Arifam pills 10mg + 1.5mg, 30pcs

Composition

Modified release tablets, pink film-coated, round, biconvex, with the company’s logo engraved on one side.

	1 tab.
amlodipine bezylate	13.87 mg,
which corresponds to the content of amlodipine	10 mg
indapamide	1.5 mg

Auxiliary substances:

hypromellose – 4 thousand-84 mg,

lactose monohydrate-104.5 mg,

magnesium stearate-2.05 mg,

povidone K-30-8.6 mg,

colloidal silicon dioxide-0.82 mg,

calcium hydrophosphate dihydrate-56.7 mg,

microcrystalline cellulose-121.16 mg,

croscarmellose sodium-10.5 mg,

pregelatinized corn starch-6.3 mg.

Composition of the film shell:

glycerol-0.61992 mg, hypromellose – 6 thousand-10.30445 mg, macrogol-6000-0.65797 mg, magnesium stearate-0.61992 mg, titanium dioxide (E 171) – 1.75162 mg, iron oxide red dye (E 172) – 0.23213 mg

Pharmacological action

Mechanism of action

Amlodipine is a calcium ion influx inhibitor, a dihydropyridine derivative (slow calcium channel blocker, or calcium ion antagonist) that inhibits the transmembrane influx of calcium ions into cardiomyocytes and vascular wall smooth muscle cells. The mechanism of antihypertensive action of amlodipine is due to the direct relaxing effect on vascular smooth muscles.

Indapamide is a sulfonamide derivative with an indole ring that belongs to the pharmacological group of thiazide-like diuretics. It works by reducing sodium reabsorption in the cortical segment of the nephron loop. Indapamide increases urinary sodium and chloride excretion and, to a lesser extent, potassium and magnesium excretion, thereby increasing diuresis and having an antihypertensive effect.

Pharmacodynamic effects

In patients with arterial hypertension, taking amlodipine 1 time / day provides a clinically significant reduction in blood pressure in the supine and standing positions for 24 hours. Due to the slow development of the effect, amlodipine usually does not cause acute hypotension.

Amlodipine does not have an undesirable effect on lipid metabolism and does not cause changes in the lipid profile of blood plasma, so it is suitable for use in patients with bronchial asthma, diabetes mellitus and gout.

The antihypertensive activity of indapamide is associated with an improvement in the elastic properties of the arteries and a decrease in arteriolar and total peripheral vascular resistance.

In phase II and III clinical trials, a 24-hour antihypertensive effect was demonstrated when indapamide was used as monotherapy in doses that did not have a pronounced diuretic effect.

Indapamide reduces hypertrophy of the left ventricle of the heart.

An increase in the dose of thiazide diuretics above certain levels is accompanied by a plateau of therapeutic effect, but is accompanied by the occurrence of adverse reactions. If the therapy does not lead to the desired therapeutic effect, the dose of the drug should not be increased.

It has also been shown that with short-term, medium-term, and long-term use in patients with arterial hypertension, indapamide has been shown to:

• It does not affect the parameters of lipid metabolism, including the level of triglycerides, cholesterol, LDL and HDL;
• it does not affect the parameters of carbohydrate metabolism, including in patients with diabetes mellitus.

Pharmacokinetics

The concomitant use of amlodipine and indapamide does not change their pharmacokinetic properties compared to the separate use of these drugs.

Amlodipine

Amlodipine is available in Arifam® in an immediate-Form of production.

Suction and distribution

Amlodipine is well absorbed when taken orally in therapeutic doses, while_cmax in blood plasma is reached 6-12 hours after oral use of the drug. Absolute bioavailability ranges from 64% to 80%. Vd is about 21 l/kg. In vitro studies have shown that approximately 97.5% of circulating amlodipine binds to plasma proteins. Simultaneous food intake does not affect the bioavailability of amlodipine.

Metabolism and elimination

The terminal T_1/2 of amlodipine from blood plasma is approximately 35-50 hours, which is consistent with taking the drug 1 time/day. Amlodipine is actively metabolized in the liver to form inactive metabolites, with 10% of the parent compound unchanged and 60% of the metabolites excreted in the urine.

