Amzaar

General characteristics. Structure:

Active ingredients: 7,84 mg of an amlodipin of a kamzilat (that corresponds to 5 mg of an amlodipin), 50 mg or 100 mg of a lozartan of potassium.

Excipients: butyl hydroxytoluene, sodium carboxymethylstarch, cellulose microcrystallic, Mannitolum, K30 povidone, кросповидон, magnesium stearate.

Structure of a cover: gipromelloza 2910, hypro rod, titanium dioxide, talc.

Pharmacological properties:

Pharmacodynamics. The combined anti-hypertensive drug containing active components with the hypotensive action supplementing each other: амлодипин (blockers of slow calcium channels, BMKK, derivative dihydropyridine) and лозартан (antagonist of receptors of angiotensin II). Active components of drug possess the different mechanism of hypotensive action: амлодипин - at the expense of a vazodilatation reduces OPSS, лозартан - due to impact on RAAS inhibits effects of angiotensin II that leads to more expressed decrease in the ABP in comparison with that against the background of monotherapy by each drug.

Amlodipin - derivative dihydropyridine, representing optically inactive mix optically of active isomers. Amlodipin blocks slow calcium channels, thereby inhibiting transmembrane transition of calcium in cells of a myocardium and smooth muscle cells of vessels. The ABP by the direct weakening effect on smooth muscles of arterial vessels reduces. In preclinical trials амлодипин had more expressed effect on smooth muscle cells in comparison with cardiomyocytes. Amlodipin does not exert a negative impact neither on AV conductivity, nor on contractility of a myocardium. Drug reduces the resilience of vessels of kidneys and increases a renal blood stream.

Researches of an amlodipin at patients with the chronic heart failure (CHF) of the II-IV functional classes on classification of NYHA showed what амлодипин does not exert a negative impact on tolerance to an exercise stress, fraction of emission or any clinical indicators, and also a metabolism, in particular, on concentration of lipids and glucose in a blood plasma. At a single dose inside the effect of an amlodipin begins in 2-4 h and remains during 24 h. The maximum hypotensive effect is reached not earlier than 4 weeks from the beginning of administration of drug. Amlodipin reduces the ABP at the patients who are in a prone position and sitting, and also at an exercise stress. As the pharmakodinamichesky effect of drug develops gradually, амлодипин does not cause sharp decrease in the ABP or reflex tachycardia. Amlodipin reduces expressiveness of a hypertrophy of a left ventricle. Hemodynamic effects of drug remain invariable at long-term use.

Amlodipina камзилат it is chemically similar with more widespread in clinical practice of an amlodipin bezilaty, but possesses in comparison with it the best photostability. According to preclinical trials both камзилат, and безилат possess identical indicators of a pharmacodynamics and pharmacokinetics. In toxicological researches of an amlodipin of a kamzilat at animals additional toxic effects or genotoksichesky potential concerning an amlodipin of a bezilat were not revealed.

Pharmakodinamichesky action of an amlodipin of a kamzilat and amlodipin of a bezilat was comparable at a single dose of a dose of 5 mg male healthy volunteers. In particular, both salts of an amlodipin had comparable effect on systolic and diastolic the ABP, and also increase in ChSS, with the maximum development of hypotensive effect in the range of 6.7-11.9 h after reception and the maximum increase in heart rate during 19 h after reception. Decrease in the systolic and diastolic ABP approximately on 13 and 15 mm of mercury., respectively, it was observed in both cases, with return of the ABP to reference values in 24 h from the reception moment that corresponds to the known pharmacokinetic and hemodynamic profile of an amlodipin of a bezilat.

Lozartan. Lozartan is a synthetic antagonist of receptors of angiotensin II (AT1 type) for intake. Angiotensin II, a powerful vasoconstrictor, is the RAAS main hormone and an important determinal factor of a pathophysiology of arterial hypertension. Angiotensin II contacts AT1 receptors which are available in many body tissues (smooth muscles of vessels, adrenal glands, kidneys and heart) and mediates such important effects as vasoconstriction and release of Aldosteronum. Angiotensin II also stimulates proliferation of smooth muscle cells of vessels.

