Amlotenzin

General characteristics. Structure:

Active ingredients: 4 mg of a perindopril rub - butylamine; 5 mg of an amlodipin (in the form of a besilat); 4 mg of a perindopril rub - butylamine; 10 mg of an amlodipin (in the form of a besilat); 8 mg of a perindopril rub - butylamine; 5 mg of an amlodipin (in the form of a besilat); 8 mg of a perindopril rub - butylamine; 10 mg of an amlodipin (in the form of a besilat).

Excipients: sodium krakhmalglikolit type A, sodium of a stearil fumarates, lactose monohydrate.

Structure of a solid gelatin capsule. For a dosage of 4 mg / 5 mg: titanium dioxide (E171), gelatin.

The fixed combination of two most modern anti-hypertensive drugs — a perindoprila and an amlodipina, allows effectively and safely, in the correct terms, to lower the ABP at patients with any degree of arterial hypertension.

For a dosage of 4 mg / 10 mg: crimson 4R (E124), orange yellow (E110), quinolinic yellow (E104), patent blue V (E131), titanium dioxide (E171), gelatin. for a dosage of 8 mg / 5 mg: orange yellow (E110), quinolinic yellow (E104), titanium dioxide (Е 171), gelatin.

For a dosage of 8 mg / 10 mg: azoruby (E122), crimson 4R (E124), quinolinic yellow (E104), titanium dioxide (Е 171), gelatin.

Indications to use:

Amlotenzin is shown for treatment of essential hypertensia and/or a stable disease of the coronary arteries demanding treatment perindoprily and amlodipiny.

Route of administration and doses:

For intake. To accept on one capsule once a day (it is more preferable in the morning) before food.

The combination of the fixed doses is not intended to start anti-hypertensive therapy. At therapeutic need the dose of drug can be changed on the basis of individual selection of doses of separate components.

Patients with a renal failure and elderly patients. At these categories of patients removal of a perindoprilat is slowed down. Therefore at such patients it is regularly necessary to control concentration of creatinine and potassium in a blood plasma. Amlotenzin can be appointed to patients with KK> 60 ml/min. and does not suit patients with KK <60 ml/min. Individual selection of doses of a perindopril and amlodipin is recommended to such patients.

The usual mode of reception is recommended to elderly patients, but increase in a dose has to be carried out with care. Change of concentration of an amlodipin in a blood plasma does not correlate with degree of manifestation of a renal failure.

Patients with a liver failure. It is necessary to be careful at purpose of drug Amlotenzin to patients with a liver failure due to the lack of recommendations about a drug dosing at such patients. Patients with a heavy liver failure should appoint drug from the lowest doses and to titrate slowly.

Children and teenagers up to 18 years. It is not necessary to appoint drug due to the lack of data on efficiency and safety of use of a perindopril and amlodipin for these groups of patients both in the form of monotherapy, and in the form of a combination therapy

Features of use:

All instructions connected with each of components separately, which are listed below extend to the fixed combination Amlotenzin.

Connected with perindoprily.
The increased sensitivity / the Quincke's disease. The patients undergoing treatment by APF inhibitors have rare messages on a Quincke's disease of the face, extremities, lips, mucous membranes, language, a glottis and/or throat, including perindoprit. These reactions can come at any time during therapy. In such cases when hypostasis affected only a face and lips, it passed without any treatment though reception of anti-histamine drugs helped to facilitate symptoms.

The Quincke's disease which is followed by throat hypostasis can lead to a lethal outcome. At a paraglossa, a glottis or a throat at which obstruction of respiratory tracts is probable, it is necessary to give immediately first aid which can include purpose of adrenaline and/or maintenance of free respiratory tracts. The patient has to be under fixed medical observation before total and final disappearance of symptoms.

The increased risk of approach of a Quincke's disease at reception of APF inhibitors exists at the patients who transferred the Quincke's disease which is not connected with reception of APF inhibitors.

It was in rare instances reported about interstinal hypostasis at the patients accepting therapy by APF inhibitors, shown abdominal pains, with or without nausea and vomiting. Interstinal hypostasis has to be included in differential diagnosis at the patients accepting APF inhibitors and feeling an abdominal pain.

