Instruction for use: Aprovel

Dosage form: film coated tablets

Active substance: Irbesartanum

ATX

C09CA04 Irbesartan

Pharmacological group

Angiotensin II receptor antagonist [Angiotensin II receptor antagonists (AT1-subtype)]

Nosological classification (ICD-10)

I10 Essential (primary) hypertension: hypertension; Arterial hypertension; Arterial hypertension crisis course; Essential Hypertension; Essential hypertension; Essential hypertension; Essential hypertension; Essential hypertension; Primary hypertension; Arterial hypertension, complications of diabetes; The sudden increase in blood pressure; Hypertensive disorders of blood circulation; hypertensive condition; hypertensive crises; arterial Hypertension; malignant Hypertension; Hypertonic disease; hypertensive crises; accelerated hypertension; malignant hypertension; The aggravation of hypertensive disease; Transient hypertension; Isolated systolic hypertension

I15 Secondary hypertension: Arterial hypertension, complications of diabetes; hypertension; The sudden increase in blood pressure; Hypertensive disorders of blood circulation; hypertensive condition; hypertensive crises; hypertension; arterial Hypertension; malignant Hypertension; hypertensive crises; accelerated hypertension; malignant hypertension; The aggravation of hypertensive disease; Transient hypertension; hypertension; Arterial hypertension; Arterial hypertension crisis course; renovascular hypertension; Hypertension symptomatic; Renal hypertension; Renovascular hypertension; renovascular hypertension; Symptomatic hypertension

N08.3 Glomerular lesions in diabetes mellitus (E10-14 + with common fourth sign .2): Nephropathy diabetic; Diabetic Nephropathy; Diabetic nephropathy in the background of type 1 diabetes mellitus; Diabetic nephropathy in patients with type I diabetes; Proteinuria in patients with type 2 diabetes mellitus

N08.8 Glomerular lesions in other diseases classified elsewhere

Composition

Tablets covered with a film coating.

active substance: Irbesartan 150 mg; 300 mg

Auxiliary substances: lactose monohydrate - 51/102 mg; MCC - 27/54 mg; Sodium croscarmellose - 12/24 mg; Magnesium stearate - 2.5 / 5 mg; Silicon dioxide colloidal - 2,5 / 5 mg; Hypromellose - 5/10 mg

Film membrane: Opadry white (lactose monohydrate - 36%, hypromellose - 28%, macrogol-3000 - 10%, titanium dioxide (E171) - 26%) - 10/20 mg; Wax Carnauba - <0.05 / 0.1 mg

Description of dosage form

150 mg tablets: biconvex, oval, film-coated white or almost white, with an engraved image of the heart on one side and number "2872" on the other.

300 mg tablets: biconvex, oval, film-coated white or almost white, with an engraved image of the heart on one side and number "2873" on the other.

Pharmachologic effect

Mode of action - hypotensive.

Pharmacodynamics

Irbesartan is a selective antagonist of angiotensin II receptors (type AT1). Irbesartan does not require metabolic activation to acquire pharmacological activity. Angiotensin II is an important component of RAAS and is involved in the pathogenesis of the development of hypertension, as well as the homeostasis of sodium.

It blocks all physiologically significant effects of angiotensin II, regardless of the source or route of its synthesis, incl. Its pronounced vasoconstrictive and aldosteronosecreting effects, realized through receptors of the AT1 type, located on the surface of the smooth muscle cells of the vessels and in the adrenal cortex. It does not possess agonistic activity to AT1 receptors and has a much greater (more than 8500 times) affinity for AT1 receptors than for AT2 receptors (receptors not related to CVS regulation).

Irbesartan does not inhibit RAAS enzymes (such as renin, ACE) and does not affect the receptors of other hormones or ion channels involved in the regulation of blood pressure and sodium homeostasis. Blocking with irbesartan AT1 receptors interrupts the feedback loop in the renin-angiotensin system, which leads to an increase in plasma concentrations of renin and angiotensin II. After taking irbesartan in recommended doses, the plasma concentration of aldosterone decreases, without significantly affecting the potassium content in the blood serum (the average value of its increase is <0.1 mEq / L). Irbesartan has no significant effect on serum concentrations of triglycerides, cholesterol and glucose. Irbesartan does not affect the concentration of uric acid in the blood serum or the rate of excretion of uric acid by the kidneys.

