Converium

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT CONVERIUM (CONVERIUM)

Composition:

Active substance: 1 tablet contains irbesartan 150 mg or 300 mg;

Excipients: lactose monohydrate (Sorbolac 400); pregelatinized starch 1551; sodium croscarmellose; colloidal anhydrous silicon dioxide; poloxamer 188; microcrystalline cellulose (type 101); magnesium stearate.

Pharmaceutical form. Tablets.

Main physico-chemical characteristics:

150 mg tablets: white, round, flat tablets with a score line, approximately 10.5 mm in diameter;

300 mg tablets: white, round, flat tablets with a score line, approximately 12.7 mm in diameter.

Pharmacotherapeutic group. Angiotensin II receptor antagonists, single-component preparations. ATC code C09C A04.

Pharmacological Properties

Pharmacodynamics

Irbesartan is a potent, orally active, selective antagonist of angiotensin II receptors (AT1 subtype). It is believed to block all physiologically significant effects of angiotensin II mediated via the AT1 receptor, regardless of the source or pathway of angiotensin II synthesis. Selective antagonism of angiotensin II receptors (AT1) leads to increased plasma renin and angiotensin II concentrations and decreased plasma aldosterone concentration. When administered at recommended doses, irbesartan does not significantly alter serum potassium levels. Irbesartan does not inhibit angiotensin-converting enzyme (kininase II), the enzyme responsible for converting angiotensin I to angiotensin II and for metabolizing bradykinin into inactive metabolites. Irbesartan does not require metabolic activation to exert its effect.

Clinical Efficacy

Arterial Hypertension. Irbesartan reduces arterial blood pressure with minimal effect on heart rate. The antihypertensive effect of once-daily administration is dose-dependent, with a tendency toward a plateau at doses above 300 mg. Doses of 150–300 mg once daily reduce seated or supine blood pressure measured at the end of the dosing interval (i.e., 24 hours after administration) by an average of 8–13/5–8 mm Hg (systolic/diastolic) more than placebo.

Maximum blood pressure reduction is achieved within 3–6 hours after dosing, and the antihypertensive effect persists for at least 24 hours. After 24 hours following recommended doses, blood pressure reduction is 60–70% of the maximum reduction observed for both diastolic and systolic pressure. Administration of 150 mg once daily provides an effect (at the end of the dosing interval and averaged over 24 hours) comparable to that achieved when the same daily dose is divided into two administrations.

The antihypertensive effect of the medicinal product Converium becomes evident within 1–2 weeks, with maximal effect achieved by 4–6 weeks of treatment initiation. The antihypertensive effect is maintained during long-term therapy. After discontinuation of treatment, blood pressure gradually returns to baseline values. No rebound syndrome with worsening hypertension after withdrawal has been observed.

Irbesartan combined with thiazide-type diuretics produces an additive antihypertensive effect. In patients in whom irbesartan monotherapy did not provide adequate blood pressure control, concomitant administration of low-dose hydrochlorothiazide (12.5 mg) once daily with irbesartan resulted in additional blood pressure reduction of at least 7–10/3–6 mm Hg (systolic/diastolic) compared to placebo.

The efficacy of irbesartan is independent of patient age or gender. As with other drugs acting on the renin-angiotensin system, patients of non-European ancestry with arterial hypertension show a markedly reduced response to irbesartan monotherapy. When irbesartan is combined with low-dose 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 are absent.

Chronic Kidney Disease in Patients with Arterial Hypertension and Type 2 Diabetes. In a double-blind, placebo-controlled trial, long-term effects (mean follow-up 2.6 years) of irbesartan on progression of kidney disease and all-cause mortality were evaluated. Dose titration of irbesartan from 75 mg to 300 mg (maintenance dose), amlodipine from 2.5 mg to 10 mg, or placebo was performed according to tolerability. Patients in all treatment groups generally 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 serum creatinine levels were observed. This indicates a slowing of progression of chronic kidney disease in patients with chronic renal insufficiency and overt proteinuria. The treatment effect was evaluated in subgroups by sex, race, age, duration of diabetes, baseline blood pressure, serum creatinine level, and albumin excretion rate. Benefits of treatment with the investigational drug on kidney function were not demonstrated in subgroups of women and patients of non-European ancestry, who constituted 32% and 26% of the total study population, respectively.

