Норваск®

General characteristics. Structure:

Active component: an amlodipina бесилат in a dose of 6,935 mg and 13,870 mg, equivalent 5 and 10 mg of an amlodipin, respectively. Excipients: cellulose fine-crystalline, calcium hydrophosphate anhydrous, sodium starch glycollate type A, magnesium stearate.

Pharmacological properties:

Pharmacodynamics. Amlodipin – derivative dihydropyridine. Contacting dihydropyridinic receptors, blocks "slow" calcium channels, inhibits transmembrane transition of calcium in cells of an unstriated muscle of heart and vessels (more – in smooth muscle cells of vessels, than in cardiomyocytes). Renders hypotensive and anti-anginal effect. The mechanism of hypotensive action of an amlodipin is caused by the direct weakening impact on unstriated muscles of vessels. Amlodipin reduces myocardium ischemia the next two ways:

1.    Expands peripheral arterioles and, thus, reduces the general peripheric resistance (afterload), at the same time heart rate practically does not change that leads to decrease in consumption of energy and need of a myocardium for oxygen.

2.    Expands coronary and peripheral arteries and arterioles both in normal, and in ischemic zones of a myocardium that increases intake of oxygen in a myocardium at patients with vasospastic stenocardia (Printsmetal's stenocardia) and prevents development of the coronary spasm caused by smoking. At patients with arterial hypertension the single daily dose of Norvask provides a lowering of arterial pressure (ABP) for 24 hours (as in situation "lying", and "standing"). Thanks to the slow beginning of action амлодипин does not cause sharp decrease in the ABP. At patients with stenocardia the single daily dose of drug increases time of performance of an exercise stress, development of the next attack of stenocardia and depression of a segment of ST detains (on 1 mm) against the background of an exercise stress, reduces the frequency of attacks of stenocardia and consumption of nitroglycerine. Use for patients with the coronary heart disease (CHD) At the patients with cardiovascular diseases (including coronary atherosclerosis with defeat of one vessel and to a stenosis of the 3rd and more arteries and atherosclerosis of carotid arteries) who had a myocardial infarction, chrezkozhny transluminal angioplasty of coronary arteries (TLP) or having stenocardia, use of Norvask prevents development of a thickening erotic-medii of carotid arteries, considerably reduces a lethality from the cardiovascular reasons, a myocardial infarction, stroke, TLP, aortocoronary shunting, leads to decrease in number of hospitalization concerning unstable stenocardia and progressing of the chronic heart failure (CHF), reduces the frequency of the interventions directed to recovery of a coronary blood-groove. Use for patients with heart failure            Norvask does not increase risk of mortality or development of complications and deaths at patients with the chronic heart failure (CHF) of the III-IV functional class (on NYHA) against the background of therapy by digoxin, diuretics and APF inhibitors. Sick HSN III-IV of a functional class on NYHA not of an ischemic etiology at use of Norvask have a probability of emergence of a fluid lungs. Norvask does not exert any adverse impact on a metabolism and concentration of lipids of a blood plasma.

Pharmacokinetics. Absorption. After intake in therapeutic doses амлодипин it is well absorbed, reaching the maximum concentration in blood in 6-12 hours after reception. Absolute bioavailability leaves 64-80%. The volume of distribution is equal to about 21 l/kg. Communication with proteins of plasma makes about 97,5%. Meal does not influence absorption of an amlodipin, gets through a blood-brain barrier. Biotransformation/removal. The elimination half-life (Т½) makes about 35 - 50 hours of plasma that corresponds to purpose of drug once a day. At patients with a liver failure and heavy HSN T½uvelichivayetsya till 56-60 o'clock. The general clearance – 0,43 l/h/kg. Stable equilibrium concentration in plasma is reached in 7-8 days of constant reception of an amlodipin, it is metabolized in a liver with formation of inactive metabolites; 10% of initial drug and 60% of metabolites are removed with urine. Removal with breast milk is unknown. During a hemodialysis is not removed. Use for patients with a renal failure. Т½ from a blood plasma at patients with a renal failure increases till 60 o'clock. Change of concentration of an amlodipin in plasma does not correlate with degree of a renal failure. Use for elderly people. At elderly time necessary for achievement of the maximum concentration of an amlodipin in a blood plasma, and its size, practically do not differ from those at more young people. At the elderly people suffering from HSN the tendency to decrease in clearance of an amlodipin is noted that concentration time and Т½ leads  till 65 o'clock to increase in the area under a curve.