The antihypertensive effect of irbesartan manifests itself after taking its first dose and becomes significant within 1-2 weeks of admission, its maximum antihypertensive effect is achieved by the 4-6th week of treatment. In long-term clinical trials, the antihypertensive effect of irbesartan has been maintained for more than one year.

Antihypertensive effect with once-a-day ingestion of irbesartan in doses up to 900 mg is dose-dependent. Irbesartan at a single dose during the day at doses of 150-300 mg reduces blood pressure, measured in the supine position or sitting at the end of the interdose interval (24 hours after receiving the dose of irbesartan, ie before taking the next dose), on average, 8- 13 / 5-8 mmHg. (SAD / DAD) compared with placebo. The antihypertensive effect of irbesartan before taking the next dose is 60-70% of the maximum values of decrease in DAD and SAD. The optimal decrease in blood pressure within 24 hours is achieved with the intake of irbesartan 1 time per day.

Irbesartan approximately in the same degree reduces BP in a standing and lying position. Orthostatic effects are rare, but as with the administration of ACE inhibitors, in patients with hyponatraemia and / or hypovolemia, excessive BP reduction with clinical manifestations is possible.

The antihypertensive effect of irbesartan and thiazide diuretics is additive. In patients with insufficient blood pressure reduction with monotherapy with irbesartan, the addition of low doses of hydrochlorothiazide (12.5 mg) once a day to its intake leads to an additional reduction in the SAD / DAD by 7-10 / 3-6 mm Hg. Compared with the addition of a placebo.

The effectiveness of irbesartan does not depend on age or sex. As with the use of other drugs that affect RAAS, the antihypertensive effect of irbesartan in patients of the Negroid race is much less pronounced. However, when irbesartan is used simultaneously with low doses of hydrochlorothiazide (for example, 12.5 mg / day), the antihypertensive response in patients of the Negroid race approximates in effectiveness to that in patients of the Caucasoid race.

After discontinuing irbesartan, blood pressure returns to the initial level gradually. The withdrawal syndrome is not observed.

In a multicenter randomized controlled active substance (amlodipine) and placebo, a double-blind clinical study of IDNT in 1715 patients with arterial hypertension and type 2 diabetes mellitus (proteinuria ≥900 mg / day and serum creatinine concentration in the 1-3 mg / dl range ), A 20% (p = .024) decrease (compared with placebo) and a 23% (p = 0.006) decrease (compared with amlodipine) of the relative risk of the first occurrence of any of the following conditions: a doubling of serum creatinine concentration, development of t rminalnoy stage renal disease or death from any cause (for achieving a comparable reduction in blood pressure when applying irbesartan and amlodipine).

In a multicenter, randomized, placebo-controlled, double-blind clinical study of the effects of irbesartan on microalbuminuria in patients with arterial hypertension and type 2 diabetes mellitus (IRMA 2) conducted in 590 patients with arterial hypertension and type 2 diabetes mellitus with microalbuminuria (20-200 (Serum creatinine concentration <1.5 mg / dl in men and <1.1 mg / dl in women), the effect of long-term treatment (over 2 years) was evaluated, With Aprovel Ū progression clinically significant proteinuria. When taking the drug at a dose of 300 mg / day, a 70% reduction in the relative risk of developing clinically significant proteinuria (compared with placebo, p = 0.0004) was demonstrated, and a relative risk of clinically significant proteinuria (in terms of Compared with placebo, p = 0.085). The delay in the progression of clinically significant proteinuria was noted already after 3 months and continued for the entire 2-year period of the clinical study. The decrease in the 24-hour Cl creatinine between treatment groups did not differ significantly. The regression of microalbuminuria to normal albuminuria (<20 mcg / min, <30 mg / day) was more frequently observed in the AprovelŪ group at a dose of 300 mg (34%) compared with the placebo group (21%).

