Pharmacological properties

Pharmacodynamics

action Mechanism. Indapamid is derivative sulfonamides with an indolovy ring, pharmacological related to thiazide diuretics, acts by sodium reabsorption inhibition in a cortical segment of kidneys. It increases excretion of sodium and chlorides with urine and, to a lesser extent, potassium and magnesium, raising thus a mocheotdeleniye and providing antihypertensive action.

Amlodipin — the inhibitor of receipt of calcium ions of group of dihydropyridines (a blocker of slow calcium channels or the antagonist of calcium ions) interfering transmembrane receipt of calcium ions in unstriated muscles of a myocardium and vessels.

Mechanism of antihypertensive action of an amlodipin consists in its ability to relax unstriated muscles of vessels.

Pharmakodinamichesky effects. Clinical trials of II and III phase showed that at use of an indapamid in monotherapy the antihypertensive effect lasts 24 h. This effect is shown in doses in which diuretic properties are minimum. Antihypertensive action of an indapamid is connected with improvement of elasticity of arteries, decrease in resistance of arterioles and OPSS. Indapamid reduces a hypertrophy of a left ventricle.

When exceeding a certain dose the therapeutic effect of thiazide and tiazidopodobny diuretics does not increase whereas the quantity of by-effects increases. In case of lack of effect of treatment it is not necessary to raise a dose.

to

Also during the short, average and long-term researches with participation of patients with AG it was shown that indapamid:

• does not influence metabolism of lipids (TG, LPNP and LPVP);
• does not influence metabolism of carbohydrates, even at patients with diabetes with AG.

reception of an amlodipin of 1 times a day provides to

At patients with AG clinically reliable decrease in the ABP for 24 h in a prone position and standing. Because of the slow beginning of action of an amlodipin its use does not lead to acute hypotension. Reception of an amlodipin was not connected with emergence of any metabolic side reactions or changes of level of lipids in blood plasma therefore it can be applied at patients with OH, gout and diabetes.

Pharmacokinetics. The concomitant use of an indapamid and an amlodipin does not change their pharmacokinetic properties in comparison with their separate use.

Indapamid. The uniform prolonged release of an indapamid is provided thanks to a matriksny system in which active ingredient is distributed.

Absorption. Indapamid who is released from a tablet is quickly and completely soaked up in a GIT. Meal increases absorption speed a little, but does not affect amount of the absorbed active ingredient.

C _max in blood plasma is reached approximately in 12 h after oral administration of a single dose, repeated use reduces fluctuations of level of an indapamid in blood plasma between two administrations of drug. There is an intraindividualny variability.

Distribution. Linking of an indapamid with proteins of blood plasma — 79%. T _½ makes 14–24 h (on average — 18 h). Level of stable concentration is reached in 7 days. Repeated reception does not lead to cumulation.

Removal. It is removed mainly with urine (70% of a dose) and a stake (22%) in the form of inactive metabolites.

Patients of high risk. At patients with a renal failure the pharmacokinetic parameters do not change.

Amlodipin. Release of an amlodipin happens immediately.

Absorption, distribution, linking with proteins of blood plasma. After oral administration in therapeutic doses amlodipin it is well absorbed, the C _max in blood is reached in 6–12 h after reception. The absolute bioavailability is 64–80%. The volume of distribution is about 21 l/kg. The researches in vitro showed that about 97.5% of the circulating amlodipin contact proteins of blood plasma. Meal does not affect bioavailability of an amlodipin.

Biotransformation/removal. T _½ amlodipina makes about 35-50 h of blood plasma that corresponds to a single dose. Amlodipin is extensively metabolized by a liver to inactive metabolites. With urine 60% of the entered dose of which 10% make amlodipin in not changed look are removed.

Use to patients with an abnormal liver function. The amount of clinical data on use of an amlodipin for patients with an abnormal liver function is limited. At patients with a liver failure the clearance of an amlodipin decreases that leads to increase in T _½ and AUC indicator approximately for 40–60%.

