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

Excipients: mannitol, low-substituted giprolose (LH-21), low-substituted giprolose (LH-11), talc, macrogol-6000, giprolose, castor oil hydrogenated, Opadrai white (Opadray 85F28751 II HP white - dry mix ready for use: polyvinyl alcohol, titanium dioxide (E171), macrogol-3000, talc).

Description:

Oval, biconvex tablets, covered with a film shell of white color.

Pharmacotherapeutic group:angiotensin II receptor antagonist

ATX: & nbsp

C.09.C.A.04 Irbesartan

Pharmacodynamics:

Irbesartan is a selective antagonist of angiotensin II receptors (type AT₁) for oral administration.

Irbesartan blocks all physiologically significant effects of angiotensin II, mediated by AT receptors₁, regardless of the source or route of 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 Firmas does not depend on age and sex. Patients of the Negroid race react weakly to monotherapy with the drug Firmas (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:

After oral administration irbesartan well absorbed. Bioavailability is 60-80%. Simultaneous food intake does not significantly affect the bioavailability of irbesartan. Connection with blood plasma proteins - 96%. The volume of distribution is 53-93 liters.

Metabolised in the liver by oxidation and conjugation with glucuronic acid to form the main inactive metabolite - irbesartan glucuronide (approximately 6%). Oxidation of irbesartan is mainly carried out with the help of cytochrome P450, the participation of isoenzyme CYP3A4 in the metabolism of irbesartan is insignificant. The pharmacokinetic parameters of irbesartan are linear and proportional in the dose range of 10 to 600 mg.

The maximum concentration in the blood plasma (C_mOh) is achieved 1.5-2 hours after ingestion. The total and renal clearance is 157-176 and 3-3.5 ml / min, respectively. The final half-life (T_1/2) is 11-15 hours. With daily single administration of irbesartan, equilibrium plasma concentration is achieved after 3 days. 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.

Special patient groups

Have female patients (in comparison with male patients) with arterial hypertension, higher concentrations of irbesartan in the blood plasma were observed. However, the differences in T_1/2and there was no accumulation of irbesartan. Correction of drug doses in female patients is not required.

The values of the area under the "concentration-time" curve (AUC) and C_mOh irbesartan in elderly patients (over 65 years of age)) slightly higher in comparison with patients of a young age (18-40 years). The final in elderly patients is slightly changed. Therefore, dose adjustment for elderly patients is not required.

Impaired renal function and hemodialysis: pharmacokinetic parameters do not change significantly. Irbesartan not removed during hemodialysis.

Impaired liver function: y patients with cirrhosis of the liver with impaired liver function of mild or moderate severity, the pharmacokinetic parameters of irbesartan do not change significantly.Pharmacokinetic studies in patients with severe hepatic insufficiency have not been conducted.

Indications:

- Essential arterial hypertension;

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

Contraindications:

- Hypersensitivity to irbesartan or other components of the drug;

- pregnancy;

- lactation period;

- age to 18 years (efficacy 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 ), severe hepatic insufficiency (lack of clinical experience), hyperkalemia, simultaneous use with lithium preparations, stenosis of aortic and mitral valves, hypertra Graphical obstructive cardiomyopathy (GOKMP), primary aldosteronism, chronic heart failure (III-IV functional class by classification NYHA), ischemic heart disease (IHD) and / or atherosclerotic lesions of the brain vessels, patients older than 75 years.

Pregnancy and lactation:

Like any drug that acts directly on the renin-angiotensin-aldosterone system, the preparation of Firmas can not be used during pregnancy. The use of angiotensin II receptor antagonists is not recommended during I 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 before the beginning of pregnancy planning. At the onset of pregnancy, the preparation of Firmas must be canceled as soon 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 Firmas preparation 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 Firmam 150 mg once daily,if the therapeutic effect is insufficient, the dose can be increased (with an interval of 2 weeks) increased to 300 mg once a day - a dose that is the preferred maintenance dose for the treatment of nephropathy.

Impaired renal function

Patients with impaired renal function are not required to change the dose.

Initial dose of the drug in patients on hemodialysis should be 75 mg / day.

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").

Patients older than 75 years

Patients older than 75 years of dose adjustment are not required, although the initial dose should be 75 mg / day.

Children and teenagers under the age of 18

It is not recommended for use in children and adolescents under 18 years of age due to the lack of data on efficacy and safety.

Side effects:

Classification of the incidence of adverse events (WHO):

very often> 1/10

often from> 1/100 to <1/10

infrequently from> 1/1000 to <1/100

rarely from> 1/10000 to <1/1000

very rarely from <1/10000, including individual messages.

Arterial hypertension

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

From the cardiovascular system: sometimes - tachycardia; infrequently - "tides" of blood to the 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 violations of the musculoskeletal system and the absence of 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 side of 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 effects were noted, the frequency of which can not be established (according to spontaneous messages).

