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

Active substance:
Valsartan	80 mg	160 mg
Excipients:
Lactose monohydrate (milk sugar)	17.7 mg	35.4 mg
Potato starch	31.52 mg	63.04 mg
Povidone low molecular weight (polyvinylpyrrolidone low molecular weight medical 12600±2700)	3.2 mg	6.4 mg
Magnesium stearate	1.6 mg	3.2 mg
Talc	4.8 mg	9.6 mg
Silica colloidal dioxide (aerosil)	3.2 mg	6.4 mg
Microcrystalline cellulose	12.8 mg	25.6 mg
Tablet casing:
Hypromellose (hydroxypropylmethylcellulose or hydroxypropylmethylcellulose)	1.92 mg	3.84 mg
Titanium dioxide	1.6 mg	3.2 mg
Macrogol 4000 (polyethylene glycol 4000)	1.5 mg	3.0 mg
Tropeolin O	0.16 mg	0.32 mg

Description:

Round tablets of biconvex form, covered with a film membrane of yellow color.

Pharmacotherapeutic group:Angiotensin II receptor antagonist

ATX: & nbsp

C.09.C.A.03 Valsartan

C.09.C.A Angiotensin II antagonists

Pharmacodynamics:

The active hormone of the renin-angiotensin-aldosterone system (RAAS) is angiotensin II, which is formed from angiotensin I with the participation of an angiotensin-converting enzyme (ACE). Angiotensin II binds to specific receptors located on cell membranes in various tissues. It has a wide range of physiological effects, including, in particular, both direct and indirect participation in the regulation of blood pressure.Being a potent vasoconstrictor, angiotensin II causes a direct pressor response. In addition, it promotes sodium retention and stimulates the secretion of aldosterone.

Valsartan - a specific antagonist of angiotensin II receptors, intended for oral administration. It has a selective antagonistic effect on the AT subtype receptors₁, which are responsible for the known effects of angiotensin II.

The consequence of the blockade AT₁-receptors is an increase in the plasma concentration of angiotensin II, which can stimulate unlocked AT₂-receptors. Has no agonistic activity against AT₁receptors. The affinity of valsartan for AT₁-receptors are approximately 20 000 times higher than for AT₂receptors.

In the treatment of valsartan in patients with arterial hypertension, there is a decrease in blood pressure, not accompanied by a change in the pulse rate.

The onset of antihypertensive action is observed 2 hours after the administration of a single dose, and a maximum after 4-6 hours; the duration of the action is more than 24 hours. For repeated prescriptions of the drug, the maximum reduction in blood pressure, regardless of the dose taken, is usually achieved within 2-4 weeks and is maintained at the achieved level during prolonged therapy.

There is no "cancellation" syndrome with sudden discontinuation of admission.

Pharmacokinetics:

After intake, absorption is rapid; However, the degree of absorption varies widely. The average absolute bioavailability of valsartan is 23%. The pharmacokinetic curve has a downward multiexponential character (half-life in αphase less than 1 hour and in the β-phase about 9 hours).

In the range of doses studied, the kinetics of valsartan is linear. With repeated use of the drug, no changes in the kinetic parameters were noted. When taking the drug once a day, cumulation is negligible. Plasma concentrations in women and men were similar.

Valsartan is bound to a significant extent (by 94-97%) with serum proteins, mainly albumin. The volume of distribution during the equilibrium state is low (about 17 liters). In comparison with the hepatic blood flow (about 30 l / h), the plasma clearance of valsartan occurs relatively slowly (about 2 l / h).

It is excreted by the intestine - 70%, by the kidneys - 30%, mostly unchanged.

Pharmacokinetics in selected groups of patients

Elderly patients

In some elderly patients, the systemic effect of valsartan was somewhat more pronounced than in young patients, but no clinical significance of this was shown.

Patients with impaired renal function

There was no correlation between renal function and systemic exposure to valsartan, which was to be expected, given that for this substance, the kidney clearance is only 30% of the total clearance value. Therefore, in patients with impaired renal function, dose adjustment is not required. but valsartan has a high degree of binding to blood plasma proteins, so its elimination in hemodialysis is unlikely.

Patients with impaired hepatic function

About 70% of the amount of absorbed dose of valsartan is excreted with bile, mostly unchanged. Valsartan does not undergo significant biotransformation and, as can be expected, systemic exposure to valsartan does not correlate with the degree of hepatic impairment. Therefore, in patients with hepatic insufficiency of non-biliary origin and in the absence of cholestasis, no adjustment of the dose of the drug is required.

Indications:

- Arterial hypertension;

- xheart failure (II-IV functional class by classification NYHA) in patients receiving standard therapy, incl. diuretics, cardiac glycosides, as well as inhibitors of the angiotensin-converting enzyme or beta-blockers (not simultaneously). The use of each of these drugs is not mandatory.

