2010/06/23

Naviten

Composition, structure and packing

Tablets, coated in white, oval, biconvex, engraved with "5046" on one side and "SOLVAY" - on the other.

1 tab. eprosartan mesilate 735.8 mg, which corresponds to the content of eprosartan 600 mg.

Excipients: microcrystalline cellulose, lactose monohydrate, pregelatinized corn starch, krospovidon, magnesium stearate, purified water.

Composition of membrane tablets: Opadry White OY-S-9603 (gipromelloza, macrogol, polysorbate 80, titanium dioxide pigment (E171)).

Clinico-pharmacological group: The antagonist of angiotensin II.

Pharmacological action

Antihypertensive medication, angiotensin receptor blockers II.

Eprosartan selectively acts on AT1 receptors located in blood vessels, heart, kidney and adrenal cortex, forming with them a strong bond with subsequent slow dissociation.

Angiotensin II binds to AT1 receptors in many tissues (including vascular smooth muscle, adrenal, kidney, heart) and causes vasoconstriction, sodium retention and release of aldosterone, the defeat of the target organs - hypertrophy of the myocardium and blood vessels.

Eprosartan prevented the development or weaken the effects of angiotensin II. It provides vasodilating, hypotensive and diuretic effect mediated.

Reduces arterial vasoconstriction TPVR, the pressure in the pulmonary circulation and reabsorption of water and sodium in the proximal segment of the renal tubules, the secretion of aldosterone. With long-term use suppresses the proliferative effect of angiotensin II on vascular smooth muscle cells and myocardium.

Permanent antihypertensive effect persists for 24 hours without the development of orthostatic arterial hypotension in response to the first dose. Stabilization of the antihypertensive effect when taken regularly in 2-3 weeks, without changing heart rate.

In patients with arterial hypertension eprosartan does not affect the concentration of TG, total cholesterol (TC) or Tc-LDL in the blood, defined by fasting. In addition, eprosartan does not affect the concentration of fasting blood glucose.

Has nefroprotektornoe effect, reducing the excretion of albumin in maintaining renal autoregulation, regardless of the degree of renal failure.

No effect on the purine metabolism, has no significant effect on the excretion of uric acid in urine.

Eprosartan does not augment these effects, both associated with bradykinin and mediated by ACE, such as cough. Incidence of dry, persistent cough in patients receiving eprosartan - 1.5%. When replacing the ACE inhibitor, eprosartan in patients suffering from cough, the frequency of persistent dry cough corresponds to a placebo.

Stopping treatment does not cause eprosartranom withdrawal syndrome.

Pharmacokinetics

Absorption

After oral administration of a single dose of 300 mg bioavailability is 13%. Cmax eprosartan in plasma is achieved in 1-2 hours

If you receive eprosartan simultaneously with the food there is clinically insignificant decrease in absorption (less than 25%), Cmax in blood plasma and the values of AUC.

Distribution

Plasma protein binding is 98% and has a permanent character in the range of therapeutic concentrations.

Vd - 13 liters. Practically not cumulative.

Withdrawal

T1 / 2 is 5-9 h. The total clearance - 130 ml / min.

We derive largely unchanged - with the feces of 90%, with the urine - 7%. A small portion (less than 2%) displayed by the kidneys as glucuronide. 20% of the concentration in urine is atsilglyukuronid eprosartan, 80% - unchanged eprosartan.

Pharmacokinetics in special clinical situations

The degree of plasma protein binding does not depend on sex, age, liver function and does not change with slightly pronounced or moderate renal insufficiency, but may be reduced in severe renal insufficiency.

Persons under 18 years of pharmacokinetics has not been studied.

In the application of eprosartan in patients with chronic renal insufficiency, moderate (QC from 30 to 59 ml / min) values of AUC and C max by 30% higher, and with severe (QC from 5 to 29 ml / min) - 50% higher compared with healthy people.

When liver failure value AUC (but not C max) increases, on average, 40%, which does not require correction of dosing regimen.

In the elderly C max and AUC values increased an average of 2 times, that does not require correction of dosing regimen.

Body weight, sex and racial differences do not affect the pharmacokinetics eprosartrana.

Statement
hypertension.

Dosage regimen

Drugs are taken by mouth, regardless of the meal.

The recommended dose is 600 mg 1 time / day in the morning. Recruitment initial dose is not required for elderly patients and for patients suffering from liver failure.

For patients with severe renal insufficiency or moderate severity (CC less than 60 ml / min) daily dose should not exceed 600 mg.

Duration of Navita not limited.