From the side of the central nervous system: headache.

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

Laboratory Indicatorsand: hyperkalemia.

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

From the digestive system: dysgeusia (perversion of taste), impaired 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 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: induce vomiting, rinse the stomach, prescribe Activated carbon. Conduct symptomatic and supportive therapy with constant monitoring of the patient. Hemodialysis is ineffective.

Interaction:

Other antihypertensives and diuretics can enhance the hypotensive effect of irbesartan. Irbesartan can be used in combination with such drugs as beta-adrene on locators, blockers of "slow" calcium channels of prolonged action and thiazide diuretics.

Prior therapy with diuretics in high doses can lead to dehydration and an increased risk of hypotension in the beginning of therapy with the drug Firmas. Simultaneous application of irbesartan with potassium preparations and potassium-sparing diuretics, as well as heparin can increase the content of potassium ions in the blood serum.

With the simultaneous appointment of irbesartan with lithium preparations a potentially reversible increase in lithium serum levels and an increase in its toxicity are potentially possible. Therefore, it is recommended to regularly monitor the lithium content in serum.

With simultaneous application from non-steroidal anti-inflammatory drugs (NSAIDs) (including, selective inhibitors of cyclooxygenase 2, acetylsalicylic acid (more than 3 g / day) and nonselective NSAIDs) possibly reducing the hypotensive effect. In the case of a combination with NSAIDs, an increased risk of renal dysfunction may occur, including acute renal failure and hyperkalemia (especially in patients with renal impairment). It should be used with caution, this combination, especially in elderly patients. Patients before the start of combination therapy need to restore BCC, and also need to monitor the function of the kidney before the start of therapy and periodically during the combination therapy.

Hydrochlorothiazide, nifedipine do not affect the pharmacokinetic parameters of irbesartan.

Irbesartan is metabolized predominantly by isoenzyme CYP2C9 and, to a lesser extent, glucuronation. There was no significant pharmacokinetic and pharmacodynamic interaction with warfarin (metabolized with the participation of isoenzyme CYP2C9). Effects of inductance inducers CYP2C9, such as rifampicin, on the pharmacokinetics of irbesartan have not been studied. Irbesartan does not affect the pharmacokinetic parameters digoxin.

Special instructions:

Violation of the water-electrolyte balance. Before prescribing the drug to the patients with dehydration (including due to diarrhea or vomiting, intensive therapy with diuretics, diets with restricted intake of table salt), it is necessary to restore BCC, to eliminate hyponatremia, because there is a risk of developing symptomatic arterial hypotension, especially after taking the first dose.

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 kidney transplant. It is recommended to control the content of potassium and creatinine ions in the blood serum in patients with renal insufficiency. There are no clinical data on the use of the Firmasm drug in patients after kidney transplantation.

Patients with arterial hypertension and type 2 diabetes mellitus with renal involvement. 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 monitor the content of potassium ions in patients who simultaneously take with the drug Firmas, potassium preparations, potassium-sparing diuretics, heparin, especially in the presence of kidney failure and / or diseases of the cardiovascular system.

Stenosis of the aortic and mitral valve, GOKMP. As with the appointment of any vasodilators, apply the preparation of Firma Must be with caution.

Primary hyperaldosteronism. The use of the drug Firmas with primary hyperaldosteronism is inexpedient.

Other. In patients whose vascular tone and kidney function are primarily dependent on the activity of the renin-angiotensin-aldosterone system (eg, patients with chronic heart failure III-IV functional class by classification NYHA, concomitant diseases of the kidneys, incl. with stenosis of the renal artery), therapy with ACE 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 ischemic 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 influence of the preparation of Firmas on the ability to drive transport and perform work that requires increased attention has not been studied. In connection with the possibility of developing dizziness or increased fatigue, care must be taken when driving vehicles.

Form release / dosage:Film-coated tablets, 75 mg, 150 mg and 300 mg.

Packaging:

7 or 14 tablets are placed in a blister.

By 4, 8, or 14 blisters (blister for 7 tablets) or 2, 4 or 7 blisters (blister for 14 tablets) in a pack of cardboard along with instructions for use.

Storage conditions:

Store at a temperature not exceeding 30 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-001422/10

Date of registration:26.02.2010

Date of cancellation:2018-02-09

The owner of the registration certificate:KRKA, dd, Novo mesto, AOKRKA, dd, Novo mesto, AO

Manufacturer: & nbsp

KRKA-RUS, LLC Russia

KRKA, d.d. Slovenia

Representation: & nbspKRKA KRKA Slovenia

Information update date: & nbsp09.02.2018

Illustrated instructions

Instructions

Firma (Firmasta)