Ibertan - instructions for use, dose, side effects, contraindications

Irbesartan blocks all physiologically significant effects of angiotensin II mediated by AT receptors₁, regardless of the source or route of the synthesis of angiotensin II. Selective antagonism to angiotensin II receptors (AT₁) leads to an increase in plasma concentrations of renin and angiotensin II and a decrease in aldosterone in the blood plasma. Serum potassium concentrations usually do not change significantly when taking irbesartan at recommended doses. Irbesartan does not inhibit angiotensin-converting enzyme (ACE) (kininase II), an enzyme involved in the synthesis of angiotensin II and splitting bradykinin to inactive metabolites.

Irbesartan does not require metabolic activation.

Irbesartan lowers blood pressure (BP) with a minimum change in the heart rate (heart rate). When administered orally at doses up to 300 mg once a day, the decrease in blood pressure is dose-dependent, but with a further increase in the dose of irbesartan, the increase in the hypotensive effect is insignificant.

The maximum decrease in blood pressure is achieved 3-6 hours after ingestion. The hypotensive effect persists for at least 24 hours after taking the drug.After 24 hours, blood pressure remains at the level of 60-70% of the maximum decrease in systolic and diastolic blood pressure when taking the recommended doses. After taking 150-300 mg once a day after 24 hours (ie at the end of the inter-dose interval), the BP (systolic / diastolic) in the patient's position "lying" or "sitting" is reduced by 8-13 / 5-8 mm Hg . Art. respectively, which is significantly more than with placebo.

Taking the drug at a dose of 150 mg once a day leads to an antihypertensive effect comparable to a double dose (the same dose divided into two doses). The stable hypotensive effect of irbesartan develops within 1-2 weeks, and the maximum therapeutic effect is 4-6 weeks after the start of therapy.

The hypotensive effect is maintained with prolonged use of the drug. After cancellation of irbesartan, blood pressure gradually returns to the initial level, the "withdrawal" syndrome is absent.

The effectiveness of the drug Ibertan does not depend on age and sex. Patients of the Negroid race react weakly to monotherapy with Ibertan (as well as all other drugs affecting the renin-angiotensin-aldosterone system). Irbesartan practically does not affect the content of uric acid in the serum or the excretion of uric acid by the kidneys.

Pharmacokinetics:

Suction

After oral administration irbesartan well absorbed, absolute bioavailability is 60-80%. Simultaneous food intake does not significantly affect the bioavailability of irbesartan. The maximum concentration in the blood plasma (C_m_Oh) is achieved 1,5-2 hours after ingestion.

Distribution

The connection with plasma proteins is approximately 96%. With a daily single dose of the drug, the equilibrium plasma concentration (Css) is reached after 3 days. The volume of distribution is 53-93 liters.

Metabolism

Irbesartan is metabolized in the liver by conjugation with glucuronic acid and oxidation. The main metabolite circulating in the blood is irbesartan glucuronide (about 6%). Research in vitro showed that irbesartan is oxidized mainly by the enzyme CYP2C9 cytochrome P 450. The effect of the isoenzyme CYP3A4 is negligible.

The pharmacokinetic parameters of irbesartan are linear and proportional in the dose range of 10 to 600 mg. At doses in excess of 600 mg (a dose twice the recommended maximum dose of the drug), the pharmacokinetics of irbesartan become nonlinear (decreased absorption).

The total clearance and renal clearance are 157-176 and 3-3.5 ml / min, respectively.

Excretion

The final half-life (T_1/2) is 11-15 hours. Irbesartan and its metabolites are excreted through the intestine with bile (80%) and kidneys (20%), with less than 2% of the dose taken irbesartan excreted by the kidneys unchanged.

Pharmacokinetics in special clinical cases

A slightly higher concentration of irbesartan in plasma is noted among women (compared to men). However, the differences in the value of T_1/2and no accumulation of irbesartan. Correction of irbesartan dose in women is not required.