Use for patients of advanced age. Time of achievement of the C _max an amlodipina in blood plasma at elderly people and at young patients is identical. At patients of advanced age the tendency to decrease in clearance of an amlodipin is noted that leads to increase in AUC and T _½ . Persons with stagnant heart failure had an expected for the studied age group of patients increase in AUC and T _½.

Indication

Lecheniye ag at patients who need treatment indapamidy and amlodipiny in the doses which are available in the fixed combinations.

Use

For oral administration.

for

1 tablet a day once, it is desirable in the morning before food. Swallow of a tablet entirely, without chewing, washing down with water. The maximum daily dose — 1 tablet (1.5 mg / 10 mg).

Use of the fixed combination is not provided by

for therapy initiation.

should carry out by

In need of change of a dose individual titration of each of combination components.

Special groups of patients

Patients with a renal failure (see CONTRAINDICATIONS and SPECIAL INSTRUCTIONS). In a renal failure of heavy degree (clearance of creatinine of 30 ml/min.) the medicament treatment is contraindicated. For patients with renal failures easy and moderate severity of correction of the recommended dose is not required.

Patients of advanced age (see. Special INSTRUCTIONS and PHARMACOLOGICAL PROPERTIES). Patients of advanced age Arifam should apply taking into account function of kidneys.

Patients with an abnormal liver function (see CONTRAINDICATIONS and SPECIAL INSTRUCTIONS). In heavy abnormal liver functions the medicament treatment is contraindicated.

are not established to

For patients with abnormal liver functions of light and moderate severity of the recommendation concerning dosing of an amlodipin therefore the dose should be selected with care and to begin treatment with the lowest dose (see. Special INSTRUCTIONS and PHARMACOLOGICAL PROPERTIES).

Contraindication

Hypersensitivity to the active ingredients, other sulfonamides derivative of dihydropyridine or any auxiliary to substances;

• renal failure of heavy degree (clearance of creatinine of 30 ml/min.);
• hepatic encephalopathy or heavy abnormal liver function;
• hypopotassemia;
• heavy arterial hypotension;
• shock (including cardiogenic);
• obstruction of an exit from a left ventricle (for example a stenosis of an aorta of heavy degree);
• heart failure with an unstable hemodynamics after an acute myocardial infarction.

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Side effects

by

Most often at use separately of an indapamid and an amlodipina it was reported about such side reactions as a hypopotassemia, drowsiness, dizziness, a headache, a disorder of vision, diplopias, palpitations, rushes of blood, an asthma, pain in abdominal area, nausea, dyspepsia, change of a rhythm of defecation, diarrhea, a constipation, makulopapulezny rash, anklebone hypostasis, muscular spasms, hypostasis, fatigue and an asthenia.

to

during treatment indapamidy and amlodipiny it was reported about side reactions with such frequency of emergence: very often (≥1/10); often (≥1/100, 1/10); infrequently (≥1/1000, ≤1/100); seldom (≥1/10,000, ≤1/1000); very seldom (≤1/10,000); frequency is unknown (it is impossible to estimate on the available data).

Infection and invasion: rhinitis (infrequently — amlodipin).

from the system of blood and lymphatic system: a leukopenia (it is very rare — indapamid and amlodipin); thrombocytopenia (it is very rare — indapamid and amlodipin); an agranulocytosis (it is very rare — indapamid); aplastic anemia (it is very rare — indapamid); hemolytic anemia (it is very rare — indapamid).

from the immune system: hypersensitivity (it is very rare — amlodipin).

from a metabolism and metabolism: hypopotassemia (often; during clinical trials the hypopotassemia (potassium level in blood plasma of 3.4 mmol/l) was observed at 10% of patients, at 4% of patients the potassium level in blood plasma was 3.2 mmol/l after 4–6 weeks of treatment, in 12 weeks of therapy the average decrease in level of potassium in blood plasma was 0.23 mmol/l (see. Special INSTRUCTIONS) — indapamid); a hyperglycemia (it is very rare — amlodipin); a hypercalcemia (it is very rare — indapamid); a hyponatremia with a hypovolemia * (frequency is unknown — indapamid).