Anaphylactoid reactions when holding procedures of an aferez of a lipoprotein of the low density (LPNP). Approach of anaphylactoid reactions at some patients who are on a hemodialysis with use of the high-line membranes or patients receiving procedures of an aferez of LPNP by means of dekstrasulfatny absorption at purpose of APF inhibitors is possible. For prevention – temporary cancellation of APF inhibitor every time before carrying out an aferez.

Anaphylactic reactions during desensitization. Anaphylactoid reactions came at some patients receiving APF inhibitors during the desensibilizing therapy (for example, gimenopterichesky poison). At some patients of these reactions it was possible to avoid by temporary cancellation of APF inhibitor, but they came in a sluachaa of careless administration of drug again.

Нейтропения/Агранулоцитоз/Тромбоцитопения/Анемия. At the patients accepting APF inhibitors the neutropenia/agranulocytosis, thrombocytopenia and anemia were noted. At patients with function of a liver is normal also lack of other complicating factors, the neutropenia comes seldom. At reception of a perindopril patients should observe extra care with kollagenozno-vascular diseases, to the patients undergoing immunodepressantny therapy, treatment by Allopyrinolum or prokainomidy or those who has all these complicating factors, in particular, at already available abnormal liver functions. At some of such patients serious infections developed. In some cases the intensive care turned out antibiotics unsuccessful. At purpose of a perindopril such patients are recommended to carry out periodic monitoring of calculation of leukocytes and to instruct patients about need to report about any symptoms of an infection (for example, pharyngalgias, heat).

Precautionary measures at the prima. Risk of hypotension: APF inhibitors can cause falling of arterial pressure. Hypotension with clinical manifestations seldom develops at hypertensive patients without associated diseases, more often it arises at patients with reduced OTsK (accepting diuretics, being on a diet with limited consumption of salt, patients on dialysis, the patients having diarrhea or vomiting) or at patients with heavy a renin - dependent hypertensia. Patients with the increased risk of approach of hypotension with clinical manifestations at treatment by Amlotenzin should carry out careful monitoring of arterial pressure, renal function and level of potassium in serum.

In case of development of hypotension, it is necessary to put the patient on a back and, if necessary, to fill OTsK by intravenous administration of 0,9% of solution of sodium chloride (9 mg/ml). The coming hypotension is not a contraindication for further administration of drug which can usually be continued surely after arterial pressure increased owing to increase in OTsK again.

Stenosis of an aorta and mitral valve / hypertrophic cardiomyopathy. As well as other APF inhibitors, perindoprit it is necessary to appoint with extra care to patients with a stenosis of the mitral valve and obstruction of an output path of a left ventricle, for example, with a stenosis of an aorta or a hypertrophic cardiomyopathy.

Renal failure. At a renal failure (the clearance of creatinine <60 ml/min.) is recommended individual titration of a dose of separate components. At patients with a renal failure usual medical examination has to include monitoring of level of potassium and creatinine.

At some patients with a bilateral renal arterial stenosis or a stenosis of an artery of the only kidney undergoing treatment by APF inhibitors cases of increase in level of urea in blood and creatinine in serum which were reversible at the therapy termination were noted. It is the most probable at patients with a renal failure. At renovascular hypertensia there is also an increased risk of heavy hypotension and renal failure.

At some patients with a hypertension without visible disturbance of vessels of kidneys increase in concentration of urea in blood and creatinine in serum was noted, usually it had insignificant and the passing character, especially at the combined reception of a perindopril and diuretic. It is the most probable at the patients who already have a renal failure.

Liver failure. In rare instances reception of APF inhibitors was followed by a syndrome which begins with cholestatic jaundice and progresses in a fulminantny necrosis of a liver and (sometimes) comes to an end with a lethal outcome. The mechanism of this syndrome is still unclear. The patients receiving APF inhibitors at which jaundice develops or considerably the level of enzymes of a liver increases, have to stop reception of APF inhibitors and undergo careful medical examination.

Cough. At therapy APF inhibitors noted cough cases. The unproductive, ongoing cough passing with the therapy termination is characteristic. The cough caused by APF inhibitor reception should be considered as a part of differential diagnosis of cough.