Pharmacokinetics

Suction. After oral administration, irbesartan is rapidly and completely absorbed, its absolute bioavailability is approximately 60-80%. Simultaneous food intake does not significantly affect the bioavailability of irbesartan. After oral administration plasma Cmax irbesartan is reached after 1.5-2 h.

Distribution. The connection with plasma proteins is approximately 96%. Binding to the cellular components of blood is negligible. Vd is 53-93 liters.

Metabolism. After ingestion or iv administration of 14C-irbesartan, 80-85% of the radioactivity circulating in the blood plasma occurs in unchanged irbesartan. Irbesartan is metabolized by the liver by oxidation and conjugation with glucuronic acid. The main metabolite in the systemic circulation is irbesartan glucuronide (approximately 6%). Oxidation of irbesartan is mainly carried out with the cytochrome P450 isoenzyme CYP2C9, the involvement of the CYP3A4 isoenzyme in the metabolism of irbesartan is insignificant. Irbesartan is not metabolized by most isoenzymes that normally participate in the metabolism of drugs (isoenzymes CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2D6 or CYP2E1), and do not induce their inhibition or induction. Irbesartan does not induce or inhibit the isoenzyme CYP3A4.

Excretion. Irbesartan and its metabolites are excreted from the body, both through the intestines (with bile) and the kidneys. After ingestion or iv administration of 14C-irbesartan, about 20% of the radioactivity is found in the urine, and the remainder in the stool. Less than 2% of the administered dose is excreted by the kidneys in the form of unchanged irbesartan. The final T1 / 2 of irbesartan is 11-15 hours. The total clearance for IV infusion of irbesartan is 157-176 ml / min, and its renal clearance is 3-3.5 ml / min. With daily single intake of irbesartan, plasma Css is achieved after 3 days, while its limited accumulation in blood plasma (less than + 20%) is observed.

Special patient groups

Floor. In women (compared with men), slightly higher plasma concentrations of irbesartan were observed. However, gender-related differences in T1 / 2 and accumulation of irbesartan were not detected. Correction of irbesartan dose in women is not required. There were no gender-related differences in the effects of irbesartan.

Elderly age. The values of AUC and Cmax of irbesartan in elderly patients (65-80 years old) with clinically normal renal and hepatic function were approximately 20-50% higher than in younger patients (18-40 years old). The final T1 / 2 they had was comparable. There were no age-related differences in the effects of irbesartan.

Violation of the function of the liver. In patients with mild (functional class A or 5-6 points on the Child-Pugh scale) and moderately expressed (functional class B or 7-9 on the Child-Pugh scale) with hepatic insufficiency due to cirrhosis, the pharmacokinetic parameters of irbesartan do not change significantly.

Impaired renal function. In patients with impaired renal function or patients undergoing hemodialysis, the pharmacokinetics of irbesartan do not change significantly. Irbesartan is not excreted from the body by hemodialysis.

Race affiliation. In volunteers without arterial hypertension AUC and T1 / 2 irbesartan in representatives of the Negroid race were approximately 20-25% higher than in the representatives of the Caucasoid race, and Cmax irbesartan in them was almost identical.

Indications for Aprovel

Arterial hypertension (monotherapy and in combination with other antihypertensive drugs, for example, thiazide diuretics, β-adrenoblockers, CCB);

Nephropathy in arterial hypertension and type 2 diabetes mellitus (as part of combined antihypertensive therapy).

Contraindications

Hypersensitivity to any of the components of the drug;

Simultaneous application with drugs containing aliskiren in patients with diabetes mellitus or mild and severe renal failure (glomerular filtration rate (GFR) <60 ml / min / 1.73 m2 body surface area);

Simultaneous use with ACE inhibitors in patients with diabetic nephropathy;

Hereditary intolerance to galactose, insufficiency of lactase or glucose-galactose malabsorption;

Severe hepatic insufficiency (functional class C or more than 9 on the Child-Pugh scale) (lack of clinical experience);

pregnancy;

The period of breastfeeding;

Age to 18 years (effectiveness and safety not established).