from mentality: insomnia (infrequently — amlodipin); changes of mood (including alarm) (infrequently — amlodipin); a depression (infrequently — amlodipin); confusion of consciousness (it is rare — amlodipin).

from nervous system: drowsiness (it is frequent (especially in an initiation of treatment) — amlodipin); dizziness (it is frequent (especially in an initiation of treatment) — amlodipin); a headache (it is rare — indapamid, it is frequent (especially in an initiation of treatment) — amlodipin); a tremor (infrequently — amlodipin); a dysgeusia (infrequently — amlodipin); a syncope (frequency is unknown — indapamid, infrequently — amlodipin); a hypesthesia (infrequently — amlodipin); paresthesia (it is rare — indapamid, infrequently — amlodipin); a hyper tone (it is very rare — amlodipin); peripheral neuropathy (it is very rare — amlodipin); extrapyramidal disorders (extrapyramidal syndrome) (frequency is unknown ― amlodipin); in case of a liver failure the developing of hepatic encephalopathy is possible (frequency is unknown — indapamid) (see CONTRAINDICATIONS and SPECIAL INSTRUCTIONS).

from an organ of sight: a disorder of vision (frequency is unknown — indapamid, it is frequent — amlodipin); a diplopia (it is frequent — amlodipin); shortsightedness (frequency is unknown — indapamid); illegibility of sight (frequency is unknown — indapamid).

from an organ of hearing and a vestibular mechanism: a ring in ears (infrequently — amlodipin); vertigo (it is rare — indapamid).

from heart: palpitations (it is frequent — amlodipin); a myocardial infarction (it is very rare — amlodipin); arrhythmia (including bradycardia, ventricular tachycardia, fibrillation of auricles) (it is very rare — indapamid, infrequently — amlodipin); Bouveret's ventricular disease like "pirouette" (potentially lethal) (frequency is unknown — indapamid) (see. Special INSTRUCTIONS and INTERACTIONS).

from vessels: rushes of blood (it is frequent — amlodipin); arterial hypotension (it is very rare — indapamid, infrequently — amlodipin); a vasculitis (it is very rare — amlodipin).

from the respiratory system, bodies of a thorax and mediastinum: an asthma (it is frequent — amlodipin); cough (infrequently — amlodipin).

from a GIT: pain in abdominal area (it is frequent — amlodipin); nausea (it is rare — indapamid, it is frequent — amlodipin); vomiting (infrequently — indapamid, infrequently — amlodipin); dyspepsia (it is frequent — amlodipin); change of a rhythm of defecation (it is frequent — amlodipin); dryness in a mouth (it is rare — indapamid, infrequently — amlodipin); pancreatitis (it is very rare — indapamid and amlodipin); gastritis (it is very rare — amlodipin); a hyperplasia of gums (it is very rare — amlodipin); diarrhea (it is frequent — amlodipin); a constipation (it is rare — indapamid, it is frequent — amlodipin).

from a gepatobiliarny system: hepatitis (frequency is unknown — indapamid, it is very rare — amlodipin); jaundice (it is very rare — amlodipin); an abnormal liver function (it is very rare — indapamid).

from skin and hypodermic cellulose: makulopapulezny rash (it is frequent — indapamid); a purpura (infrequently — indapamid, infrequently — amlodipin); an alopecia (infrequently — amlodipin); decolouration of skin (infrequently — amlodipin); a hyperhidrosis (infrequently — amlodipin); an itching (infrequently — amlodipin); rash (infrequently — amlodipin); a dieback (infrequently — amlodipin); a Quincke's disease (it is very rare — indapamid, it is very rare — amlodipin); a small tortoiseshell (it is very rare — indapamid, infrequently — amlodipin); a toxic epidermal necrolysis (it is very rare — indapamid); Stephens's syndrome — Johnson (it is very rare — indapamid, it is very rare — amlodipin); a multiformny erythema (it is very rare — amlodipin); exfoliative dermatitis (it is very rare — amlodipin); a Quincke's edema (it is very rare — amlodipin); reactions of photosensitivity (it was reported about cases of reactions of photosensitivity — indapamid, it is very rare — amlodipin) (see. Special INSTRUCTIONS).

