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

Antihypertensive agent. It is a specific antagonist of angiotensin II receptors. Has 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-receptor increases the plasma concentration of angiotensin II, which can stimulate unblocked AT₂-receptors. Has no agonistic activity against AT₁receptors. The affinity of valsartan for AT₁-receptors are approximately 20 000 times higher than to AT₂receptors.

Does not inhibit angiotensin-converting enzyme. It does not interact and does not block the receptors of other hormones or ion channels, which are important for the regulation of the functions of the cardiovascular system. Does not affect the level of total cholesterol, triglycerides, glucose and uric acid in the blood plasma.

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

Pharmacokinetics:

After oral administration valsartan It is rapidly absorbed from the digestive tract, the degree of absorption is characterized by individual differences. Absolute bioavailability averages 23%. The pharmacokinetic curve of valsartan has a multiexponential character (half-life in the α-phase <1 h and half-life in the β-phase - about 9 hours), the kinetics is linear.

With the course application of changes in pharmacokinetic parameters were not noted.

When taking valsartan with food, AUC is reduced by 48%, with about 8 hours after taking valsartan in plasma are the same in patients who took it with food and fasting. The decrease in AUC is not accompanied by a clinically significant decrease in the therapeutic effect.

When taking valsartan once a day, the cumulation is not very pronounced. The concentrations of valsartan in the blood plasma in women and men were the same.

The binding with plasma proteins, mainly with albumins, is 94-97%. V_d in the equilibrium state is about 17 liters.

The plasma clearance of valsartan is about 2 l / h. It is excreted with feces - 70% and with urine - 30%, mostly unchanged.

With biliary cirrhosis or obstruction of the bile ducts, the vascartan AUC increases approximately 2-fold.

Indications:

Treatment of arterial hypertension.

Treatment of chronic heart failure (IIHA functional class according to NYHA classification) in patients receiving traditional therapy with diuretics, digitalis preparations, as well as with ACE inhibitors or beta-blockers.

ICD-10

IX.I10-I15.I10 Essential [primary] hypertension

IX.I30-I52.I50 Heart failure

Contraindications:

Pregnancy, hypersensitivity to valsartan.

Carefully:

Caution should be exercised in appointing patients with sodium deficiency and / or a pronounced decrease volume of circulating blood (due to an increased risk of developing excessive arterial hypotension), with bilateral renal artery stenosis or renal artery stenosis of a single kidney (control of creatinine and urea nitrogen in the serum is required), with marked renal impairment (creatinine clearance less than 10 ml / min), severe liver dysfunction, biliary cirrhosis, bile duct obstruction, with the concomitant use of potassium-sparing diuretics, potassium or potassium supplements.

With caution apply during work drivers of vehicles and people whose profession is associated with increased concentration of attention.

Pregnancy and lactation:

I trimester - recommendations FDA category C; II-III trimesters - recommendations of category D. The use of the drug during these periods causes fetal and neonatal hypotension, neonatal hypoplasia of the skull, anuria, reversible and irreversible renal failure, intrauterine or neonatal death, oligohydramnion.

There is no information on the penetration of human milk into human milk, it penetrates into the breast milk of rats. It is recommended not to use the drug or stop breastfeeding.

Dosing and Administration:

Take inside at a dose of 80 mg 1 time per day or 40 mg 2 times a day, daily. If there is no adequate effect, the daily dose can be gradually increased.

The maximum daily dose is 320 mg in 2 divided doses.

Side effects:

From the cardiovascular system: Arterial hypotension, postural dizziness, postural hypotension.

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

From the digestive system: diarrhea, nausea, increased bilirubin levels.

From the urinary system: rarely - renal dysfunction, increased levels of creatinine and urea nitrogen (especially in chronic heart failure).

From the side of metabolism: hyperkalemia.

On the part of the hematopoiesis system: neutropenia, a decrease in hemoglobin and hematocrit.

Allergic reactions: rarely - angioedema, rash, itching, serum sickness, vasculitis.

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

Overdose:

Bradycardia due to excitation of the vagus nerve, hypotension, tachycardia. There is no specific antidote.

Treatment: correction of hypotension, dehydration and electrolyte disorders.

Interaction:

With the simultaneous use of diuretics in high doses, it is possible to develop arterial hypotension.

With the simultaneous use of potassium-sparing diuretics, heparin, biologically active additives or substitutes for salt containing potassium, the development of hyperkalemia is possible.

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

At simultaneous application with lithium carbonate the case of development of lithium intoxication is described.

Special instructions:

With hyponatremia and / or a decrease in the volume of circulating blood, as well as against the background of therapy with high doses of diuretics in rare cases valsartan can cause severe arterial hypotension.Before the start of treatment should be done correction of water-salt metabolism.

In patients with renovascular hypertension, which developed again due to stenosis of the renal artery, the level of urea and creatinine in the serum should be regularly monitored during the treatment period. Data on safety of use in patients with creatinine clearance less than 10 ml / min are absent.

Due to the inhibition of RAAS in susceptible patients, changes in renal function are possible. With the use of ACE inhibitors and angiotensin receptor antagonists, oliguria and / or augmentation of azotemia were observed in patients with chronic heart failure of severe course, and acute renal failure with a risk of death was rare.

Safety and effectiveness of valsartan in children is not established.

When using valsartan, it is advisable to use caution when driving and controlling machinery.

Instructions

Valsartan (Valsartanum)