Aprovel tablets: instructions for use and price

Pharmacodynamics and pharmacokinetics

Pharmacodynamics

Angiotensin II receptor antagonist. Causes an increase in renin and angiotensin II in the blood and a decrease in the concentration of aldosterone . The concentration of potassium in the blood does not change. Dose-dependently reduces blood pressure, but when used above 900 mg/day, the increase in hypotensive effect is insignificant. A decrease in blood pressure is observed after 3–6 hours, the effect persists for 24 hours. The hypotensive effect increases over 1–2 weeks, and the maximum is detected after 1–1.5 months. Efficiency does not depend on gender. The drug does not affect the level of uric acid in the blood. There is no withdrawal syndrome noted.

Irbesartan does not affect renal function in patients with diabetic nephropathy , glomerulonephritis , and therefore is the drug of choice in these patients.

Pharmacokinetics

Well absorbed, bioavailability 60-80%. The maximum concentration is determined in the blood after 1.5-2 hours, equilibrium - after 3 days. 96% protein bound.

Metabolized by the cytochrome P450 CYP2C9 system of the liver. Excreted by the liver and kidneys. T1/2 is 11–14 hours. For patients with impaired function of these organs, as well as for elderly people, no dose adjustment is performed.

Aprovel TB 150mg N 28

Active substance:

Irbesartan*

Pharmacological group

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

Compound

Film-coated tablets	1 table
active substance:
irbesartan	150 mg
300 mg
excipients: lactose monohydrate - 51/102 mg; MCC - 27/54 mg; croscarmellose sodium - 12/24 mg; magnesium stearate - 2.5/5 mg; colloidal silicon dioxide - 2.5/5 mg; hypromellose - 5/10 mg
film shell: Opadry white (lactose monohydrate - 36%, hypromellose - 28%, macrogol-3000 - 10%, titanium dioxide (E171) - 26%) - 10/20 mg; carnauba wax - <0.05/0.1 mg

Description of the dosage form

Tablets 150 mg: biconvex, oval, film-coated, white or almost white, engraved with a heart on one side and the number “2872” on the other.

Tablets 300 mg: biconvex, oval, film-coated, white or almost white, engraved with a heart on one side and the number “2873” on the other.

pharmachologic effect

Pharmacological action - hypotensive.

Pharmacodynamics

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

Blocks all physiologically significant effects of angiotensin II, regardless of the source or route of its synthesis, incl. its strongly pronounced vasoconstrictor and aldosterone-secreting effects, realized through AT1 type receptors located on the surface of vascular smooth muscle cells and in the adrenal cortex. It does not have agonistic activity for AT1 receptors and has a much greater (more than 8500 times) affinity for AT1 receptors than for AT2 receptors (receptors not associated with the regulation of the cardiovascular system).

Irbesartan does not inhibit RAAS enzymes (such as renin, ACE) and does not affect other hormone receptors or ion channels involved in the regulation of blood pressure and sodium homeostasis. Blocking AT1 receptors with irbesartan interrupts the feedback chain 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 having a significant effect on the content of potassium in the blood serum (the average increase is <0.1 mEq/L). Irbesartan does not have a 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 appears after taking its first dose and becomes significant within 1–2 weeks of administration; its maximum antihypertensive effect is achieved by the 4–6th week of treatment. In long-term clinical studies, the antihypertensive effect of irbesartan was observed to persist for more than one year.

The antihypertensive effect with a single daily dose of irbesartan in doses up to 900 mg is dose-dependent. Irbesartan, when taken once a day in doses of 150–300 mg, reduces blood pressure, measured in a lying or sitting position at the end of the interdose interval (24 hours after taking a dose of irbesartan, i.e. before taking the next dose), by an average of 8– 13/5–8 mm Hg. (sBP/dBP) compared with placebo. The antihypertensive effect of irbesartan before taking the next dose is 60–70% of the maximum values for the reduction in DBP and SBP. The optimal reduction in blood pressure within 24 hours is achieved by taking irbesartan once a day.

Irbesartan reduces blood pressure to approximately the same extent in a standing and lying position. Orthostatic effects are rare, but as with ACE inhibitors, in patients with hyponatremia and/or hypovolemia, an excessive decrease in blood pressure with clinical manifestations is possible.

The antihypertensive effect of irbesartan and thiazide diuretics is additive. In patients with insufficient reduction in blood pressure during monotherapy with irbesartan, adding low doses of hydrochlorothiazide (12.5 mg) once a day to its administration leads to an additional reduction in sBP/dBP by 7-10/3-6 mmHg. compared to adding placebo.