The values of the area under the concentration-time curve (AUC) and C_m_Oh irbesartan were slightly higher in elderly patients (over 65 years), than in young patients (18-40 years old). T_1/2did not differ significantly. Correction of irbesartan dose in elderly patients is not required.

Impaired renal function: in patients with impaired renal function or on hemodialysis, the pharmacokinetic parameters of irbesartan have been changed insignificantly. Irbesartan is not excreted from the body by hemodialysis.

Impaired liver function: in patients with cirrhosis of mild or moderate severity, the pharmacokinetic parameters of irbesartan have changed insignificantly.Pharmacokinetic studies in patients with severe impairment of liver function were not performed.

Indications:

- Arterial hypertension;

- Nephropathy in arterial hypertension and type 2 diabetes mellitus (in combination with other antihypertensive drugs).

Contraindications:

- Hypersensitivity to irbesartan or other components of the drug;

- hereditary intolerance to galactose, insufficiency of lactase or impaired absorption of glucose and galactose;

- Pregnancy;

- lactation period;

- age to 18 years (efficiency and safety not established).

Carefully:

Hyponatremia, diet with restriction of consumption of table salt, bilateral stenosis of the renal arteries or stenosis of the artery of a single functioning kidney, dehydration (including diarrhea, vomiting), previous diuretic therapy, renal failure, hemodialysis, condition after kidney transplantation (lack of clinical experience ), marked hepatic insufficiency (lack of clinical experience), hyperkalemia, simultaneous use with lithium preparations, stenosis of aortic and mitral valves,hypertrophic obstructive cardiomyopathy, primary hyperaldosteronism, chronic heart failure (NYHA class III-IV), ischemic heart disease (CHD), and / or atherosclerotic cerebral vascular disease, patients older than 75 years.

Pregnancy and lactation:

Like any drug that acts directly on the renin-angiotensin-aldosterone system, the drug Ibertan can not be used in pregnancy. The use of angiotensin II receptor antagonists is not recommended during the first trimester of pregnancy. The drug is contraindicated in the II-III trimesters of pregnancy, as the use of fetotoxic effects in the II-III trimesters of pregnancy can cause fetotoxic effects (decreased kidney function, low blood pressure, osteoporosis of the fetal bones) and neonatal toxic effects (renal failure, arterial hypotension, hyperkalemia). In case of taking the drug in II-III trimesters of pregnancy, it is necessary to perform ultrasound examination of the kidneys and bones of the fetal skull.

The transition to appropriate alternative antihypertensive therapy should be performed beforeplanning of pregnancy. At the onset of pregnancy, the drug must be discontinued as early as possible.

It is not known whether irbesartan in breast milk. If it is necessary to prescribe the drug during lactation, the question of stopping breastfeeding should be solved.

Dosing and Administration:

Inside, 1 time per day, regardless of food intake, washed down with water.

Usually the recommended initial and maintenance dose is 150 mg once a day. Patients with dehydration, with reduced circulating blood volume (bcc) (including diarrhea, vomiting), with hyponatremia, against diuretic therapy or diets with restriction of intake of salt, or who are on hemodialysis, or patients older than 75 years are recommended an initial the dose of the drug is 75 mg / day.

If the therapeutic effect is insufficient, the dose of the drug is increased to 300 mg / day. Further increase in the dose with an interval of 1-2 weeks (more than 300 mg / day) does not lead to an increase in the severity of the hypotensive effect. In the absence of the effect of monotherapy, it is possible to combine with another antihypertensive drug, for example, with low doses of diuretics (hydrochlorothiazide).

For the treatment of nephropathy, patients with hypertension and type 2 diabetes mellitus are recommended an initial dose of Ibertan 150 mg once a day, if the therapeutic effect is insufficient, the dose may be increased (with an interval of 2 weeks) to 300 mg once a day.

Impaired renal function

Patients with impaired renal function do not need dose adjustment.

Impaired liver function

Patients with a malfunction of the liver of mild to moderate severity of correction of the doses of the drug is not required. Clinical experience in patients with severe impairment of liver function is absent (see the section "With caution").

