Aprovel, 300 mg 14 pcs

Pharmaceutical effects:

Aprovesartan is an antihypertensive drug, a selective angiotensin II receptor antagonist (type AT1).
Irbesartan is a potent, active by oral administration selective angiotensin II receptor antagonist (type AT1). It blocks all physiologically relevant effects of angiotensin II realized through AT1 receptors, regardless of the source or pathway of angiotensin II synthesis. Specific antagonistic action against angiotensin II receptors (AT1) results in increased plasma concentrations of renin and angiotensin II and decreased plasma concentrations of aldosterone. Serum concentrations of potassium ions do not change significantly when using the recommended doses of the drug. Irbesartan does not inhibit kininase-II (angiotensin-converting enzyme), by which angiotensin II is formed and bradykinin is degraded to inactive metabolites. Irbesartan does not require metabolic activation to manifest its action.

Irbesartan reduces blood pressure (BP) with minimal change in heart rate. When administered in doses up to 300 mg once daily, the blood pressure decrease is dose-dependent, but the increase in hypotensive effect is small with further increase in dose of irbesartan.

The maximum BP decrease is achieved 3-6 hours after oral administration, and the hypotensive effect is maintained for at least 24 hours. Within 24 hours of taking the recommended doses of irbesartan, the BP reduction is 60-70% compared to the maximum hypotensive response of diastolic and systolic BP to the drug. When administered once daily in a dose of 150-300 mg, the magnitude of blood pressure decrease by the end of interdose interval (i.e., 24 hours after drug administration) in patient lying or sitting position is on average 8-13/5-8 mmHg (systolic/diastolic BP) greater compared to that when taking placebo.

Dose of 150 mg once daily produces the same hypotensive response (decrease in blood pressure before taking another dose of the drug and average decrease in blood pressure over 24 hours) as the same dose divided into two doses.

The hypotensive effect of the drug Aprovel develops within 1-2 weeks, and the maximum therapeutic effect is achieved 4-6 weeks after the beginning of treatment. Hypotensive effect against the background of long-term treatment is maintained. After discontinuation of treatment, BP gradually returns to the initial value. There is no withdrawal syndrome after discontinuation of the drug.
Aprovel efficacy does not depend on age and sex. Patients of Negro race are less responsive to Aprovel motor therapy (as to all other drugs affecting the renin-angiotensin-aldosterone system).
Irbesartan has no effect on serum uric acid content or urinary excretion of uric acid.
Pharmacokinetics: After oral administration irbesartan is well absorbed, its absolute bioavailability is approximately 60-80%. Simultaneous intake of food does not significantly affect the bioavailability of irbesartan.
Binding to plasma proteins is approximately 96%. Binding with cellular components of blood is insignificant. The volume of distribution is 53-93 liters.

After oral administration or intravenous administration of 14C-irbesartan, 80-85% of circulating plasma radioactivity is due to unchanged irbesartan. Irbesartan is metabolized by the liver by oxidation and conjugation to glucuronic acid. Irbesartan is oxidized primarily by cytochrome P450 CYP2C9, with little involvement of the CYP3A4 isoenzyme in the metabolism of irbesartan. The main metabolite in the systemic bloodstream is irbesartan glucuronide (approximately 6%).

Irbesartan has linear and dose-proportional pharmacokinetics in the dose range of 10 to 600 mg; at doses over 600 mg (twice the recommended maximum dose of the drug), irbesartan kinetics become nonlinear (decreased absorption). After oral administration, maximum plasma concentrations are reached after 1.5-2 hours. Total clearance and renal clearance are 157-176 and 3-3.5 ml/min, respectively. The terminal elimination half-life of irbesartan is 11-15 hours. When taking the drug once daily, the equilibrium plasma concentration (Csas) is reached after 3 days. When irbesartan is taken once daily, limited plasma accumulation (less than 20%) is observed. Women (compared to men) have slightly higher plasma concentrations of irbesartan. However, no gender-related differences in the elimination half-life and accumulation of irbesartan have been observed. No dose adjustment is required for irbesartan in women. The values of AUC (area under the pharmacokinetic curve of concentration-time) and Cmax (maximum plasma concentration) of irbesartan in elderly patients (≥65 years) are slightly higher than in younger patients, but the terminal elimination half-lives are not significantly different. No dose adjustment is required in elderly patients.

Irbesartan and its metabolites are excreted with both bile and urine. After ingestion or intravenous administration of 14C-irbesartan, about 20% of the radioactivity is detected in the urine and the rest in the feces. Less than 2% of the administered dose is excreted in the urine as unchanged irbesartan.

With impaired renal function: In patients with impaired renal function or patients undergoing hemodialysis, the pharmacokinetics of irbesartan do not change significantly. Irbesartan is not eliminated from the body during hemodialysis.

