Naviten^® (Tablets) Instructions for Use

Marketing Authorization Holder

Solvay Pharmaceuticals GmbH (Germany)

ATC Code

C09CA02 (Eprosartan)

Active Substance

Eprosartan (Rec.INN registered by WHO)

Dosage Form

Naviten®

Film-coated tablets, 600 mg: 14, 28, or 56 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets white, oval, biconvex, with an engraving “5046” on one side and “SOLVAY” on the other.

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

Tablet coating composition Opadry white OY-S-9603 (hypromellose, macrogol, polysorbate 80, colorant titanium dioxide (E171)).

14 pcs. – blisters (1) – cardboard packs.
14 pcs. – blisters (2) – cardboard packs.
14 pcs. – blisters (4) – cardboard packs.

Clinical-Pharmacological Group

Angiotensin II receptor antagonist

Pharmacotherapeutic Group

Angiotensin II receptor antagonist

Pharmacological Action

Antihypertensive drug, angiotensin II receptor blocker.

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

Angiotensin II binds to AT₁ receptors in many tissues (including vascular smooth muscle, adrenal glands, kidneys, heart) and causes vasoconstriction, sodium retention, and aldosterone release, target organ damage – myocardial and vascular hypertrophy.

Eprosartan prevents the development or attenuates the effects of angiotensin II. It has vasodilating, antihypertensive, and mediated diuretic effects.

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

The constant antihypertensive effect persists for 24 hours without the development of orthostatic arterial hypotension in response to the first dose. Stabilization of the antihypertensive effect with regular use occurs after 2-3 weeks, without changes in heart rate.

In patients with arterial hypertension, Eprosartan does not affect the concentrations of triglycerides, total cholesterol, or LDL cholesterol in the blood, determined on an empty stomach. Furthermore, Eprosartan does not affect fasting blood glucose concentration.

It has a nephroprotective effect, reducing albumin excretion while maintaining renal autoregulation regardless of the degree of renal failure.

Does not affect purine metabolism, does not have a significant effect on the excretion of uric acid in the urine.

Eprosartan does not enhance effects associated with bradykinin and mediated by ACE, such as cough. The frequency of cases of dry, persistent cough in patients receiving Eprosartan is 1.5%. When replacing an ACE inhibitor with eprosartan in patients who suffered from cough, the frequency of dry persistent cough corresponds to placebo.

Discontinuation of eprosartan treatment does not cause withdrawal syndrome.

Pharmacokinetics

Absorption

After oral administration in a single dose of 300 mg, the bioavailability of the drug is 13%. C_max of eprosartan in blood plasma is reached in 1-2 hours.

When eprosartan is taken simultaneously with food, a clinically insignificant decrease in absorption (less than 25%), C_max in plasma, and AUC values is observed.

Distribution

Plasma protein binding is 98% and is constant over the range of therapeutic concentrations.

V_d – 13 L. Practically does not accumulate.

Elimination

T_1/2 is 5-9 hours. Total clearance – 130 ml/min.

It is excreted mainly unchanged – 90% with feces, 7% with urine. A small part (less than 2%) is excreted by the kidneys in the form of glucuronides. 20% of the concentration in urine is eprosartan acyl glucuronide, 80% is unchanged Eprosartan.

Pharmacokinetics in special clinical cases

The degree of plasma protein binding does not depend on gender, age, liver function and does not change with mild or moderate renal failure, but may decrease with severe renal failure.

Pharmacokinetics in persons under 18 years of age have not been studied.

When using eprosartan in patients with chronic renal failure of moderate severity (creatinine clearance from 30 to 59 ml/min), AUC and C_max values are 30% higher, and with severe degree (creatinine clearance from 5 to 29 ml/min) – 50% higher compared to healthy people.

In hepatic insufficiency, the AUC value (but not C_max) increases, on average, by 40%, which does not require adjustment of the dosage regimen.

In elderly individuals, C_max and AUC values increase on average by 2 times, which does not require adjustment of the dosage regimen.

Body weight, gender and racial differences do not affect the pharmacokinetics of eprosartan.

Indications

• Arterial hypertension.

ICD codes

Dosage Regimen

The drug is taken orally regardless of meals.

The recommended dose is 600 mg once/day in the morning. No initial dose adjustment is required for elderly patients and for patients suffering from hepatic insufficiency.

For patients with severe or moderate renal failure (creatinine clearance less than 60 ml/min) the daily dose should not exceed 600 mg.

The duration of use of Naviten^® is not limited.

Adverse Reactions

The overall frequency of side effects recorded in patients taking Eprosartan is comparable to that with placebo. These effects were usually mild and short-lived, so discontinuation of the course of treatment was required in only 4.1% of patients receiving Eprosartan during placebo-controlled clinical studies (6.5% in the placebo group).