In a placebo-controlled, double-blind study evaluating long-term effects (2-year follow-up) of irbesartan on microalbuminuria in patients with arterial hypertension and type 2 diabetes, it was shown that irbesartan 300 mg in patients with microalbuminuria slows 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 of 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 indicate no statistically significant benefits of this combination therapy on renal and/or cardiovascular clinical outcomes or mortality, while an increased risk of hyperkalemia, acute kidney injury, and/or arterial hypotension was observed compared to monotherapy. Given the similar pharmacodynamic characteristics of the drugs mentioned, 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 effect of adding 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, arterial hypotension, and renal dysfunction was observed, along with a higher incidence of cardiovascular mortality and stroke.

Pharmacokinetics

Absorption. After oral administration, irbesartan is well absorbed; studies indicate absolute bioavailability is approximately 60–80%. Co-administration with food does not significantly affect irbesartan bioavailability.

Distribution. Plasma protein binding is approximately 96%, with negligible binding to blood cells. Volume of distribution ranges from 53 to 93 liters.

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

Linearity/Non-linearity. The pharmacokinetics of irbesartan are linear and proportional to dose over the range of 10 to 600 mg. Less than proportional increases in oral absorption are observed at doses above 600 mg (twice the maximum recommended dose); the mechanism of this is unknown. Maximum plasma concentration (Cmax) is reached within 1.5–2 hours after oral administration. Total and renal clearance are 157–176 and 3–3.5 mL/min, respectively. Terminal elimination half-life of irbesartan is 11–15 hours. Steady-state plasma concentrations are achieved within 3 days of once-daily administration. With once-daily dosing, accumulation of irbesartan in plasma is minimal (< 20%). In women with arterial hypertension, slightly higher plasma concentrations of irbesartan were observed. However, no differences in elimination half-life or accumulation were noted. Dose adjustment is not required for women. In elderly individuals (> 65 years), area under the concentration-time curve (AUC) and Cmax values for irbesartan were slightly higher than in younger patients (18–40 years). However, terminal elimination half-life was not significantly altered. Dose adjustment is not required for elderly patients.

Elimination. Irbesartan and its metabolites are excreted via bile and kidneys. After oral or intravenous administration of 14C-irbesartan, approximately 20% of the radioactive label is recovered in urine, the remainder in feces. Less than 2% of the administered dose is excreted unchanged in urine.

Pediatric Population. The pharmacokinetics of irbesartan were evaluated in 23 children with arterial hypertension after single and multiple (once daily) doses of irbesartan (2 mg/kg) up to a maximum daily dose of 150 mg for 4 weeks. Of these 23 children, 21 were evaluable for pharmacokinetic comparison with adult patients (12 children aged 12 years and older, 9 children aged 6 to 12 years). Results showed that Cmax, AUC, and clearance were comparable to those in adult patients receiving 150 mg irbesartan daily. With repeated once-daily dosing, limited accumulation of irbesartan (18%) in plasma was observed.

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

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

Clinical characteristics.

Indications.

Treatment of essential arterial hypertension in adults.

Treatment of chronic kidney disease in adult patients with arterial hypertension and type 2 diabetes mellitus, as part of an antihypertensive therapy regimen.

Contraindications.

Hypersensitivity to the active substance or to any of the excipients.

Second and third trimesters of pregnancy.

Concomitant use of the drug Converium with aliskiren-containing medications is contraindicated in patients with diabetes mellitus or renal dysfunction (glomerular filtration rate (GFR) < 60 mL/min/1.73 m²).

Interaction with other medicinal products and other forms of interaction.

Diuretics and other antihypertensive agents. The risk of developing arterial hypotension during irbesartan administration may be increased when used concomitantly with other antihypertensive agents; however, irbesartan has been safely used with certain other antihypertensive agents, such as beta-blockers, long-acting calcium channel blockers, and thiazide diuretics. Prior treatment with high doses of diuretics may lead to hypovolemia and increase the risk of arterial hypotension following initiation of Converium (see section "Special precautions").

Aliskiren-containing agents or ACE inhibitors. 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 events such as arterial hypotension, hyperkalemia, and impaired renal function (including acute renal failure), compared to using a single agent affecting the RAAS (see sections "Pharmacodynamics", "Contraindications", and "Special precautions").

