INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT ROTAZAR (ROTAZAR)

Composition:

Active substance: irbesartan;

One film-coated tablet contains irbesartan 75 mg, or 150 mg, or 300 mg;

Excipients: sodium croscarmellose; lactose monohydrate; microcrystalline cellulose; pregelatinized starch 1500; magnesium stearate; poloxamer 188; colloidal anhydrous silicon dioxide;

film coating Opadry® II White 85F18422 (polyvinyl alcohol; polyethylene glycol; titanium dioxide (E 171); talc).

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties: white, oval-shaped, biconvex film-coated tablets.

Pharmacotherapeutic group.

Angiotensin II receptor antagonists (not combined). ATC code C09CA04.

Pharmacological Properties

Pharmacodynamics

Mechanism of action

Irbesartan is a potent, orally active, selective antagonist of angiotensin II receptors (AT1 type). It blocks all effects of angiotensin II mediated by the AT1 receptor, regardless of the source or pathway of angiotensin II synthesis. Selective antagonism of angiotensin II receptors (AT1 type) leads to increased plasma renin and angiotensin II levels, as well as decreased plasma aldosterone concentration. Irbesartan, when administered at recommended doses, has no clinically significant effect on serum potassium levels. Irbesartan does not inhibit ACE (kininase II), the enzyme responsible for converting angiotensin I to angiotensin II and for degrading bradykinin into inactive metabolites. Irbesartan is active without metabolic activation.

Clinical efficacy

Arterial hypertension

Irbesartan reduces arterial blood pressure with minimal effect on heart rate. The antihypertensive effect is dose-dependent, with a tendency toward a plateau at doses above 300 mg. When administered at doses of 150–300 mg once daily, the mean reduction in seated or supine blood pressure at trough (i.e., 24 hours after dose administration) is approximately
8–13/5–8 mm Hg (systolic/diastolic) greater than placebo.

The maximum reduction in blood pressure occurs within 3–6 hours after administration of irbesartan, and the antihypertensive effect persists for at least 24 hours. With recommended doses, the blood pressure reduction at 24 hours post-dose is 60–70% of the peak diastolic and systolic response. Administration of irbesartan 150 mg once daily provides a minimal effect and average 24-hour response similar to that observed with irbesartan administered twice daily at the same total daily dose.

The antihypertensive effect of irbesartan develops within 1–2 weeks, with maximal effect achieved within 4–6 weeks of initiating therapy. This antihypertensive effect is maintained during long-term treatment. After discontinuation of irbesartan, blood pressure gradually returns to baseline levels. Rebound hypertension has not been observed.

The blood pressure-lowering effects of irbesartan and thiazide diuretics are additive. In patients in whom monotherapy with irbesartan does not provide adequate blood pressure control, adding a low dose of hydrochlorothiazide (12.5 mg) once daily results in an additional placebo-corrected reduction in blood pressure of 7–10/3–6 mm Hg (systolic/diastolic) at trough.

The antihypertensive efficacy of irbesartan is independent of patient age or sex. As with other drugs affecting the renin-angiotensin system, patients of non-European ancestry with arterial hypertension show a markedly reduced response to irbesartan monotherapy. However, when irbesartan is combined with a low dose of hydrochlorothiazide (e.g., 12.5 mg daily), the antihypertensive response in these patients approaches that observed in patients of European ancestry.

Clinically significant effects of irbesartan on plasma uric acid levels or urinary uric acid excretion have not been observed.

Chronic kidney disease in patients with arterial hypertension and type 2 diabetes

In a double-blind, placebo-controlled trial, the long-term effects (mean follow-up of 2.6 years) of irbesartan on progression of kidney disease and all-cause mortality were evaluated. Dose titration of irbesartan was performed from 75 mg to 300 mg (maintenance dose), amlodipine from 2.5 mg to 10 mg, or placebo, depending on tolerability. Patients in all treatment groups typically received 2 to 4 antihypertensive agents. The study results showed no effect of irbesartan treatment on all-cause mortality; however, a positive trend toward reduced risk of end-stage renal disease and a statistically significant reduction in the risk of doubling of serum creatinine levels were observed. This indicates a slowing of progression of chronic kidney disease in patients with chronic renal insufficiency and overt proteinuria.

