол, quinidine and the third class of antiarrhytmic drugs (for example, Amiodaronum). The concomitant use with anticonvulsant drugs (for example, Phenytoinum, carbamazepine) and Rifamycinum can lead to decrease in level of a lerkanidipin in a blood plasma and, in this regard, to decrease in anti-hypertensive effect of a lerkanidipin.

At a concomitant use of digoxin it is necessary to carry out regular control on symptoms of intoxication by digoxin.

Administration of drug with midazolam at advanced age leads to increase in absorption of a lerkanidipin and reduction of speed of an absortion.

Metoprolol reduces bioavailability of a lerkanidipin by 50%, bioavailability of a metoprolol at the same time remains without changes. This effect can arise owing to reduction of a hepatic blood-groove which is caused by beta adrenoblockers therefore it can be shown also at use with other drugs of this group.

Cimetidinum in a dose of 800 mg a day does not lead to considerable changes of a kontsetration of a lerkanidipin in a blood plasma, however, extra care as at higher doses of Cimetidinum bioavailability of a lerkanidipin and consequently also its anti-hypertensive effect, can increase is required. At simultaneous use with simvastatiny, drug should be accepted since morning, and симвастатин - in the evening. Fluoxetine does not exert any impact on pharmacokinetics of a lerkanidipin.

Reception of a lerkanidipin along with warfarin does not exert impact on pharmacokinetics of the last. Lerkanidipin can be applied at the same time with beta adrenoblockers, diuretics, inhibitors of the angiotensin-converting enzyme (ACE). Ethanol can strengthen anti-hypertensive action of a lekarnidipin.

Contraindications:

• Hypersensitivity to a lerkanidipin, other derivatives of a digidropiridiny row or any component of drug;
• Chronic heart failure in a decompensation stage;
• Unstable stenocardia, obstruction of the vessels proceeding from a left ventricle of heart, recently postponed myocardial infarction (within 1 month);
• Heavy abnormal liver functions, renal failures (glomerular filtration rate less than 39 ml/min.);
• Simultaneous use with powerful inhibitors of an isoenzyme CYP3A4 (кетоконазол, итраконазол, erythromycin), and also with grapefruit juice, cyclosporine;
• Pregnancy and period of feeding by a breast; use for women of childbearing age, not using reliable contraception;
• Children's age up to 18 years (efficiency and safety are not established);
• Deficit of lactase, lactose intolerance, glyukozo-galaktozny malyabsortion.

With care

• Abnormal liver functions easy and moderate severity;
• A sick sinus syndrome (without pacemaker);
• Left ventricular failure and coronary heart disease;
• Chronic heart failure;
• Concomitant use of beta adrenoblockers, digoxin.

Use at pregnancy and during breastfeeding
Drug is contraindicated at pregnancy and during breastfeeding.

Overdose:

Symptoms: a peripheral vazodilatation with the expressed lowering of arterial pressure (ABP) and reflex tachycardia, increase in frequency and duration of attacks of stenocardia, a myocardial infarction.

Treatment: symptomatic therapy.

Storage conditions:

At a temperature not above 30 °C. To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

Tablets film coated 10 mg, 20 mg.
On 7, 14, 15, 25, 28, 30 tablets in the blister from opaque film PVC / aluminum foil. On 1, 2, 3, 4, 5, 6, 7 blisters with the application instruction in a cardboard pack.