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

Lithium. Increased serum lithium concentrations and lithium toxicity have been reported during concomitant use of lithium with angiotensin-converting enzyme (ACE) inhibitors. Very rare cases of similar effects have been reported with irbesartan. Therefore, this combination is not recommended (see section "Special precautions"). If combination therapy is necessary, careful monitoring of serum lithium levels is advised.

Nonsteroidal anti-inflammatory drugs (NSAIDs). When angiotensin II antagonists are used concomitantly with nonsteroidal anti-inflammatory drugs (specifically: selective COX-2 inhibitors, acetylsalicylic acid (> 3 g/day), and nonselective NSAIDs), attenuation of the antihypertensive effect may occur. As with ACE inhibitors, concomitant use of angiotensin II antagonists and NSAIDs may lead to worsening of renal function, including acute renal failure, and to increased serum potassium levels, particularly in patients with pre-existing renal impairment. This combination should be used with caution, especially in elderly patients. Patients should be adequately hydrated, and monitoring of renal function at the start of combined therapy and periodically thereafter is advisable.

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 with concomitant administration of irbesartan and repaglinide. Dose adjustment of repaglinide may be required when used concomitantly with irbesartan (see section "Special precautions").

Additional information on irbesartan interactions. Hydrochlorothiazide does not affect the pharmacokinetics of irbesartan. Irbesartan is metabolized primarily by the CYP2C9 enzyme and, to a lesser extent, via glucuronidation. No significant pharmacokinetic or pharmacodynamic interactions were observed when irbesartan was coadministered with warfarin (a drug metabolized by CYP2C9). The effect of CYP2C9 inducers such as rifampicin on the pharmacokinetics of irbesartan has not been evaluated. The pharmacokinetics of digoxin were not altered when coadministered with irbesartan.

Special precautions for use.

Intravascular hypovolemia. In patients who have developed hypovolemia and/or hyponatremia due to intensive diuretic therapy, restricted salt intake, diarrhea, or vomiting, symptomatic arterial hypotension may occur, especially after the first dose of the drug. These conditions should be corrected prior to initiating treatment with Converium.

Renovascular hypertension. 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 solitary functioning kidney when treated with drugs affecting the renin-angiotensin-aldosterone system (RAAS). Although such adverse effects have not been documented with Converium, similar effects should be anticipated when using any angiotensin II receptor antagonists.

Renal impairment and kidney transplantation. During treatment with Converium in patients with impaired renal function, periodic monitoring of serum potassium and creatinine levels is recommended. Experience with Converium in patients who have recently undergone kidney transplantation is lacking.

Patients with arterial hypertension, type 2 diabetes, and chronic kidney disease. The effects of irbesartan on both the kidneys and the cardiovascular system are not uniform in patients with advanced-stage chronic kidney disease. In particular, its benefits are less pronounced in women and in individuals of non-Caucasian race.

Dual blockade of the renin-angiotensin-aldosterone system (RAAS). Evidence supports that concomitant use of ACE inhibitors, angiotensin II receptor antagonists, or aliskiren increases the risk of arterial hypotension, hyperkalemia, and worsening renal function (including acute renal failure). Therefore, dual RAAS blockade by combining ACE inhibitors, angiotensin II receptor antagonists, or aliskiren is not recommended (see sections "Interaction with other medicinal products and other forms of interaction" and "Pharmacodynamics"). If such dual blockade therapy is considered absolutely necessary, it should be administered only under specialist supervision with frequent monitoring of renal function, electrolyte levels, and blood pressure. ACE inhibitors and angiotensin II receptor antagonists must not be used concomitantly in patients with diabetic nephropathy.

Intestinal angioedema. Cases of intestinal angioedema have been reported in patients taking angiotensin II receptor blockers, including irbesartan (see section "Adverse reactions"). These patients experienced 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 symptoms completely resolve.

Hyperkalemia. As with other drugs affecting the renin-angiotensin-aldosterone system, hyperkalemia may occur during treatment with Converium, particularly in the presence of renal dysfunction, marked proteinuria due to diabetic nephropathy, and/or heart failure. Careful monitoring of serum potassium levels is recommended in patients at risk of this complication (see section "Interaction with other medicinal products and other forms of interaction").