Surgical intervention / anesthesia. At surgical intervention or during anesthesia the drugs causing hypotension, Amlotenzin can block formation of angiotensin II, as a result of compensatory release of a renin. It is recommended to stop treatment a day before operation. At approach of the hypotension which is presumably connected with this mechanism of action it is necessary to increase OTsK.

Hyperpotassemia. At some patients undergoing treatment by APF inhibitors, including perindoprily cases of the increased content of potassium in blood serum were noted. Risk factors for development of a hyperpotassemia: a renal failure, deterioration in function of kidneys, age> 70 years, a diabetes mellitus, the accidental phenomena, such as an organism obezvozhennost, an acute cordial decompensation, a metabolic acidosis, a concomitant use of kaliysberegayushchy diurtik (Spironolactonum, эплеренон, Triamterenum or amiloride), potassium additives or kaliysoderzhashchy substitutes of salt, and also reception of other medicines causing increase in level of potassium in serum (for example, heparin). Reception of potassium additives, kaliysberegayushchy diuretics and kaliysoderzhashchy substitutes of salt, especially to patients with an abnormal liver function, can potvest to the significant growth of level of potassium in serum. The hyperpotassemia can cause serious, sometimes fatal, arrhythmia. In need of the accompanying purpose of a perindopril and the above-stated drugs, their reception has to be carried out with care and at regular monitoring of content of potassium in blood serum.

Patients with the diabetes accepting peroral antidiabetic drugs or insulin within the first month treatment by APF inhibitor should carry out careful glycemic control.

Connected with amlodipiny.
Precautionary measures at reception. Safety and efficiency of an amlodipin at hypertensive crisis was not established.

At patients with the damaged function of a liver the elimination half-life is extended and AUC values are higher, the recommended doses are not established therefore it is necessary to begin reception with care, from the lowest doses of a scale of a dosage and also to be careful at increase in a dose. Patients with a heavy liver failure need slow titration of a dose and careful observation.

Treatment of patients with heart failure demands care. In long-term placebo - a controlled research at patients with heavy heart failure (NYHA a class III and IV) cases of a fluid lungs were higher at the patients in group accepting therapy amlodipiny than in group of placebo. Blockers of calcium channels, including амлодипин, have to be applied with care at patients with congestive heart failure since at them the risk of cardiovascular complications and mortality in the future can increase.

Increase in a dosage at elderly patients has to be carried out with care.

Use of an amlodipin for patients with a renal failure can be used in usual doses. Changes of concentration of an amlodipin in plasma do not correlate with degree of a renal failure, амлодипин is not removed by dialysis. During treatment drug recommends to exclude the use of alcoholic beverages.

At Amlotenzin's use it is necessary to use adequate measures of contraception. This medicine contains lactoses monohydrate, it is not necessary to appoint to patients with a rare inherited disorder of tolerance to a galactose, hereditary deficit of lactase or a syndrome of disturbance of absorption of a klyukozy-galactose.

Amlotenzin is contraindicated to use at pregnancy and in the period of a lactation (breastfeeding).

It is not recommended to the prima to children up to 18 years, due to the lack of data on efficiency and safety of use for children.

In need of control of motor transport in work with mechanisms during use of drug it is necessary to consider possibility of dizziness or fatigue.

Side effects:

Frequency of undesirable reactions which were observed or during conduct of clinical trials or were received from spontaneous messages on development of undesirable reactions is defined as follows: often (> 1/100 - <1/10); infrequently (> 1/1000 - <1/100); seldom (> 1/10 000 - <1/1000); very seldom (<1/10 000), it is unknown (frequency cannot be determined by the data which are available for today).

The side effects connected with amlodipiny.

Disturbances from blood and lymphatic system. Very seldom: Leukopenia, neutropenia, thrombocytopenia.

Disturbances of metabolism and food. Very seldom: hypoglycemia. Infrequently: increase in body weight, decrease in body weight.

Mental disorders. Infrequently: sleeplessness, changes of mood.

Disturbances from a nervous system: Often: drowsiness, dizziness, headache. Infrequently: tremor, giposteziya, paresthesia. Very seldom: hyper tone, peripheral neuropathy.