From the central nervous system rarely – headache, dizziness, asthenia.

From the cardiovascular system very rarely – decreased blood pressure (including postural hypotension).

Dermatological reactions very rarely – rash, skin itching.

Allergic reactions rarely – urticaria; very rarely – angioedema, facial edema.

Other rarely – cough.

Contraindications

• Pregnancy;
• Lactation period;
• Childhood and adolescence under 18 years (efficacy and safety not established);
• Hypersensitivity to the components of the drug.

With caution the drug should be used in severe heart failure (NYHA functional class III and IV); bilateral renal artery stenosis; stenosis of the renal artery of a single kidney; decreased circulating blood volume due to vomiting, diarrhea, taking diuretics in high doses.

The safety of using Naviten^® in patients with end-stage renal failure (creatinine clearance less than 5 ml/min, uremia grade II), as well as in patients on hemodialysis, has not been established.

Use in Pregnancy and Lactation

Naviten^® is contraindicated during pregnancy and lactation.

If pregnancy is diagnosed, the drug should be discontinued and the patient should be warned about possible adverse consequences.

If it is necessary to use the drug during lactation, breastfeeding should be discontinued.

Use in Hepatic Impairment

No initial dose adjustment is required for patients suffering from hepatic insufficiency.

Use in Renal Impairment

For patients with severe or moderate renal failure (creatinine clearance less than 60 ml/min) the daily dose should not exceed 600 mg.

The safety of using Naviten^® in patients with end-stage renal failure (creatinine clearance less than 5 ml/min, uremia grade II), as well as in patients on hemodialysis, has not been established.

Special Precautions

With a decrease in circulating blood volume, dehydration, or a decrease in electrolyte content (for example, during treatment with high doses of diuretics, repeated vomiting, prolonged diarrhea, salt-free and low-salt diet), taking the drug can cause a sharp decrease in blood pressure (symptomatic hypotension). Such disorders should be eliminated before prescribing Naviten^®.

Transient decrease in blood pressure is not a reason to discontinue the drug, since in this case blood pressure stabilizes with further use.

In patients whose renal function depends on the activity of the renin-angiotensin-aldosterone system (RAAS) (for example, patients with severe heart failure, bilateral renal artery stenosis, or stenosis of the artery of a single kidney), during treatment with ACE inhibitors, oliguria and/or progressive azotemia may develop and in rare cases – severe renal failure. Due to insufficient experience with the use of angiotensin II receptor antagonists in patients with severe heart failure or renal artery stenosis, impaired renal function during the use of Naviten^® due to suppression of the RAAS cannot be ruled out.

Before prescribing Naviten^® to patients with renal failure and periodically during the course, renal function should be monitored. If during this period there is a deterioration in renal function, treatment should be reconsidered.

Naviten^® can be used in combination with thiazide diuretics (including hydrochlorothiazide) and calcium channel blockers (including extended-release nifedipine); with lipid-lowering agents (including lovastatin, simvastatin, pravastatin, fenofibrate, gemfibrozil and nicotinic acid).

Effect on ability to drive vehicles and mechanisms

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

During the treatment of arterial hypertension, caution should be exercised when driving vehicles and engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions, as dizziness and weakness may occur.

Overdose

There is limited data on overdose in humans. The drug is well tolerated when taken orally. The drug has been shown to be effective in daily doses up to 1.2 g when taken for 8 weeks, with no dose-dependent relationship in the frequency of adverse effects identified.

Symptoms most likely pronounced decrease in blood pressure.

Treatment symptomatic therapy.

Drug Interactions

No clinically significant interaction of Naviten^® with other drugs has been observed.

With simultaneous use, Naviten^® did not affect the pharmacokinetics of digoxin and the pharmacodynamics of warfarin, glibenclamide.

No changes in the pharmacokinetic parameters of Naviten^® were observed when used simultaneously with ranitidine, ketoconazole, fluconazole.

With simultaneous use of Naviten^® with thiazide diuretics (including hydrochlorothiazide), with slow calcium channel blockers (including extended-release nifedipine), an enhancement of the hypotensive effect is observed, while the development of clinically significant adverse reactions is not expected.

With simultaneous use of ACE inhibitors with lithium preparations, a reversible increase in the concentration of lithium in the blood plasma and an increase in the risk of its toxic effects are possible. This interaction cannot be excluded when using eprosartan (careful monitoring of lithium concentration in patients receiving such a combination is necessary).

Storage Conditions

List B. The drug should be stored out of the reach of children, in a dry place at a temperature not exceeding 25°C (77°F).

Shelf Life

Shelf life – 3 years.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.