from a musculoskeletal system and connective tissue: anklebone hypostasis (it is frequent — amlodipin); an arthralgia (infrequently — amlodipin); myalgia (infrequently — amlodipin); spasms of muscles (it is frequent — amlodipin); a dorsodynia (infrequently — amlodipin); aggravation of the available system lupus erythematosus is possible (frequency is unknown — indapamid).

from an urinary system: urination disturbance (infrequently — amlodipin); a nocturia (infrequently — amlodipin); a pollakiuria (infrequently — amlodipin); a renal failure (it is very rare — indapamid).

from a reproductive system and mammary glands: erectile dysfunction (infrequently — amlodipin); a gynecomastia (infrequently — amlodipin).

General disturbances and reactions in the injection site: hypostasis (it is very frequent — amlodipin); fatigue (it is rare — indapamid, it is frequent — amlodipin); thorax pain (infrequently — amlodipin); an asthenia (it is frequent — amlodipin); pain (infrequently — amlodipin); an indisposition (infrequently — amlodipin).

Results of laboratory researches: increase in body weight (infrequently — amlodipin); degrowth of a body (infrequently — amlodipin); lengthening of an interval of Q-T on the ECG (see. Special INSTRUCTIONS and INTERACTIONS) (frequency is unknown — indapamid); increase in level of glucose in blood (frequency is unknown — indapamid) (the expediency of prescribing of these diuretics has to be carefully weighed before appointment to patients with gout or diabetes); increase in level of uric acid in blood (frequency is unknown — indapamid) (the expediency of prescribing of these diuretics has to be carefully weighed before appointment to patients with gout or diabetes); increase in level of liver enzymes (frequency is unknown — indapamid, it is very rare ** — amlodipin).

* Can lead

to dehydration and developing of orthostatic hypotension; the accompanying loss of ions of chlorine can cause a secondary compensatory metabolic alkalosis (frequency and expressiveness of this phenomenon low).

** generally owing to a cholestasia.

Report on the suspected side reactions during the post-registration period of medicine is very important

. It allows to conduct continuous monitoring of balance of an indicator advantage/risk of drug. Experts in the field of health care are obliged to report through national reporting system about any cases of the suspected side reactions.

Special instructions

Hepatic encephalopathy. with an abnormal liver function the use of tiazidopodobny diuretics can cause developing of hepatic encephalopathy in patients, especially in case of an imbalance of electrolytes. in that case use of an arifam should be stopped immediately because of existence of an indapamid in its structure.

Photosensitivity. At use of thiazide and tiazidopodobny diuretics it was reported about cases of emergence of reactions of photosensitivity (see. Side EFFECTS). At emergence of reaction of photosensitivity during treatment the administration of medicament is recommended to be stopped. If there is a need for restoration of its use, it is recommended to protect vulnerable areas from the sun or sources of artificial ultraviolet.

Precautionary measure at use

Hypertensive crisis. Case studies on safety and efficiency of an amlodipin in a condition of hypertensive crisis did not carry out.

Balance of water and electrolytes

• sodium Level in blood plasma. Before an initiation of treatment and then through regular intervals it is necessary to determine sodium level in blood plasma. Decrease in level of sodium in blood plasma can be asymptomatic in the beginning therefore monitoring is necessary. At patients of advanced age and patients with cirrhosis the monitoring should be carried out more often (see. Side EFFECTS and OVERDOSE). Any treatment by diuretics can lead to a hyponatremia, sometimes with very serious consequences. The hyponatremia in combination with a hypovolemia can lead to dehydration and orthostatic hypotension. The accompanying loss of ions of chlorine can lead to a secondary compensatory metabolic alkalosis; frequency and expressiveness of this effect insignificant.
• potassium Level in blood plasma. Decrease in level of potassium in blood plasma with emergence of a hypopotassemia is the main risk at use of thiazide and tiazidopodobny diuretics. It is necessary to prevent emergence of a hypopotassemia (3.4 mmol/l) at patients with high risk, such as patients of advanced age, patients who eat insufficiently and/or take many drugs, patients with cirrhosis which is followed by hypostases and ascites, patients with an ischemic heart disease and heart failure. In such cases the hypopotassemia increases cardiotoxicity of cardiac glycosides and risk of developing of arrhythmias.