Lozartan selectively blocks AT1 receptors. Both in vitro, and in vivo лозартан and it pharmacological the active carboxylated metabolite of E-3174 block all physiologically connected effects of angiotensin II, irrespective of a source or a way of its synthesis in an organism.

Lozartan does not possess agonistic action and does not block receptors of other hormones or ion channels participating in regulation of cardiovascular activity. In addition, лозартан does not inhibit APF splitting bradykinin. Respectively, at reception of a lozartan potentiation of the undesirable effects mediated by bradikinin is not observed.

At reception of a lozartan elimination of negative feedback of angiotensin II and secretion of a renin leads to increase in activity of a renin of ARP plasma that, in turn, increases concentration of angiotensin in a blood plasma. Despite these changes, hypotensive action and decrease in concentration of Aldosteronum in a blood plasma remain, pointing to effective blockade of AT1 receptors. In 3 days after the termination of reception of a lozartan, activity of a renin of plasma and concentration of angiotensin in a blood plasma decrease to reference values.

Pharmacokinetics. Amlodipina безилат. Absorption. At reception in therapeutic doses амлодипин it is well absorbed, and Cmax in a blood plasma is observed in 6-12 h. Absolute bioavailability is estimated in the range from 64 to 80%. Meal does not influence absorption of an amlodipin.

Distribution. Css is reached in 7-8 days of reception. Vd makes about 21 l/kg. Linkng with proteins of plasma - 98%.

Metabolism. The plasma clearance makes 7 ml/min. Amlodipin is substantially metabolized in a liver to inactive metabolites.

Removal. T1/2 makes 30-40 h 10% of an amlodipin and 60% of metabolites are removed by kidneys.

Pharmacokinetics in special clinical cases. T1/2 of an amlodipin is increased at patients with a liver failure.

Amlodipina камзилат. The comparative research of pharmacokinetics of an amlodipin of a kamzilat and referensny drug of an amlodipin of a bezilat at a single dose in a dose of 5 mg showed similar profiles of absorption. Cmax in a blood plasma, on average, made 3,6 ng/ml for an amlodipin of a bezilat and 3.7 ng/ml - for an amlodipin of a kamzilat, and time of their achievement made respectively 6.9 h and 7.3 p. T1/2 made respectively 42.2 h and 39.3 h. The obtained data correspond to the application instruction and literary data for an amlodipin of a bezilat. Thus, bioequivalence of an amlodipin of a kamzilat in a dose of 5 mg was shown to original drug of an amlodipin to a bezilat in the same dose.

Lozartan. Absorption. At intake, лозартан it is well soaked up. System bioavailability of tablets of a lozartan makes about 33%, Cmax of a lozartan and its active metabolite in plasma is observed in 1 and 3-4 h, respectively.

Distribution. As лозартан, and its active metabolite more than for 99% contact proteins of plasma, mainly - albumine. Vd of a lozartan makes 34 l.

Metabolism. Lozartan is exposed to metabolism of primary passing through a liver with formation of the active carboxylated metabolite, and also other, inactive metabolites. About 14% in/in the dose of a lozartan entered or accepted inside turn into its active metabolite. At in introduction or intake of a 14C-mechenny lozartan of potassium, the most part of a radioactive label in a blood-groove corresponded to a lozartan and its active metabolite. The minimum level of biotransformation of a lozartan observed in clinical trials to an active metabolite made 1%.

Removal. The clearance of a lozartan and its active metabolite makes 60 ml/min. and 50 ml/min. respectively. Renal clearance - 74 ml/min. and 26 ml/min., respectively. At intake about 4% of a dose are removed by kidneys in not changed look, and 6% - in the form of an active metabolite. The pharmacokinetics of a lozartan and its active metabolite is linear at intake in doses to 200 mg.

At intake, concentration of a lozartan and its active metabolite about 2 p and 6-9 h respectively decrease polieksponentsialno, with final T1/2. In a dose of 100 mg at reception of 1 times/days, лозартан, its active metabolite is kumulirut in plasma.

Lozartan and his metabolites is brought by kidneys and through intestines with bile. At intake and in introduction of a 14C-mechenny lozartan at the person, 35% and 43% of radioactivity, respectively, a lozartan and its active metabolite 58% and 50% - in Calais are found in urine.