With caution under such conditions as:

Stenosis of the aortic or mitral valve or hypertrophic obstructive cardiomyopathy;

Hypovolemia, hyponatremia, arising in the treatment of diuretics, hemodialysis;

Adherence to a diet with restriction of consumption of table salt, diarrhea, vomiting (danger of excessive blood pressure lowering);

Patients with renal function, depending on the activity of RAAS (including patients with hypertension with bilateral or unilateral stenosis of the renal arteries or chronic cardiac insufficiency III-IV functional class (according to the NYHA classification) (see "Special instructions");

Ischemic heart disease and / or clinically significant atherosclerosis of cerebral vessels (with excessive decrease in blood pressure there is a risk of increasing ischemic disorders, up to the development of acute myocardial infarction and stroke);

Renal failure (requires control of potassium and creatinine concentrations in the blood), recent kidney transplantation (lack of clinical experience);

Concurrent use of NSAIDs, including selective COX-2 inhibitors (increased risk of renal dysfunction, including the possibility of developing acute renal failure and an increase in serum potassium, especially in elderly patients, patients with hypovolemia, including those taking diuretics, or with impaired function Kidneys (see "Interaction");

Use in combination with ACE inhibitors or aliskiren, (In comparison with monotherapy with double blockade of RAAS), there is an increased risk of excessive blood pressure lowering, hyperkalemia and renal dysfunction (see "Special instructions").

Application of pregnancy and breastfeeding

Experience with the use of the drug AprovelŪ during pregnancy is absent. Taking into account the fact that when the ACE inhibitors were taken in the II and III trimesters of pregnancy, the developing fetus was damaged and died, irbesartan, like any other drug that directly affects RAAS, cannot be used during pregnancy (I, II, III trimesters). When diagnosing pregnancy during treatment with AprovelŪ, it should be stopped as soon as possible.

It is not known whether irbesartan or its metabolites are excreted in breast milk. During breastfeeding, taking AprovelŪ is contraindicated. Therefore, after evaluating the ratio of the perceived benefit from taking the drug to the mother and the potential risk to the baby, stop breastfeeding or taking AprovelŪ.

Side effects

The following undesirable phenomena are presented in accordance with the following gradations of their incidence (according to the WHO classification: very often (≥1/10), often (≥1 / 100, <1/10), infrequently (≥1 / 1000, <1 / 100), rarely (≥1 / 10000, <1/1000), very rarely (<1/10000, including individual messages), unknown frequency (it is not possible to determine the frequency of occurrence of an undesirable phenomenon according to available data).

The safety of AprovelŪ was studied in clinical trials in approximately 5,000 patients, including 1,300 patients with hypertension taking the drug for more than 6 months, and 400 patients taking the drug for one year or more. The adverse events in patients taking AprovelŪ were usually mild and transitory, and their frequency was not related to the magnitude of the dose taken and was not dependent on sex, age, or race.

In placebo-controlled studies in which 1,655 patients took irbesartan (on average for 1-3 months), discontinuation of treatment due to the development of any clinical or laboratory adverse events was required in 3.3% of patients taking AprovelŪ, And in 4.5% of patients taking placebo (the differences were statistically significant).

Adverse events observed in placebo-controlled clinical trials with the use of AprovelŪ in hypertension are probably or probably associated with its administration, or without an established relationship with the administration of the drug

The incidence of the following adverse events with irbesartan was statistically not significantly different from that observed with placebo.

From the nervous system: often - dizziness, headache; Infrequently - orthostatic dizziness.

From the heart: rarely - swelling, tachycardia.

From the respiratory system, chest and mediastinum: infrequently - cough.

From the digestive tract: often - nausea / vomiting; Infrequently - diarrhea, indigestion / heartburn.

From the genitals and the breast: infrequently - sexual dysfunction.