Patients with the extended interval of Q-T of congenital or iatrogenic genesis also treat risk group. At such patients the hypopotassemia and bradycardia can contribute to the development of arrhythmias of heavy degree, including Bouveret's ventricular disease like "pirouette" which can be lethal.

more frequent control of level of potassium in blood plasma is necessary for

In all above-mentioned cases. The first determination of level of potassium in blood plasma should be executed within 1 week of treatment. At identification of a hypopotassemia it is necessary to correct potassium level in blood plasma.

• calcium Level in blood plasma. Thiazide and tiazidopodobny diuretics can reduce excretion of calcium with urine and lead to slight and temporary increase of level of calcium in blood plasma. Emergence of a hypercalcemia can be connected with not diagnosed hyper parathyroidism. In such cases it is necessary to stop treatment and to survey function of epithelial bodies.

glucose Level in blood. Because of existence of an indapamid as a part of medicament the control of level of glucose in blood is important for patients with diabetes, especially in the presence of a hypopotassemia.

Heart failure. Patients with heart failure Arifam should appoint with care. In long placebo - a controlled research with participation of patients with heart failure of heavy degree (III and IV class on NYHA) the frequency of cases of developing of a fluid lungs was higher at use of an amlodipin, than placebo. To patients with stagnant heart failure to appoint antagonists of calcium, including amlodipin, follows with care as they increase risk of emergence of cardiovascular events and death.

Function of kidneys. Thiazide and tiazidopodobny diuretics are most effective when function of kidneys is not broken or disturbances are insignificant (creatinine level in blood plasma of 25 mg/l, that is adults have 220 µmol/l). At patients of advanced age the creatinine level in blood plasma is corrected taking into account age, body weight and a floor.

Hypovolemia caused by loss of water and sodium owing to intake of diuretics in an initiation of treatment is associated with decrease in glomerular filtration. It can lead to increase in level of urea and creatinine in blood plasma. This tranzitorny functional renal failure has no consequences at patients with normal function of kidneys, but can strengthen the available renal failure.

At patients with a renal failure amlodipin can be applied in usual doses. Fluctuations of concentration of an amlodipin in blood plasma do not depend on severity of a renal failure. Amlodipin is not exposed to dialysis.

Research on studying efficiency of the combined medicament Arifam with participation of patients with dysfunction of kidneys was not conducted. For persons with a renal failure the dose of medicament should be selected according to a dosage of each component at use in monotherapy.

Level of uric acid in blood. In view of existence of an indapamid as a part of medicament at patients with the increased level of uric acid in blood the increase in quantity of attacks of gout is possible.

Function of a liver. At patients with an abnormal liver function note lengthening of T _½ an amlodipina and AUC; recommendations concerning the mode of dosing are absent. Therefore treatment amlodipiny needs to be begun with the lowest dose. Drug should be used with care in an initiation of treatment and at increase in a dose.

Case studies on studying efficiency of the combined medicament Arifam with participation of patients with dysfunction of a liver were not conducted. Because of properties of an indapamid and amlodipin Arifam is contraindicated to patients with an abnormal liver function of heavy degree. At patients with an abnormal liver function of easy and moderate degree medicament should be used with care.

Patients of advanced age. At patients of advanced age Arifam it is necessary to apply taking into account function of kidneys (see USE and Pharmacokinetics).

Excipients. Arifam patients should not appoint with rare hereditary intolerance of a galactose, insufficiency of Lappa lactase or malabsorption of glucose and a galactose.