Pharmacokinetics in special clinical cases. Elderly patients with the raised ABP have a concentration of a lozartan and his active metabolite in plasma slightly differs from those at young patients. At women with the raised ABP concentration of a lozartan in plasma are twice higher, than at men whereas concentration of its active metabolite does not differ between floors. At patients with moderately or so-so the expressed alcoholic cirrhosis, concentration of a lozartan and its active metabolite in plasma at intake increased, respectively, in 5 and 1,7 times in comparison with those at young male volunteers.

Concentration of a lozartan in plasma does not change at patients with clearance of creatinine higher than 10 ml/min. In comparison with patients with normal function of kidneys, AUC of a lozartan is twice higher, than at the patients who are on a hemodialysis. Concentration in plasma of its active metabolite do not change at patients with a renal failure and the patients who are on a hemodialysis. лозартан, its active metabolite can be removed by means of a hemodialysis.

Комбинаиця амлодипин + лозартан. In comparative clinical trials of combined use of an amlodipin of a kamzilat and lozartan and use of a combination of an amlodipin of a kamzilat with lozartany in doses of 5/50 mg and 5/100 mg, pharmacokinetic indicators in both cases matched both for an amlodipin, and for a lozartan and its active metabolite of E-3174. Bioequivalence between a combination and joint reception on values Cmax, AUC for an amlodipin of a kamzilat, a lozartan and E-3174 in both doses, except for Cmax of a lozartan in a combination of 5/50 mg was shown. As therapeutic activity of a lozartan mostly is caused by its active metabolite, was concluded that the combination of 5/50 mg therapeutic is equivalent jointly to the appointed amlodipin of 5 mg and a lozartan of 50 mg.

Indications to use:

— arterial hypertension at patients to whom the combination therapy is shown.

Route of administration and doses:

Amzaar accept inside, irrespective of meal, with a small amount of water of 1 times/days. It is necessary to begin treatment with drug Amzaar in case of preliminary titration of doses of an amlodipin and a lozartan, respectively 1 tablet of Amzaar of 5 mg +50 mg or 5 mg +100 mg. If necessary direct transition from monotherapy amlodipiny or lozartany on therapy by drug Amzaar is possible.

Amzaar patients whose ABP in insufficient degree is controlled amlodipiny or lozartany in the same doses that are present at a combination (5/50 mg or 5/100 mg) can appoint.

The patients who are at the same time accepting лозартан and амлодипин can be translated on Amzaar with the same doses of these drugs.

With a renal failure at KK from 50 to 20 ml/min. dose adjustment is not required from patients. Amzaar is not recommended to apply at patients with KK less than 20 ml/min. and at patients on a hemodialysis as dose adjustment of components of drug can be required.

Amzaar's use for patients with reduced OTsK (for example is not recommended, at reception of diuretics in high doses). At the same time in case of completion of OTsK Amzaar's reception is possible if lower dose of a lozartan - 25 mg is not recommended.

Drug use Amzaar perhaps at patients with a liver failure (less than 9 points on a scale of Chayld-Pyyu) which according to the decision of the doctor allows appointment of a lozartan in a dose of 50 mg.

Amzaar it is possible to apply at patients 65 years at portability of a dose of a lozartan of 50 mg are more senior.

Amzaar is not recommended to apply at children and teenagers aged up to 18 years because of insufficiency of data on efficiency and safety in this group.

Features of use:

Use at pregnancy and feeding by a breast. Pregnancy. Amzaar is contraindicated at pregnancy, and his reception has to be immediately stopped at pregnancy establishment.

Toxic and lethal impact on an organism of a fruit and newborn. Amlodipin. The medicines which are directly influencing RAAS can cause damages and death of a fruit and the newborn at appointment to pregnant women. Isolated cases of use of APF inhibitors at pregnancy are described.