Contraindications:

- Hypersensitivity to any of the components of the drug;

- severe violations of the liver (biliary cirrhosis, cholestasis);

- pregnancy, the period of breastfeeding;

- age under 18 years (effectiveness and safety not established);

- lactose intolerance, lactase defecit, glucose-galactose malabsorption syndrome.

Carefully:

Two-sided stenosis of the renal arteries, stenosis of the artery of a single kidney, while observing a diet with a restriction of sodium intake, conditions accompanied by a decrease in the volume of circulating blood (including diarrhea, vomiting), mild and moderate impairment of liver function of non-biliary origin, without cholestasis on the background of obstruction bile ducts; renal failure (creatinine clearance less than 10 ml / min),hemodialysis, after kidney transplantation, hyperaldosteronism, aortic and mitral stenosis, hypertrophic cardiomyopathy.

Pregnancy and lactation:

The use of the drug during pregnancy is contraindicated.

In case of pregnancy during treatment, the drug should be canceled.

During lactation, breastfeeding should be stopped.

Dosing and Administration:

Inside, not liquid, regardless of food intake.

With arterial hypertension: the recommended dose is 80 mg once a day. Antihypertensive effect develops within 2 weeks of treatment; The maximum effect is observed after 4 weeks. Those patients who can not achieve an adequate reduction in blood pressure, a daily dose can be increased to 160 mg or additionally prescribed diuretic drugs. The maximum daily dose is 320 mg.

Patients with impaired renal function or patients with hepatic impairment not accompanied by cholestasis, no dose changes are required.

Valsafors can also be administered together with other antihypertensive drugs.

In chronic heart failure (CHF): the recommended initial dose is 40 mg 2 times a day. It is possible to gradually increase the dose to 80 mg 2 times a day, with good tolerability - up to 160 mg 2 times a day. The maximum daily dose is 320 mg divided into 2 doses.

In patients who are simultaneously receiving diuretics, as well as in patients with chronic heart failure regular monitoring of renal function, blood pressure. When clinical signs of arterial hypotension appear, it is necessary to reduce the dose.

Side effects:

Frequency of side effects: "very often" (≥1 / 10), "often" (≥1 / 100, <1/10), "infrequently" (≥1 / 1000, <1/100), "rarely" (≥ 1/10 000, <1/1000), "very rarely" (<1/10 000), including individual messages.

From the central nervous system: often - dizziness, incl. postural; infrequently - headache, vertigo, insomnia; rarely - a syncope (when used after a heart attack).

From the respiratory system: often - infections of the upper respiratory tract, pharyngitis, rhinitis, sinusitis, infrequently - cough.

From the cardiovascular system: often - marked decrease in blood pressure and orthostatic hypotension; rarely - (when used after a heart attack) heart failure.

From the digestive system: infrequently - pain in the abdomen, nausea, diarrhea.

From the skin and subcutaneous fat: rarely - skin rash.

From the musculoskeletal system: often - back pain, arthralgia; frequency unknown - myalgia, muscle weakness, myositis, rhabdomyolysis.

From the genitourinary system: infrequently - decreased libido; very rarely - renal dysfunction.

Allergic reactions: very rarely - angioedema, skin rash, itching; frequency is unknown - hypersensitivity reactions, including serum sickness and vasculitis.

Laboratory indicators: rarely - an increase in the content of serum nitrogen urea; frequency unknown - decrease in the concentration of hemoglobin and hematocrit, neutropenia, thrombocytopenia, hypercreatininaemia; hyperbilirubinemia, increased activity of hepatic transaminases, hyperkalemia.

Other: often - general weakness; infrequently - edema, asthenia, increased fatigue.

Overdose:

Symptoms: marked reduction in blood pressure.

Treatment: gastric lavage, intravenously 0.9% solution of sodium chloride. Hemodialysis is ineffective.

Interaction:

Clinically significant interactions with such drugs as: cimetidine, warfarin, furosemide, digoxin, atenolol, indomethacin, hydrochlorothiazide, amlodipine and glibenclamide not found.

Because the valsartan does not undergo any significant metabolism, it is unlikely that clinically significant interactions with other drugs at the metabolic level, which are the result of induction or inhibition of the cytochrome P450 system.

Although valsartan is largely associated with blood plasma proteins, there is no significant interaction with diclofenac, furosemide and warfarin.

When combined with diuretics (especially in high doses), the hypotensive effect may increase.

Simultaneous use with potassium-sparing diuretics (for example, spironolactone, triamterene, amiloride), preparations of potassium or salts containing potassium, can lead to an increase in the potassium content, in the blood serum. If such combination treatment is considered necessary, care should be taken.

When used simultaneously with lithium preparations (lithium carbonate), a reversible increase in lithium content in the blood plasma and an increase in its toxicity with the development of lithium intoxication are possible. Caution is advisable to use lithium drugs in conjunction with the preparation Valsafors, in such patients it is recommended to control the concentration of lithium in the blood plasma.