Common disorders: often - increased fatigue; Infrequently - pain in the chest.

Laboratory and instrumental data: clinically significant changes in laboratory parameters were not observed in patients with arterial hypertension during controlled clinical trials. There is no special monitoring of laboratory parameters for patients with hypertension taking AprovelŪ.

Adverse events observed in controlled clinical trials with AprovelŪ in patients with nephropathy in hypertension and type 2 diabetes (IDNT and IRMA 2 clinical trials)

Adverse events were similar to those in patients with hypertension, with the exception of orthostatic symptoms (dizziness (10.2%) (with placebo 6%), orthostatic dizziness (5.4%) (with placebo 2.7%) and orthostatic Hypotension (5.4%) (when taking placebo 3.2%).

The percentage of discontinuation due to orthostatic symptoms with AprovelŪ, compared with placebo, was 0.3 vs 0.5%, orthostatic dizziness 0.2 vs 0.0%, and orthostatic hypotension 0.0 vs. 0.0% respectively.

From the laboratory indicators: hyperkalemia. In the clinical study IDNT, the percentage of patients with hyperkalemia (> 6 mEq / L) was 18.6% in the AprovelŪ group compared with 6% in the placebo group. In the IRMA clinical study, 2% of patients with hyperkalemia (<6 mEq / L) were 1% in the AprovelŪ group, and there was no hyperkalaemia in the placebo group.

In the IDNT clinical study, the frequency of discontinuation due to hyperkalaemia with AprovelŪ and placebo was 2.1 and 0.36%, respectively. In the clinical study IRMA, the frequency of discontinuation due to the development of hyperkalemia when taking AprovelŪ and placebo was 0.5% and 0%, respectively.

Undesirable effects observed during post-marketing use of AprovelŪ

From the side of the immune system: very rare - like all angiotensin II receptor antagonists, very rare cases of allergic reactions, such as urticaria, angioedema, were noted.

The following undesirable phenomena have been identified with the use of irbesartan from the time the drug AprovelŪ entered the market.

From the side of metabolism and nutrition: an unknown frequency - hyperkalemia.

From the side of the nervous system: unknown frequency - vertigo.

From the liver and bile ducts: an unknown frequency - an increase in the activity of liver enzymes and bilirubin concentration in the blood, hepatitis, jaundice.

From the side of the organ of hearing: unknown frequency - ringing in the ears.

From the side of the musculoskeletal and connective tissue: an unknown frequency is myalgia.

On the part of the kidneys and urinary tract: an unknown frequency - a violation of kidney function, incl. Cases of development of renal failure in patients at risk (see "Special instructions").

Common violations: unknown frequency - asthenia.

Interaction

Based on data from in vitro studies, the interaction of irbesartan with drugs metabolized by isoenzymes CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2E1 or CYP3A4 is not expected. Irbesartan is generally metabolized by the CYP2C9 isoenzyme and less exposed to glucuronidation. No significant pharmacokinetic and pharmacodynamic interactions were observed with the simultaneous use of irbesartan with warfarin, a drug metabolized by the isoenzyme CYP2C9.

Irbesartan does not change the pharmacokinetics of digoxin and simvastatin.

With the combined use of irbesartan with hydrochlorothiazide or nifedipine, the pharmacokinetics of irbesartan does not change.

With medications containing aliskiren. The combination of AprovelŪ with drugs containing aliskiren is contraindicated in patients with diabetes mellitus or moderate to severe renal insufficiency (GFR <60 mL / min / 1.73 m2 body surface area) and is not recommended in other patients (see Contraindications, With care, "Special instructions").

With ACE inhibitors. The use of the drug AprovelŪ in combination with ACE inhibitors is contraindicated in patients with diabetic nephropathy and is not recommended in other patients (see "Contraindications", Cautious, "Special instructions").

With preparations of potassium and potassium-sparing diuretics, heparin. Based on the experience gained with the use of other drugs that affect RAAS, with the simultaneous use of potassium preparations; Substitutes for salt containing potassium; Potassium-sparing diuretics or others capable of increasing the potassium content in the blood of drugs (heparin), it is possible to increase the potassium content in the blood serum.