Treatment effects were assessed in subgroups by sex, race, age, duration of diabetes, baseline blood pressure, serum creatinine level, and albumin excretion rate. In subgroups of women and patients of non-European ancestry, which constituted 32% and 26% of the total study population, respectively, the renal benefits of irbesartan treatment were not demonstrated.

In a placebo-controlled, double-blind, long-term study (2-year follow-up) evaluating the effects of irbesartan on microalbuminuria in patients with arterial hypertension and type 2 diabetes, treatment with irbesartan 300 mg in patients with microalbuminuria was shown to slow progression of kidney dysfunction to overt proteinuria (urinary albumin excretion rate (UAER) > 300 mg/day and an increase in UAER of at least 30% from baseline).

The slowing of progression to clinical proteinuria was evident as early as 3 months into treatment and was sustained throughout the 2-year study period. Cases of regression to normoalbuminuria (<30 mg/day) were more frequent in the irbesartan group (34%) than in the placebo group (21%).

Dual blockade of the renin-angiotensin-aldosterone system (RAAS)

Results from two randomized, controlled trials of combining an ACE inhibitor with an angiotensin II receptor antagonist show no statistically significant benefits of combination therapy over monotherapy regarding renal and/or cardiovascular clinical outcomes or mortality. However, an increased risk of hyperkalemia, acute kidney injury, and/or symptomatic hypotension was observed with combination therapy compared to monotherapy. Given the similar pharmacodynamic profiles of these agents, these findings are also applicable to other ACE inhibitors and angiotensin II receptor antagonists. Therefore, ACE inhibitors and angiotensin II receptor antagonists should not be used concomitantly in patients with diabetic nephropathy.

In a study evaluating the addition of aliskiren to standard therapy with an ACE inhibitor or angiotensin II receptor antagonist in patients with type 2 diabetes and chronic kidney disease, cardiovascular disease, or both, an increased risk of hyperkalemia, hypotension, renal dysfunction, and higher rates of cardiovascular mortality and stroke were observed.

Pharmacokinetics

Absorption

After oral administration, irbesartan is well absorbed, with a bioavailability of approximately 60–80%. Co-administration with food does not have any clinically significant effect on irbesartan bioavailability.

Distribution

Plasma protein binding of irbesartan is approximately 96%, while binding to blood cellular components is negligible. The volume of distribution of irbesartan ranges from 53 to 93 liters.

Metabolism

After oral or intravenous administration of 14C-irbesartan, 80–85% of plasma radioactivity is attributable to unchanged irbesartan. Irbesartan is metabolized in the liver via glucuronidation and oxidation. The main circulating metabolite is the glucuronide conjugate (approximately 6%). In vitro studies indicate that irbesartan is primarily oxidized by the CYP2C9 isoenzyme of the cytochrome P450 system, with minor involvement of CYP3A4.

Excretion

Irbesartan and its metabolites are excreted both via bile and urine. After both oral and intravenous administration of 14C-irbesartan, approximately 20% of radioactivity is excreted in urine, and the remainder in feces. Less than 2% of the dose is excreted unchanged in urine.

Linearity/Non-linearity

Irbesartan exhibits linear, dose-proportional pharmacokinetics over the dose range of 10 mg to 600 mg. Less than dose-proportional increases in absorption were observed after oral administration of doses exceeding 600 mg (twice the maximum recommended dose); the mechanism of this phenomenon is not fully understood. Maximum plasma concentration (Cmax) is reached within 1.5–2 hours after oral administration. Total and renal clearance are 157–176 mL/min and 3–3.5 mL/min, respectively. The terminal elimination half-life (t1/2) of irbesartan is 11–15 hours. Steady-state plasma concentrations are achieved within 3 days of once-daily dosing. With repeated once-daily administration, limited accumulation of irbesartan in plasma is observed (<20%).