Pharmacokinetics in special patient groups

There are very limited clinical data on the use of amlodipine in patients with severe hepatic impairment. In patients with hepatic insufficiency, the clearance of amlodipine decreases, which leads to an increase in T_1/2 and an increase in AUC by approximately 40-60%.

Use in elderly patients. The time to reach_cmax of amlodipine in blood plasma does not differ in the elderly and young people. Clearance of amlodipine in elderly patients tends to decrease, resulting in increased AUC and T_1/2. Increases in AUC and T_1/2 in patients with congestive heart failure were consistent with the expected values for these age groups of patients.

Indapamide

Indapamide 1.5 mg in Arifam ® modified release preparation is distributed in a special carrier matrix, which allows for the gradual release of indapamide.

Suction

The released portion of indapamide is rapidly and completely absorbed from the gastrointestinal tract. Food intake slightly increases the rate of absorption, but does not affect the completeness of absorption.

_{Cmax of} the drug in blood plasma is reached approximately 12 hours after oral use of a single dose; with repeated doses, fluctuations in the concentration of the drug in blood plasma in the interval between two doses of the drug are smoothed out. Intraindividual variability of drug absorption parameters is observed.

Distribution

The binding of indapamide to plasma proteins is 79%. T_1/2 is 14-24 hours (average 18 hours). C_ss is reached in 7 days. Repeated admission does not lead to accumulation.

Deduction

Excretion of the drug occurs mainly in the urine (70% of the dose) and in the feces (22%) in the form of inactive metabolites.

Pharmacokinetics in special patient groups

In patients with renal insufficiency, the pharmacokinetic parameters do not change.

Indications

• arterial hypertension in patients who require therapy with amlodipine and indapamide.

Contraindications

• severe renal failure (CC <30 ml/min);
• severe hepatic insufficiency, or hepatic encephalopathy;
• hypokalemia;
• severe hypotension;
• shock (including cardiogenic shock);
• obstruction of the outflow tract of the left ventricle (e. g., aortic stenosis high degree);
• heart failure after acute myocardial infarction with unstable hemodynamics;
• galactose intolerance, lactase deficiency or glucose-galactose malabsorption (because the drug contains lactose);
• the period of breastfeeding;
• children’s age up to 18 years;
• hypersensitivity to the active substances, to other sulfonamides, a derivative of dihydropyridine or to any of excipients.

With caution, the drug should be prescribed in patients with reduced BCC (diuretics, salt-free diet, vomiting, diarrhea), patients with mild to moderate hepatic impairment, peripheral edema and ascites, CHD, chronic heart failure, patients with prolonged QT interval, bradycardia, chronic heart failure of functional class III-IV according to NYHA classification, diabetes mellitus, renal artery stenosis (including bilateral), patients with a single functional kidney, with renal failure, gout, elderly patients.

Side effects

The most commonly observed adverse reactions during treatment with amlodipine and indapamide include drowsiness, dizziness, headache, palpitations, facial flushing, abdominal pain, nausea, lower leg edema, swelling, and fatigue.

The following adverse reactions were observed during treatment with amlodipine and indapamide. Frequency is classified as follows: very common (≥1/10); common (≥1/100, <1/10); uncommon (≥1/1000, <1/100); rare (≥1/10 000, <1/1000); very rare (

