Irbetan

Irbetan is a medicinal product that has a hypotensive effect. When used, it weakens systemic peripheral vascular resistance, and in addition, reduces overall blood pressure, pressure within the pulmonary circulation, and cardiac afterload.

The development of maximum drug activity occurs after 3-6 hours from the moment of administration, and the therapeutic effect lasts for 24 hours. To achieve a stable clinical effect, it is necessary to take the drug for a period of 1-2 weeks. [ 1 ]

Indications Irbetan

It is used for diseases such as primary hypertension and high blood pressure in people with kidney pathologies.

It can also be prescribed in combination for antihypertensive therapy of type 2 diabetes mellitus.

Release form

The release of the therapeutic substance is realized in tablets - 10 pieces in a cell pack; in a box - 2 such packs.

Pharmacodynamics

When taken orally, irbesartan acts as a potent, selective antagonist of the angiotensin-2 (AT1) terminal. The component is capable of blocking any effects of angiotensin-2 that are mediated by the AO1 terminal, regardless of the method or source of angiotensin-2 binding.

Selective antagonism of angiotensin-2 (AT1) terminals results in an increase in plasma renin and angiotensin-2 levels and a decrease in plasma aldosterone levels. [ 2 ]

At the serum potassium level, irbesartan itself has no significant effect (at the recommended dosages). The substance is not inhibited by ACE (kininase-2), an enzyme that catalyzes the formation of angiotensin-2, as well as the degradation of bradykinin to the state of metabolic elements that do not have a therapeutic effect. Irbesartan is active even without metabolic stimulation. [ 3 ]

Pharmacokinetics

Orally administered irbesartan is well absorbed, with bioavailability in the range of 60-80%. Taking it with food does not alter the bioavailability of the drug.

Intraplasmic protein synthesis of irbesartan is approximately 96%, but synthesis with cellular blood elements is very weak. The distribution volume of the drug is in the range of 53-93 l.

When 14C-irbesartan is administered orally or intravenously, 80-85% of the radioactive particles circulating in the blood plasma are unchanged irbesartan.

Intrahepatic metabolic processes occur through oxidation and glucuronide conjugation. Glucuronide is the main circulating metabolic component of the drug (about 6%). There is evidence that oxidation of irbesartan is mainly realized through the enzyme CYP2C9 of hemoprotein P450; isoenzyme CYP3A4 has very little effect on metabolic processes.

The pharmacokinetics of irbesartan are linear and depend on the dosage size (in the range of 0.01-0.6 g). A weaker dose-related increase in drug absorption was noted with oral administration of portions greater than 0.6 g (this is twice the maximum permissible dosage), but the mechanism of this reaction is not determined. Plasma Cmax values are reached after 1.5-2 hours from the moment of drug administration.

The level of renal and systemic clearance of the drug is 3-3.5, and also 157-176 ml per minute.

The terminal half-life of irbesartan is 11-15 hours. The equilibrium intraplasmic index is observed after 3 days from the start of therapy (1-time administration per day). Multiple administration of the drug 1-time per day leads to limited accumulation of the drug in the blood plasma (<20%).

Irbesartan and its metabolic components are excreted via bile and urine. Following oral administration and administration of 14C-irbesartan, approximately 20% of the radioactive components are excreted via urine and the remainder via faeces. Less than 2% of the dose is excreted as unchanged element via urine.

Dosing and administration

Irbetan should be taken once a day, at the same time, regardless of food intake. The tablets are swallowed without chewing, washed down with plain water.

The most commonly used initial and maintenance dose is 0.15 g of the drug. If necessary, after 3-4 weeks it can be increased to 0.3 g. With a subsequent increase in dosage, the effectiveness of the drug does not increase.

• Application for children

Not prescribed in pediatrics (under 18 years of age).

Use Irbetan during pregnancy

Irbetan is prohibited for use during pregnancy, since it affects the activity of the RAAS, which can negatively affect the intrauterine development of the fetus, causing the development of oligohydraminosis, delayed cranial ossification and deterioration of kidney function.

It is also possible that the child will develop a neonatal toxic reaction – decreased blood pressure, hyperkalemia and renal failure.

If pregnancy occurs while taking the medicine, the treatment should be stopped immediately. At the same time, the renal function and the condition of the skull of the fetus should be checked by ultrasound - if the patient, due to carelessness, continued to use the medicine for a long time already during pregnancy.

When planning conception, it is necessary to choose an alternative method of treatment.

Contraindications

Main contraindications:

• severe intolerance to the components of the drug;
• breastfeeding and gestation;
• lactase deficiency, galactosemia and glucose-galactose malabsorption.

The medication is used with special caution in the following situations:

• stenosis affecting the arteries of both kidneys or the artery of the only functioning kidney;
• liver failure or severe heart failure;
• dehydration;
• excess of the element Na in the body;
• prolonged diarrhea or vomiting;
• salt-free diet;
• dialysis procedures;
• primary aldosteronism;
• mitral or aortic stenosis;
• hypertrophic type of cardiomyopathy that has an obstructive nature.

Side effects Irbetan

Side effects associated with drug administration are usually temporary and mild. These include:

• tachycardia, increased fatigue, orthostatic collapse, dizziness, tinnitus and headaches;
• vomiting, constipation, dyspepsia, nausea, heartburn, diarrhea and dysgeusia;
• liver dysfunction and hepatitis;
• renal dysfunction;
• cough;
• arthralgia or pain affecting the joints, chest or muscles;
• epidermal hyperemia, Quincke's edema, leukocytoclastic vasculitis, urticaria and rashes;
• impotence;
• hyperkalemia or decreased blood hemoglobin levels;
• myalgia or cramps affecting the muscles.

Overdose

To date, no cases of Irbetane intoxication have been reported. In the case of taking extremely high doses (more than 0.9 g per day), tachycardia or bradycardia may develop, as well as a sharp drop in blood pressure.

In such cases, gastric lavage and activated carbon are performed. In addition, it is necessary to establish medical supervision of the patient and perform symptomatic actions, if necessary.

Hemodialysis procedures will be ineffective in case of poisoning with the drug.

Interactions with other drugs

Irbetan can be combined with thiazide-type diuretics, substances that block the action of Ca channels, and also with ACE inhibitors.

In cases where, before the administration of the drug, the patient has been treated for a long time using large doses of diuretics, the risk of a decrease in blood pressure at the initial stage of therapy increases due to dehydration of the body.

Combination with potassium-sparing diuretics and potassium-containing dietary supplements may increase plasma potassium levels.

The drug cannot be combined with amiodarone, fluconazole and rifamipicin, as well as with cimetidine, lithium, sulfaphenazole, omeprazole and ketoconazole.

Administration of the drug together with NSAIDs may lead to a weakening of its therapeutic activity.

Storage conditions

Irbetan should be stored in a dark place, out of reach of children. Temperature values - no higher than +25оC.

Shelf life

Irbetan can be used for a period of 36 months from the date of manufacture of the medicinal product.

Analogues

The analogs of the drug are the substances Converium, Votum and Irsar with Angizar, and also Aprovel, Diosar and Ibertan with Valzar, as well as Coaprovel and Diostar.