Hypoglycemia. Irbesartan may cause hypoglycemia, especially in patients with diabetes mellitus. When administering the drug to 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").

Lithium. Concomitant use of lithium-containing drugs and Converium is not recommended (see section "Interaction with other medicinal products and other forms of interaction").

Aortic and mitral valve stenosis, obstructive hypertrophic cardiomyopathy. As with other vasodilators, special precautions should be taken in patients with aortic or mitral valve stenosis or obstructive hypertrophic cardiomyopathy.

Primary hyperaldosteronism. Patients with primary hyperaldosteronism generally do not respond to antihypertensive drugs that act by inhibiting the renin-angiotensin system. Therefore, use of Converium is not recommended in such patients.

General warnings. In patients in whom 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 primary renal disease, including renal artery stenosis), treatment with ACE inhibitors or angiotensin II receptor antagonists affecting this system has been associated with episodes of acute hypotension, azotemia, oliguria, or (rarely) acute renal failure. 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 II antagonists have been found to be less effective in lowering blood pressure in Black patients compared to other racial groups, likely due to a higher prevalence of low renin levels in the Black hypertensive population (see section "Pharmacological properties").

Use during pregnancy. Angiotensin II receptor antagonists should not be initiated during pregnancy. Women planning to become pregnant and currently receiving angiotensin II receptor antagonists 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, if necessary, alternative therapy initiated (see sections "Contraindications" and "Use during pregnancy or breastfeeding").

Pediatric use. Irbesartan has been studied in children aged 6 to 16 years; however, available data are insufficient to extend its indications to pediatric use until additional data are obtained.

Lactose. This medicinal product contains lactose. Patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption should not take this medicinal product.

Use during pregnancy or breastfeeding.

Pregnancy. Use of angiotensin II receptor antagonists (ARBs) is not recommended during the first trimester of pregnancy (see section "Special precautions for use"). ARBs are contraindicated during the second and third trimesters of pregnancy (see sections "Adverse reactions" and "Special precautions for use"). Epidemiological data on teratogenic risk associated with ACE inhibitors during the first trimester of pregnancy are inconclusive, but a small increased risk cannot be excluded. As there are no controlled epidemiological data on risk 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 treatment with an established safety profile during pregnancy. If pregnancy is confirmed, angiotensin II receptor antagonists should be discontinued immediately and, if necessary, alternative therapy initiated. It is known that use of angiotensin II receptor antagonists during the second and third trimesters of pregnancy induces human fetotoxicity (impaired renal function, oligohydramnios, delayed skull ossification) and neonatal toxicity (renal failure, arterial hypotension, hyperkalemia). 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 the development of arterial hypotension (see sections "Contraindications" and "Special precautions for use").

Breastfeeding. As information on the use of Converium during breastfeeding is currently unavailable, the use of Converium is not recommended in such patients. Preference should be given to alternative medicinal products with better-established safety profiles during breastfeeding, especially when nursing newborns or preterm infants. It is unknown whether irbesartan or its metabolites are excreted in human milk. Available pharmacodynamic/toxicological data from studies in rats have demonstrated excretion of irbesartan or its metabolites in milk.

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

Ability to affect reaction speed when driving or operating machinery. Based on the pharmacodynamic properties of irbesartan, its effect on this ability is unlikely. However, when driving vehicles or operating machinery, it should be considered that dizziness or increased fatigue may occur during treatment.

Method of administration and dosages.

The medication is intended for oral administration.

The usual recommended initial and maintenance dose is 150 mg once daily, independent of food intake. Converium 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 in elderly patients over 75 years of age.

In patients in whom the 150 mg once-daily dose of Converium does not provide adequate control, the dose may be increased to 300 mg, or additional antihypertensive agents may be prescribed. In particular, it has been shown that adding a diuretic such as hydrochlorothiazide provides an additive effect to Converium (see section "Interaction with other medicinal products and other forms of interaction").

In patients with hypertension and type II diabetes, therapy with irbesartan should be initiated at a dose of 150 mg once daily and titrated to 300 mg once daily, which is the preferred maintenance dose for treating chronic kidney disease. The benefits of Converium regarding renal function in patients with hypertension and type II diabetes have been demonstrated in studies where irbesartan was used in addition to other antihypertensive agents, when necessary, to achieve target blood pressure (see section "Pharmacological properties").