Adverse reactions	Frequency
	Indapamide	Amlodipine
Blood and lymphatic system disorders
Leukocytopenia	Very rare	Very rare
Thrombocytopenia	Very rare	Very rare
Agranulocytosis	Very rare	–
Aplastic anemia	Very rare	–
Hemolytic anemia	Very rare	–
From the immune system
Allergic reactions	–	Very rare
From the side of metabolism and nutrition
Hypokalaemia	In clinical trials, hypokalaemia (plasma potassium <3.4 mmol/L) was observed in 10% of patients, and the levels of potassium in the blood were significantly reduced. After 12 weeks of treatment, the average decrease in plasma potassium levels was 0.23 mmol / l (see section “Special instructions”).	–
Hyperglycemia	–	Very rare
Hypercalcemia	Very rare	–
Hyponatremia with hypovolemia 1	Frequency unknown	–
Mental disorders
Insomnia	–	Infrequently
Mood changes (including anxiety)	–	Infrequently
Depression	–	Infrequently
Confusion of consciousness	–	Rarely
Nervous system disorders
Drowsiness	–	Often (especially at the beginning of treatment)
Dizziness	–	Often (especially at the beginning of treatment)
Headache	Rarely	Often (especially at the beginning of treatment)
Tremor	–	Infrequently
Taste changes	–	Infrequently
Syncope	Frequency unknown	Infrequently
Reduced sensitivity	–	Infrequently
Paresthesias	Rarely	Infrequently
Vertigo	Rarely	–
Hypertonus	–	Very rare
Peripheral neuropathy	–	Very rare
From the side of the visual organ
Visual impairment (including diplopia)	–	Infrequently
Myopia	Frequency unknown	–
Blurred vision	Frequency unknown	–
Decreased visual acuity	Frequency unknown	–
From the side of the organ of hearing and labyrinth disorders
Tinnitus	–	Infrequently
From the side of the heart
Heartbeat	–	Often
Myocardial infarction	–	Very rare
Arrhythmia (including bradycardia, ventricular tachycardia, and atrial fibrillation)	Very rare	Very rare
Pirouette-type tachycardia (potentially fatal)	Frequency unknown (see sections “Drug interactions” and “Special instructions”)	–
From the side of blood vessels
Flushes of blood to the skin of the face	–	Often
Arterial hypotension	Very rare	Infrequently
Vasculitis	–	Very rare
Respiratory system disorders
Shortness	of breath-	Infrequently
Rhinitis	–	Infrequently
Cough	–	Very rare
From the digestive system
Abdominal pain	–	Often
Nausea	Rarely	Often
Vomiting	Infrequently	Infrequently
Dyspepsia	–	Infrequently
Changes in bowel function (including diarrhea and constipation)	–	Infrequently
Dry mouth	Rarely	Infrequently
Pancreatitis	Very rare	Very rare
Gastritis	–	Very rare
Gum hyperplasia	–	Very rarely
Constipation	Rarely	Infrequently
Liver and biliary tract disorders
Hepatitis	Frequency unknown	Very rare
Jaundice	–	Very rare
Increased liver enzyme activity	Frequency unknown	Very rare 2
Impaired liver function	Very rare	–
Possible development of hepatic encephalopathy in case of hepatic insufficiency	The frequency is unknown (see sections “Contraindications” and “Special instructions”)	–
Skin and subcutaneous tissue disorders
Macular-papular rash	Is Common	–
Magenta	Infrequently	Infrequently
Alopecia	–	Infrequently
Changing skin color	–	Infrequently
Hyperhidrosis	–	Infrequently
Itching	–	Infrequently
Skin rash	–	Infrequently
Exanthema	–	Infrequently
Angioedema	Very rare	Very rare
Urticaria	Very rare	Very rare
Toxic epidermal necrolysis	Very rare	–
Stevens-Johnson syndrome	Very rare	Very rare
Erythema multiforme	–	Very rare
Exfoliative dermatitis	–	Very rare
Angioedema	–	Very rare
Photosensitivity	Cases of photosensitivity reactions are described (see the section “Special instructions”).	Very rare
Possible exacerbation of pre existing acute SLE	Frequency unknown	–
Musculoskeletal and connective tissue disorders
Lower leg edema	–	Often
Arthralgia	–	Infrequently
Myalgia	–	Infrequently
Muscle spasms	–	Infrequently
Back pain	–	Infrequently
From the urinary system
Violation of urination	–	Infrequently
Nocturia	–	Infrequently
Increased urination	–	Infrequently
Kidney failure	Very rare	–
From the genitals and breast
Impotence	–	Infrequently
Gynecomastia	–	Infrequently
Common disorders and symptoms
Edema	–	Often
Increased fatigue	Rarely	Often
Chest pain	–	Infrequently
Asthenia	–	Infrequently
Pain	–	Infrequently
Malaise	–	Infrequently
Laboratory and instrumental data
Weight gain	–	Infrequently
Weight	loss-	Infrequently
Prolongation of the QT interval on the electrocardiogram	Frequency unknown (see sections “Drug interaction” and “Special instructions”)	–
Increased uric acid and blood glucose levels during treatment	Frequency unknown The advisability of prescribing these diuretics to patients with gout or diabetes mellitus should be carefully evaluated	–