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

After discontinuation of irbesartan, blood pressure returns to its original level gradually. There is no withdrawal syndrome observed.

In a multicenter, randomized, active substance (amlodipine) versus placebo, double-blind clinical trial, the IDNT trial was conducted in 1715 hypertensive patients with type 2 diabetes mellitus (proteinuria ≥900 mg/day and serum creatinine concentration in the range of 1–3 mg/dL ), showed a 20% (p=0.024) reduction (compared with placebo) and 23% (p=0.006) reduction (compared with amlodipine) in the relative risk of the first occurrence of any of the following conditions: doubling of serum creatinine concentration, development of end-stage disease renal failure or death from any cause (if a comparable reduction in blood pressure is achieved when using irbesartan and amlodipine).

In a multicenter, randomized, placebo-controlled, double-blind clinical trial examining the effects of irbesartan on microalbuminuria in patients with hypertension and type 2 diabetes mellitus (IRMA 2), conducted in 590 patients with arterial hypertension and type 2 diabetes mellitus with microalbuminuria (20–200 mcg/min, 30–300 mg/day) and normal renal function (serum creatinine <1.5 mg/dL in men and <1.1 mg/dL in women), the effect of long-term treatment (over 2 years) was assessed. with Aprovel® on the progression of 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 was demonstrated (compared with placebo, p = 0.0004), and at a dose of 150 mg - a 39% reduction in the relative risk of developing clinically significant proteinuria (by compared with placebo, p=0.085). A slowdown in the progression of clinically significant proteinuria was noted after 3 months and continued throughout the entire 2-year clinical study period. The decrease in 24-hour Cl creatinine did not differ significantly between treatment groups. Regression of microalbuminuria to normal albuminuria levels (<20 mcg/min; <30 mg/day) was more often observed in the Aprovel® drug group at a dose of 300 mg (34%) compared to the placebo group (21%).

Pharmacokinetics

Suction. After oral administration, irbesartan is rapidly and completely absorbed, its absolute bioavailability is approximately 60–80%. Concomitant food intake does not significantly affect the bioavailability of irbesartan. After oral administration, the plasma Cmax of irbesartan is achieved within 1.5–2 hours.

Distribution. The binding to plasma proteins is approximately 96%. Binding to cellular components of blood is negligible. Vd is 53–93 l.

Metabolism. After oral or intravenous administration of 14C-irbesartan, 80–85% of the radioactivity circulating in the blood plasma is unchanged irbesartan. Irbesartan is metabolized by the liver by oxidation and conjugation with glucuronic acid. The main metabolite found in the systemic circulation is irbesartan glucuronide (approximately 6%). The oxidation of irbesartan is carried out mainly by the cytochrome P450 isoenzyme CYP2C9; the participation of the CYP3A4 isoenzyme in the metabolism of irbesartan is insignificant. Irbesartan is not metabolized by most isoenzymes that are usually involved in the metabolism of drugs (isoenzymes CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2D6 or CYP2E1), and does not cause their inhibition or induction. Irbesartan does not induce or inhibit the CYP3A4 isoenzyme.

Excretion. Irbesartan and its metabolites are excreted from the body, both through the intestines (with bile) and the kidneys. After oral or intravenous administration of 14C-irbesartan, about 20% of the radioactivity is found in the urine, and the rest in the feces. Less than 2% of the administered dose is excreted by the kidneys as unchanged irbesartan. The final half-life of irbesartan is 11–15 hours. The total clearance of intravenously administered irbesartan is 157–176 ml/min, and its renal clearance is 3–3.5 ml/min. With a daily single dose of irbesartan during the day, plasma Css is achieved after 3 days, while its limited accumulation in the blood plasma is observed (less than +20%).

Special patient groups

Floor. Women (compared to men) had slightly higher plasma concentrations of irbesartan. However, no gender-related differences in T1/2 and accumulation of irbesartan were detected. No dose adjustment of irbesartan is required in women. There were no gender-related differences in the effects of irbesartan.

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

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

Renal dysfunction. 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. In volunteers without arterial hypertension, the AUC and T1/2 of irbesartan in representatives of the Negroid race were approximately 20–25% higher than in representatives of the Caucasian race, and the Cmax of irbesartan was almost the same.

