Aprovel tablets 300mg #28

Aprovel instruction

You can buy Aprovel here

Aprovel is an antihypertensive agent.

Release form and composition

The dosage form of Aprovel is film-coated tablets: oval, biconvex, white or almost white, on one side there is an engraving of an image of the heart, on the other - the numbers 2872 (150 mg tablets) or 2873 (300 mg tablets).
Composition of tablets:
    active substance: irbesartan - 150 or 300 mg;
    auxiliary components: microcrystalline cellulose, lactose monohydrate, hypromellose, colloidal silicon dioxide, magnesium stearate, croscarmellose sodium;
    film shell: carnauba wax, Opadry white (macrogol-3000, hypromellose, lactose monohydrate, titanium dioxide E 171).

Pharmacodynamics

Aprovel's active ingredient is irbesartan, a selective angiotensin II receptor antagonist (type AT1), which does not require metabolic activation to acquire its pharmacological activity.
Angiotensin II is an essential component of the renin-angiotensin-aldosterone system (RAAS). It is involved in the pathogenesis of hypertension and in sodium homeostasis.
Irbesartan blocks all physiologically significant effects of angiotensin II, regardless of the pathway or source of its synthesis, including the pronounced aldosterone-secreting and vasoconstrictor effects realized through AT1 receptors located in the adrenal cortex and on the surface of vascular smooth muscle cells.
Irbesartan does not have agonistic activity for AT1 receptors, but it has a significantly higher (> 8500 times) affinity for them compared to AT2 receptors, which are not associated with the regulation of the cardiovascular system.
The drug does not inhibit such RAAS enzymes as angiotensin-converting enzyme (ACE) and renin. In addition, it does not affect other hormone receptors and ion channels, which are involved in the regulation of sodium homeostasis and blood pressure.
Due to the fact that irbesartan blocks AT1-receptors, the feedback loop in the renin-angiotensin system is interrupted, as a result of which the plasma concentrations of renin and angiotensin II increase. When taken in therapeutic doses, the drug helps to reduce the concentration of aldosterone, while it does not significantly affect the level of potassium in the blood serum (this indicator increases on average by no more than 0.1 mEq / l). Also, the drug has no significant effect on serum concentrations of triglycerides, glucose and cholesterol, the concentration of uric acid in the blood serum and the rate of excretion of uric acid by the kidneys.
The hypotensive effect of Aprovel is manifested already after taking the first dose, it becomes significant within 1-2 weeks, the maximum effect reaches after 4-6 weeks. Long-term clinical studies have shown persistence of the antihypertensive effect for a period of more than 1 year.
When the drug is taken once a day in doses up to 900 mg, the hypotensive effect has a dose-dependent effect. If a dose in the range of 150 to 300 mg is prescribed, irbesartan lowers blood pressure (BP), measured in the supine and sitting position at the end of the interdose interval (that is, before taking the next dose, after 24 hours) compared with placebo: systolic blood pressure ( systolic blood pressure) - on average by 8-13 mm Hg. Art., diastolic blood pressure (DAP) - by 5-8 mm Hg. st. At the end of the interdose interval, the antihypertensive effect is expressed by 60–70% of the maximum values ​​of the decrease in SBP and DBP. The optimal reduction in blood pressure within 24 hours is achieved by taking April 1 time per day.
The decrease in blood pressure in the lying and standing positions is noted approximately equally.
Orthostatic effects are rare. However, in patients with hypovolemia and / or hyponatremia, an excessive decrease in blood pressure is possible, accompanied by clinical manifestations.
A mutual enhancement of the antihypertensive effect is observed when taking irbesartan in combination with thiazide diuretics. Therefore, in the case of insufficient decrease in blood pressure in patients receiving monotherapy with irbesartan, in addition, hydrochlorothiazide is prescribed in low doses (12.5 mg) once a day. When taking such a combination, an additional decrease in systolic and diastolic blood pressure is noted by 7-10 and 3-6 mm Hg. Art. respectively, compared with patients who received placebo for irbesartan.
The gender and age of the patient do not affect the severity of the action of Aprovel. Its effect is markedly reduced in patients of the Negroid race. However, when low doses of hydrochlorothiazide are added to irbesartan, the antihypertensive response in representatives of this race approaches that in patients of the Caucasian race.
After discontinuation of therapy, blood pressure gradually returns to its original level. The drug does not cause withdrawal symptoms.
In a multicenter, randomized, controlled, double-blind clinical study IDNT, in which 1715 patients with arterial hypertension and concomitant type 2 diabetes mellitus (serum creatinine concentration 1-3 mg / dL, proteinuria ≥ 900 mg / day) took part, decrease by 20% (p = 0.024) compared with placebo and by 23% (p = 0.006) compared with amlodipine in the relative risk of developing for the first time any of the following conditions: a 2-fold increase in serum creatinine concentration, development of end-stage renal failure, death for any reason (taking into account the achievement of a comparable decrease in blood pressure in patients receiving irbesartan and patients taking amlodipine).
A multicenter, randomized, placebo-controlled, double-blind clinical study was also conducted, in which the effects of irbesartan on microalbuminuria (20-200 μg / minute, 30-300 mg / day) were studied in patients with arterial hypertension and concomitant type 2 diabetes mellitus (IRMA 2). The study involved 590 patients with these diseases and normal renal function (serum creatinine concentration in men - <1.5 mg / dL, in women - <1.1 mg / dL). Objective of the observation - the effect of long-term (2 years) use of Aprovel on the progression of clinically significant proteinuria. In patients who received the drug in a daily dose of 300 mg, there was a decrease in the risk of developing clinically significant proteinuria by 70% compared with placebo (p = 0.0004), and in a daily dose of 150 mg - by 39% (p = 0.085). A slowdown in the progression of this condition was noted already after 3 months and continued throughout the two-year study period. The decrease in daily creatinine clearance between the study groups of patients did not have significant differences. Regression of microalbuminuria to normal levels of albuminuria (<20 μg / minute; <30 mg / day) was more often observed in the group of patients receiving Aprovel at a daily dose of 300 mg, which is 34% compared with the placebo group - 21%.

