Валсафорс

General characteristics. Structure:

Active agent:
Valsartan                                                                        of 80               mg 160 mg

Excipients:
Lactoses monohydrate (sugar milk)                             17,7            mg 35,4 mg
Starch of potato                                                    31,52          mg 63,04 mg
Povidone low-molecular (polyvinylpirrolidone
low-molecular medical 12600 ± 2700)              3,2               mg 6,4 mg
Magnesium stearate                                                                 of 1,6               mg 3,2 mg
Talc                                                                                 of 4,8               mg 9,6 mg
Silicon dioxide colloid (aerosil)                            of 3,2                mg 6,4 mg
Cellulose of microcrystallic                                     12,8             mg 25,6 mg
Tablet cover:
Gipromelloza of an oksipropilmetiltsellyuloz or
gidroksipropilmetiltsellyuloza)                                      1,92             mg 3,84 mg
Titanium dioxide                                                                  of 1,6               mg 3,2 mg
Macrogoal 4000 (polyethyleneglycol 4000)                         of 1,5                mg 3,0 mg
Tropeolin About                                                                       0,16             mg 0,32 mg

Pharmacological properties:

Pharmacodynamics. Renin-angiotensin-aldosteronovoy of system (PAAC) is active hormone angiotensin II which is formed of angiotensin I with the participation of an angiotensin-converting enzyme (APF). Angiotensin II contacts the specific receptors located on cellular membranes in various fabrics. It has a wide range of the physiological effects including, in particular, both the direct, and mediated participation in regulation of arterial pressure. Being powerful vasoconstrictive substance, angiotensin II causes the direct pressor answer. Besides, it promotes a delay of sodium and stimulates secretion of Aldosteronum.
Valsartan is the specific antagonist of receptors of angiotensin II intended for intake. It has selective antagonistic effect on AT1 subtype receptors which are responsible for the known effects of angiotensin II.
Increase in plasma concentration of angiotensin II which can stimulate not blocked AT2 receptors is a consequence of blockade of AT1 receptors. Has no agonistic activity concerning AT1 receptors. Affinity of a valsartan to AT1 receptors is about 20 000 times higher, than to AT2 receptors.
At treatment valsartany patients with arterial hypertension the lowering of arterial pressure which is not followed by pulse rate change is noted. The beginning of anti-hypertensive action is noted in 2 h after reception of a single dose, and at most - in 4-6 h; action duration - more than 24 h. At repeated purposes of drug the maximum lowering of arterial pressure, regardless of the accepted dose, is usually reached within 2-4 weeks and supported at the reached level during long therapy.
There is no syndrome of "cancellation" at the sudden termination of reception.

Pharmacokinetics. After intake absorption - bystry, however extent of absorption varies over a wide range. The average size of absolute bioavailability of a valsartan makes 23%. The pharmacokinetic curve has the descending multiexponential character (an elimination half-life in a α-phase less than 1 h and in a β-phase about 9 h).
In the range of the studied doses the kinetics of a valsartan has linear character. At repeated use of drug of changes of kinetic indicators it was not noted. At administration of drug once a day cumulation insignificant. Concentration of drug in a blood plasma at women and men were identical.
Valsartan substantially (for 94-97%) contacts serum proteins, is preferential with albumine. Distribution volume in the period of equilibrium a state low (about 17 l). In comparison with a hepatic blood-groove (about 30 l/h), the plasma clearance of a valsartan occurs rather slowly (about 2 l/h).
It is removed by intestines – 70%, kidneys – 30%, it is preferential in not changed look.
Pharmacokinetics at separate groups of patients
 Patients of advanced age
 Some patients of advanced age had a little more expressed system influence of a valsartan, than at patients of young age, however, was not shown to any clinical importance of it.
Patients with a renal failure
 Correlation between function of kidneys and system influence of a valsartan was not revealed, as it was necessary to expect, considering that for this substance the renal clearance makes only 30% of the size of the general clearance.
Therefore with a renal failure of dose adjustment of drug it is not required from patients. However валсартан has high extent of linkng with proteins of a blood plasma therefore its removal at a hemodialysis is improbable.
Patients with an abnormal liver function
 About 70% of size of the soaked-up dose of a valsartan are removed with bile, is preferential in not changed look. Valsartan is not exposed to considerable biotransformation, and as it is possible to expect, system influence of a valsartan does not correlate with degree of abnormal liver functions. Therefore correction of a dose of drug is not required from patients with a liver failure of not biliary origin and in the absence of a cholestasia.

Indications to use:

- Arterial hypertension.
- Chronic heart failure (the II-IV functional class on NYHA classification) at the patients receiving standard therapy including diuretics, cardiac glycosides, and also inhibitors of an angiotensin-converting enzyme or beta adrenoblockers (not at the same time). Use of each of the listed drugs is not obligatory.

Route of administration and doses:

Inside, without chewing, irrespective of meal.
At arterial hypertension: the recommended dose makes 80 mg of 1 times a day. The anti-hypertensive effect develops within 2 weeks of treatment; the maximum effect is noted in 4 weeks. To that patients at whom it is not possible to reach an adequate lowering of arterial pressure the daily dose can be increased to 160 mg or diuretic means are in addition appointed. 
The maximum daily dose makes 320 mg.
The patient with a renal failure or the patient with the liver failure which is not followed by a cholestasia, changes of a dose of drug are not required.
Валсафорс it can be appointed also together with other antihypertensives.
At the chronic heart failure (CHF): the recommended initial dose makes 40 mg 2 times a day. Perhaps gradual increase in a dose up to 80 mg 2 times a day, at good tolerance - to 160 mg 2 times a day. The maximum daily dose - 320 mg, divided into 2 receptions.
At the patients who are at the same time receiving diuretics and also at patients with chronic heart failure regular control of function of kidneys, arterial pressure is necessary. At emergence of clinical signs of arterial hypotension, it is necessary to reduce doses.

