Conoverum 300 mg tablets # 30

CONVERIUM instructions for use

Composition

active ingredient: 1 tablet contains irbesartan 150 mg or 300 mg
auxiliary substances: lactose monohydrate (sorbolac 400) corn starch 1551; sodium croscarmellose; silicon dioxide colloidal poloxamer 188; cellulose microcrystalline (type 101), magnesium stearate.

Dosage form

Pills.

Pharmacological group

Angiotensin II receptor antagonists. ATS code C09C A04.

Indications

Essential hypertension.
Arterial hypertension in patients with kidney disease and type II diabetes mellitus in blood pressure.

Contraindications

Hypersensitivity to the components of the drug (see formulation of the drug).
Intolerance to galactose, deficiency of Lappa lactase or malabsorption of glucose-galactose.

Dosing and Administration

The initial and maintenance dose is 150 mg once a day with food or on an empty stomach. Converium at a dose of 150 mg once a day usually provides a better 24-hour blood pressure control than a 75 mg dose. However, at the beginning of therapy, a dose of 75 mg can be used, especially for patients on hemodialysis, or for patients aged 75 years.

For patients who do not have sufficient blood pressure to be regulated at a dose of 150 mg once a day, the dose of Converium can be increased to 300 mg once a day or an additional antihypertensive drug can be prescribed additionally. In particular, it has been shown that the addition of a diuretic, such as hydrochlorothiazide, to the therapy with the Converium preparation has an additional effect.

For patients with hypertension and type II diabetes, treatment should begin with a dose of 150 mg irbesartan once a day, then increase to 300 mg once a day, which is the best maintenance dose for treating patients with kidney disease.

The drug Converium has a positive nephroprotective effect on the kidneys in patients with arterial hypertension and type II diabetes. To achieve the target level of blood pressure Aprovel is used as an addition to other antihypertensive agents, if necessary.

Renal failure. For patients with impaired renal function, dose adjustment is not required. Patients on hemodialysis need a lower initial dose (75 mg).

Decrease of BCC. The reduced volume of fluid / circulating blood and / or the lack of sodium must be adjusted before starting the use of the drug Converium.

Liver failure. For patients with mild to moderate hepatic insufficiency, dose adjustment is not required. Clinical experience of the drug in patients with severe hepatic insufficiency is absent.

Patients of advanced age. Although patients aged 75 years or older should be initiated with a dose of 75 mg, no dose adjustment is usually required.

Application in pediatrics. Irbesartan is not recommended for the treatment of children and adolescents due to inadequate data on its safety and efficacy.

Adverse Reactions

The incidence of adverse reactions described below was very often (> 1/10), often (> 1/100, <1/10), infrequently (> 1/1000, <1/100), rarely (> 1 / 1000, <1/100), very rarely (<1/10 000). Within each group, side effects are presented in order of decreasing importance.

From the nervous system: often - dizziness.

From the cardiovascular system: rarely - tachycardia, hyperemia.

From the respiratory system: rarely - cough.

From the side of the digestive tract: often - nausea, vomiting rarely - diarrhea, indigestion / heartburn.

On the part of the reproductive system and mammary glands: sometimes - sexual dysfunction.

General condition: often - fatigue; sometimes - a pain in the chest.

Laboratory tests: widespread - a significant increase in the level of CK in the plasma, was not accompanied by clinical manifestations of the musculoskeletal system.

Arterial hypertension in patients with kidney disease and type II diabetes mellitus. In addition to the side effects described above, orthostatic dizziness and orthostatic hypotension were observed in diabetic patients with arterial hypertension, had microalbuminuria and normal renal function (infrequently side effects).

In patients with diabetes with hypertension, had chronic renal failure and severe proteinuria, there were additional side effects, indicated below.

From the nervous system: often - orthostatic dizziness.

From the side of the vascular system: often - orthostatic hypotension.

From the musculoskeletal system: often - osteo-muscular pain.

Laboratory research. In patients with diabetes who used irbesartan, hyperkalemia was more common. When 300 mg of irbesartan was used, people with diabetes with hypertension had microalbuminuria and normal kidney function, hyperkalemia (> 5.5 meq / mol) was observed in 29.4% (very common side effects). In patients with diabetes with arterial hypertension, had chronic renal failure and severe proteinuria, and took irbesartan, hyperkalemia (> 5.5 meq / mol) was observed in 46.3% (very common side effects). A decrease in hemoglobin, which was not clinically significant, was observed in patients with arterial hypertension and progressive diabetic nephropathy who take irbesartan (common side effects).