In one study, slightly higher plasma concentrations of irbesartan were observed in female patients with arterial hypertension compared to males. However, no differences in t1/2 or accumulation between males and females were observed. Dose adjustment of irbesartan is not required in female patients.

Special patient populations

Elderly patients

AUC and Cmax values of irbesartan were slightly higher in elderly patients (≥65 years) compared to younger patients (18–40 years). However, the terminal t1/2 was not significantly different. Dose adjustment is not required in elderly patients.

Patients with renal impairment

Pharmacokinetic parameters of irbesartan are not significantly altered in patients with renal insufficiency or in patients undergoing hemodialysis. Irbesartan is not removed by hemodialysis.

Patients with hepatic impairment

Pharmacokinetic parameters of irbesartan are not significantly altered in patients with mild to moderate hepatic cirrhosis. Studies in patients with severe hepatic dysfunction have not been conducted.

Clinical characteristics.

Indications.

Treatment of essential arterial hypertension in adult patients.
Treatment of chronic kidney disease in adult patients with arterial hypertension and type 2 diabetes (as part of antihypertensive therapy) (see sections "Pharmacodynamics", "Contraindications", "Interaction with other medicinal products and other forms of interactions", and "Special precautions").

Contraindications.

Hypersensitivity to the active substance and/or to any of the excipients of the medicinal product.
Concomitant use with aliskiren-containing products in patients with diabetes mellitus or renal dysfunction (glomerular filtration rate < 60 mL/min/1.73 m²) (see sections "Pharmacodynamics" and "Interaction with other medicinal products and other forms of interactions").
Pregnancy and planned pregnancy.
Breastfeeding.
Pediatric use under 18 years of age.

Interaction with other medicinal products and other forms of interactions.

Diuretics and other antihypertensive agents

When used concomitantly with other antihypertensive agents, there may be an increased risk of developing arterial hypotension, although irbesartan has been safely used with certain antihypertensive agents such as beta-blockers, long-acting calcium channel blockers, and thiazide diuretics. Prior treatment with high doses of diuretics may also lead to hypovolemia and increase the risk of arterial hypotension following initiation of irbesartan (see section "Special precautions").

Aliskiren-containing agents or ACE inhibitors

Clinical trial data have shown that dual blockade of the renin-angiotensin-aldosterone system (RAAS) by combining ACE inhibitors, angiotensin II receptor antagonists, or aliskiren is associated with an increased incidence of adverse reactions such as arterial hypotension, hyperkalemia, and renal impairment (including development of acute renal failure), compared to use of a single agent acting on the RAAS (see sections "Pharmacodynamics", "Contraindications", and "Special precautions").

Potassium supplements and potassium-sparing diuretics

Due to experience with other medicinal products affecting the renin-angiotensin system, concomitant use of potassium-sparing diuretics, potassium supplements, potassium-containing salt substitutes, or other medicinal products that may increase plasma potassium levels (e.g., heparin) may lead to increased plasma potassium levels and is therefore not recommended (see section "Special precautions").

Lithium

Concomitant use of angiotensin II receptor antagonists, including irbesartan, with lithium preparations may increase lithium plasma concentrations and enhance its toxic effects. Such combination is not recommended (see section "Special precautions"). If concomitant use is necessary, careful monitoring of plasma lithium levels is advised.

Non-steroidal anti-inflammatory drugs (NSAIDs)

Concomitant use of angiotensin II antagonists, including irbesartan, with NSAIDs (including selective COX-2 inhibitors, acetylsalicylic acid (> 3 g/day), and non-selective NSAIDs) may result in reduced antihypertensive effect.

As with ACE inhibitors, concomitant use of angiotensin II antagonists and NSAIDs may also lead to renal impairment, including development of acute renal failure, and increased plasma potassium levels, particularly in patients with pre-existing renal impairment. Such combination should be used with caution, especially in elderly patients. Adequate hydration should be ensured, and renal function should be monitored at the start of such combination therapy and periodically thereafter.