Side effect

The overall incidence of side effects reported in patients taking eprosartan is comparable to that of placebo. These effects were usually inconspicuous and short, so the termination of treatment required in only 4.1% of patients treated with eprosartan in placebo-controlled clinical studies (6.5% - in the placebo group).

From the side of the central nervous system: rarely - headache, dizziness, asthenia.

Since the cardiovascular system: a very rare - BP reduction (including postural hypotension).

Dermatological reactions: very rare - rash, itchy skin. Allergic reactions: seldom - urticaria, very rarely - angioedema, swelling of the face.

Other: rarely - cough.

Contraindications
Pregnancy
lactation;
childhood and adolescence to 18 years (effectiveness and safety have not been established);
Hypersensitivity to the drug's components.

With care use in patients with severe heart failure (III and IV functional class according to the classification NYHA); bilateral renal artery stenosis, renal artery stenosis of a single kidney, reducing the BCC as a result of vomiting, diarrhea, diuretic usage in high doses

. Health & Safety Navita in patients with renal disease (QA less than 5 ml / min, the degree of uremia II), as well as in patients on hemodialysis has not been established.

Pregnancy and lactation

Navita is contraindicated in pregnancy and lactation.

In the case of diagnosing pregnancy drug should be removed and warn the patient about possible undesirable consequences.

If necessary, use during lactation breastfeeding should be discontinued.

Application for violations of liver function

Recruitment initial dose is not required for patients suffering from liver failure.

Application for violations of renal function

For patients with severe renal insufficiency or moderate severity (CC less than 60 ml / min) daily dose should not exceed 600 mg.

Health & Safety Navita in patients with renal disease (QA less than 5 ml / min, uremia II degree), as well as in patients on hemodialysis has not been established.

Cautions

When reducing the BCC, dehydration or reduced content of electrolytes (eg, during treatment with high doses of diuretics, repeated vomiting, prolonged diarrhea, and salt-free diet giposolevoy) receiving the drug can cause a sharp decline in BP (symptomatic hypotension). Before the appointment Navita such violations should be removed.

Transient blood pressure reduction is not the cause of drug discontinuation because In this case, BP stabilized with a further reception.

Patients whose kidney function is dependent on the activity of the renin-angiotensin-aldosterone system (RAAS) (eg, patients with severe heart failure with bilateral renal artery stenosis or stenosis of the artery of a sole kidney) during treatment with ACE inhibitors may develop an oliguria and / or progressive azotemia and in rare cases - severe renal insufficiency. Due to insufficient experience in the application of angiotensin II receptor antagonists in patients with severe heart failure or renal artery stenosis can not be excluded for renal dysfunction during treatment with Navita due to suppression of RAAS.

Before the appointment Navita patients with renal failure and periodically during the course should monitor renal function. If in this period there is deterioration of renal function, treatment should be reconsidered.

Navita can be used in combination with thiazide diuretics (including those with hydrochlorothiazide) and calcium channel blockers (including those with acting nifedipine), a lipid-lowering drugs (including those with lovastatin, simvastatin, pravastatin, phenofibrate , gemfibrozilom and nicotinic acid).

Effects on ability to drive vehicles and management mechanisms

Based on the pharmacodynamic properties of eprosartan should not affect the ability to drive a car and use of machines and mechanisms.

During the treatment of hypertension need to be careful when driving and occupation of potentially hazardous activities that require high concentration and quickness of psychomotor reactions in connection with the fact that you may experience dizziness and weakness.

Overdose

There are limited data on overdose in humans. The drug was well tolerated when administered. The effectiveness of the drug in daily doses up to 1.2 g at the reception for 8 weeks, with the dependence of the frequency of adverse effects on the dose was not found.

Symptoms: most likely pronounced decrease in blood pressure.

Treatment: the holding of symptomatic therapy.

Drug Interactions

Clinically meaningful interactions Navita with other drugs was not observed.

With simultaneous application Navita had no effect on digoxin pharmacokinetics and pharmacodynamics of warfarin, glibenclamide.

There were no changes in pharmacokinetic parameters Navita at its simultaneous application with ranitidine, ketoconazole, fluconazole.

With simultaneous application of Navita with thiazide diuretics (including those with hydrochlorothiazide), a slow calcium channel blockers (including those with acting nifedipine) observed increased hypotensive effect, while not expected to develop clinically significant adverse reactions.

With the simultaneous use of ACE inhibitors with lithium therapy may be a reversible increase in the concentration of lithium in blood plasma and increase the risk of its toxic effects. We can not exclude this interaction and the application of eprosartan (requires careful monitoring of lithium concentrations in patients receiving a combination).

Terms and Conditions of storage

The product should be stored out of reach of children, dry place at temperatures not above 25 ° C. Shelf life - 3 years.