Disturbances from an organ of sight. Infrequently: visual disturbances.

Disturbances from an acoustic organ. Infrequently: sonitus.

Cordial frustration. Often: cardiopalmus. Infrequently: to a syncope. Seldom: stenokardichesky pain. Very seldom: a myocardial infarction, it is possible owing to an excessive lowering of arterial pressure at patients of group of high risk; arrhythmia (including bradycardia ventricular tachycardia and fibrillation of auricles).

Vascular disorders. Often: hyperemia. Infrequently: the hypotension and effects connected with hypotension. Very seldom: vasculitis.

Disturbances from a GIT. Very seldom: hyperplasia of gums. Often: abdominal pain, nausea. Infrequently: vomiting, dyspepsia, disturbance of a vermicular movement of intestines, dryness in a mouth, taste change. Very seldom: pancreatitis, gastritis.

Gepatobiliarnye disturbance. Very seldom: hepatitis, cholestatic jaundice.

Disturbances from skin and hypodermic fabrics. Very seldom: Quincke's edema, erythema (different types). Infrequently: an alopecia, a purpura, skin discolorations, the strengthened sweating, an itch, rash. Very seldom: photosensitivity, Stephens-Johnson's syndrome.

From a musculoskeletal system. Often: flowing off of anklebones. Infrequently: arthralgia, mialgiya, mialgiya, muscular spasms, dorsodynia.

Disturbances from kidneys and urinary tract. Infrequently: disturbance of an urination, nocturia, increase of an urination.

Disturbances from reproductive system and a mammary gland. Infrequently: impotence, gynecomastia.

Complications of the general character and reaction in an injection site. Often: hypostasis, peripheral hypostasis, fatigue. Infrequently: stethalgia, adynamy, pain, indisposition.

Laboratory indicators. Very seldom: increase in activity of enzymes: ALT, nuclear heating plant (usually corresponds to a cholestasia).

The side effects connected with perindoprily.

Disturbances from blood and lymphatic system. Very seldom: a leukopenia/neutropenia, an agranulocytosis or a pancytopenia, thrombocytopenia, hemolitic anemia at patients with inborn insufficiency of G-6PDH.

Disturbances from immune system. Very seldom: allergic reactions: small tortoiseshell.

Disturbances of metabolism and food. Frequency is unknown: hypoglycemia.

Mental disorders. Infrequently: changes of mood, frustration of a dream.

Disturbances from a nervous system. Often: dizziness, headache, paresthesia, вертиго. Very seldom: confusion of consciousness.

Disturbances from an organ of sight. Often: visual disturbances.

Disturbances from an acoustic organ. Often: sonitus.

Cordial frustration. Very seldom: stenocardia, a myocardial infarction, it is possible owing to an excessive lowering of arterial pressure at patients of group of high risk, arrhythmia (including bradycardia ventricular tachycardia and fibrillation of auricles).

Vascular disorders. Often: the hypotension and effects connected with hypotension. Very seldom: a stroke, it is possible owing to excess decrease in the ABP at patients of group of high risk. Frequency is unknown: vasculitis.

Disturbances from a GIT. Often: abdominal pain, nausea, vomiting, dyspepsia, dysgeusia, diarrhea, lock. Infrequently: dryness in a mouth. Very seldom: pancreatitis.

Gepatobiliarnye disturbance. Very seldom: hepatitis, cholestatic jaundice.

Disturbances from skin and hypodermic fabrics. Infrequently: Quincke's disease of the person, extremities, lips, mucous membranes, language, throat, throat, perspiration. Very seldom: erythema. Often: itch, rash.

From a musculoskeletal system. Often: muscular sudorg.

Disturbances from kidneys and urinary tract. Infrequently: renal failures. Very seldom: acute renal failure.

Disturbances from reproductive system and a mammary gland. Infrequently: impotence.

Complications of the general character and reaction in an injection site. Often: adynamy.

Laboratory indicators. Seldom: Increase in level of bilirubin and activity of liver enzymes in serum. Frequency is unknown: increase in serumal concentration of urea and creatinine, hyperpotassemia.