Repaglinide

Irbesartan may inhibit the OATP1B1 transporter. In a clinical study, administration of irbesartan one hour prior to repaglinide increased the Cmax and AUC of repaglinide (a substrate of the OATP1B1 transporter) by 1.8 and 1.3 times, respectively. In another study, no significant pharmacokinetic interaction was observed when irbesartan and repaglinide were administered concomitantly. Dose adjustment of repaglinide may be required when these medicinal products are used together (see section "Special precautions").

Additional information on irbesartan interactions

Hydrochlorothiazide has been reported not to interfere with the pharmacokinetics of irbesartan.

Irbesartan is metabolized primarily by the CYP2C9 enzyme and to a lesser extent by glucuronidation. No significant pharmacokinetic or pharmacodynamic interactions were observed when irbesartan was co-administered with warfarin (a medicinal product metabolized by CYP2C9).

The effect of CYP2C9 inducers such as rifampicin on the pharmacokinetics of irbesartan has not been evaluated.

When irbesartan was co-administered with digoxin, the pharmacokinetics of digoxin were not altered.

Special precautions for use.

Risk of intravascular hypovolemia

Hypovolemia and/or hyponatremia due to intensive diuretic therapy, restricted dietary salt intake, diarrhea, or vomiting may lead to symptomatic arterial hypotension, especially after the first dose of irbesartan. Such conditions should be corrected prior to initiating treatment with the medicinal product.

Risk of renovascular hypertension

When using medicinal products affecting the RAAS, there is an increased risk of severe arterial hypotension and renal failure in patients with bilateral renal artery stenosis or stenosis of the artery of a single functioning kidney. Similar effects may also occur with any angiotensin II receptor antagonists.

Patients with renal impairment and kidney transplant recipients

Periodic monitoring of plasma potassium and creatinine levels is recommended in patients with impaired renal function receiving this medicinal product. Experience with irbesartan in patients who have recently undergone kidney transplantation is lacking.

Patients with hypertension, type 2 diabetes, and chronic kidney disease

Clinical trial results showed that the effects of irbesartan on both renal and cardiovascular outcomes were not consistent across all patient groups. In particular, benefits were less pronounced in women and in individuals of non-Caucasian race.

Risk of dual blockade of the RAAS

Concomitant use of ACE inhibitors, angiotensin II receptor antagonists, or aliskiren has been shown to increase the risk of arterial hypotension, hyperkalemia, and renal dysfunction (including acute kidney injury). Therefore, dual blockade of the RAAS by combining ACE inhibitors, angiotensin II receptor antagonists, or aliskiren is not recommended (see sections "Pharmacodynamics" and "Interaction with other medicinal products and other forms of interaction"). If such dual blockade therapy is considered absolutely necessary, it should be administered only under specialist supervision and with frequent monitoring of renal function, electrolyte levels, and blood pressure. ACE inhibitors and angiotensin II receptor antagonists should not be used concomitantly in patients with diabetic nephropathy.

Risk of hyperkalemia

As with other medicinal products affecting the RAAS, hyperkalemia may occur during treatment with irbesartan, particularly in the presence of renal dysfunction, overt proteinuria due to diabetic nephropathy, and/or heart failure. Careful monitoring of plasma potassium levels is recommended in patients at risk of this complication (see section "Interaction with other medicinal products and other forms of interaction").

Risk of hypoglycemia

Irbesartan may cause hypoglycemia, especially in patients with diabetes mellitus. When used in patients receiving insulin or antidiabetic agents, appropriate monitoring of plasma glucose levels should be considered. Dose adjustments of insulin or antidiabetic agents may be required as clinically indicated (see section "Interaction with other medicinal products and other forms of interaction").

Concomitant use with lithium preparations

The medicinal product is not recommended for concomitant use with lithium-containing preparations (see section "Interaction with other medicinal products and other forms of interaction").

Use in patients with aortic and mitral valve stenosis, obstructive hypertrophic cardiomyopathy

Like other vasodilators, the medicinal product should be used with particular caution in patients with aortic or mitral valve stenosis or obstructive hypertrophic cardiomyopathy.