1 leads to dehydration and orthostatic hypotension. Concomitant loss of chlorine ions can lead to secondary compensatory metabolic alkalosis: the frequency and severity of this effect are insignificant.

2 most often in combination with cholestasis.

Extremely rare cases of extrapyramidal syndrome have been reported with amlodipine.

Interaction

Amlodipine

Dantrolene (intravenous use): ventricular fibrillation and fatal cardiovascular collapse were observed in animals with hyperkalemia after verapamil and intravenous dantrolene use. Due to the risk of developing hyperkalemia, it is recommended to avoid the combined use of slow calcium channel blockers, such as amlodipine, in patients with a predisposition to malignant hyperthermia, as well as in the treatment of malignant hyperthermia.

The use of amlodipine with grapefruit or grapefruit juice is not recommended, since in some patients the bioavailability of amlodipine may increase, which leads to increased effects of lowering blood pressure.

Cytochrome CYP3A4 inhibitors: Concomitant use of amlodipine with strong or moderate CYP3A4 inhibitors (protease inhibitors, azole antifungal drugs, macrolides such as erythromycin or clarithromycin, verapamil or diltiazem) can lead to a significant increase in the concentration of amlodipine. The clinical manifestations of these pharmacokinetic abnormalities may be more pronounced in elderly patients. It may be necessary to monitor the clinical condition and adjust the dose.

CYP3A4 inducers: There is no information on the effect of cytochrome CYP3A4 inducers on amlodipine. Concomitant use of inducers of CYP3A4 (e. g. rifampicin, St. John’s wort) may lead to a decrease in the concentration of amlodipine in the blood plasma. Amlodipine should be used with caution in combination with CYP3A4 inducers.

Effect of amlodipine on other medications

Amlodipine has an additional antihypertensive effect when taken simultaneously with other drugs that have an antihypertensive effect.

In clinical drug interaction studies, amlodipine did not affect the pharmacokinetics of atorvastatin, digoxin, warfarin, or cyclosporine.

Simvastatin: concomitant use of multiple doses of amlodipine 10 mg and simvastatin 80 mg resulted in a 77% increase in simvastatin concentrations compared to simvastatin monotherapy. In patients receiving amlodipine, the dose of simvastatin should not exceed 20 mg / day.

Indapamide

Combinations of medications that are not recommended

Lithium preparations

With simultaneous use of indapamide and lithium preparations, an increase in the level of lithium in the blood plasma may occur with signs of overdose, as with a salt-free diet (reduced urinary excretion of lithium). However, if the use of diuretics is necessary, careful monitoring of plasma lithium and dosage adjustment is required.

Combinations that require special precautions to be taken

Drugs that cause pirouette-type tachycardia:

• antiarrhythmic drugs of class IA (quinidine, gedragingen, disopyramide);
• antiarrhythmic class III (amiodarone, sotalol, dofetilide, ibutilide);
• some antipsychotics: phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, triptorelin), benzamide (amisulpride, sulpiride, sultopride, tiapride), butyrophenones (droperidol, haloperidol);
• others: bepridil, cisapride, was diphemanil, erythromycin for/in the introduction, halofantrine, mizolastine, pentamidine, sparfloxacin, moxifloxacin, vancomycin for/in the introduction.