With NSAIDs, including selective inhibitors of COX-2. With simultaneous use of angiotensin II receptor antagonists and NSAIDs (including selective inhibitors of COX-2), the antihypertensive effect of irbesartan may be weakened. In elderly patients, patients with hypovolemia or impaired renal function, the use of NSAIDs, including COX-2 inhibitors, concomitantly with angiotensin II receptor antagonists, including irbesartan, can lead to impaired renal function, including the possible development of acute renal failure. These effects are usually reversible. Periodically, kidney function should be monitored in patients who simultaneously take irbesartan and NSAIDs, including COX-2 inhibitors.

With lithium preparations. An increase in serum lithium concentrations and an increase in its toxicity was reported with the simultaneous use of lithium salts and irbesartan.

With diuretics and other antihypertensive drugs. With the simultaneous use of irbesartan and other antihypertensive agents, an increase in antihypertensive action is possible. Irbesartan was used without any problems simultaneously with other antihypertensive drugs, such as β-blockers, long-acting CCB and thiazide diuretics. Prior treatment with diuretics in high doses can lead to hypovolemia and an increased risk of excessive BP reduction at the beginning of treatment with AprovelŪ.

Dosing and Administration

Inside, regardless of food intake, the tablet is swallowed whole, washed down with water. Usually the initial dose is 150 mg once a day. Patients who, in order to achieve target BP values, require additional reduction, the dose can be increased to 300 mg once a day.

In the case of insufficient blood pressure lowering with monotherapy with AprovelŪ, diuretics (eg, hydrochlorothiazide 12.5 mg / day) or other antihypertensive agents (eg, beta-blockers or long-acting CCB) can be added to treatment.

In patients with nephropathy with arterial hypertension and type 2 diabetes mellitus, the preferred maintenance dose is 300 mg once daily.

Individual patient groups

Children and teenagers. At the moment, the safety and efficacy of the drug in patients of childhood and adolescence is not established.

Patients of advanced age. Usually, elderly patients do not need a dose reduction. In patients who received AprovelŪ in clinical studies, overall, there was no difference in efficacy and safety between patients 65 years of age and older and younger.

Patients with hepatic insufficiency. Usually, in patients with impaired liver function (mild and moderate severity), dose reduction is not required. The experience of using the drug in patients with severe hepatic insufficiency is absent.

Patients with renal insufficiency. Usually, patients with renal insufficiency (regardless of its severity) do not need a dose reduction.

Patients with hypovolemia. In patients with severe hypovolemia and / or hyponatremia, such as patients receiving intensive diuretic therapy or who are on hemodialysis, hypovolemia and hyponatremia should be corrected before using AprovelŪ.

Overdose

The experience of using the drug in adults at doses up to 900 mg / day for 8 weeks did not reveal any toxicity.

Treatment: There is no specific information regarding the treatment of an overdose of AprovelŪ. The patient should be carefully monitored, the treatment should be symptomatic and supportive; Induction of vomiting and / or gastric lavage. Irbesartan is not removed from the body during hemodialysis.

Special instructions

Excessive reduction in blood pressure - patients with hypovolemia. The use of AprovelŪ until now has rarely been accompanied by excessive reduction in blood pressure in patients with hypertension without concomitant diseases. As with the use of ACE inhibitors, excessive reduction in blood pressure accompanied by clinical symptoms can develop in patients with hyponatremia / hypovolemia (for example, as a result of intensive diuretic therapy, diarrhea or vomiting, a diet restricting intake of table salt), as well as in patients On hemodialysis. Before using AprovelŪ, it is necessary to correct hypovolemia and / or hyponatraemia.