Ability to influence speed of response at control of vehicles or work with other mechanisms. Arifam has insignificant or moderate impact on ability to run vehicles and to work with mechanisms:

• indapamid does not affect attentiveness, but in some cases there can be various reactions connected with decrease in the ABP, especially in an initiation of treatment or at simultaneous use with other antihypertensive drugs. As a result, the ability to run vehicles or to work with other automated systems can worsen;
• amlodipin can have insignificant or moderate impact on ability to run vehicles and to work with mechanisms. If the patients accepting amlodipin had such side reactions as dizziness, the headache, fatigue or nausea, their reaction can be reduced. It is recommended to be careful, especially in an initiation of treatment.

Use during pregnancy or feeding by a breast. Considering influence of components of the combined medicament Arifam on a course of pregnancy and feeding by a breast:

use of medicament during pregnancy is not recommended to

• ;
medicament is contraindicated to
• during feeding by a breast.

Pregnancy

Caution, connected with indapamidy. Data on use of an indapamid for pregnant women are absent or are limited (less than 300 cases). Decrease in OCK of the pregnant woman and an uteroplacental krovenapolneniye can be a consequence of prolonged use of thiazide diuretic in the III trimester of pregnancy that can cause fetoplacental ischemia and an arrest of development of a fruit. Besides, in rare instances at the newborn noted a hypoglycemia and thrombocytopenia. Researches on animals did not reveal the direct or mediated toxic influence on reproductibility.

Caution, connected with amlodipiny. The research on safety of use of an amlodipin for pregnant women was not conducted. In researches on animals at use of high doses the toxic impact on reproductibility is revealed.

Feeding by a breast

Caution, connected with indapamidy. The amount of data on penetration indapamida / metabolites in breast milk is insufficient. Can develop hypersensitivity to derivatives of sulfonamides and a hypopotassemia. The risk for newborns/babies cannot be excluded. Indapamid treats tiazidopodobny diuretics which use during feeding by a breast is connected with reduction or even oppression of a lactation.

Caution, connected with amlodipiny. There are no data on penetration of an amlodipin into breast milk.

Fertility

Caution, connected with indapamidy. Researches of reproductive toxicity showed lack of influence on fertility of males and females of rats. Influence on fertility of the person is not expected.

Caution, connected with amlodipiny. At some patients at use of blockers of calcium channels noted reversible biochemical changes in a spermatozoon head. Clinical data on potential impact of an amlodipin on fertility are not enough. In one research on animals side reactions on fertility of males are revealed.

Children. Safety and efficiency of the medicament Arifam for children did not study. Data are absent.

Interaction

Interaction, connected with indapamidy

not recommended combinations

Lities. Increase in concentration of lithium in blood plasma with emergence of symptoms of overdose, similar to symptoms of a saltless diet is possible (removal of lithium with urine decreases). However if use of diuretics is really necessary, it is necessary to control carefully lithium level in blood plasma and to adjust a diuretic dose.

Combination, demanding care at use

Drugs which can cause development of Bouveret's ventricular disease like "pirouette":

• antiarrhytmic medicaments of the class IA (quinidine, hydroquinidine, Disopyramidum);
• antiarrhytmic medicaments of class III (Amiodaronum, sotalol, dofetilid, ibutilid);
• some antipsychotic drugs:
• a fenotiazina (Chlorpromazinum, tsiamemazin, levomepromazinum, thioridazine, trifluoperazin);
• benzamides (amisulprid, Sulpiridum, sultoprid, tiaprid);
• phenyl propyl ketones (Droperidolum, haloperidol);
• other medicines: bepridit, tsizaprid, difemanit, erythromycin in/in, galofantrin, mizolastin, pentamidine, sparfloksatsin, moxifloxacin, Vincaminum in /

Raises century risk of developing of ventricular arrhythmias, in particular Bouveret's ventricular disease like "pirouette" (the hypopotassemia is risk factor).

Before purpose of such combination check existence of a hypopotassemia and if necessary correct potassium level. It is necessary to control a clinical condition of the patient, level of electrolytes in blood plasma and to carry out ECG monitoring.

in the presence of a hypopotassemia should use medicaments which do not cause Bouveret's ventricular disease like "pirouette".