Indications to use:

Arterial hypertension (both in monotherapy, and in combination with other antihypertensives). Stable stenocardia and vasospastic stenocardia  (Printsmetal's stenocardia) (both in monotherapy, and in combination with other anti-anginal means).

Route of administration and doses:

Inside, once a day, washing down with the necessary volume of water (100 ml). At arterial hypertension and stenocardia the usual initial dose makes 5 mg, depending on individual reaction of the patient, it can be increased to maximum - 10 mg. Use for elderly people. It is recommended to apply in usual doses, change of a dose of drug is not required. Use for patients with the broken function of a liver. In spite of the fact that Т½Норваска, as well as all BMKK,  increases at patients with this pathology, any changes of a dosage of drug with the broken function of a liver usually are not required from patients (see the section "Special Instructions"). Use at a renal failure. It is recommended to apply in usual doses, however it is necessary to consider possible insignificant increase Т½. Change of the mode of dosing of Norvask at simultaneous use of thiazide diuretics, beta adrenoblockers or APF inhibitors is not required.

Features of use:

At treatment of arterial hypertension Norvask can be applied in a combination with thiazide diuretics, alpha and beta adrenoblockers, APF inhibitors, nitrates of the prolonged action, sublingual nitroglycerine, NPVP, antibiotics and peroral hypoglycemic means. For treatment of stenocardia it is possible to appoint Norvask as means of monotherapy or in a combination with other anti-anginal means, including at patients, refractory to treatment by nitrates and/or beta adrenoblockers in adequate doses. Norvask does not exert any adverse impact on a metabolism and lipids of a blood plasma and can be applied at treatment of patients with bronchial asthma, a diabetes mellitus and gout. Norvask can be applied and when the patient is predisposed to vasospasm/vasoconstriction. To patients of low growth and patients with the expressed abnormal liver function the smaller dosage can be required by patients with small body weight. During treatment control of body weight and observation at the stomatologist is necessary (for prevention of morbidity, bleeding and a hyperplasia of gums). Influence on ability of driving and use of the equipment Though against the background of inclusion of Norvask of any negative influence on ability to drive the car or other technical means was not observed, however, owing to possible excessive decrease in the ABP, development of dizziness, drowsiness, etc. in by-effects it is necessary to belong attentively to individual effect of drug in the specified situations, especially in an initiation of treatment and at change of the mode of dosing.

Side effects:

Further as the frequency of side reactions it is understood: frequent (> 1%), infrequent (<1%), rare (<0,1%), very rare (<0,01%).

Cardiovascular system: peripheral hypostases (anklebones and feet), heartbeat,  it is not frequent – excessive decrease in the ABP, orthostatic hypotension, a vasculitis;  seldom – development or aggravation of heart failure; оченьредко – disturbances of a heart rhythm (including bradycardia, ventricular tachycardia and atrial fibrillation),  a myocardial infarction, thorax pains, migraine.

From a musculoskeletal system: not often – an arthralgia, myotonia, a mialgiya, a dorsodynia, arthrosis, it is rare – a myasthenia.

Central and peripheral nervous system: the feeling of heat and "inflows" of blood to face skin, increased fatigue, dizziness, a headache, drowsiness,  is not frequent – an indisposition, a syncope, the increased sweating, an adynamy, hypesthesias, paresthesias, peripheral neuropathy, a tremor, sleeplessness, lability of mood, unusual dreams, nervousness, a depression, alarm; seldom – spasms, apathy, agitation;  very seldom – an ataxy, amnesia.

Digestive tract: an abdominal cavity pain, nausea, it is not frequent – vomiting, changes of the mode of defecation (including a lock, a meteorism), dyspepsia, diarrhea, anorexia, dryness in a mouth, thirst, it is rare – a hyperplasia of gums, increase in appetite, is very rare – gastritis, pancreatitis, a hyperbilirubinemia, jaundice (usually cholestatic), increase in activity of "hepatic" transaminases, hepatitis. System of a hemopoiesis: very seldom – a Werlhof's disease, thrombocytopenia, a leukopenia,

Metabolic disturbances: very seldom – a hyperglycemia.

System of breath: not often – short wind, rhinitis, it is very rare – cough.

Urinogenital system: not often – the speeded-up urination, an urodynia, a nocturia, impotence, a gynecomastia very seldom – a dysuria, a polyuria.