Pharmacokinetics

After oral administration of Aprovel, irbesartan is rapidly and completely absorbed from the gastrointestinal tract. The absolute bioavailability of the drug is about 60-80%, food intake has no significant effect on this indicator. The maximum plasma concentration (Cmax) is observed after 1.5–2 hours.
It is characterized by a high bond with plasma proteins - 96%, a slight bond with the cellular components of the blood. The volume of distribution varies in the range of 53–93 liters.
After oral administration of 14-C-irbesartan (as well as after intravenous administration), about 80–85% of the radioactivity circulating in the plasma is accounted for by unchanged irbesartan. The drug is metabolized in the liver by oxidation and conjugation with glucuronic acid. The main metabolite determined in the systemic circulation is irbesartan glucuronide (about 6%). The oxidation of irbesartan is carried out mainly with the participation of the isoenzyme of the cytochrome P450 system CYP2C9, the participation of the CYP3A4 isoenzyme is insignificant. Most isoenzymes that are usually involved in the metabolism of drugs (CYP2D6, CYP2A6, CYP2E1, CYP2B6, CYP1A2, CYP1A1) are not involved in the metabolism of the drug. Irbesartan, in turn, does not induce or inhibit them, nor does it inhibit or induce the CYP3A4 isoenzyme.
Irbesartan and its metabolites are excreted from the body with bile through the intestines and kidneys. After intravenous administration and oral administration of 14-C-irbesartan, about 20% of radioactivity is found in urine, the rest in feces. In unchanged form, the kidneys excrete less than 2% of the dose of irbesartan.
The total clearance of irbesartan administered intravenously is 157–176 ml / min, its renal clearance is 3–3.5 ml / min. With daily intake of the drug 1 time per day, the plasma equilibrium concentration is reached after 3 days.
The terminal half-life (T1 / 2) is 11-15 hours.
Special patient groups:
    gender: in women, the plasma concentrations of irbesartan are slightly higher than in men, however, differences in the half-life and accumulation of the drug were not revealed, there were no differences in the effects of April, therefore, its dose adjustment for women is not required;
    race: T1 / 2 and AUC (area under the concentration-time curve) in Negroid volunteers without hypertension is approximately 20-25% higher than in Caucasians, while the maximum concentration in volunteers of both races was almost the same ;
    impaired renal function: with impaired renal function and hemodialysis, the pharmacokinetic parameters of irbesartan do not change significantly; hemodialysis does not remove the drug from the body;
    impaired liver function: with mild and moderate impairment of hepatic function [functional classes A (5-6 points on the Child-Pugh scale) and B (7-9 points on the Child-Pugh scale), respectively] due to liver cirrhosis, there are no significant differences in the pharmacokinetics of irbesartan have;
    elderly age (65–80 years): Cmax and AUC in elderly people with normal liver and kidney function are approximately 20–50% higher than in patients aged 18–40 years, the terminal half-lives are approximately the same, the effects of irbesartan in patients are different ages do not change.