Increased risk of ventricular arrhythmias, especially pirouette-type tachycardia (hypokalemia as a risk factor)

Before prescribing drugs that cause pirouette-type tachycardia while taking Arifam®, a study should be conducted to detect hypokalemia and correct if necessary. Monitoring of the clinical condition, plasma electrolytes and ECG is required.

In the presence of hypokalemia, drugs that do not cause tachycardia of the “pirouette”type should be used.

NSAIDs (systemic use), including selective COX-2 inhibitors, high-dose salicylic acid (≥3 g / day)

Possible reduction of the antihypertensive effect of indapamide. Risk of acute renal failure in patients with dehydration (reduced glomerular filtration rate). At the beginning of treatment, hydration and monitoring of renal function should be performed.

ACE inhibitors

Risk of sudden hypotension and / or acute renal failure at the beginning of treatment with an ACE inhibitor against the background of an existing decrease in sodium levels (especially in patients with renal artery stenosis).

In patients with arterial hypertension, if previous treatment with diuretics could cause a decrease in sodium levels, it is necessary:

• 3 days before starting treatment with an ACE inhibitor, stop taking diuretics. In the future, if necessary, the use of diuretics can be resumed;
• or appoint an ACE inhibitor at a low initial dose and gradually increase the dose.

In patients with chronic heart failure, treatment with ACE inhibitors should be initiated at low doses, with possible preliminary reductions in diuretic doses.

In all cases, renal function (plasma creatinine) should be monitored during the first weeks of treatment with an ACE inhibitor.

Other drugs that cause hypokalemia: amphotericin B (IV), gluco-and mineralocorticoids (systemic use), tetracosactide, laxatives that stimulate intestinal motility

Increased risk of hypokalemia (additive effect). Monitoring of the potassium concentration in the blood plasma should be carried out and, if necessary, its correction. This is especially true with concomitant treatment with cardiac glycosides. Laxatives that do not stimulate intestinal motility should be used.

Cardiac Glycosides

Hypokalemia increases the toxic effects of cardiac glycosides. Monitoring of blood potassium concentration and ECG parameters should be performed, as well as correction of treatment if necessary.

Baclofen

Increased antihypertensive effect. At the beginning of treatment, hydration and monitoring of renal function should be performed.

Allopurinol

Concomitant use with indapamide may increase the risk of hypersensitivity reactions to allopurinol.

Drug combinations that require attention

Potassium-sparing diuretics (amiloride, spironolactone, triamterene)

Although the combination may be appropriate in some patients, hypokalemia or hyperkalemia may occur (especially in patients with renal insufficiency and diabetes mellitus). Plasma potassium concentrations and ECG readings should be monitored and treatment should be reviewed if necessary.

Metformin

Functional renal failure, which may occur with diuretics, especially loop diuretics, and concomitant use of metformin increases the risk of lactic acidosis. Metformin should not be used if the plasma creatinine level exceeds 15 mg / l (135 mmol/l) in men and 12 mg/l (110 mmol/l) for women.

Iodine-containing contrast agents

Diuretic-induced dehydration is associated with an increased risk of acute renal failure, especially when using high-dose iodine-containing contrast agents. Before the introduction of an iodine-containing drug, fluid loss should be compensated.

Tricyclic antidepressants, antipsychotics

There is an increased risk of orthostatic hypotension and increased antihypertensive effect (additive effect).

Calcium Salts

Due to a decrease in urinary calcium excretion, there is a risk of hypercalcemia.

Cyclosporine, tacrolimus

There is a risk of increased plasma creatinine levels without any changes in the circulating cyclosporine concentration, even in the absence of water / sodium loss.

Corticosteroids, tetracosactide (systemic use)

Reduced antihypertensive effect (water/sodium retention due to corticosteroid use).

How to take, course of use and dosage

Inside,1 tab. 1 time / day, preferably in the morning. The tablet should be swallowed without chewing and washed down with water.

Special patient groups

Patients with impaired renal function (see sections “Contraindications” and “Special instructions”)

In severe renal impairment (creatinine clearance less than 30 ml / min), the drug is contraindicated. No dose adjustment is required in patients with mild to moderate renal impairment.