Use in patients with primary hyperaldosteronism

Patients with primary hyperaldosteronism usually do not respond to antihypertensive drugs acting through inhibition of the renin-angiotensin system. Therefore, use of the medicinal product for treatment of such patients is not recommended.

Intestinal angioedema

Cases of intestinal angioedema have been reported in patients taking angiotensin II receptor blockers, [including irbesartan] (see section "Adverse reactions"). These patients presented with abdominal pain, nausea, vomiting, and diarrhea. Symptoms resolved after discontinuation of angiotensin II receptor blockers. If intestinal angioedema is diagnosed, irbesartan should be discontinued and appropriate monitoring initiated until complete resolution of symptoms.

General precautions

In patients whose vascular tone and renal function depend primarily on the activity of the renin-angiotensin-aldosterone system (e.g., patients with severe congestive heart failure or underlying renal disease, including renal artery stenosis), treatment with ACE inhibitors or angiotensin II receptor antagonists affecting this system has been associated with acute hypotension, azotemia, oliguria, and sometimes acute renal failure (see section "Special precautions for use"). As with any antihypertensive agent, excessive reduction in blood pressure in patients with ischemic heart disease or ischemic cerebrovascular disease may lead to myocardial infarction or stroke. Similar to ACE inhibitors, irbesartan and other angiotensin antagonists appear to be less effective in lowering blood pressure in Black patients compared to patients of other races, possibly because hypertension in the Black population is more frequently associated with low renin levels (see section "Pharmacodynamics").

Use during pregnancy

Angiotensin II receptor antagonists should not be initiated during pregnancy. If continued use of an angiotensin II receptor antagonist is considered necessary, pregnant women or women planning pregnancy should be switched to alternative antihypertensive therapy with a well-established safety profile during pregnancy. If pregnancy is confirmed, angiotensin II receptor antagonists should be discontinued immediately, and alternative therapy initiated if necessary (see sections "Contraindications" and "Use during pregnancy or breastfeeding").

Use in children

Irbesartan has been studied in a pediatric population aged 6 to 16 years; however, current data are insufficient to extend its indications for use in children until additional data become available.

Warnings concerning excipients

The medicinal product contains less than 1 mmol (23 mg)/dose of sodium, i.e., essentially "sodium-free".

The medicinal product also contains lactose and therefore should not be used in patients with rare hereditary conditions such as galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption syndrome.

Use during pregnancy or breastfeeding

Pregnancy

The medicinal product is contraindicated in pregnant women and women who are planning to become pregnant. If pregnancy is confirmed during treatment, the medicinal product should be discontinued immediately and replaced with another medicinal product approved for use during pregnancy.

Epidemiological data on the teratogenic risk associated with ACE inhibitor use during the first trimester of pregnancy are inconclusive, but a small increased risk cannot be excluded. As there are no controlled epidemiological data on the risk associated with angiotensin II receptor antagonists, similar risks may exist for this class of drugs. Except when continuation of therapy is considered necessary, women planning pregnancy should be switched to alternative antihypertensive therapy with an established safety profile during pregnancy. Upon confirmation of pregnancy, angiotensin II receptor antagonists must be discontinued immediately, and alternative therapy initiated if necessary.

It is known that use of angiotensin II receptor antagonists during the second and third trimesters of pregnancy induces fetotoxicity (impaired renal function, oligohydramnios, delayed skull ossification) and neonatal toxicity (renal failure, arterial hypotension, hyperkalemia) in humans.

If angiotensin II receptor antagonists are used from the second trimester of pregnancy, ultrasound monitoring of fetal renal function and skull ossification is recommended.

Newborns whose mothers were treated with angiotensin II receptor antagonists should be closely monitored for signs of arterial hypotension (see sections "Contraindications" and "Special precautions for use").

Breastfeeding period

As information on the use of irbesartan during breastfeeding is currently lacking, use of the medicinal product in such patients is not recommended. Alternative medicinal products with a better-established safety profile during breastfeeding should be preferred, especially when nursing newborns or preterm infants.