Use in II and III trimesters of pregnancy of the drugs which are directly influencing RAAS is connected with such damages of a fruit and the newborn as arterial hypotension, a neonatal hypoplasia of bones of a skull, an anury, a reversible and irreversible renal failure, death. Also cases of the oligogidroamnion which presumably developed as a result of reduced function of kidneys at a fruit were noted. In these cases олигогидроамнион it was associated with contractures of extremities, craniofacial deformations and a hypoplasia of lungs of a fruit. In addition, cases of premature births, delays of pre-natal development and a patent ductus arteriosus were noted, however bonds with influence of drug in these cases it was revealed not. The listed side effects, apparently, are not a consequence of use of drug in the first trimester of pregnancy. Nevertheless, the pregnant women accepting drugs MACAWS in the I trimester have to be surely informed on effects of reception of these drugs in the II-III trimesters.

Depending on duration of gestation it is possible to apply a stress test on uterine reductions, the besstressovy test or assessment of a biophysical profile of a fruit. At the same time, both the doctor, and the patient have to be informed that he олигогидроамнион can be shown after development of irreversible damages of a fruit. The children who were affected by drugs MACAWS in the anamnesis of in utero have to be under medical observation because of the increased probability of arterial hypotension, an oliguria and a hyperpotassemia. In case of an oliguria, first of all, correction of the ABP and renal perfusion is necessary. The exchange hemotransfusion or a hemodialysis are necessary for correction of arterial hypotension and/or as substitution of function of kidneys.

Lozartan. In II and III trimesters of pregnancy of the drugs operating on RAAS serious damages or even death of the developing fruit therefore at pregnancy establishment reception of a lozartan has to be immediately stopped can cause use. As the renal perfusion of a fruit depending on RAAS develops from the II trimester of pregnancy; the risk for a fruit increases at reception of a lozartan in II or the III trimester.

Lactation period. It is unknown whether there is excretion of an amlodipin and/or a lozartan in breast milk, but in preclinical trials at animals considerable concentration of an amlodipin and/or active metabolite of a lozartan in breast milk were noted. Amzaar is not recommended to apply during breastfeeding.

Use at abnormal liver functions. Drug use Amozartan is possible at patients with a liver failure (less than 9 points on a scale of Chayld-Pyyu) which according to the decision of the doctor allows appointment of a lozartan in a dose of 50 mg.

Use at renal failures. At clearance of creatinine from 50 to 20 ml/min. of dose adjustment it is not required. Amozartan is not recommended to apply at patients with clearance of creatinine less than 20 ml/min. and at patients on a hemodialysis as dose adjustment of components of drug can be required.

Use for children. Amozartan is not recommended to apply at patients more young than 18 years because of insufficiency of data on efficiency and safety in this group (see the section "Contraindications").

Use for elderly patients. Amozartan it is possible to use drug at patients 65 years at portability of a dose of a lozartan of 50 mg are more senior.

Special instructions. Patients with reduced OTsK. At patients with reduced OTsK (for example, at reception of high doses of diuretics, the expressed diarrhea, vomiting and other states leading to a hypovolemia) at the beginning of Amzaar's therapy symptomatic arterial hypotension can develop. Before Amzaar's appointment deficit of OTsK has to be eliminated. For patients whose daily dose of a lozartan makes 25 mg, Amzaar's use is not recommended.

The special instructions and precautionary measures relating to an amlodipin. Thanks to long T1/2 in a blood plasma, the vazodilatation which developed as a result of reception of an amlodipin can remain also after its cancellation. Thus, purpose of other vazodilatator after cancellation of an amlodipin should be carried out with care, at individual assessment of a dose, an interval of dosing and active control of a condition of the patient.

During treatment control of body weight and consumption of table salt, purpose of the corresponding diet is necessary. Maintenance of hygiene of teeth and frequentation of the stomatologist is necessary (for prevention of morbidity, bleeding and a hyperplasia of gums).

The special instructions and precautionary measures relating to a lozartan. The hyperpotassemia (content of potassium in plasma> 5.5 mmol/l) was noted at 1.5% of the patients accepting лозартан in the form of monotherapy. In one of these cases drug withdrawal was not required. Joint with lozartany purpose of kaliysberegayushchy diuretics (for example, Spironolactonum, Triamterenum, amiloride), drugs of potassium, kaliysoderzhashchy substitutes of salt, and also drugs which reception can lead to increase in potassium concentration in plasma (for example, heparin) has to be proved (especially at elderly patients with a renal failure), and the content of potassium has to be in plasma under control.

