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 combined hypotensive therapy).

Active ingredient

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.

How to take, the dosage

The starting and maintenance doses are 150 mg once daily.

If necessary, the dose can be increased to 300 mg once daily.

Aprovel can be taken with food or on an empty stomach. The tablets should be swallowed whole with water.

Interaction

In concomitant use of Aprovelle and thiazide diuretics, the hypotensive effect of the drugs is additive.

The concomitant use of Aprovelle with potassium-saving diuretics, potassium preparations may lead to increased serum potassium levels.

Special Instructions

Patients with bilateral renal artery stenosis should be prescribed Aprovelle with caution because of the possible risk of severe arterial hypotension and acute renal failure.

Pre-treatment with high-dose diuretics prior to administration of Aprovelle may lead to dehydration and increase the risk of arterial hypotension at the beginning of treatment with Aprovelle. In dehydrated patients or patients with sodium ion deficiency as a result of intensive treatment with diuretics, restriction of salt intake with food, diarrhea or vomiting, as well as in patients undergoing hemodialysis the dose should be corrected towards its reduction.

The results of experimental studies

In studies conducted on laboratory animals no mutagenic, clastogenic or carcinogenic effects of Aprovelle were found.

Pediatric use

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

Impact on driving and operating ability

There are no reports about the effect of taking Aprovel on driving and operating ability.

Contraindications

– pregnancy;
– lactation;
– childhood and adolescence under 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.

CNS disorders: often – dizziness.

Cardiovascular system: sometimes – tachycardia, hot flashes.

Respiratory system: sometimes – cough.

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

As to the sexual system: sometimes – sexual dysfunction.

The body in general: often – fatigue; sometimes – pain in the chest.

Laboratory findings: often – significant increase of CPK (1.7%), not accompanied by clinical manifestations of the musculoskeletal system.

In patients with arterial hypertension and type 2 diabetes mellitus and microalbuminuria with normal renal function, orthostatic dizziness and orthostatic hypotension were observed in 0.5% of patients (more frequently than in placebo). In diabetic patients with hypertension with microalbuminuria and normal renal function, hyperkalemia (over 5.5% mmol/L) occurred in 29.4% of patients in the group receiving irbesartan 300 mg dose and 22% of patients in the group receiving placebo.

In patients with arterial hypertension with diabetes mellitus, chronic renal insufficiency, and marked proteinuria, the following additional adverse reactions were noted in 2% of patients (more often than when receiving placebo).

CNS side effects: often – orthostatic dizziness.

Cardiovascular system: often – orthostatic hypotension.

Muscular system disorders: often – bone and muscle pain.

Laboratory findings: hyperkalemia (more than 5.5% mmol/l) occurred in 46.3% of patients in the group of patients receiving irbesartan and 26.3% of patients in the placebo group. A decrease in hemoglobin levels that was not clinically significant was seen in 1.7% of patients receiving irbesartan.

The following adverse reactions were also identified in the post-marketing period:

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

Metabolism disorders: very rare – hyperkalemia.

CNS disorders: very rare – headache, tinnitus.

Digestive system disorders: very rarely – dyspepsia, liver dysfunction, hepatitis.

Muscular system disorders: very rare – myalgia, arthralgia.

A urinary system disorders: very rarely – renal function disorders (including individual cases of renal failure in predisposed patients).

Overdose

Taking the drug in a dose of up to 900 mg/day for 8 weeks did not reveal any toxicity.

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

Pregnancy use

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

If it is necessary to prescribe the drug during lactation, discontinuation of breastfeeding should be considered.

Similarities