Indications of the drug Aprovel®

arterial hypertension (monotherapy and in combination with other antihypertensive drugs, such as thiazide diuretics, β-blockers, CCBs);

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

Contraindications

hypersensitivity to any of the components of the drug;

simultaneous use with drugs containing aliskiren in patients with diabetes mellitus or moderate to severe renal failure (glomerular filtration rate (GFR) <60 ml/min/1.73 m2 body surface);

simultaneous use with ACE inhibitors in patients with diabetic nephropathy;

hereditary galactose intolerance, lactase deficiency or glucose-galactose malabsorption;

severe liver failure (functional class C or more than 9 points on the Child-Pugh scale) (lack of experience in clinical use);

pregnancy;

breastfeeding period;

age under 18 years (efficacy and safety have not been established).

Use caution in conditions such as:

aortic or mitral valve stenosis or hypertrophic obstructive cardiomyopathy;

hypovolemia, hyponatremia that occur during treatment with diuretics, hemodialysis;

following a diet with limited salt intake, diarrhea, vomiting (risk of excessive reduction in blood pressure);

patients with renal function dependent on the activity of the RAAS (including patients with arterial hypertension with bilateral or unilateral renal artery stenosis or chronic heart failure of functional class III–IV (according to the NYHA classification) (see “Special Instructions”);

coronary heart disease and/or clinically significant cerebral atherosclerosis (with an excessive decrease in blood pressure, there is a risk of increased ischemic disorders, including the development of acute myocardial infarction and stroke);

renal failure (requires monitoring of potassium levels and creatinine concentrations in the blood), recent kidney transplantation (lack of experience in clinical use);

simultaneous use of NSAIDs, including selective COX-2 inhibitors (increased risk of developing renal dysfunction, including the possibility of acute renal failure and increased potassium levels in the blood serum, 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, because (compared to monotherapy with double blockade of the RAAS) there is an increased risk of developing an excessive decrease in blood pressure, hyperkalemia and renal dysfunction (see “Special Instructions”).

Use during pregnancy and breastfeeding

There is no experience with the use of Aprovel® during pregnancy. Considering that damage and death of the developing fetus were observed when taking ACE inhibitors in the second and third trimesters of pregnancy, irbesartan, like any other drug that acts directly on the RAAS, should not be used during pregnancy (I, II, III trimesters). If pregnancy is diagnosed during treatment with Aprovel®, you should stop taking it as soon as possible.

It is not known whether irbesartan or its metabolites are excreted into breast milk. During breastfeeding, taking Aprovel® is contraindicated. Therefore, after assessing the ratio of the expected benefit of taking the drug for the mother and the potential risk for the child, either breastfeeding or taking Aprovel® should be stopped.

Side effects

The following adverse events are presented in accordance with the following gradations of the frequency of their occurrence (according to the WHO classification: very often (≥1/10); often (≥1/100, <1/10); infrequently (≥1/1000, <1/ 100); rare (≥1/10000, <1/1000); very rare (<1/10000, including isolated reports); unknown frequency (it is not possible to determine the frequency of occurrence of an adverse event based on available data).

The safety of Aprovel® was studied in clinical studies in approximately 5,000 patients, including 1,300 patients with hypertension who took the drug for more than 6 months, and 400 patients who took the drug for one year or more. Adverse events in patients taking Aprovel® were usually moderate and transient, and their frequency was not related to the dose taken and did not depend on gender, age or race.

In placebo-controlled studies in which 1965 patients took irbesartan (for an average of 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 Aprovel®. 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 the drug Aprovel® for arterial hypertension, probably or possibly related to its use, or without an established relationship with the drug.

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

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

From the heart: infrequently - edema, tachycardia.

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

From the gastrointestinal tract: often - nausea/vomiting; uncommon - diarrhea, dyspepsia/heartburn.

From the genital organs and mammary gland: infrequently - sexual dysfunction.

General disorders: often - increased fatigue; infrequently - chest pain.

Laboratory and instrumental data: during controlled clinical studies, clinically significant changes in laboratory parameters were not observed in patients with arterial hypertension. No special monitoring of laboratory parameters is required for patients with arterial hypertension taking Aprovel®.

Adverse events observed in controlled clinical studies when using the drug Aprovel® in patients with nephropathy due to arterial hypertension and type 2 diabetes mellitus (clinical studies IDNT and IRMA 2)

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

The rate of treatment discontinuation due to orthostatic symptoms with Aprovel®, compared with placebo, was 0.3 versus 0.5% for dizziness, 0.2 versus 0.0% for orthostatic dizziness, and 0.0 versus 0.0% for orthostatic hypotension. 0.0% respectively.