Features of use:

Deficit in an organism of sodium and/or the reduced the volume of the circulating blood (VCB)
At patients with the expressed deficit in an organism of sodium and/or reduced OTsK, for example, of the diuretics receiving high doses, in rare instances in an initiation of treatment Valsaforsom can arise clinically expressed arterial hypotension.
Before an initiation of treatment it is necessary to carry out correction of contents in an organism of sodium and/or volume of the circulating blood, for example, by reduction of a dose of diuretic. In case of development of arterial hypotension, the patient it is necessary to lay on a back, and, if necessary, to carry out intravenous infusion of normal saline solution. After the ABP is stabilized, treatment can be continued.
Renal artery stenosis
Considering that other medicines influencing reninangiotenzin-aldosteronovy system (RAAS) can cause increase in level of urea and creatinine in blood serum in patients with a bilateral or unilateral renal artery stenosis, as a precautionary measure systematic control of these indicators is recommended.
Renal failures
Patients with a renal failure do not need correction of a dose of drug. However, at the expressed disturbances (when the clearance of creatinine makes less than 10 ml/min.) it is recommended to be careful.
Abnormal liver function
Correction of a dose of drug is not required from patients with a liver failure. Valsartan is brought mainly in not changed view with bile, however at patients with obstruction of biliary tract the clearance of a valsartan is reduced. At purpose of drug this patients should observe extra care.
Chronic heart failure
Owing to oppression of RAAS at sensitive patients changes of function of kidneys are possible. Patients with heavy chronic heart failure have a treatment by APF inhibitors and antagonists of angiotenzinovy receptors can be followed by an oliguria and/or increase of an azotemia and (seldom) acute renal failure and/or death. Therefore assessment of extent of dysfunction is necessary for a pochek of patients with heart failure.

Influence on ability to drive the car and to work with mechanisms.

At purpose of a valsafors, also as well as other anti-hypertensive means, it is recommended to be careful during the driving of the car and control of the mechanisms requiring special attention and speed of psychomotor reactions.

Side effects:

From the central nervous system: often – a headache, dizziness, including postural, вертиго; infrequently – sleeplessness; sometimes – a syncope (at use after the postponed myocardial infarction).
From respiratory system: often – cough, infections of upper parts of respiratory tracts, pharyngitis, rhinitis, sinusitis.
From cardiovascular system: often – the expressed lowering of arterial pressure and orthostatic hypotension; sometimes (at use after the postponed myocardial infarction) – heart failure.
From digestive tract: often – nausea, diarrhea, an abdominal pain.
From integuments and a hypodermic fatty tissue: seldom – skin rash.
From skeletal and muscular system: often – a dorsodynia, a mialgiya, an arthralgia.
From urinogenital system: infrequently – decrease in a libido; very seldom - a renal failure.
Allergic reactions: very seldom – a Quincke's disease, skin rash, an itch, hypersensitivity reactions, including a serum disease and a vasculitis.
From laboratory parameters: seldom – decrease in concentration of hemoglobin and a hematocrit, a neutropenia, thrombocytopenia, a giperkreatininemiya, a hyperbilirubinemia, increase in activity of "hepatic" transaminases, increase in a serumal urea nitrogen; often - a hyperpotassemia.
Others: often – the general weakness; infrequently – hypostases, an adynamy, increased fatigue.

Interaction with other medicines:

Clinically significant interactions with such medicines, as: Cimetidinum, warfarin, furosemide, digoxin, атенолол, indometacin, a hydrochlorothiazide, амлодипин and Glibenclamidum it is not revealed.
As валсартан is not exposed to a little essential metabolism, for it clinically significant interactions with other medicines on a metabolic rate which are a consequence of induction or inhibition of system of P450 cytochrome are improbable. In spite of the fact that валсартан substantially contacts proteins of a blood plasma, any significant interaction with diclofenac, furosemide and warfarin is not revealed. Simultaneous use with kaliysberegayushchy diuretics (for example, Spironolactonum, Triamterenum, amiloride), drugs of potassium or the salts containing potassium can lead to increase in potassium concentration in blood serum. If such combined treatment is recognized as necessary, it is necessary to be careful.

Contraindications:

Hypersensitivity to any of drug components.
Heavy abnormal liver functions (biliary cirrhosis, cholestasia).
Pregnancy, the breastfeeding period, age up to 18 years (efficiency and safety are not established). Lactose intolerance, deficit of lactase, syndrome of glyukozo-galaktozny malabsorption. 
Use at pregnancy Use of drug at pregnancy is contraindicated.
In case of approach of pregnancy during treatment, drug should be cancelled.
In the period of a lactation it is necessary to stop breastfeeding.

Overdose:

Symptoms: the expressed decrease in the ABP.
Treatment: if drug was accepted recently, it is necessary to cause vomiting.
At the expressed lowering of arterial pressure – intravenous administration of normal saline solution. It is improbable that валсартан it is possible to bring out of an organism by means of a hemodialysis.

Storage conditions:

In the dry, protected from light place at a temperature not above 25 °C. To store in the places unavailable to children. Period of validity 2 years. Not to apply after a period of validity.

Issue conditions:

According to the recipe

Packaging:

Tablets, coated, 80 mg and 160 mg.
10 or 14 tablets in a blister strip packaging, 28 tablets in polymeric or glass jars.
2, 3 blister strip packagings on 10 tablets, or 1, 2 blister strip packagings on 14 tablets, or each can with the application instruction invest in a cardboard pack.