Side effects:

The incidence of adverse events by WHO classification: very often (more than 1/10); often (more than 1/100, less than 1/10); infrequently (more than 1/1 000, less than 1/100); rarely (more than 1/10 000, less than 1/1 000); very rarely (less than 1/10 000), including individual reports.

Arterial hypertension

From the central nervous system (CNS): often - dizziness, fatigue, asthenia.

From the cardiovascular system: infrequently - a tachycardia, "tides" of a blood to a skin of the face.

From the respiratory system: infrequently - cough.

From the musculoskeletal system: infrequently - pain in the chest.

From the digestive system: often - nausea and / or vomiting; infrequently diarrhea, dyspepsia and / or heartburn.

On the part of the reproductive system: infrequently, sexual dysfunction.

Laboratory data: often - an increase in the content of creatinine phosphokinase (without clinical disorders of the musculoskeletal system and absence, hyperkalemia).

Nephropathy in arterial hypertension and type 2 diabetes mellitus

From the side of the central nervous system: often - dizziness when changing the position of the body (the transition from the "lying" position to the "standing" position).

From the cardiovascular system: often - marked decrease in blood pressure, incl. orthostatic hypotension.

From the musculoskeletal system: often - musculoskeletal pain.

Laboratory indicators: very often - hyperkalemia, a decrease in hemoglobin (clinically insignificant).

During the post-marketing application the following undesirable phenomena were also noted, the frequency of which can not be established (according to spontaneous reports).

From the side of the central nervous system: headache.

Allergic reactions: rarely - reactions of hypersensitivity (skin rash, hives, angioedema), leukocyte vasculitis.

Laboratory indicators: hyperkalemia.

From the side of the hearing organ: noise in ears.

From the digestive system: dysgeusia (perversion of taste), a violation of liver function, hepatitis.

From the musculoskeletal system: arthralgia, myalgia (in some cases, associated with an increase in creatinine phosphokinase), muscle cramps.

From the urinary system: very rarely - a violation of kidney function (including individual cases of advanced renal failure in patients at risk).

With the development of severe side effects, treatment should be discontinued.

Overdose:

The intake of irbesartan in a dose of up to 900 mg / day for 8 weeks was not accompanied by symptoms of intoxication.

Symptoms: marked decrease in blood pressure, tachycardia; rarely - aetiology.

Treatment: gastric lavage, reception of activated charcoal, symptomatic and supportive treatment. Hemodialysis is ineffective.

Interaction:

Diuretics and other antihypertensives can enhance the hypotensive effect of irbesartan. but irbesartan can be used in combination with such drugs as beta-adrenoblockers, blockers of "slow" calcium channels of prolonged action and thiazide diuretics. Prior treatment with diuretics in high doses can lead to dehydration of the body and increases the risk of excessive blood pressure lowering.

Preparations replenishing the potassium deficiency in the body, potassium-sparing diuretics and heparin at simultaneous application with irbesartanum can increase the maintenance or contents of a potassium in blood serum.

With simultaneous application lithium preparations and irbesartan, a reversible increase in the lithium content of serum and an increase in its toxicity are possible. If there is a need for this combination, then during the treatment should be carefully monitored lithium in the blood serum.

Non-steroidal anti-inflammatory drugs (NSAIDs).

In the case of simultaneous use of angiotensin II antagonists and NSAIDs (including selective inhibitors of cyclooxygenase 2, acetylsalicylic acid (more than 3 g / day) and nonselective NSAIDs), a hypotensive effect can be reduced.In the case of irbesartan combined with NSAIDs could potentially increase the risk of renal impairment, until the development of acute renal failure and hyperkalemia (especially in patients with already compromised renal function). It should be used with caution, this combination, especially in elderly patients. Patients before the start of combination therapy need to restore BCC, as well as need to monitor the function of the kidney before the start of therapy and periodically during the combination therapy.

Hydrochlorothiazide, nifedipine did not affect the pharmacokinetics of irbesartan.