Elderly patients (see sections “Special instructions” and “Pharmacokinetics”)

Arifam® may be prescribed to elderly patients based on renal function.

Patients with impaired liver function (see sections “Contraindications” and “Special instructions”)

In severe liver damage, therapy with Arifam® is contraindicated. Dosage recommendations for amlodipine are not established for patients with mild to moderate hepatic impairment, so the dose should be selected with caution, and treatment should begin with the lowest dose (see sections “Special Instructions” and “Pharmacokinetics”).

Children and teenagers

Currently, there are no data on the safety and efficacy of Arifam® in children and adolescents.

Overdose

Information about overdose of Arifam® absent.

Amlodipine

Information about intentional overdose in humans is limited.

The available data demonstrate that a significant overdose can lead to excessive peripheral vasodilation and possibly reflex tachycardia. There were cases of severe and probably prolonged systemic hypotension up to the development of shock with a fatal outcome.

In cases of clinically significant hypotension due to an overdose of amlodipine, active support for the functioning of the cardiovascular system is required, including frequent monitoring of cardiac and respiratory functions, lifting of limbs, monitoring of BCC and diuresis.

Vasoconstrictors may be effective in restoring vascular tone and blood pressure if there are no contraindications to their use. Intravenous use of calcium gluconate may help eliminate calcium channel blockage.

In some cases, gastric lavage may be appropriate. In healthy volunteers, the use of activated charcoal for 2 hours after taking 10 mg of amlodipine resulted in a decrease in the rate of absorption of amlodipine.

Since amlodipine binds to a high degree of protein, dialysis is unlikely to be effective.

Indapamide

Indapamide showed no toxicity when administered at doses up to 40 mg, i. e. 27 times higher than the therapeutic dose.

Signs of acute poisoning are mainly water-electrolyte disorders (hyponatremia, hypokalemia). The clinical picture may include nausea, vomiting, hypotension, muscle spasms, vertigo, drowsiness, confusion, polyuria or oliguria, possibly up to anuria (due to hypovolemia).

Initial emergency measures include rapid elimination of the ingested substances (a) by gastric lavage and/or use of activated charcoal, followed by restoration of the water-electrolyte balance to normal in a specialized department.

Special instructions

Hepatic encephalopathy

When liver function is impaired, thiazide-like diuretics can cause hepatic encephalopathy, especially in the case of electrolyte imbalance. Due to the presence of indapamide in the composition, if this phenomenon develops, the use of Arifam® should be stopped immediately.

Photosensitivity

Cases of photosensitivity reactions when taking thiazide and thiazide-like diuretics are described (see the section “Side effects”). If a photosensitivity reaction occurs during treatment, it is recommended to stop treatment. If repeated use of a diuretic is considered necessary, it is recommended to protect exposed parts of the body from exposure to the sun or artificial ultraviolet rays.

Hypertensive crisis

The safety and efficacy of amlodipine in hypertensive crisis have not been established.

Water-electrolyte balance

The content of sodium ions in the blood plasma. Before starting treatment, it is necessary to determine the content of sodium ions in the blood plasma. While taking the drug, this indicator should be regularly monitored. All diuretics can cause hyponatremia, which sometimes leads to serious complications. Hyponatremia at the initial stage may not be accompanied by clinical symptoms, so regular laboratory monitoring is necessary. More frequent monitoring of sodium ions is indicated in elderly patients and patients with cirrhosis of the liver (see sections “Side effects” and “Overdose”).

The content of potassium ions in the blood plasma. Depletion of potassium reserves with the development of hypokalemia is the main risk associated with the use of thiazide and thiazide-like diuretics. It is necessary to prevent the development of hypokalemia ( In such patients, hypokalemia increases the cardiotoxicity of cardiac glycosides and the risk of arrhythmia.

Individuals with an extended QT interval are also at risk, regardless of the origin of this disorder – congenital or iatrogenic. Hypokalemia, as well as bradycardia, are factors contributing to the occurrence of severe arrhythmia, in particular, potentially fatal tachycardia of the “pirouette” type.