Reception of a lozartan can lead to the tranzitorny arterial hypotension accompanied with shock, a faint and short wind.

Patients with a liver failure. According to pharmacokinetics researches, at patients with cirrhosis substantial increase of concentration of a lozartan in plasma is observed. Use of a lozartan is not recommended at patients with a heavy liver failure (more than 9 points on a scale of Chayld-Pyyu), and also at patients with a liver failure (less than 9 points on a scale of Chayld-Pyyu) to whom the dose decline of a lozartan to 25 mg/days is recommended.

Patents with a renal failure. Owing to suppression of RAAS at a part of the patients accepting лозартан changes of function of kidneys, reversible at drug withdrawal, were noted.

At patients whose renal function can depend on activity of RAAS (for example, at chronic heart failure of the III-IV functional class on NYHA classification) use of APF inhibitors was followed by an oliguria and/or the accruing azotemia and, occasionally, acute renal failure and/or a lethal outcome. The similar picture was observed also at use of a lozartan for such patients. In clinical trials use of APF inhibitors for patients about one - or a bilateral renal artery stenosis, led to increase in concentration of creatinine and an urea nitrogen in plasma. The similar effect was observed also at reception of a lozartan at this group, it was reversible at drug withdrawal.

Influence on ability of driving and work with mechanisms. Patients should be careful at control of vehicles and other mechanisms at administration of drug Amzaar, considering risk of development of dizziness.

Side effects:

Determination of frequency of side reactions according to WHO: very often (> 1/10); often (> 1/100, <1/10); infrequently (> 1/1000, <1/100), it is rare (> 1/10 000, <1/1000) and is very rare (<1/10 000), including separate messages; frequency is unknown (it is impossible to estimate frequency according to the available data).

Co of the party of a nervous system: often - dizziness, a headache; infrequently - drowsiness.

From the alimentary system: infrequently - a lock, discomfort in a stomach, dyspepsia, vomiting, an ezofagealny reflux.

From skin and hypodermic fabrics: infrequently - a skin itch, a small tortoiseshell.

From cardiovascular system: infrequently - a heart consciousness, "inflows" of blood to face skin, orthostatic hypotension.

From respiratory system: infrequently - an asthma.

From an acoustic organ and labyrinth disturbances: infrequently - a rotatory vertigo.

From an urinary system: infrequently - the increased urination frequency.

General frustration: infrequently - an adynamy, discomfort or a stethalgia, feeling of overflow in a stomach, peripheral hypostases.

The side effects noted at reception of components of Amzaar (an amlodipin and a lozartan), can also be its potential side effects in spite of the fact that these side effects were not noted in clinical trials and in the post-registration period of use of Amzaar.

Amlodipin.

From a nervous system: often - a headache (especially in an initiation of treatment), dizziness, increased fatigue, drowsiness; infrequently - a febricula, hyperesthesias, paresthesias, a peripheral neuropathy, a tremor, sleeplessness, unusual dreams, a hyperexcitability, uneasiness; very seldom - migraine, apathy, agitation, an ataxy, amnesia, an adynamy, the increased sweating.

From mentality: infrequently - lability of mood, a depression.

From the alimentary system: often - nausea, abdominal pains; infrequently - vomiting, a lock or diarrhea, a meteorism, dyspepsia, anorexia, dryness of a mucous membrane of an oral cavity, thirst; seldom - a hyperplasia of gums, increase in appetite; very seldom - the pancreatitis, gastritis, jaundice (caused by a cholestasia), a hyperbilirubinemia, increase in activity of hepatic transaminases, hepatitis.

From cardiovascular system: often - a heart consciousness; infrequently - excessive decrease in the ABP; very seldom - a syncope, an asthma, a vasculitis, orthostatic hypotension, development or aggravation of a current of HSN, disturbance of a heart rhythm (including bradycardia, ventricular tachycardia and atrial fibrillation), a myocardial infarction, thorax pain, a fluid lungs, hypostases of the lower extremities.

From system of a hemopoiesis: very seldom - a Werlhof's disease, a leukopenia, thrombocytopenia.