NPVP (system use), including selection TsOG-2 inhibitors and acetylsalicylic acid in high doses (≥3 g/days). At simultaneous use the easing of antihypertensive effect of an indapamid is possible. At the dehydrated patients the risk of emergence of OPN (decrease in glomerular filtration) increases. Before an initiation of treatment it is necessary to restore water balance and to check function of kidneys.

APF Inhibitors. With deficiency of sodium the treatment by APF inhibitors can cause sudden arterial hypotension and/or OPN (especially in patients with a renal artery stenosis).

with AG at which the previous therapy by diuretic resulted in deficiency of sodium it is necessary for

For patients:

• for 3 days prior to treatment by APF inhibitors to stop use of diuretics and then, if necessary, to resume their reception;
or to begin with
• use of APF inhibitor with a low initial dose with its gradual increase.

should begin with

At patients with stagnant heart failure use of APF inhibitor with the minimum dose, perhaps, after a dose decline of the accompanying diuretic which removes potassium.

In all cases needs to carry out monitoring of function of kidneys (creatinine level in blood plasma) within the first weeks of treatment by APF inhibitors.

Other connections which can entail emergence of a hypopotassemia: Amphotericinum B in/in, GKS and mineralokortikoid (system use), tetrakozaktid, the depletive stimulating a vermicular movement. The risk of emergence of a hypopotassemia (additive effect) increases. It is necessary to control potassium level in blood plasma and to correct it if necessary. It needs especially to be remembered at simultaneous treatment with cardiac glycosides. It is recommended to apply the depletive which is not stimulating a vermicular movement.

foxglove Drugs. Decrease in level of potassium in blood promotes increase in expressiveness of toxic effects of medicaments of a foxglove. It is necessary to control potassium level in blood and the ECG and also in case of need to reconsider therapy.

Baclofenum. The antihypertensive effect increases. In an initiation of treatment it is necessary to restore water balance of the patient and to control function of kidneys.

Allopyrinolum. Simultaneous use with indapamidy can lead to increase in frequency of emergence of reactions of hypersensitivity to Allopyrinolum.

Combination, requiring attention

Kaliysberegayushchy diuretics (amiloride, Spironolactonum, Triamterenum). Despite rationality of purpose of this combination to some patients, emergence of a hypopotassemia or hyperpotassemia is possible (especially at patients with a renal failure or patients with diabetes). It is necessary to control potassium level in blood plasma, to carry out ECG monitoring and, if necessary, to reconsider therapy.

Metformin. The risk of developing of the lactic acidosis caused by metformin in view of possible development of the functional renal failure connected with use of diuretics, especially loopback increases. It is not necessary to appoint metformin if creatinine level in blood plasma exceeds 15 mg/l (135 µmol/l) at men and women have 12 mg/l (110 µmol/l).

Yodokontrastny means. In the presence of dehydration caused by use of diuretics the risk of development of OPN increases, especially at reception of high doses of yodokontrastny means. It is necessary to restore water balance before use of yodokontrastny means.

Imipraminopodobny antidepressants, neuroleptics. The antihypertensive effect and risk of developing orthostatic hypotension (additive effect) increases.

Calcium (salts). Emergence of a hypercalcemia in connection with decrease in elimination of calcium with urine is possible.

Cyclosporine, takrolimus. Increase in level of creatinine in blood plasma without change of level of the circulating cyclosporine, even in the absence of deficiency of water and sodium is possible.

GKS, tetrakozaktid (systemic action). Probable decrease in antihypertensive effect (a delay of water and ions of sodium under the influence of GKS).

Interaction, connected with amlodipiny

Dantrolen (infusion). In researches on animals after use of verapamil and a dantrolen in/in noted fibrillation of ventricles of heart with a lethal outcome and cardiovascular collapse in combination with a hyperpotassemia. At tendency of the patient to emergence of a malignant hyperthermia and at its treatment it is recommended to avoid simultaneous use of blockers of calcium channels, such as amlodipin, because of risk of emergence of a hyperpotassemia.

is not recommended to be applied amlodipin together with grapefruit or grapefruit juice as at some patients the bioavailability can increase that will lead to strengthening of hypotensive effec