It is unknown whether irbesartan or its metabolites are excreted in human breast milk. Available pharmacodynamic/toxicological data from studies in rats have demonstrated excretion of irbesartan or its metabolites into breast milk.

Fertility

Irbesartan had no effect on fertility in rats or on their offspring up to dose levels causing the first signs of maternal toxicity.

Ability to influence the speed of reactions when driving or operating machinery.

Due to its pharmacodynamic properties, influence on this ability is unlikely. However, when driving or operating machinery, it should be considered that dizziness or increased fatigue may occur during treatment.

Method of Administration and Dosage

The medicinal product is intended for oral administration.

Treatment of essential arterial hypertension in adult patients

The usual recommended initial and maintenance dose of the medicinal product is 150 mg once daily, regardless of food intake. Irbesartan at a dose of 150 mg once daily generally provides better 24-hour blood pressure control than 75 mg. However, initiating treatment with a dose of 75 mg should be considered, particularly in patients undergoing hemodialysis and elderly patients (aged 75 years and older).

For patients in whom a dose of 150 mg once daily does not provide adequate control, the dose may be increased to 300 mg or other antihypertensive agents may be added (see sections "Pharmacodynamics", "Contraindications", "Interaction with other medicinal products and other forms of interaction", and "Special precautions for use"). In particular, it has been shown that adding a diuretic such as hydrochlorothiazide has an additive effect to that of irbesartan.

Treatment of chronic kidney disease in adult patients with arterial hypertension and type 2 diabetes

The usual recommended initial dose of the medicinal product is 150 mg once daily, regardless of food intake. The dose should be titrated up to a maintenance dose of 300 mg once daily.

The benefits of irbesartan on renal function in patients with hypertension and type 2 diabetes have been demonstrated in clinical studies where irbesartan was used in addition to other antihypertensive agents, if necessary, to achieve target blood pressure (see sections "Pharmacodynamics", "Contraindications", "Interaction with other medicinal products and other forms of interaction", and "Special precautions for use").

Special patient categories

Patients with renal impairment

Dosage adjustment is not required in these patients.

For patients undergoing hemodialysis, consideration should be given to using a lower initial dose of irbesartan (75 mg) (see section "Special precautions for use").

Patients with hepatic impairment

Dosage adjustment is not required in patients with mild to moderate hepatic dysfunction. There is no clinical experience with the use of irbesartan in patients with severe hepatic dysfunction.

Elderly patients

Generally, dosage adjustment is not required in these patients. In patients aged 75 years and older, initiation of treatment with a dose of 75 mg should be considered.

Children

The safety and efficacy of irbesartan in children under 18 years of age have not been established. The medicinal product is contraindicated in children under 18 years of age.

Overdose

Symptoms

When irbesartan was administered to adult patients at doses up to 900 mg/day for 8 weeks, no toxic reactions were observed. The most likely manifestations of overdose are hypotension and tachycardia; bradycardia may also occur.

Treatment

Continuous monitoring of the patient's condition should be performed, and symptomatic and supportive therapy should be administered as needed. Induction of emesis, gastric lavage, and administration of adsorbents are also recommended. Irbesartan is not removed by hemodialysis.

Adverse Reactions

In placebo-controlled studies involving patients with arterial hypertension, the overall incidence of adverse reactions was similar between the groups receiving irbesartan (56.2%) and placebo (56.5%). Discontinuation of irbesartan due to any clinical or laboratory adverse reaction occurred less frequently in the irbesartan group (3.3%) than in the placebo group (4.5%). The incidence of adverse reactions was independent of dose (within the recommended dose range), sex, age, race, or duration of treatment.

Among patients with arterial hypertension and diabetic microalbuminuria with normal renal function, orthostatic dizziness and orthostatic hypotension occurred in 0.5% of patients receiving irbesartan (i.e., uncommonly), but more frequently than in the placebo group.

The adverse reactions listed below were observed in placebo-controlled clinical trials in which 1965 patients with arterial hypertension received irbesartan. Terms marked with an asterisk (*) indicate additional adverse reactions reported more frequently in patients with arterial hypertension, diabetes mellitus, chronic renal failure, and overt proteinuria, occurring in >2% of patients and at a higher frequency than in the placebo group.