Laboratory indicators: hyperkalemia. In the IDNT clinical trial, the percentage of patients with hyperkalemia (>6 mEq/L) was 18.6% in the Aprovel group compared to 6% in the placebo group. In the IRMA 2 clinical trial, the percentage of patients with hyperkalemia (<6 mEq/L) was 1% in the Aprovel® group, and no hyperkalemia was observed in the placebo group.

In the IDNT clinical trial, treatment discontinuation rates due to hyperkalemia with Aprovel and placebo were 2.1% and 0.36%, respectively. In the IRMA clinical trial, the rate of treatment discontinuation due to hyperkalemia when taking Aprovel® and placebo was 0.5 and 0%, respectively.

Adverse events observed during post-marketing use of Aprovel®

From the immune system: very rarely - as with all angiotensin II receptor antagonists, very rare cases of allergic reactions, such as urticaria, angioedema, have been reported.

The following adverse events have been identified with the use of irbesartan since the launch of Aprovel® on the market.

Metabolism and nutrition: unknown frequency - hyperkalemia.

From the nervous system: unknown frequency - vertigo.

From the liver and biliary tract: unknown frequency - increased activity of liver enzymes and bilirubin concentration in the blood, hepatitis, jaundice.

On the part of the hearing organ: unknown frequency - ringing in the ears.

Musculoskeletal and connective tissue disorders: unknown frequency - myalgia.

From the kidneys and urinary tract: unknown frequency - renal dysfunction, incl. cases of renal failure in patients at risk (see “Special Instructions”).

General disorders: unknown frequency - asthenia.

Interaction

Based on data from in vitro studies, interaction of irbesartan with drugs metabolized by isoenzymes CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2E1 or CYP3A4 is not expected. Irbesartan is mainly metabolized by the CYP2C9 isoenzyme and is subject to glucuronidation to a lesser extent. Significant pharmacokinetic and pharmacodynamic interactions were not observed when irbesartan was co-administered with warfarin, a drug metabolized by the CYP2C9 isoenzyme.

Irbesartan does not change the pharmacokinetics of digoxin and simvastatin.

When irbesartan is co-administered with hydrochlorothiazide or nifedipine, the pharmacokinetics of irbesartan does not change.

With medications containing aliskiren. The combination of Aprovel® with medicinal products containing aliskiren is contraindicated in patients with diabetes mellitus or moderate to severe renal impairment (GFR <60 ml/min/1.73 m2 body surface area) and is not recommended in other patients (see "Contraindications" With caution, "Special instructions").

With ACE inhibitors. The use of Aprovel® in combination with ACE inhibitors is contraindicated in patients with diabetic nephropathy and is not recommended in other patients (see “Contraindications”, “Precautions”, “Special Instructions”).

With potassium supplements and potassium-sparing diuretics, heparin. Based on the experience gained with the use of other drugs that affect the RAAS, with the simultaneous use of potassium preparations; salt substitutes containing potassium; potassium-sparing diuretics or others that can increase the potassium level in the blood of drugs (heparin), it is possible to increase the potassium level in the blood serum.

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

With lithium preparations. Increased serum concentrations of lithium and increased toxicity have been reported with the simultaneous use of lithium salts and irbesartan.

With diuretics and other antihypertensive drugs. With simultaneous use of irbesartan and other antihypertensive drugs, the antihypertensive effect may be enhanced. Irbesartan has been used concomitantly with other antihypertensive agents, such as β-blockers, long-acting CCBs, and thiazide diuretics, without any problems. Previous treatment with diuretics in high doses may lead to hypovolemia and an increased risk of excessive reduction in blood pressure at the beginning of treatment with Aprovel®.

Directions for use and doses

Inside, regardless of food intake, the tablet is swallowed whole with water. Usually the initial dose is 150 mg 1 time per day. For patients in whom additional blood pressure reduction is required to achieve target blood pressure values, the dose can be increased to 300 mg once a day.

In case of insufficient reduction in blood pressure during monotherapy with Aprovel®, diuretics (for example, hydrochlorothiazide 12.5 mg/day) or other antihypertensive drugs (for example, beta-blockers or long-acting CCBs) may be added to treatment.

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

Selected patient groups

Children and teenagers. To date, the safety and effectiveness of the drug in pediatric and adolescent patients have not been established.