From an urinary system: infrequently - the speeded-up urination, an urodynia, a nocturia; very seldom - a dysuria, a polyuria.

From generative organs and a mammary gland: infrequently - a gynecomastia, impotence.

From respiratory system: infrequently - short wind, rhinitis; very seldom - cough.

From a musculoskeletal system: infrequently - muscular spasms, a mialgiya, an arthralgia, a dorsodynia, arthrosis; seldom - a myasthenia.

From integuments: often - "inflows" of blood to face skin; seldom - exfoliative dermatitis, Stephens-Johnson's syndrome; very seldom - an alopecia, a xerodermia, cold sweat, disturbance of a xanthopathy.

Allergic reactions: very seldom - a skin itch, rash (including erythematic, makulo-papular rash, a small tortoiseshell), a Quincke's edema, a mnogoformny erythema, photosensitivity reactions.

From sense bodys: infrequently - a ring in ears, a diplopia, accommodation disturbance, a xerophthalmia, conjunctivitis, eye pain; very seldom - a parosmiya.

From a metabolism: very seldom - a hyperglycemia.

Others: infrequently - decrease in body weight, increase in body weight, nasal bleeding.

Lozartan.

From a nervous system: often - dizziness, an adynamy, a headache, fatigue the increased weakness, sleeplessness; infrequently - disturbance of cerebral circulation, a sleep disorder, drowsiness, a dysmnesia, a peripheral neuropathy, paresthesias, hyperesthesias, a tremor, an ataxy, a rotatory vertigo, a memory impairment, migraine, nervousness.

Disturbances of mentality: infrequently - concern, alarming disorder, confusion of consciousness, a depression, unusual dreams, panic frustration.

From the alimentary system: often - nausea, diarrhea, dyspepsia, an abdominal pain; infrequently - anorexia, taste disturbance, a lock, a dentagra, dryness in a mouth, a meteorism, gastritis, hepatitis, an abnormal liver function, pancreatitis.

From skin and hypodermic fabrics: infrequently - an alopecia, a xeroderma, skin rash, erubescence, Shenleyn-Genokh's purpura, a photosensitization, an itch, the increased sweating.

From cardiovascular system: infrequently - a myocardial infarction, stenocardia, disturbances of a heart rhythm (a ciliary arrhythmia, a sinus bradycardia, tachycardia, ventricular tachycardia, fibrillation of ventricles), a heart consciousness, orthostatic hypotension, a syncope (syncope), arterial hypotension, a vasculitis.

From blood and lymphatic system: infrequently - anemia; seldom - thrombocytopenia.

From respiratory system: often - short wind, bronchitis, dry cough, discomfort in a throat, nasal bleeding, rhinitis, laryngitis, a stethalgia.

From an acoustic organ and labyrinth disturbances: infrequently - a ring in ears.

From an urinary system: infrequently - disturbance of frequency of an urination, a nocturia, an infection of urinary tract, is very rare - a renal failure.

From an organ of sight: infrequently - a sight illegibility, feeling of a burning/prick in an eye, conjunctivitis, decrease in visual acuity.

From generative organs and a mammary gland: infrequently - decrease in a libido, impotence.

From a metabolism and food: infrequently - gout.

From a musculoskeletal system: often - spasms, skeletal and muscular pain, a swelling of joints, rigidity of joints; infrequently - an arthralgia, arthritis, fibromyalgia; seldom - рабдомиолиз.

Allergic reactions: infrequently - a small tortoiseshell, a Quincke's disease.

General frustration: a face edema, fever, an adynamy, the increased weakness.

Interaction with other medicines:

The hypotensive effect of Amzaar can amplify at simultaneous use with other antihypertensives therefore co-administration of various antihypertensives has to be proved.

Amlodipin. Amlodipin it is possible to apply safely to therapy of arterial hypertension together with thiazide diuretics, alpha adrenoblockers or APF inhibitors. Unlike other BMKK of clinically significant interaction of an amlodipin (the III generation of BMKK) it was not revealed at combined use with NPVS, including and with indometacin.