Indications for use

    arterial hypertension (Aprovel can be used both as a monopreparation and in combination with other antihypertensive drugs, for example, calcium channel blockers, thiazide diuretics or beta-blockers);
    nephropathy in arterial hypertension and type 2 diabetes mellitus (Aprovel is prescribed in complex antihypertensive therapy).

Contraindications

Absolute:
    severe hepatic impairment (functional class C,> 9 points on the Child-Pugh scale);
    hereditary galactose intolerance, lactase deficiency, glucose-galactose malabsorption;
    age up to 18 years;
    During pregnancy and breastfeeding;
    the need for the simultaneous administration of ACE inhibitors to patients with diabetic nephropathy;
    the combined prescription of medicines containing aliskiren in patients with diabetes mellitus, moderate or severe renal failure (glomerular filtration rate <60 ml / min / 1.73 m2 of body surface);
    hypersensitivity to Aprovel's components.
Relative:
    ischemic heart disease and / or clinically significant atherosclerosis of the cerebral vessels (in the case of an excessive decrease in blood pressure, an increase in ischemic disorders is possible, up to the development of stroke and acute myocardial infarction);
    hypertrophic obstructive cardiomyopathy;
    aortic / mitral stenosis;
    hypovolemia / hyponatremia due to hemodialysis or the use of diuretics;
    adherence to a diet that restricts the consumption of table salt, or diarrhea, vomiting (possibly an excessive decrease in blood pressure);
    recent history of kidney transplantation;
    renal failure (potassium levels and blood creatinine levels should be monitored);
    renal function dependent on the RAAS, including arterial hypertension with bilateral / unilateral renal artery stenosis or chronic heart failure III – IV functional class in accordance with the NYHA classification;
    the simultaneous use of aliskiren or ACE inhibitors (due to the risk of an excessive decrease in blood pressure, the development of renal dysfunction and hyperkalemia);
    the simultaneous appointment of non-steroidal anti-inflammatory drugs, including selective COX-2 inhibitors (the risk of impaired renal function, including an increase in serum calcium levels and the development of acute renal failure, especially in old age, with hypovolemia, existing renal dysfunction, increases).

Instructions for the use: method and dosage

Aprovel should be taken orally, swallowing the tablets whole, with sufficient water. Time of meals does not matter.
At the beginning of therapy, 150 mg is usually prescribed 1 time per day. If the effect is insufficient, the dose is increased to 300 mg, or a diuretic is additionally prescribed (for example, hydrochlorothiazide at a dose of 12.5 mg) or another antihypertensive agent (for example, a long-acting slow calcium channel blocker or a beta-blocker).
With nephropathy, patients with arterial hypertension and type 2 diabetes mellitus usually require a maintenance dose of 300 mg once a day.
Patients with severe hypovolemia and / or hyponatremia should be corrected for violations of the water-electrolyte balance before the appointment of Aprovel.