Elderly patients. Typically, dose reduction is not required in elderly patients. In patients who received Aprovel® in clinical studies, there were generally no differences in efficacy and safety between patients aged 65 years and older and younger patients.

Patients with liver failure. Typically, in patients with hepatic impairment (mild to moderate severity), no dose reduction is required. There is no experience with the use of the drug in patients with severe liver failure.

Patients with renal failure. Typically, in patients with renal failure (regardless of its severity), dose reduction is not required.

Patients with hypovolemia. In patients with severe hypovolemia and/or hyponatremia, such as patients receiving intensive diuretic therapy or on hemodialysis, hypovolemia and hyponatremia should be corrected before starting Aprovel®.

Overdose

Experience with the use of the drug in adults in doses up to 900 mg/day for 8 weeks did not reveal any toxicity.

Treatment: There is no specific information regarding the treatment of overdose of Aprovel®. The patient should be closely monitored, treatment should be symptomatic and supportive; induction of vomiting and/or gastric lavage. Irbesartan is not removed from the body by hemodialysis.

special instructions

Excessive decrease in blood pressure - patients with hypovolemia. The use of the drug Aprovel® has so far rarely been accompanied by an excessive decrease in blood pressure in patients with arterial hypertension without concomitant diseases. As with the use of ACE inhibitors, an excessive decrease 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, following a diet with limited sodium intake), as well as in patients undergoing on hemodialysis. Before starting the use of Aprovel®, it is necessary to correct hypovolemia and/or hyponatremia.

Patients with renal function dependent on the activity of the RAAS. As a consequence of RAAS inhibition, deterioration of renal function can be expected in predisposed patients. In patients with renal function dependent on the activity of the RAAS (with arterial hypertension and renal artery stenosis of one or both kidneys; with NYHA functional class III and IV CHF), treatment with drugs that affect the RAAS was associated with oliguria and/or progressive azotemia and rarely with acute renal failure and/or death. The possibility of a similar effect when using angiotensin II receptor antagonists, including irbesartan, cannot be excluded.

Kidney failure and kidney transplantation. When using the drug Aprovel® in patients with renal failure, periodic monitoring of potassium levels and creatinine concentrations in the blood serum is recommended. There are no clinical data regarding the use of Aprovel® 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 Aprovel® in slowing the progression of renal and cardiovascular disorders had varying degrees of severity in different groups of patients; it was less pronounced in women and non-Caucasian patients.

In the IDNT clinical trial in patients with hypertension and type 2 diabetes mellitus with proteinuria (≥900 mg/day) in the subgroup of patients at high risk of renal artery stenosis, no patients receiving Aprovel® experienced an acute early increase in creatinine concentration in serum associated with renal artery stenosis.

Double blockade of the RAAS when combining the drug Aprovel® with ACE inhibitors or aliskiren. Double blockade of the RAAS when using a combination of Aprovel® with ACE inhibitors or aliskiren is not recommended, because Compared with monotherapy, there is an increased risk of a sharp decrease in blood pressure, the development of hyperkalemia and renal dysfunction.

The use of Aprovel® in combination with aliskiren is contraindicated in patients with diabetes mellitus or renal failure with a GFR <60 ml/min/1.73 m2 of body surface area (see “Contraindications”, “Interaction”) and is not recommended in other patients.

The use of Aprovel® in combination with ACE inhibitors is contraindicated in patients with diabetic nephropathy (see “Contraindications”, “Interactions”) and is not recommended in other patients.

Hyperkalemia. As with the use of other drugs that affect the RAAS, hyperkalemia may develop during treatment with Aprovel®, especially in the presence of renal failure and/or heart disease. In such patients, it is recommended to monitor serum potassium levels.

Aortic or mitral valve stenosis, hypertrophic obstructive cardiomyopathy. As with the use of other vasodilators, caution should be exercised when taking Aprovel® in patients with aortic or mitral stenosis or hypertrophic obstructive cardiomyopathy.

Primary hyperaldosteronism. Patients with primary hyperaldosteronism usually do not respond to antihypertensive drugs that act through inhibition of the RAAS. Therefore, the use of Aprovel® in such cases is not advisable.