During the postmarketing period, the following additional side effects were reported. Since these data are obtained from spontaneous messages, it is impossible to determine the frequency of their occurrence.

From the side of the immune system: as in the case of other angiotensin II receptor antagonists, there have rarely been reports of hypersensitivity reactions such as rash, hives, angioedema.

Metabolic disorders: hyperkalemia.

From the nervous system: headache.

From the organs of hearing: noise in the ears.

From the side of the digestive tract: dysgeusia (change in taste sensations).

From the liver block: hepatitis, a violation of the liver.

From the musculoskeletal system: arthralgia, myalgia (in some cases it is associated with an increase in the level of CK in the serum), muscle cramps.

On the part of the urinary system: a violation of kidney function, including renal failure in patients at high risk (see "Features of the application").

From the skin and subcutaneous tissue: leukocytoclastic vasculitis.

Adverse reactions in pediatrics. At the age of 6 to 16 years, patients with hypertension, there were such side effects: headache (7.9%), arterial hypotension (2.2%), dizziness (1.9%), cough (0.9%) . Most often, deviations from the norm of such laboratory indicators were observed: an increase in the level of creatinine (6.5%) and an increase in the level of CK (CC) in 2% of patients in this age group.

Overdose

The experience of using the drug in the treatment of adults at doses up to 900 mg per day for 8 weeks showed no toxicity of the drug. The most likely manifestations of an overdose can be expressed in arterial hypotension and tachycardia; bradycardia may also be a manifestation of an overdose.

There is no specific information regarding the treatment of an overdose of Conoverium. The patient needs to be carefully monitored, the treatment should be symptomatic and supportive. The proposed measures include provocation of vomiting and / or gastric lavage. In the treatment of overdose, it may be useful to use activated carbon. Irbesartan is not excreted during hemodialysis.

Use during pregnancy and lactation

Pregnancy: angiotensin II receptor antagonists are not recommended for use during pregnancy.
There are no epidemiological data confirming the presence of a teratogenic risk with the use of ACE inhibitors during the first trimester of pregnancy, however, even the slightest possibility of risk can not be ruled out. Since no controlled epidemiological risk data are collected with the use of angiotensin II receptor antagonists (ARA II), similar risks may exist for the drugs of this group.

If it is necessary to prescribe ARA AI to patients who plan pregnancy, before its onset, it is necessary to switch to alternative therapy with antihypertensive drugs, the safety of which is confirmed during pregnancy.

If pregnancy is diagnosed, the use of ARA AI should be discontinued and replaced with alternative therapy if necessary.

It has been confirmed that the use of ARA II during the second and third trimesters of pregnancy is the cause of fetotoxicity in humans (decreased renal function, oligohydraminosis, skull ossification delay) and neonatal toxicity (kidney failure, hypotension, hyperkalemia).

When using ARA II from the second trimester of pregnancy, it is recommended to perform an ultrasound examination of the kidneys and bones of the skull.

Infants, whose mothers took ARA AI, should be under constant observation on the development of hypotension.

The period of breastfeeding The use of the drug Converium is contraindicated in the period of breastfeeding.

Children

Safety and effectiveness of the drug in children are not established.

Application features

Decrease of BCC. Symptomatic hypotension, especially after the first dose, may occur in patients with reduced BCC and / or reduced sodium concentration due to intensive diuretic therapy, diets with limited salt intake, diarrhea, or vomiting. These indicators should be adjusted to the norm before the start of the Converium preparation.

Arterial Renovascular Hypertension. When using drugs that affect renin-angiotensin-aldosterone, there is an 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 kidney. Although similar cases with the use of the drug Converium was not observed, with the use of angiotensin I receptor antagonists, and one can expect the appearance of similar effects.

Renal failure and kidney transplantation. In the case of using the drug Converium for the treatment of patients with impaired renal function, it is recommended to conduct regular monitoring of serum potassium and serum creatinine levels. The experience of using the drug Converium for the treatment of patients with recent kidney transplantation does not exist.

Patients with arterial hypertension, kidney disease and type II diabetes mellitus.

Hyperkalemia. As with the use of other drugs that affect renin-angiotensin-aldosterone, hyperkalemia may develop during treatment with Converium, especially in the presence of kidney failure, severe proteinuria due to diabetic nephropathy and / or heart failure. It is recommended that the concentration of potassium in the blood serum be carefully controlled in patients at risk.

Lithium. At the same time, lithium and Converium are not recommended.

Stenosis of aortic and mitral valves, obstructive hypertrophic cardiomyopathy. Like other vasodilators, it is necessary to be especially careful in patients with stenosis of the aortic or mitral valve, obstructive hypertrophic cardiomyopathy.