Hepatic impairment: In patients with mild to moderately severe cirrhosis the pharmacokinetic parameters of irbesartan are not significantly altered. No pharmacokinetic studies have been performed in patients with severe hepatic impairment.

Indications

– Essential hypertension

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

Pharmacological effect

Pharmaceutical action:

Aprovel is an antihypertensive drug, a selective antagonist of angiotensin II receptors (type AT1).
Irbesartan is a potent, orally active, selective antagonist of angiotensin II receptors (type AT1). It blocks all physiologically significant effects of angiotensin II through AT1 receptors, regardless of the source or pathway of angiotensin II synthesis. The specific antagonistic effect on angiotensin II receptors (AT1) leads to an increase in plasma concentrations of renin and angiotensin II and a decrease in plasma aldosterone concentrations. When using the recommended doses of the drug, the serum concentration of potassium ions does not change significantly. Irbesartan does not inhibit kininase-II (angiotensin-converting enzyme), which produces angiotensin II and destroys bradykinin to inactive metabolites. For the effect of irbesartan to occur, its metabolic activation is not required.

Irbesartan reduces blood pressure (BP) with minimal changes in heart rate. When taken in doses up to 300 mg once a day, the decrease in blood pressure is dose-dependent, however, with a further increase in the dose of irbesartan, the increase in the hypotensive effect is insignificant.

The maximum reduction in blood pressure is achieved 3-6 hours after taking the drug orally, and the hypotensive effect persists for at least 24 hours. 24 hours after taking the recommended doses of irbesartan, the reduction in blood pressure is 60-70% compared to the maximum hypotensive response to the drug in diastolic and systolic blood pressure. When taken once a day at a dose of 150-300 mg, the magnitude of the decrease in blood pressure by the end of the interdose interval (i.e., 24 hours after taking the drug) with the patient lying or sitting by an average of 8-13/5-8 mm Hg. (systolic/diastolic blood pressure) is higher compared to placebo.

Taking the drug at a dose of 150 mg once a day causes the same hypotensive response (decrease in blood pressure before taking the next dose of the drug and the average decrease in blood pressure over 24 hours) as taking the same dose divided into two doses.

The hypotensive effect of the drug Aprovel develops within 1-2 weeks, and the maximum therapeutic effect is achieved 4-6 weeks after the start of treatment. The hypotensive effect persists during long-term treatment. After cessation of treatment, blood pressure gradually returns to its original value. When the drug is discontinued, there is no withdrawal syndrome.
The effectiveness of Aprovel does not depend on age and gender. Patients of the Negroid race respond less poorly to motor therapy with Aprovel (as well as to all other drugs that affect the renin-angiotensin-aldosterone system).
Irbesartan does not affect the level of uric acid in the blood serum or the excretion of uric acid in the urine.
Pharmacokinetics: After oral administration, irbesartan is well absorbed, its absolute bioavailability is approximately 60-80%. Concomitant food intake does not significantly affect the bioavailability of irbesartan.
The binding to plasma proteins is approximately 96%. Binding to cellular components of blood is negligible. The distribution volume is 53-93 liters.

After oral or intravenous administration of 14C-irbesartan, 80-85% of the radioactivity in circulating plasma is unchanged irbesartan. Irbesartan is metabolized by the liver by oxidation and conjugation with glucuronic acid. The oxidation of irbesartan is carried out mainly by cytochrome P450 CYP2C9; the participation of the isoenzyme CYP3A4 in the metabolism of irbesartan is insignificant. The main metabolite found in the systemic circulation is irbesartan glucuronide (approximately 6%).

Irbesartan has linear and dose-proportional pharmacokinetics in the dose range from 10 to 600 mg; at doses above 600 mg (a dose twice the recommended maximum dose of the drug), the kinetics of irbesartan becomes nonlinear (decreased absorption). After oral administration, maximum plasma concentrations are reached within 1.5-2 hours. Total clearance and renal clearance are 157-176 and 3-3.5 ml/min., respectively. The terminal half-life of irbesartan is 11-15 hours. With a daily single dose of the drug, equilibrium plasma concentration (Css) is achieved after 3 days. When taking irbesartan once a day daily, its accumulation in the blood plasma is limited (less than 20%). Women (compared to men) have slightly higher plasma concentrations of irbesartan. However, there are no gender-related differences in the half-life and accumulation of irbesartan. No dose adjustment of irbesartan is required in women. The values ​​of AUC (area under the pharmacokinetic concentration-time curve) and Cmax (maximum plasma concentration) of irbesartan in elderly patients (≥65 years) are slightly higher than in younger patients, but their terminal half-lives do not differ significantly. No dose adjustment is required in elderly patients.

Irbesartan and its metabolites are excreted from the body, both in bile and urine. 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 in the urine as unchanged irbesartan.