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

Impact on the ability to drive vehicles or engage in other potentially hazardous activities. The effect of Aprovel® on the ability to drive vehicles or engage in other potentially hazardous activities that require increased attention and high speed of psychomotor reactions has not been studied. However, based on its pharmacodynamic properties, the drug Aprovel® should not affect the ability to drive vehicles and engage in other potentially hazardous activities (work at height, work as an air traffic controller, work with machinery, etc.). But if dizziness and weakness occur, attention may decrease and psychomotor reactions may slow down. In patients who have such adverse reactions, the decision about the possibility of engaging in any potentially hazardous activities should be made by the doctor individually.

Release form

Film-coated tablets, 150 mg, 300 mg. 14 pcs. in a blister made of PVC/PVDC/aluminum foil; in a cardboard box 1, 2 or 4 bl.

Manufacturer

Sanofi Winthrop Industries. 1 rue de la Vierge, Ambares et Lagrave F-33565, Carbon Blanc Cedex, France.

The legal entity in whose name the registration certificate was issued. Sanofi Pharma Bristol-Myers Squibb SNC, France.

Consumer complaints should be sent to: 125009, Russia, Moscow, st. Tverskaya, 22.

Tel.; Fax.

Conditions for dispensing from pharmacies

On prescription.

Storage conditions for the drug Aprovel®

At a temperature not exceeding 30 °C.

Keep out of the reach of children.

Indications for use

Aprovel is used for:

primary hypertension;
secondary hypertension;
kidney damage due to diabetes and other diseases.

It is prescribed with caution for hyponatremia , aortic valve stenosis , renal artery stenosis , coronary heart disease , severe liver and kidney failure .

Instructions for use of Aprovel (Method and dosage)

The tablet is taken orally without chewing. Treatment begins with 150 mg 1 time per day, this dose provides blood pressure control for 24 hours. If ineffective, the dose is increased to 300 mg.

For type II diabetes mellitus with arterial hypertension, 150 mg/day is initially prescribed and increased to 300 mg, since this dose is more preferable in the treatment of nephropathy . For persons over 75 years of age and patients on hemodialysis, the drug is prescribed at an initial dose of 75 mg. Prescribing a diuretic enhances the effect of the drug.

The drug Co Aprovel is a combination of Irbesartan + hydrochlorothiazide in dosages of 150 mg/12.5 mg and 300 mg/12.5 mg.

Instructions for use of Aprovel contain information that impaired renal and liver function in patients does not require dose adjustment.

Compound

Film-coated tablets	1 table
active substance:
irbesartan	150 mg
300 mg
excipients: lactose monohydrate - 51/102 mg; MCC - 27/54 mg; croscarmellose sodium - 12/24 mg; magnesium stearate - 2.5/5 mg; colloidal silicon dioxide - 2.5/5 mg; hypromellose - 5/10 mg
film shell: Opadry white (lactose monohydrate - 36%, hypromellose - 28%, macrogol-3000 - 10%, titanium dioxide (E171) - 26%) - 10/20 mg; carnauba wax - <0.05/0.1 mg

Interaction

Aprovel when used with potassium supplements can cause an increase in potassium in the blood. Thiazide diuretics enhance its hypotensive effect.

Drugs containing aliskiren should not be used in combination with Aprovel for diabetes mellitus or renal failure , since there is a high risk of a significant decrease in blood pressure, impaired renal function and the occurrence of hyperkalemia .

When used with lithium , monitoring of lithium in the blood is recommended.

NSAIDs weaken the hypotensive effect, increase potassium levels and the risk of renal dysfunction.

Irbesartan does not affect the pharmacokinetics of digoxin .

Use during pregnancy and breastfeeding

Analogs

Level 4 ATC code matches:
Telmisartan

Irbesartan

Presartan

Nortivan

Candesartan

Kozaar

Teveten

Blocktran

Cardosal

Valsartan

Losartan

Atakand

Diovan

Valsacor

Mikardis

Vazar

Valz

Lorista

Lozap

Ibertan , Irsar , Irbesartan , Firmasta .

Reviews

Many patients note the effectiveness and ease of use of this drug. In terms of its hypotensive effect, this drug is not inferior to ACE . The hypotensive effect lasts 24 hours, so Aprovel is taken once a day. Patients note a dose-dependent decrease in blood pressure.

“With Aprovel, I achieved stabilization of blood pressure after a stroke. I measure my blood pressure 3 times a day."

“I started taking this drug after Lisinopril, which caused a sore throat and coughing.”

Side effects are transient and the main thing is that there are no undesirable effects characteristic of ACE (in particular, cough). It is noted that the main disadvantage of this drug is its rather high cost.