Allergic reactions: not often – a skin itch, rash, it is very rare – a Quincke's disease, a multiformny ertiyema, a small tortoiseshell.

Others: not often – an alopecia, "ring" in ears, increase/decrease in body weight, a vision disorder, a diplopia, accommodation disturbance, a xerophthalmia, conjunctivitis, eye pain, a food faddism, a fever, nasal bleeding; seldom – dermatitis;  very seldom - a parosmiya, a xerodermia, "cold" sweat, disturbance of a xanthopathy.

Interaction with other medicines:

It is possible to expect that inhibitors of a microsomal oxidation will increase concentration of an amlodipin in plasma, strengthening risk of side effects, and inductors of microsomal enzymes of a liver – to reduce. Cimetidinum: at simultaneous use of an amlodipin with Cimetidinum the pharmacokinetics of an amlodipin does not change. Grapefruit juice: the concomitant single dose of 240 ml of grapefruit juice and 10 mg of an amlodipin inside is not followed by essential change of pharmacokinetics of an amlodipin. Unlike other BMKK of clinically significant interaction of drug Norvask (the III generation of BMKK)  it was not revealed at combined use with non-steroidal anti-inflammatory drugs (NPVP), especially indometacin. Strengthening of anti-anginal and hypotensive action of BMKK at combined use with thiazide and "loopback" diuretics, verapamil, APF inhibitors, beta adrenoblockers and nitrates, and also increase in their hypotensive action at combined use with alfa1-adrenoblockers, neuroleptics is possible. Though when studying drug Norvask of a negative inotropic effect was usually not observed, nevertheless, some BMKK can increase expressiveness of negative inotropic effect of the antiarrhytmic drugs causing lengthening of an interval of QT (for example, Amiodaronum and quinidine). At combined use of BMKK with lithium drugs (for Norvask data are absent) possibly strengthening of manifestation of their neurotoxicity (nausea, vomiting, diarrhea, an ataxy, a tremor, a sonitus). Amlodipin does not influence  in vitro extent of linkng with proteins of a blood plasma of digoxin, Phenytoinum, warfarin and indometacin. Aluminum/magnesium the containing antacids: their single dose has no significant effect on pharmacokinetics of an amlodipin. Sildenafil (Viagra): the single dose of 100 mg of a sildenafil at patients with essential hypertensia does not exert impact on parameters of pharmacokinetics of an amlodipin. Atorvastatin: repeated use of an amlodipin in a dose of 10 mg and an atorvastatina in a dose  of 80 mg is not followed by considerable changes of indicators of pharmacokinetics of an atorvastatin. Digoxin: at simultaneous use of an amlodipin with digoxin at healthy volunteers serumal levels and renal clearance of digoxin do not change. Ethanol (alkogolsoderzhashchy drinks): at single and repeated use in a dose of 10 mg амлодипин has no significant effect on ethanol pharmacokinetics. Warfarin: амлодипин does not influence the changes of a prothrombin time caused by warfarin. Cyclosporine: амлодипин does not cause considerable changes of pharmacokinetics of cyclosporine.

Contraindications:

Hypersensitivity to an amlodipin and other derivatives of dihydropyridine, and also the excipients which are a part of drug. Heavy arterial hypotension.

Overdose:

Symptoms: the expressed decrease in the ABP with possible development of reflex tachycardia and an excessive peripheral vazodilatation (there is a probability of emergence of the expressed and persistent arterial hypotension, including with development of shock and a lethal outcome). Treatment: purpose of absorbent carbon (especially in the first 2 hours after overdose), a gastric lavage (in some cases), giving of sublime situation to extremities, active maintenance of function of cardiovascular system, monitoring of indicators of cardiac performance and lungs, control of volume of the circulating blood and a diuresis. For recovery of a tone of vessels and the ABP if there are no contraindications, there can be useful a use of vasoconstrictive drugs. Use intravenous administration of a gluconate of calcium. As амлодипин substantially contacts serum proteins  - the hemodialysis is not effective.

Storage conditions:

At a temperature not above 25 °C. To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

Tablets on 5 and 10 mg. On 10 or 14 tablets in a blister strip packaging from a PVH/Al-folgi; on the 3rd blister strip packagings on 10 tablets or on 1 blister strip packaging on 14 tablets together with the application instruction in a cardboard pack.