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

Liver dysfunction: In patients with mild or moderately severe liver cirrhosis, the pharmacokinetic parameters of irbesartan do not change significantly. Pharmacokinetic studies have not been conducted in patients with severe hepatic impairment.

Special instructions

Aprovel should be prescribed with caution to patients with bilateral renal artery stenosis due to the possible risk of severe arterial hypotension and acute renal failure.

Treatment with diuretics in high doses prior to the administration of Aprovel can lead to dehydration and increases the risk of developing arterial hypotension at the beginning of treatment with Aprovel. In dehydrated patients or in patients with a deficiency of sodium ions as a result of intensive treatment with diuretics, restriction of salt intake from food, diarrhea or vomiting, as well as in patients on hemodialysis, a dose adjustment is necessary to reduce it.

Experimental results

In studies conducted on laboratory animals, the mutagenic, clastogenic and carcinogenic effects of the drug Aprovel were not established.

Use in pediatrics

The safety and effectiveness of the drug in children have not been established.

Impact on the ability to drive vehicles and operate machinery

There are no indications about the effect of taking Aprovel on the ability to drive vehicles and operate machinery.

Active ingredient

Irbesartan

Composition

1 tablet contains irbesartan 300 mg;

excipients:

lactose monohydrate,

pregelatinized corn starch,

croscarmellose sodium,

poloxamer 188,

silicon dioxide colloidal aqueous,

microcrystalline cellulose,

magnesium stearate.

Pregnancy

Aprovel is contraindicated for use during pregnancy. If pregnancy occurs during treatment, the drug should be discontinued immediately.

If it is necessary to prescribe the drug during lactation, the issue of stopping breastfeeding should be decided.

Contraindications

– pregnancy;
– lactation;
– children and adolescents up to 18 years of age;
– hypersensitivity to the components of the drug Aprovel.

Side Effects

In placebo-controlled studies (1965 patients received irbesartan), the following adverse reactions were noted.

From the side of the central nervous system: often – dizziness.

From the cardiovascular system: sometimes – tachycardia, hot flashes.

From the respiratory system: sometimes – cough.

From the digestive system: often – nausea, vomiting; sometimes – diarrhea, dyspepsia, heartburn.

From the reproductive system: sometimes – sexual dysfunction.

On the part of the body as a whole: often – fatigue; sometimes – chest pain.

From the laboratory parameters: often – a significant increase in CPK (1.7%), not accompanied by clinical manifestations from the musculoskeletal system.

In patients with arterial hypertension and diabetes mellitus type 2 and microalbuminuria with normal renal function, orthostatic dizziness and orthostatic hypotension were observed in 0.5% of patients (more often than when taking placebo). In diabetic patients with high blood pressure with microalbuminuria and normal renal function, hyperkalemia (more than 5.5% mmol/l) occurred in 29.4% of patients in the group receiving irbesartan at a dose of 300 mg, and 22% of patients in the group receiving placebo.

In patients with arterial hypertension with diabetes mellitus, chronic renal failure and severe proteinuria, the following additional adverse reactions were observed in 2% of patients (more often than when taking placebo).

From the side of the central nervous system: often – orthostatic dizziness.

From the cardiovascular system: often – orthostatic hypotension.

From the musculoskeletal system: often – pain in the bones and muscles.

From the laboratory parameters: hyperkalemia (more than 5.5% mmol/l) occurred in 46.3% of patients in the group of patients receiving irbesartan, and in 26.3% of patients in the placebo group. A decrease in hemoglobin levels, which was not clinically significant, was observed in 1.7% of patients receiving irbesartan.

During the post-marketing period, the following adverse reactions were also identified:

Allergic reactions: rarely – rash, urticaria, angioedema (as with other angiotensin II receptor antagonists).

Metabolic disorders: very rarely – hyperkalemia.

From the side of the central nervous system: very rarely – headache, ringing in the ears.

From the digestive system: very rarely – dyspepsia, liver dysfunction, hepatitis.

From the musculoskeletal system: very rarely – myalgia, arthralgia.

From the urinary system: very rarely – renal dysfunction (including isolated cases of renal failure in predisposed patients).

Interaction

With the simultaneous use of Aprovel and thiazide diuretics, the hypotensive effect of the drugs is additive.

The simultaneous use of Aprovel with potassium-sparing diuretics and potassium supplements may lead to an increase in potassium levels in the blood serum.

Overdose

When taking the drug at a dose of up to 900 mg/day for 8 weeks, no toxicity was detected.

Treatment: in case of accidental use of the drug in high doses, gastric lavage and symptomatic therapy are indicated. Irbesartan is not removed from the body by hemodialysis.

Storage conditions

At a temperature not exceeding 30 °C

Shelf life

3 years

Manufacturer

Sanofi Winthrop Industries, France