Artinova^® (Tablets) Instructions for Use

ATC Code

C09CA03 (Valsartan)

Active Substance

Valsartan (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Angiotensin II receptor antagonist

Pharmacotherapeutic Group

Angiotensin II receptor antagonist

Pharmacological Action

Antihypertensive agent. It is a specific antagonist of angiotensin II receptors. It exerts a selective antagonistic effect on AT₁ receptors, which are responsible for the realization of the effects of angiotensin II.

Due to the blockade of AT₁ receptors, the plasma concentration of angiotensin II increases, which may stimulate unblocked AT₂ receptors. It has no agonistic activity towards AT₁ receptors. The affinity of valsartan for AT₁ receptors is approximately 20,000 times higher than for AT₂ receptors.

It does not inhibit ACE. It does not interact with or block receptors of other hormones or ion channels important for the regulation of the cardiovascular system functions. It does not affect the plasma levels of total cholesterol, triglycerides, glucose, and uric acid.

The onset of the antihypertensive effect of valsartan after a single oral dose is observed within 2 hours after administration, and the maximum effect is achieved within 4-6 hours.

Pharmacokinetics

After oral administration, Valsartan is rapidly absorbed from the gastrointestinal tract, and the extent of absorption is characterized by individual variations. The absolute bioavailability averages 23%. The pharmacokinetic curve of valsartan is multi-exponential (T_1/2 in the α-phase < 1 hour and T_1/2 in the β-phase – about 9 hours), and the kinetics are linear.

No changes in pharmacokinetic parameters were noted during course use.

When valsartan is taken with food, the AUC decreases by 48%, while approximately 8 hours after administration, plasma concentrations of valsartan are the same in patients who took it with food and on an empty stomach. The decrease in AUC is not accompanied by a clinically significant reduction in the therapeutic effect.

When valsartan is taken once daily, accumulation is insignificant. Plasma concentrations of valsartan were similar in women and men.

Plasma protein binding, primarily to albumin, is 94-97%. The V_d at steady state is about 17 L.

The plasma clearance of valsartan is about 2 L/h. It is excreted in feces – 70% and in urine – 30%, predominantly unchanged.

In biliary cirrhosis or obstruction of the biliary tract, the AUC of valsartan increases approximately 2-fold.

Indications

Treatment of arterial hypertension.

Treatment of chronic heart failure (NYHA functional class II-IV) in patients receiving conventional therapy with diuretics, digitalis preparations, as well as ACE inhibitors or beta-blockers.

ICD codes

Dosage Regimen

For arterial hypertension, initiate therapy at 80 mg taken orally once daily. An alternative starting regimen is 40 mg taken twice daily.

If adequate blood pressure control is not achieved, the daily dose may be increased. Titrate the dose based on individual patient response.

The maximum recommended daily dose is 320 mg. Administer the maximum daily dose in two divided doses.

For chronic heart failure (NYHA class II-IV), the recommended starting dose is 40 mg taken twice daily.

Titrate the dose for heart failure patients upward to 80 mg twice daily and then to 160 mg twice daily, as tolerated by the patient. The target maintenance dose is 160 mg twice daily.

Dosage adjustment may be necessary for patients with hepatic impairment or biliary obstruction.

Regularly monitor blood pressure, renal function, and serum potassium levels during therapy, particularly after dose adjustments.

Take tablets with or without food. Adhere strictly to the prescribed dosing schedule.

Adverse Reactions

Cardiovascular system: arterial hypotension, postural dizziness, postural hypotension.

Central nervous system: dizziness, headache.

Digestive system: diarrhea, nausea, increased bilirubin level.

Urinary system: rarely – impaired renal function, increased levels of creatinine and blood urea nitrogen (especially in chronic heart failure).

Metabolism: hyperkalemia.

Hematopoietic system: neutropenia, decreased hemoglobin and hematocrit.

Allergic reactions: rarely – angioedema, rash, pruritus, serum sickness, vasculitis.

Other: fatigue, general weakness, cough, pharyngitis, increased risk of viral infections.

Contraindications

Pregnancy, hypersensitivity to valsartan.

Use in Pregnancy and Lactation

Valsartan is contraindicated for use during pregnancy.

It is not known whether Valsartan is excreted in human breast milk. Use during lactation (breastfeeding) is not recommended.

In experimental studies, it has been shown that Valsartan is excreted in the breast milk of rats.

Use in Renal Impairment

In patients with renovascular hypertension secondary to renal artery stenosis, serum urea and creatinine levels should be regularly monitored during treatment. There are no data on the safety of use in patients with CC less than 10 ml/min.

Due to the inhibition of the RAAS, changes in renal function are possible in predisposed patients.

Pediatric Use

The safety and efficacy of valsartan use in children have not been established.

Special Precautions

In cases of hyponatremia and/or reduced circulating blood volume, as well as during therapy with high doses of diuretics, Valsartan may, in rare cases, cause pronounced arterial hypotension. Correction of water and electrolyte balance disorders should be carried out before starting treatment.

In patients with renovascular hypertension secondary to renal artery stenosis, serum urea and creatinine levels should be regularly monitored during treatment. There are no data on the safety of use in patients with CC less than 10 ml/min.

Use with particular caution in patients with biliary tract obstruction.

Due to the inhibition of the RAAS, changes in renal function are possible in predisposed patients. When using ACE inhibitors and angiotensin receptor antagonists in patients with severe chronic heart failure, oliguria and/or increasing azotemia have been observed, and acute renal failure with a risk of fatal outcome has rarely developed.

The safety and efficacy of valsartan use in children have not been established.

Effect on ability to drive vehicles and operate machinery

When using valsartan, caution is recommended when driving vehicles and operating machinery.

Drug Interactions

With simultaneous use of diuretics in high doses, the development of arterial hypotension is possible.

With simultaneous use of potassium-sparing diuretics, heparin, dietary supplements, or salt substitutes containing potassium, the development of hyperkalemia is possible.

With simultaneous use with indomethacin, a decrease in the antihypertensive effect of valsartan is possible.

A case of lithium intoxication has been described with simultaneous use with lithium carbonate.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

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.