Primary aldosteronism. Patients with primary aldosteronism usually do not respond to antihypertensive drugs acting by inhibiting renin-angiotensin. Therefore, it is not recommended to use Conoverum for the treatment of such patients.

General features. Patients whose vascular tone and renal function depend mainly on the activity of renin-angiotensin-aldosterone (eg in patients with severe congestive heart failure or underlying kidney disease, including renal artery stenosis), treatment with ACE inhibitors or angiotensin II receptor antagonists that affect on this system, was associated with acute arterial hypotension, azotemia, oliguria, sometimes with acute renal failure. As with any antihypertensive agent, excessive reduction in blood pressure in patients with ischemic cardiopathy or ischemic cardiovascular disease can lead to myocardial infarction or stroke. Like ACE inhibitors, irbesartan and other angiotensin antagonists appear to be less effective in lowering blood pressure in blacks than in other races, possibly because low-renin states are more likely to occur among patients with a Negroid race with hypertension.

It is contraindicated to use the drug to treat patients with rare hereditary problems - galactose intolerance, Lappease lactase deficiency or malabsorption of glucose-galactose.

The ability to influence the reaction rate when driving vehicles or other mechanisms

The impact on the ability to drive and perform work requiring increased attention has not been studied. The pharmacokinetic properties of irbesartan indicate that its effect on this ability is unlikely.

When driving a vehicle or working with machinery, it should be taken into account that dizziness and fatigue may occur during treatment.

Interaction with other drugs and other interactions

Diuretics and other antihypertensive drugs. Other antihypertensive drugs can enhance the antihypertensive effect of irbesartan; despite this, Converium has been safely used with other antihypertensive agents, such as b-blockers, long-acting calcium channel blockers and thiazide diuretics. Prior treatment with a high dose of diuretics can lead to dehydration of the body and increase the risk of developing arterial hypotension at the beginning of Converia treatment.

Potassium supplements and diuretics that retain potassium. The experience with other medications that affect renin-angiotensin-aldosterone shows that simultaneous use of diuretics, potassium, potassium supplements, salt substitutes containing potassium, or other drugs that can increase potassium levels in the serum (for example, heparin) , can lead to an increase in potassium levels in the serum. Therefore, it is not recommended to simultaneously use such drugs with Converium.

Lithium. The reverse increase in the concentration of lithium in the blood plasma and its toxicity was noted with the simultaneous use of lithium with ACE inhibitors. In rare cases, similar effects were observed with irbesartan. Therefore, this combination is not recommended. If it is necessary, careful monitoring of the level of lithium in the blood plasma is recommended.

Non-steroidal anti-inflammatory drugs. With the simultaneous use of angiotensin II antagonists with non-steroidal anti-inflammatory drugs (eg selective inhibitors of COX-2, acetylsalicylic acid (> 3 g per day) and nonselective NSAIDs), their antihypertensive effect may be weakened.

As with ACE inhibitors, simultaneous use of angiotensin II antagonists and NSAIDs may increase the risk of renal dysfunction, including the likelihood of developing acute renal failure, and lead to an increase in serum potassium, especially in patients with impaired renal function. This combination should be used with caution, especially in elderly patients. It is necessary to conduct appropriate fluid saturation and monitor kidney function at the beginning of the combination therapy and periodically afterwards.

Additional information on the interaction of irbesartan. Hydrochlorothiazide does not affect the pharmacokinetics of irbesartan. Irbesartan is metabolized by CYP2C9 and to a lesser extent by glucuronization. No significant pharmacokinetic or pharmacodynamic interactions were observed with the simultaneous use of irbesartan with warfarin, which is metabolized by CYP2C9. The effect of inducers of CYP2C9, such as rifampicin, on the pharmacokinetics of irbesartan has not been studied. The pharmacokinetics of digoxin did not change with its simultaneous use with irbesartan.

Pharmacological properties

Pharmacodynamics. Irbesartan is a potent orally active selective antagonist of angiotensin II receptors (type AT 1). It is believed that it blocks all physiologically significant effects of angiotensin II mediated through the AT 1 receptor, regardless of the source or route of the synthesis of angiotensin II. Selective antagonistic action against angiotensin II receptors (AT 1) leads to an increase in the concentration of renin and angiotensin II in plasma and to a decrease in plasma aldosterone concentration. When administered at recommended doses, the serum potassium level does not change significantly. Irbesartan does not inhibit ACE (kininase II), an enzyme that produces angiotensin II, performs metabolic degradation of bradykinin with the formation of inactive metabolites. To demonstrate its effect, irbesartan does not require metabolic activation.