Strengthening of hypotensive action of BMKK at combined use with thiazide and "loopback" diuretics, APF inhibitors and nitrates, and also strengthening of their hypotensive action at combined use with alfa1-adrenoblockers, neuroleptics is possible.

Combined use of an amlodipin with CYP3A4 inhibitors demands careful control of symptoms of hypotension and peripheral hypostases. At co-administration of diltiazem in a dose of 180 mg/days and an amlodipina in a dose of 5 mg/days to elderly patients system exposure of an amlodipin increases by 60%.

Erythromycin at combined use raises Cmax of an amlodipin at young patients for 22%, and at elderly - for 50%. At the same time, strong CYP3A4 inhibitors (кетоконазол, итраконазол, ритонавир) can increase concentration of an amlodipin in plasma in a bigger degree.

In spite of the fact that exact quantitative assessment of interaction of an amlodipin and the inductors CYP3A4 (for example, the rifampicin, a St. John's Wort which is made a hole) is not received, against the background of their combined use constant control of the ABP is recommended.

Beta adrenoblockers at co-administration with amlodipiny can cause an aggravation of a course of heart failure.

Though when studying an amlodipin of negative inotropic effect usually did not observe, nevertheless, some BMKK can increase expressiveness of negative inotropic effect of the antiarrhytmic means causing lengthening of an interval of QT (for example, Amiodaronum and quinidine).

The single dose of 100 mg of a sildenafil at patients arterial hypertension does not exert impact on parameters of pharmacokinetics of an amlodipin.

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.

Ethanol (the drinks containing alcohol): амлодипин at single and repeated use in a dose of 10 mg does not influence ethanol pharmacokinetics.

Neuroleptics and изофлуран - strengthening of hypotensive action of derivatives of dihydropyridine.

At in introduction of a dantrolen against the background of treatment amlodipiny the collapse, arrhythmias, decrease in force of cordial reductions and a hyperpotassemia are possible.

Drugs of calcium can reduce effect of BMKK.

At combined use of an amlodipin with drugs of lithium strengthening of manifestation of a neurotoxicity (nausea, vomiting, diarrhea, an ataxy, a tremor, a sonitus) is possible.

Amlodipin does not change cyclosporine pharmacokinetics.

Also its renal clearance does not exert impact on concentration in blood serum of digoxin.

Has no significant effect on effect of warfarin (prothrombin time).

Cimetidinum does not influence pharmacokinetics of an amlodipin.

In the researches in vitro амлодипин does not influence linkng with proteins of a blood plasma of digoxin, Phenytoinum, warfarin and indometacin.

Grapefruit juice: the concomitant single dose of 240 mg of grapefruit juice and 10 mg of an amlodipin inside is not followed by essential change of pharmacokinetics of an amlodipin.

Aluminum - or magniysoderzhashchy antacids: their single dose has no significant effect on pharmacokinetics of an amlodipin.

Lozartan. As well as at use of other means blocking formation of angiotensin II and its effects, the accompanying purpose of kaliysberegayushchy diuretics (for example, Spironolactonum, Triamterenum, amiloride), potassium additives and kaliysoderzhashchy substitutes of salt, can lead to increase in content of potassium in blood serum.

With renal failures which received treatment of NPVS including the selection TsOG-2 inhibitors, co-administration of APF inhibitors and/or drugs MACAWS, including лозартан, can cause further deterioration in function of kidneys up to development of an acute renal failure in some patients. Usually this effect is reversible. NPVS, including the selection TsOG-2 inhibitors, can reduce effect of blockers of receptors of angiotensin II, including лозартан. Therefore the hypotensive effect of antagonists of receptors of angiotensin II can be weakened at simultaneous use of NPVS, in particular, of the selection TsOG-2 inhibitors. Thus, simultaneous use of Amzaar with NPVS needs to be carried out with care at patients with a renal failure.

Double blockade of RAAS: it is established that at patients with atherosclerosis, heart failure or diabetes with damage of target organs double blockade of RAAS (simultaneous use of APF inhibitors and drugs MACAWS) is associated with more frequent complications of therapy in the form of arterial hypotension, a faint (syncope), a hyperpotassemia and renal failures (including, an acute renal failure) in comparison with monotherapy by each drug. In this regard, the combined treatment by APF inhibitors and drugs MACAWS demands the individualized approach and constant control of functional activity of kidneys.