The frequency of the adverse reactions listed below was determined according to the following criteria: very common (≥1/10); common (≥1/100, <1/10); uncommon (≥1/1,000, <1/100); rare (≥1/10,000, <1/1,000); very rare (<1/10,000); frequency not known (cannot be estimated from available data). Within each frequency group, adverse reactions are listed in order of decreasing severity.

Additionally listed are adverse reactions identified from post-marketing experience with irbesartan. These adverse reactions were reported via spontaneous reports.

Blood and lymphatic system disorders:

Frequency not known – anemia, thrombocytopenia.

Immune system disorders:

Frequency not known – hypersensitivity reactions, including anaphylactic reactions, anaphylactic shock, angioedema, rash, urticaria.

Metabolism and nutrition disorders:

Frequency not known – hyperkalemia, hypoglycemia.

Nervous system disorders:

Common – dizziness, orthostatic dizziness*; frequency not known – vertigo, headache.

Ear and labyrinth disorders:

Frequency not known – tinnitus.

Cardiac disorders:

Uncommon – tachycardia.

Vascular disorders:

Common – orthostatic hypotension*; uncommon – flushing.

Respiratory, thoracic and mediastinal disorders:

Uncommon – cough.

Gastrointestinal disorders:

Common – nausea, vomiting; uncommon – diarrhea, dyspepsia, heartburn; rare – intestinal angioedema; frequency not known – dysgeusia.

Hepatobiliary disorders:

Uncommon – jaundice; frequency not known – hepatitis, hepatic function abnormalities.

Skin and subcutaneous tissue disorders:

Frequency not known – leukocytoclastic vasculitis.

Musculoskeletal and connective tissue disorders:

Common – muscle and bone pain*; frequency not known – arthralgia, myalgia (in some cases associated with elevated plasma creatine kinase levels), muscle spasms.

Renal and urinary disorders:

Frequency not known – renal dysfunction, including cases of renal failure in patients at increased risk of this complication (see section "Special precautions").

Reproductive system and breast disorders:

Uncommon – sexual dysfunction.

General disorders:

Common – increased fatigue; uncommon – chest pain.

Investigations:

Very common – hyperkalemia* (in patients with diabetes mellitus receiving irbesartan, hyperkalemia occurred more frequently than in patients receiving placebo. In patients with arterial hypertension, diabetes mellitus, microalbuminuria, and normal renal function, hyperkalemia (≥5.5 mEq/L) was observed in 29.4% of patients in the irbesartan 300 mg group and in 22% of patients in the placebo group. In patients with arterial hypertension, diabetes mellitus, chronic renal failure, and overt proteinuria, hyperkalemia (≥5.5 mEq/L) was observed in 46.3% of patients in the irbesartan group and in 26.3% of patients in the placebo group); common – increased plasma creatine kinase levels (1.7%) (none of these increases were associated with clinically identifiable musculoskeletal manifestations).

A decrease in hemoglobin levels* was observed in 1.7% of patients with advanced-stage arterial hypertension and diabetic nephropathy treated with irbesartan, which was not clinically significant.

Reporting suspected adverse reactions

Reporting of suspected adverse reactions after product authorization is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are encouraged to report any suspected adverse reactions through the national pharmacovigilance system.

Shelf life.

3 years.

Storage conditions.

Store at temperatures not exceeding 25°C in a place inaccessible to children.

Packaging.

14 film-coated tablets in a blister, 2 blisters in a cardboard box.

Prescription status.

Prescription only.

Manufacturer.

UORLD MEDICIN ILAC SAN. VE TIC. A.S./
WORLD MEDICINE ILAC SAN. VE TIC. A.S.

Manufacturer's address and location of operations.

15 Temmuz Mahallesi Cami Yolu Caddesi No:50 Gunesli Bagcilar/Istanbul, Turkey.

Marketing authorization holder.

LLC "WORLD MEDICINE", Ukraine /
WORLD MEDICINE, LLC, Ukraine.

Rotazar