Side effects

Side effects by frequency of development are classified as follows: very often - ≥ 1/10, often - from ≥ 1/100 to <1/10, infrequently - from ≥ 1/1000 to <1/100, rarely - from ≥ 1/10 000 to <1/1000, very rarely - <1/10 000 (including individual messages), unspecified frequency - it is not possible to determine the frequency from the available data.
The safety of April was studied in clinical trials in which 5000 people took part, including 1300 patients with arterial hypertension who received the drug for a period of more than 6 months, and 400 patients who received the drug for 1 year or more. Adverse reactions were usually transient and mild. Their frequency did not depend on the age, gender and race of the patient, as well as on the dose of irbesartan.
In placebo-controlled studies, 1965 patients took irbesartan (on average, for 1-3 months). Cancellation of therapy due to the development of adverse reactions was required in 3.3% of patients receiving Aprovel, and 4.5% of patients receiving placebo.
Side effects registered in placebo-controlled studies in patients with arterial hypertension who received Aprovel, which may be associated with taking the drug, and those reactions whose relationship has not been proven (the frequency is approximately comparable to that when taking placebo):
    from the digestive system: often - nausea, vomiting; infrequently - heartburn, dyspepsia, diarrhea;
    on the part of the cardiovascular system: infrequently - edema, flushing of the skin of the face, tachycardia;
    from the respiratory system: infrequently - cough;
    from the nervous system: often - headache, dizziness; infrequently - orthostatic dizziness;
    on the part of the reproductive system: infrequently - sexual dysfunction;
    general reactions: often - increased fatigue; infrequently - chest pain.
Side effects reported in controlled clinical trials (IDNT and IRMA 2) in patients with nephropathy, arterial hypertension and type 2 diabetes mellitus who received Aprovel (adverse reactions are similar to those in patients with arterial hypertension, with the exception of orthostatic symptoms):
    on the part of the cardiovascular system: often (5.4%) - orthostatic hypotension (when taking placebo - 3.2%);
    from the nervous system: very often (10.2%) - dizziness (when taking placebo - 6%); often (5.4%) - orthostatic dizziness (when taking placebo - 2.7%).
Aprovel withdrawal rate due to orthostatic symptoms was:
    with dizziness - 0.3% (placebo - 0.5%);
    with orthostatic dizziness - 0.2% (placebo - 0%);
    with orthostatic hypotension - 0% (placebo - 0%).
Hyperkalemia in patients with arterial hypertension and diabetes mellitus occurred more often with irbesartan than with placebo. In the IDNT clinical trial, the discontinuation rate due to the development of hyperkalemia was 2.1% with Aprovel and 0.36% with placebo. In the clinical study IRMA, the rates were 0.5% and 0%, respectively, for April and placebo.
Side effects noted during the post-marketing use of Aprovel:
    from the immune system: very rarely - allergic reactions (urticaria, angioedema);
    from the side of metabolism: unknown frequency - hyperkalemia;
    from the nervous system: unspecified frequency - vertigo;
    from the liver and biliary tract: unknown frequency - increased activity of liver enzymes and the concentration of bilirubin in the blood, jaundice, hepatitis;
    on the part of the urinary system: an unknown frequency - impaired renal function, up to the development of renal failure in patients at risk;
    from the musculoskeletal system: unknown frequency - myalgia;
    from the organ of hearing and labyrinth disorders: unknown frequency - ringing in the ears;
    general reactions: unknown frequency - asthenia.

Overdose

In studies using Aprovel in a daily dose of up to 900 mg for 8 weeks, no toxicity was detected.
In case of overdose, it is recommended to induce vomiting and / or gastric lavage. The patient must be provided with constant medical supervision, if necessary, prescribe symptomatic and / or supportive therapy. Hemodialysis is ineffective. There is no specific information regarding the treatment of irbesartan overdose.

Special instructions

April rarely causes an excessive decrease in blood pressure in hypertensive patients without other underlying medical conditions. An excessive decrease in blood pressure with clinical symptoms while taking irbesartan, as well as ACE inhibitors, is possible with hyponatremia / hypovolemia (for example, due to diarrhea / vomiting, intensive diuretic therapy, adherence to a diet that restricts the consumption of sodium chloride), as well as in patients on hemodialysis. Violations of the water and electrolyte balance should be corrected before taking Aprovel.
In patients with ischemic heart disease and / or severe atherosclerosis of the cerebral vessels, a significant decrease in blood pressure is fraught with the development of a stroke or myocardial infarction, therefore, drug treatment should be carried out under regular blood pressure monitoring.
Irbesartan, like other drugs that affect the RAAS, can cause hyperkalemia, especially in patients with heart disease and / or renal failure. Such patients need constant monitoring of the concentration of potassium in the blood serum.
Patients with primary hyperaldosteronism usually do not respond to antihypertensive drugs that inhibit the RAAS, therefore, the appointment of Aprovel is inappropriate.