Clinical efficacy in arterial hypertension. Aprovel lowers blood pressure with minimal changes in heart rate. Lowering blood pressure when taking one time per day has a dose-dependent manner, with a tendency to reach a plateau at doses of 300 mg. Doses of 150-300 mg when receiving 1 once a day reduces blood pressure as measured when the patient is in the supine position or sitting at the end of action (i.e., 24 hours after dosing) by an average of 8-13 / 5 -8 mmHg. Art. (Systolic / diastolic) greater than placebo.

Maximum blood pressure reduction achieved within 3-6 hours after drug administration, the hypotensive effect is maintained for 24 hours.

24 hours after receiving the recommended doses blood pressure reduction is 60-70% compared to the maximum reduction of systolic and diastolic pressure. The drug in a dose of 150 mg 1 time per day has the effect (the actions and the minimum of the average for 24 hours) similar to that achieved in the distribution of the daily dose into 2 doses.

The antihypertensive effect of the drug is Konverium for 1-2 weeks, and the effect is most pronounced at 4-6 weeks of starting treatment. The antihypertensive effect is maintained with prolonged treatment. After cessation of treatment blood pressure gradually returns to its initial value. Withdrawal symptoms in the form of strengthening of hypertension after the drug was not observed.

Aprovel thiazide-type diuretics additive exhibits a hypotensive effect. Patients who have one irbesartan not provide the desired effect, the simultaneous use of a low dose of hydrochlorothiazide (12.5 mg) irbesartan 1 time per day caused a greater reduction in blood pressure for at least 7-10 / 3-6 mm Hg. Art. (Systolic / diastolic) compared to placebo.

Pharmacokinetics. After oral administration, irbesartan is well absorbed: studies have shown that bioavailability is approximately 60-80%. Simultaneous take food did not significantly influence the bioavailability of irbesartan. Plasma protein binding is approximately 96%, while binding to blood cells is negligible. The volume of distribution - 53-93 liters. Upon receiving administration or 14 C 80-85% irbesartan circulating plasma radiolabel falls on unmodified irbesartan. Irbesartan is metabolized in the liver by conjugation to glucuronide and oxidation. The main blood circulating metabolite is irbesartan-glucuronide (approximately 6%). Studies in vitro data suggest that irbesartan is oxidized mainly by the enzyme CYP2C9 cytochrome P450; CYP3A4 isozyme it has almost no effect.

Pharmacokinetics of irbesartan in a dosage range from 10 to 600 mg is linear and proportional to the dose. Less than proportional increase in oral absorption is observed at doses of 600 mg (twice the maximum recommended dose) the mechanism of this is unknown. The maximum plasma concentration (C max) is reached in 1.5-2 hours after oral administration of the drug. Overall renal clearance and make 157-176 and 3-3.5 ml / min, respectively. Terminal half-life of irbesartan - 11-15 hours. Equilibrium plasma concentrations are established in 3 days after the onset of the drug 1 time per day. In applying 1 time per day in the plasma accumulation of irbesartan is low (<20%). In this study, in women with hypertension were observed somewhat higher plasma concentrations of irbesartan.However, differences in half-life and accumulation of irbesartan were not in time. For women to change the dose. In the elderly (> 65 years), the value of area under the curve "concentration-time" drug (AUC) and C max for irbesartan were slightly higher than in younger patients (18-40 years). However, the terminal half-life is not significantly changed. For elderly patients correct dose of the drug is required.

Irbesartan and its metabolites are excreted through the bile and kidneys. Upon receiving or administration of 14 C irbesartan about 20% of the radioactivity found in urine, and the rest - the faeces. Less than 2% of irbesartan received the dose excreted in the urine in an unmodified form.

Impaired renal function. In patients with renal impairment or in patients undergoing hemodialysis, the pharmacokinetic parameters of irbesartan are not significantly altered. Irbesartan is not removed from the body during hemodialysis.

Abnormal liver function. Pharmacokinetic parameters do not vary significantly irbesartan in patients with liver cirrhosis mild or moderate severity. Studies in patients with severe liver failure was not performed.

Basic physical and chemical properties

Tablets 150 mg: white, round, flat tablets with a notch, about 10.5 mm in diameter;
Tablets 300 mg: white, round, flat tablets with a notch, about 12.7 mm in diameter.

Shelf life

3 years.

Storage conditions

Store at a temperature not higher than 25 ° C in the original packaging of the reach of children.

Packaging

10 tablets in a blister pack. 3 or 10 blisters per box.

Category of leave

On prescription.