In all the above situations, it is necessary to measure the concentration of potassium in the blood plasma more often. The first measurement of the level of potassium ions in the blood plasma should be carried out within the first week after the start of treatment.

If hypokalemia occurs, appropriate treatment should be prescribed.

The content of calcium in the blood plasma. Thiazide and thiazide-like diuretics may reduce urinary calcium excretion and cause a slight and temporary increase in plasma calcium levels. True hypercalcemia may be associated with previously undiagnosed hyperparathyroidism.Treatment should be discontinued before parathyroid function is evaluated.

Blood glucose level in blood plasma

Due to the presence of indapamide, it is necessary to monitor blood glucose levels in patients with diabetes mellitus, especially in the presence of hypokalemia.

Heart failure

Patients with heart failure should be treated with caution. In a long-term placebo-controlled study in patients with severe heart failure (NYHA class III and IV), the incidence of pulmonary edema was higher in the amlodipine-treated group than in the placebo group. Calcium channel blockers, including amlodipine, should be used with caution in patients with congestive heart failure, as they may increase the risk of cardiovascular events and death.

Kidney function

Thiazide and thiazide-like diuretics are fully effective only in patients with normal or slightly impaired renal function (plasma creatinine levels below 25 mg / l, i. e. 220 mmol / l in adult patients). In elderly patients, normal plasma creatinine levels should be calculated based on age, body weight, and gender.

At the beginning of treatment, patients may experience a decrease in GFR due to hypovolemia, which, in turn, is caused by the loss of water and sodium ions against the background of taking diuretics. This can lead to an increase in the concentration of urea and creatinine in the blood plasma. Such transient functional renal failure is not clinically relevant for normal renal function, but may exacerbate pre – existing renal failure.

In patients with renal insufficiency, amlodipine can be used in normal doses. Changes in the concentration of amlodipine in blood plasma do not correlate with the degree of impaired renal function. Amlodipine is not eliminated from the body by dialysis.

The effects of the combined drug Arifam® in patients with impaired renal function have not been studied. In case of impaired renal function, the dose of the drug should be selected taking into account the content of individual components.

Uric acid

Due to the presence of indapamide, patients with hyperuricemia may have an increased risk of developing gout attacks.

Liver function

In patients with impaired liver function, T_1/2 and AUC of amlodipine increase. Dosage recommendations for such patients are not established. Amlodipine should be started at the lowest possible dose and precautions should be taken both at the beginning of treatment and when increasing the dose.

The effects of combined amlodipine + indapamide therapy in patients with hepatic impairment have not been studied. Taking into account the effects of separate use of indapamide and amlodipine, Arifam® is contraindicated for use in patients with severe hepatic impairment, and caution should be exercised in the treatment of patients with mild to moderate hepatic impairment.

Elderly patients

Elderly patients can take Arifam® based on renal function (see sections “Dosage regimen” and “Pharmacological action”).

Auxiliary substances

Arifam® It should not be used for the treatment of patients with rare hereditary diseases associated with galactose intolerance, lactase deficiency and glucose-galactose malabsorption.

Influence on the ability to drive motor vehicles and manage mechanisms

Arifam® it has a small or moderate impact on the ability to drive vehicles and work with mechanisms.

Amlodipine has a minor or moderate effect on the ability to drive vehicles and work with mechanisms. If patients receiving amlodipine experience dizziness, headache, fatigue, or nausea, their ability to respond may be impaired. Caution is recommended, especially at the beginning of treatment.

Indapamide does not affect mindfulness, but in some cases, various reactions may occur associated with a decrease in blood pressure, especially at the beginning of treatment or when another antihypertensive drug is added. As a result, the ability to drive vehicles and work with mechanisms may be impaired.

Storage conditions

The drug should be stored out of the reach of children at a temperature not exceeding 30°C.

Shelf

life is 2 years.

Active ingredient

Amlodipine, Indapamide

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as directed by your doctor

Indications

Hypertension