With the simultaneous use of valsartan with non-steroidal anti-inflammatory drugs (including selective inhibitors of cyclooxygenase-2 (COX-2) or acetylsalicylic acid in a daily dose of more than 3 g / day and other non-selective nonsteroidal anti-inflammatory drugs), a decrease in the hypotensive effect of valsartan is possible. The simultaneous use of valsartan (and other angiotensin II receptor antagonists) and non-steroidal anti-inflammatory drugs (NSAIDs) increases the risk of renal dysfunction including acute renal failure (usually reversible) and an increase in potassium in the blood plasma (hyperkalemia), especially in elderly patients and patients with impaired renal function. Care should be taken when using valsartan and NSAIDs concomitantly.After the beginning of combination therapy, as well as during the treatment, it is necessary to control the volume of circulating blood and the function of the kidneys.

By the results of the study in vitro valsartan is a substrate for the liver protein-transporters OATP1B1 and MRP2. Simultaneous administration of the preparation Valsafors with inhibitors of the transporter protein OATP1B1 (rifampicin, ciclosporin) and with an inhibitor of the transporter protein MRP2 (ritonavir) can increase the systemic exposure of valsartan (the maximum concentration in the blood plasma FROM_max and the area under the pharmacokinetic curve of the AUC).

Special instructions:

Deficiency in the body of sodium and / or reduced volume of circulating blood (BCC)

In patients with severe sodium deficiency and / or reduced bcc, for example, receiving high doses of diuretics, in rare cases, clinically pronounced arterial hypotension may occur at the onset of Valsafors treatment.

Before the start of treatment should be corrected the content of sodium ions in the body and / or the volume of circulating blood, for example, by decreasing the dose of the diuretic.

In case of development of arterial hypotension, the patient should be placed on his back and, if necessary, an intravenous infusion of saline.After the blood pressure stabilizes, the treatment can be continued.

Stenosis of the renal artery

Given that other drugs that affect the renin-angiotensin-aldosterone system (RAAS) can cause a rise in serum urea and creatinine in patients with bilateral or unilateral stenosis of the renal artery, systematic monitoring of these indicators is recommended as a precautionary measure.

Impaired renal function

Patients with impaired renal function do not need to adjust the dose of the drug. However, with pronounced disorders (when creatinine clearance is less than 10 ml / min), caution is recommended.

Impaired liver function

Patients with hepatic insufficiency do not need to adjust the dose of the drug. Valsartan is excreted mainly unchanged with bile, but in patients with bile duct obstruction the clearance of valsartan is reduced. When prescribing the drug, these patients should be very careful.

Chronic heart failure

Due to oppression of RAAS in sensitive patients, changes in renal function are possible.In patients with severe chronic heart failure, treatment with ACE inhibitors and angiotensin receptor antagonists may be accompanied by oliguria and / or augmentation of azotemia and (rarely) acute renal failure and / or fatal. Therefore, it is necessary to assess the degree of impaired renal function in patients with heart failure.

With chronic heart failure valsartan can be prescribed as a monotherapy or together with other agents - diuretics, cardiac glycosides, as well as ACE inhibitors or beta-blockers.

In patients with chronic heart failure, caution should be exercised when using a combination of an ACE inhibitor, a beta adrenoblocker and a valsartan.

With arterial hypertension valsartan can be prescribed both as a monotherapy, and together with other antihypertensive agents, in particular with diuretics.

With hyperaldosteronism, it is necessary to control the level of aldosterone in biological fluids.

Effect on the ability to drive transp. cf. and fur:

It should be used with caution during work, requiring increased attention and speed of motor and mental reactions.

Form release / dosage:

Film-coated tablets, 80 mg, 160 mg.

Packaging:

For 28 tablets in cans of glass with screwed plastic caps or cans of glass with lids stretched polyethylene, or in cans of polymer.

Free space in the bank in the absence of a seal plugs filled with cotton wool medical hygroscopic.

For 10 or 14 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

Each can, 2, 3 contourcell packs of 10 tablets or 1, 2 contour packs of 14 tablets together with the instructions for use are placed in a pack of cardboard.

Storage conditions:

In a dry, the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LS-000991

Date of registration:21.06.2011 / 11.01.2016

Expiration Date:Unlimited

The owner of the registration certificate:Pharmaplant Fabrication Chemistry Product GmbH Pharmaplant Fabrication Chemistry Product GmbH Germany

Manufacturer: & nbsp

SYNTHESIS, OJSC Russia

Representation: & nbspSYNTHESIS JSC Joint-Stock Kurgan Society of Medical Preparations and Products SYNTHESIS JSC Joint-Stock Kurgan Society of Medical Preparations and Products Russia

Information update date: & nbsp20.01.2017

Illustrated instructions

Instructions

Valsaphors (Valsaforce)