Patients with kidney function, depending on the activity of RAAS. As a consequence of inhibition of RAAS, we can expect a worsening of kidney function in predisposed patients. In patients with renal function dependent on RAAS activity (with arterial hypertension and renal artery stenosis of one or both kidneys, with NYHA class III and IV CHF), treatment with drugs that affect RAAS was associated with oliguria and / or Progressive azotemia and rarely with acute renal failure and / or death. It is impossible to exclude the possibility of such an effect when using angiotensin II receptor antagonists, including irbesartan.

Renal failure and kidney transplant. When using AprovelŪ in patients with renal insufficiency, periodic monitoring of the potassium content and serum creatinine concentration is recommended. There are no clinical data on the use of AprovelŪ in patients who have recently undergone a kidney transplant.

Patients with arterial hypertension and type 2 diabetes mellitus with impaired renal function. The beneficial effect of AprovelŪ on slowing the progression of renal and cardiovascular disorders had varying degrees of severity in different groups of patients, less pronounced in women and patients not belonging to the Europoid race.

In a clinical study of IDNT in patients with arterial hypertension and type 2 diabetes mellitus with proteinuria (≥900 mg / day) in a subgroup of patients at high risk of renal artery stenosis, no patient who received AprovelŪ received an acute early increase in creatinine concentration in Serum, associated with stenosis of the renal arteries.

Double blockade of RAAS in the combination of AprovelŪ with ACE inhibitors or aliskiren. Double blockade of RAAS with the use of a combination of AprovelŪ with ACE inhibitors or aliskiren is not recommended. In comparison with monotherapy there is an increased risk of a sharp decrease in blood pressure, the development of hyperkalemia and impaired renal function.

The use of AprovelŪ in combination with aliskiren is contraindicated in patients with diabetes mellitus or renal insufficiency with GFR <60 mL / min / 1.73 m2 of body surface (see "Contraindications", "Interaction") and is not recommended in other patients.

The use of AprovelŪ in combination with ACE inhibitors is contraindicated in patients with diabetic nephropathy (see "Contraindications", "Interaction") and is not recommended in other patients.

Hyperkalemia. As with the use of other drugs that affect RAAS, hyperlokemia may develop in the treatment with AprovelŪ, especially if there is renal failure and / or heart disease. In such patients it is recommended to monitor the potassium content in the blood serum.

Stenosis of the aortic or mitral valve, hypertrophic obstructive cardiomyopathy. As with the use of other vasodilators, care should be taken when taking AprovelŪ with patients with aortic or mitral stenosis or with hypertrophic obstructive cardiomyopathy.

Primary hyperaldosteronism. Patients with primary hyperaldosteronism usually do not respond to antihypertensive drugs acting through inhibition of RAAS. Therefore, the use of AprovelŪ in such cases is impractical.

Patients with IHD and / or clinically significant atherosclerosis of cerebral vessels. As with the use of other antihypertensive drugs, a significant reduction in blood pressure in patients with ischemic heart disease and / or severe cerebral arteriosclerosis can lead to the development of myocardial infarction or stroke. Treatment of such patients should be carried out under the strict control of blood pressure.

Impact on the ability to drive vehicles or engage in other potentially hazardous activities. The effect of AprovelŪ on the ability to drive vehicles or engage in other potentially hazardous activities requiring increased attention and high speed of psychomotor reactions has not been studied. However, based on its pharmacodynamic properties, AprovelŪ should not affect the ability to drive vehicles and engage in other potentially hazardous activities (altitude work, air traffic controller work, work with machinery, etc.). But in the case of dizziness and weakness, attention may decrease and psychomotor reactions may slow down. In patients who have such undesirable reactions, the decision on the possibility of engaging in any potentially dangerous activities should be taken by the doctor individually.

Release form

Tablets, film-coated, 150 mg, 300 mg. 14 pieces each. In a blister of PVC / PVDC / aluminum foil; In a cardboard bundle 1, 2 or 4 bl.

Conditions of supply of pharmacies

On prescription.

Storage conditions of the drug Aprovel

At a temperature of no higher than 30 ° C.

Keep out of the reach of children.

The shelf life of the drug Aprovel

3 years.

Do not use beyond the expiration date printed on the package.