Influence on the ability to drive vehicles and complex mechanisms

The effect of April on cognitive and psychomotor functions has not been studied, but given the pharmacodynamic properties of irbesartan, this effect is unlikely. In patients who develop weakness or dizziness during treatment, it is possible to slow down psychophysical reactions and reduce concentration of attention, in this case, the decision on the possibility of engaging in any potentially hazardous activities is made together with the doctor on an individual basis.

Application during pregnancy and lactation

There is no sufficient experience of using Aprovel during pregnancy. However, it has been established that in the II and III trimesters, ACE inhibitors can cause damage and intrauterine death of the fetus. In this regard, irbesartan, which acts directly on the RAAS, is contraindicated in pregnant women in all trimeters. If pregnancy is diagnosed while taking the drug, treatment should be interrupted as soon as possible.
It has not been established whether irbesartan and / or its metabolites are excreted in breast milk, therefore, Aprovel is also prohibited for women who are breastfeeding. If its appointment is clinically justified, breastfeeding should be discontinued.

Childhood use

According to the instructions, Aprovel is not used in pediatrics, since there is not enough data confirming its safety in children and adolescents under the age of 18.

With impaired renal function

The drug should be used with caution in the following cases:
    kidney transplantation in the recent past (due to the lack of clinical experience with the use of irbesartan);
    renal failure (careful monitoring of potassium levels and blood creatinine concentration is necessary);
    renal function depending on the activity of the RAAS, including arterial hypertension with bilateral / unilateral renal artery stenosis or chronic heart failure III – IV functional class in accordance with the NYHA classification (due to the risk of deteriorating renal function).

For violations of liver function

For mild to moderate hepatic impairment, dose adjustment is usually not required.
Due to the lack of clinical experience with the use of Aprovel, it is contraindicated in patients with severe hepatic impairment (functional class C,> 9 points on the Child-Pugh scale).

Use in the elderly

No dose adjustment of Aprovel is required for elderly patients.

Drug interactions

The combination of Aprovel with aliskiren or ACE inhibitors leads to a double blockade of the RAAS. The use of such combinations is not recommended, since the risk of a sharp decrease in blood pressure, impaired renal function and the development of hyperkalemia increases. The use of Aprovel along with aliskiren is contraindicated in patients with diabetes mellitus and renal failure (glomerular filtration rate <60 ml / min / 1.73 m2 of body surface). The use of Aprovel in combination with ACE inhibitors is strictly contraindicated in patients with diabetic nephropathy; it is not recommended for all other patients.
Irbesartan can increase the concentration of lithium in the serum and increase its toxicity.
In patients who received high doses of diuretics before April, hypovolemia may develop, the risk of an excessive decrease in blood pressure increases at the beginning of irbesartan.
Non-steroidal anti-inflammatory drugs (NSAIDs), including selective COX-2 inhibitors, can weaken the hypotensive effect of angiotensin II receptor antagonists, which include irbesartan. In the elderly, patients with hypovolemia and patients with impaired renal function, NSAIDs can cause deterioration of renal function, up to the development of acute renal failure. These phenomena are usually reversible. In this regard, when using such a combination, careful monitoring of renal function is required.
There is experience with the use of other drugs that affect the RAAS, simultaneously with potassium-sparing diuretics, potassium-containing salt substitutes, potassium preparations and other drugs that can increase the plasma level of potassium (for example, heparin). There are isolated reports of an increase in serum potassium concentration. Taking into account the effect of irbesartan on the RAAS, when using Aprovel, it is recommended to monitor serum potassium levels.
With the simultaneous use of other antihypertensive drugs, an increase in the hypotensive effect is possible. Irbesartan was used without any undesirable effects in combination with thiazide diuretics, beta-blockers and long-acting slow calcium channel blockers.

Terms and conditions of storage

Store at temperatures up to 30 ° C out of reach of children.
The shelf life is 3 years.

Reviews

Reviews about Aprovel are mostly positive. Patients note the effectiveness of the drug, dose-dependent decrease in blood pressure and ease of administration - once a day, since the hypotensive effect lasts for 24 hours. Side effects, according to reviews, are transient. An additional advantage of the drug is the absence of adverse reactions characteristic of angiotensin-converting enzyme inhibitors (including cough). The main disadvantage of Aprovel is considered to be rather high cost.

Terms of sell

You can buy Aprovel without a prescription from a doctor.