Interaction with other medicines:

Connected with perindoprily. The patients accepting diuretic drugs especially at patients with decrease have volemias and/or deficit of salt, after the beginning treatment by APF inhibitor can be observed the expressed lowering of arterial pressure. At diuretic cancellation, increase in OTsK or reception of salt before an initiation of treatment, and also purpose of low initial doses of a perindopril and their gradual increase reduces risk of development of hypotension.

At some patients accepting perindoprit, there can come the hyperpotassemia though usually the content of potassium remains within norm. The combined reception of a perindopril with kaliysberegayushchy diuretics (for example, Spironolactonum, Triamterenum or amiloride), potassium additives and kaliysoderzhashchy substitutes of salt is not recommended, owing to possible substantial increase of level of potassium in blood serum. If simultaneous use of these drugs is necessary because of the expressed hypopotassemia, then at their reception it is necessary to observe extra care and to carry out private monitoring of content of potassium in blood serum.

At a concomitant use of lithium and APF inhibitors there were cases of reversible increase in concentration of lithium in serum and toxicity cases. The accompanying reception of thiazide diuretics can increase risk of toxicity of lithium and strengthen the risk of toxicity of lithium which is already increased owing to reception of APF inhibitors. Perindoprit a combination and lithium is not recommended, but if the combined reception is necessary, then it is necessary to carry out careful monitoring of level of lithium in blood serum.

Use of NPVP, including aspirin> = 3 g/day, can reduce hypotensive effect of APF inhibitors. NPVP and APF inhibitors render the additive effect on increase in content of potassium in a blood plasma that can lead to deterioration in function of kidneys. These effects have reversible character. In rare instances the renal failure, especially at patients with a renal failure, for example, at elderly patients can develop or at an organism obezvozhennost.

The accompanying reception of hypotensive and vasodilating drugs can lead to strengthening of hypotensive action of a perindopril. The concomitant use of nitroglycerine and other nitrates or other vasodilators, can lead to further decrease in the ABP.

The combined reception of APF inhibitors and antidiabetic drugs (insulin, peroral hypoglycemic drugs) can lead to strengthening of effect of decrease in level of glucose in the blood with risk of approach of a gipoklikemiya arising in the first weeks of the combined treatment and at patients with a renal failure.

The concomitant use of APF inhibitors with some anesthetics, tricyclic antidepressants and antipsychotic drugs can lead (neuroleptics) to a further lowering of arterial pressure and increase in risk of development of orthostatic hypotension.

At combined use with sympathomimetics the hypotensive effect of APF inhibitors can decrease.

Perindopril can be appointed along with acetylsalicylic acid (use as a trombolitik), with trombolitika, beta-blockers and/or nitrates.

Antiacid drugs and tetracyclines reduce the speed and completeness of absorption of a perindopril from a GIT.

Nitritoidny reactions (include rushes of blood to the person, nausea, vomiting and hypotension) at simultaneous use with gold injections (sodium ауротиомалат) and APF inhibitors were seldom noted.

Alcohol strengthens hypotensive effect of APF inhibitors.

Connected with amlodipiny.
Not recommended combinations: Dantrolen (infusion). At animals at reception of verapamil and a dantrolen in/in the fibrillation of ventricles and a cardiovascular collapse associated with a hyperpotassemia, leading to a lethal outcome were observed. Because of risk of a hyperpotassemia it is recommended to avoid combinations with blockers of calcium channels, such as амлодипин, at the patients inclined to a malignant hyperthermia and at treatment of a malignant hyperthermia.

The combinations demanding care. The inductors CYP3A4 – are not present data on their effect on амлодипин. Simultaneous to the prima of an amlodipin with the inductors CYP3A4 (rifampicin, Hypericum perforatum (the St. John's Wort which is made a hole)) can lead to decrease in plasma concentration of an amlodipin. Amlodipin along with the inductors CYP3A4 has to be applied with care.

CYP3A4 inhibitors: the simultaneous primneniye of an amlodipin with strong silt moderate CYP3A4 inhibitors (protease inhibitors, azolny antifungal means, macroleads, such as erythromycin or кларитромицин, verapamil or diltiazem) can be led to significant increase in exposure of an amlodipin. The clinical effect of these changes can be shown more at elderly patsiyet. In such cases clinical monitoring and correction of a dose can be necessary.