Significant interaction of drug with such medicines as a hydrochlorothiazide, digoxin, warfarin, Cimetidinum and phenobarbital was not noted pharmacokinetically.

Reception of Rifampinum, the inductor of medicinal metabolism, reduces concentration of a lozartan and its active metabolite.

At the person two inhibitors of an isoenzyme CYP3A4 are studied. Ketokonazol does not influence biotransformation of the lozartan entered intravenously to an active metabolite, and erythromycin does not render clinically significant effect on pharmacokinetics of a lozartan at intake.

Flukonazol, CYP2C9 isoenzyme inhibitor, reduces concentration of an active metabolite and increases concentration of a lozartan in a blood plasma, however, the pharmakodinamichesky importance of combined use of a lozartan and inhibitors of an isoenzyme CYP2C9 is not established. It is shown that persons whose organism will not transform лозартан to an active metabolite have very rare and specific defect of an isoenzyme of CYP2C9. These data demonstrate that biotransformation of a lozartan to an active metabolite is mediated preferential by CYP2C9 isoenzyme, but not CYP3A4.

Contraindications:

— a heavy liver failure (more than 9 points on a scale of Chayld-Pyyu);

— hemodynamically expressed stenosis of the mouth of an aorta;

— shock;

— age up to 18 years (efficiency and safety are not established);

— heavy arterial hypotension;

— pregnancy;

— period of a lactation (breastfeeding);

— hypersensitivity to drug components.

With care:

— patients with reduced OTsK, for example, at reception of diuretics in high doses, the expressed diarrhea, vomiting and other states leading to a hypovolemia;

— the patients who are on a diet with restriction of table salt;

— patients with a renal failure (KK <20 ml/min.) and the patients who are on a hemodialysis;

— hyperpotassemia;

— arterial hypotension;

— a liver failure (less than 9 points on a scale of Chayld-Pyyu);

— SSSU (the expressed bradycardia, tachycardia);

— chronic heart failure of not ischemic etiology (the II-IV functional class on NYHA classification);

— aortal stenosis, mitral stenosis;

— hypertrophic subaortic stenosis;

— an acute myocardial infarction (and within 1 month after it);

— advanced age.

Overdose:

Cases of overdose of Amzaar are unknown. Data on overdose of an amlodipin and lozartan, accepted separately are included below.

Amlodipin. Symptoms: the overdose of an amlodipin can lead to an excessive peripheral vazodilatation and, perhaps, reflex tachycardia. In the described cases the long-term expressed hypotensive effect was noted, up to a depressed case and a lethal outcome.

Treatment: reception of absorbent carbon by healthy volunteers directly or during 2 h after intake of 10 mg of an amlodipin considerably reduces absorption of the last. If necessary the gastric lavage is shown. Clinically significant arterial hypotension at Amzaar's overdose demands carrying out a package of measures for normalization of a condition of cardiovascular system, it is necessary to raise the patient's legs, to exercise constant control behind functional indicators of heart and respiratory system, OTsK and volume of a diuresis. For recovery of a tone of vessels and the ABP introduction of vasoconstrictors can be required, previously having convinced of lack of contraindications to their use. For elimination of blockade of calcium channels effectively intravenous administration of calcium of a gluconate. Removal of an amlodipin by means of a hemodialysis is improbable.

Lozartan. The person has limited data on overdose of drug. Symptoms: arterial hypotension and tachycardia; development of bradycardia owing to parasympathetic (vagal) stimulation is possible.

Treatment: when developing symptomatic arterial hypotension, it is necessary to appoint a maintenance therapy. лозартан, its active metabolite can be removed from an organism by means of a hemodialysis.

Storage conditions:

Drug should be stored in the place, unavailable to children, at a temperature not above 30 °C. A period of validity - 2 years (in blisters), 3 years (in bottles).

Issue conditions:

According to the recipe

Packaging:

10 pieces - blisters (1) - packs cardboard.
10 pieces - blisters (3) - packs cardboard.
300 pieces - bottles polyethylene (1) - packs cardboard.