Irbesartan is metabolized predominantly by the isoenzyme CYP2C9 and, to a lesser extent, by glucuronation. No significant pharmacokinetic or pharmacodynamic interactions were observed with the combination of irbesartan with warfarin (metabolized by the isoenzyme CYP2C9). A study of the effect of inducers of CYP2C9 activity, such as rifampicin, no pharmacokinetics of irbesartan have been performed.

Irbesartan does not change pharmacokinetics digoxin.

Special instructions:

Violation of the water-electrolyte balance. In dehydrated patients, as well as with sodium deficiency (as a result of intensive treatment with diuretics, diarrhea or vomiting, restriction of intake of table salt with food) and in patients on hemodialysis, symptomatic arterial hypotension may develop, especially after taking the first dose of the drug. Such patients need to restore BCC, to eliminate hyponatremia before the appointment of the drug Ibertan.

Renovascular hypertension. Potentially increased risk of severe arterial hypotension and renal failure in patients with bilateral stenosis of the renal arteries or stenosis of the artery of a single functioning kidney.

Renal failure and condition after kidney transplantation. In the case of the use of Ibertan in patients with renal insufficiency, periodic monitoring of the content of potassium and serum creatinine is indicated. There is no experience with irbesartan in patients after kidney transplantation.

Patients with arterial hypertension, type 2 diabetes and nephropathy. The favorable effect of irbesartan on slowing the progression of renal andcardiovascular lesions has a different degree of severity in different groups of patients: less pronounced in women and in patients not belonging to the Europoid race.

Hyperkalemia. It is recommended to control the content of potassium ions in patients taking potassium preparations, potassium-sparing diuretics, heparin concurrently with the preparation of Ibertan, especially in the presence of kidney failure and / or diseases from the cardiovascular system.

Stenosis of the aortic or mitral valve, hypertrophic obstructive cardiomyopathy (GOKMP). As with the use of other vasodilators, it is necessary to apply Ibertan with caution.

Primary hyperaldosteronism. Hypotensive drugs acting through the inhibition of the renin-angiotensin-aldosterone system (RAAS) are usually ineffective in patients with primary hyperaldosteronism. Therefore, the use of the drug Ibertan in such cases is not advisable.

Other. Patients whose vascular tone and renal function are predominantly dependent on RAAS activity (for example, patients with chronic cardiac insufficiency III-IV functional class according to NYHA classification, concomitant renal diseases, incl.with stenosis of the renal artery), therapy with angiotensin converting enzyme inhibitors or angiotensin II receptor antagonists is accompanied by the development of arterial hypotension, azotemia, oliguria and, in rare cases, acute renal failure. As with other antihypertensive drugs, a significant reduction in blood pressure in patients with coronary heart disease and / or atherosclerotic lesions of the cerebral vessels can lead to the development of myocardial infarction, stroke. When treating such patients should strictly control the level of blood pressure.

Effect on the ability to drive transp. cf. and fur:

The effect of the drug Ibertan on the ability to drive and perform work requiring increased attention has not been studied. However, during the treatment period, care must be taken when driving a vehicle and engaging in potentially dangerous activities requiring increased concentration and speed of psychomotor reactions, as dizziness and / or increased fatigue may occur during treatment.

Form release / dosage:

Tablets, film-coated, 75 mg, 150 mg, 300 mg.

Packaging:

For 14 tablets are placed in a foil blister Al / PVC / PCTFE.

2 blisters together with instructions for use are placed in a pack of cardboard.

Storage conditions:

In a dry, the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-000554

Date of registration:14.07.2011

Expiration Date:14.07.2016

Date of cancellation:2018-04-12

The owner of the registration certificate:Pharmaceutical factory "POLFARMA" JSCPharmaceutical factory "POLFARMA" JSC Poland

Manufacturer: & nbsp

Pharmaceutical Works POLPHARMA, S.A. Poland

Representation: & nbspAKRIKHIN OJSC AKRIKHIN OJSC Russia

Information update date: & nbsp12.04.2018

Illustrated instructions

Instructions

Ibertán (Ibertan)