The effect of an amlodipin reduces pressure, supplementing effect of other anti-hypertensive drugs.

In clinical trials of interaction амлодипин did not make impact on pharmacokinetics of an atorvastatin, digoxin, warfarin or cyclosporine.

Reception of an amlodipin with grapefruit or grapefruit juice is not recommended since at some patients bioavailability of an amlodipin can increase that can lead to increase in effect of pressure decrease.

Connected with Amlotenzin.
The combinations demanding extra care. Baclofenum: increases expressiveness of hypotensive effect. To carry out monitoring of arterial pressure and renal function, and also, if necessary, to adapt a dose of anti-hypertensive drug.

The combinations demanding care:
- hypotensive drugs (such as beta-blockers) and vazodilatator: the combined reception of these drugs can lead to strengthening of hypotensive effect of a perindopril and amlodipin. The combined reception of nitroglycerine, other nitrates or vazodilatator can lead to a further lowering of arterial pressure and, therefore, has to be appointed with care;
- corticosteroids, тетракозакид: reduce hypotensive effect (the delay of salt and water caused by action of corticosteroids);
- alpha blockers (Prazozinum, алфузозин, доксазозин, тамсулозин, теразозин): strengthening of hypotensive effect and the increased risk of development of orthostatic hypotension;
- амифостин: possible strengthening of hypotensive effect of an amlodipin;
- tricyclic antidepressants / antipsychotic drugs / the anesthetizing drugs: strengthening of hypotensive effect and the increased risk of development of orthostatic hypotension.

Contraindications:

Connected with perindoprily:

- hypersensitivity to a perindopril or other APF inhibitors;

- the Quincke's disease in the anamnesis connected with the previous therapy by APF inhibitors;

- hereditary or idiopathic Quincke's disease;

- pregnancy and period of a lactation (breastfeeding).

Connected with amlodipiny:

- the expressed hypotension;

- hypersensitivity to an amlodipin or to other dihydropyridines;

- shock, including cardiogenic shock;

- obstruction of the taking-out path of a left ventricle (for example at a heavy aortal stenosis);

- heart failure after an acute myocardial infarction (during the first 28 days).

Connected with amlotenziny:

- hypersensitivity to auxiliary components of drug;

- hereditary intolerance of a galactose. deficit of lactase or malabsorption of a glucose/galactose.

Overdose:

Information on drug overdose Amlotenzin at people is absent.

Symptoms. The overdose of an amlodipin according to the available data can lead to excessive vasodilation and possible reflex tachycardia.

Treatment. Clinically significant hypotension caused by overdose of an amlodipin demands support of parameters CCC, including regular monitoring of cordial and respiratory function, a raising of extremities and control of volume of the circulating blood and volume of the emitted urine.

Vasopressor drugs if to their reception there are no contraindications, can help to recover a vascular tone and arterial pressure, intravenous administration of a gluconate of calcium can help to eliminate effects of blockade of calcium channels.

Due to the high ability of an amlodipin contacts proteins, dialysis is ineffective.

Perindoprit symptoms of overdose, as well as all APF inhibitors, can include hypotension, circulator shock, disturbance of electrolytic balance, a renal failure, a hyperventilation, tachycardia, a cardiopalmus, bradycardia, dizziness, uneasiness, cough.

Treatment: it is recommended to carry out intravenous infusion with usual normal saline solution. In case of development of hypotension of the patient it is necessary to put on a back. At an opportunity it is necessary to consider treatment option angiotensin II in the form of infusion and/or intravenous administration of catecholamines. Perindopril is brought from a system blood-groove by a hemodialysis. At bradycardia, resistant to therapy, carrying out electrocardiostimulation is shown. It is necessary to control constantly the vital indicators, level of electrolytes and creatinine in serum.

Storage conditions:

In the place protected from moisture and light at a temperature not above 25 °C. To store in the place, unavailable to children. Period of validity 2 years.

Issue conditions:

According to the recipe

Packaging:

On 10 capsules in a blister strip packaging. On the 3rd blister strip packagings together with the application instruction in a pack from a cardboard.