Special patient groups.

Renal impairment. Dose adjustment of the medication is not required in patients with impaired renal function. For patients undergoing hemodialysis, careful consideration should be given to initiating treatment with a lower dose (75 mg) (see section "Special precautions for use").

Hepatic impairment. Dose adjustment is not required in patients with mild to moderate hepatic dysfunction. There is no clinical experience with the use of the medication in patients with severe hepatic dysfunction.

Elderly patients. Although initiating treatment with a 75 mg dose should be considered in patients aged 75 years and older, dose adjustment is generally not required.

Children. The safety and efficacy of Converium in pediatric patients (under 18 years of age) have not been established. Current data are insufficient to extend the indications for use of the medication to children until additional data become available (see sections "Adverse reactions," "Pharmacodynamics," and "Pharmacokinetics").

Overdose.

No toxic reactions were observed in adult patients treated with doses up to 900 mg/day for 8 weeks. The most likely manifestations of irbesartan overdose are hypotension and tachycardia; bradycardia may also occur. There is currently no specific antidote for Converium overdose. The patient's condition should be closely monitored, and treatment should be symptomatic and supportive. Recommended measures include induction of emesis and/or gastric lavage. Activated charcoal may be beneficial in managing overdose. Irbesartan is not removed by hemodialysis.

Adverse reactions

The frequency of occurrence 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 based on available data).

Blood and lymphatic system disorders: frequency not known – anaemia, thrombocytopenia.

Immune system disorders: frequency not known – hypersensitivity reactions, such as anaphylactic reactions, anaphylactic shock, angioedema, rash, urticaria.

Metabolism and nutrition disorders: frequency not known – hyperkalaemia, hypoglycaemia.

Nervous system disorders: common – dizziness, orthostatic dizziness; frequency not known – vertigo, headache.

Aural and vestibular 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 – diarrhoea, 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 with an increased risk of this complication (see section "Special precautions for use").

Reproductive system and breast disorders: uncommon – sexual dysfunction.

General disorders: common – increased fatigue; uncommon – chest pain.

Investigations: very common – hyperkalaemia in patients with diabetes mellitus receiving irbesartan occurs more frequently than in patients not receiving it. In patients with hypertension, diabetes mellitus, microalbuminuria, and normal renal function, hyperkalaemia (≥ 5.5 mEq/L) was observed in 29.4% of patients receiving irbesartan 300 mg and in 22% of patients not receiving it. In patients with hypertension, diabetes mellitus, chronic renal failure, and overt proteinuria, hyperkalaemia (≥ 5.5 mEq/L) was observed in 46.3% of patients receiving irbesartan and in 26.3% of patients not receiving it.

In patients treated with irbesartan, a significant increase in plasma creatine kinase levels was commonly observed (1.7%). None of these increases were associated with clinically identifiable musculoskeletal symptoms. A decrease in haemoglobin levels, not clinically significant, was observed in 1.7% of patients with hypertension and advanced-stage diabetic nephropathy treated with irbesartan.

Pediatric population. In children and adolescents aged 6 to 16 years with arterial hypertension, the following adverse reactions were observed: headache (7.9%), arterial hypotension (2.2%), dizziness (1.9%), cough (0.9%). The most common laboratory abnormalities were increased creatinine levels (6.5%) and increased creatine kinase levels in 2% of children receiving the medicinal product.

Reporting of suspected adverse reactions. Reporting suspected adverse reactions after marketing authorization is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare and pharmacy professionals, as well as patients or their legal representatives, should report any suspected adverse reactions and lack of efficacy of the medicinal product through the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua

Shelf life. 3 years.

Storage conditions. Store at a temperature not exceeding 25 °C in the original packaging, in a place inaccessible to children.

Packaging. 10 tablets in a blister. 3 or 10 blisters in a cardboard box.

Prescription status. Prescription only.

Manufacturer.

Medocemie LTD (Central Factory)/Medochemie LTD (Central Factory).

Manufacturer's address.

1-10 Constantinoupoleos Street, Limassol, 3011, Cyprus.