Universal reference book for medicines
Product name: VALSACOR ® (VALSACOR ® )

Active substance: valsartan

Type: Angiotensin II receptor antagonist

Manufacturer: KRKA (Slovenia)
Composition, form of production and packaging
The tablets covered with a film cover of
pink color, round, biconcave, with risk on one side.

1 tab.

valsartan 80 mg

Excipients: lactose monohydrate, microcrystalline cellulose, povidone, croscarmellose sodium, silicon dioxide colloidal, anhydrous, magnesium stearate.

The composition of the shell: hypromellose, titanium dioxide (E171), iron dye red oxide (E172), macrogol 4000.

7 pcs.
- blisters (4) - packs of cardboard.
14 pcs.
- blisters (7) - packs of cardboard.
The tablets covered with a film coat of brownish-yellow color, oval, biconcave, with a risk on one side.

1 tab.

valsartan 160 mg

Excipients: lactose monohydrate, microcrystalline cellulose, povidone, croscarmellose sodium, silicon dioxide colloidal, anhydrous, magnesium stearate.

The composition of the shell: hypromellose, titanium dioxide (E171), iron dye oxide yellow (E172), iron oxide red (E172), macrogol 4000.

7 pcs.
- blisters (4) - packs of cardboard.
14 pcs.
- blisters (7) - packs of cardboard.
The tablets covered with a film membrane of light brown color, oval, biconcave, with a risk on one side.

1 tab.

valsartan 320 mg

Excipients: lactose monohydrate - 120 mg, microcrystalline cellulose - 164 mg, povidone - 6 mg, croscarmellose sodium - 8 mg, silicon colloidal dioxide - 4 mg, magnesium stearate - 18 mg.

Composition of the film membrane: hypromellose - 11.2 mg, titanium dioxide (E171) - 2.4 mg, iron dye oxide yellow (E172) -1 mg, iron oxide red (E172) 0.2 mg, macrogol 4000-1.2 mg.

14 pcs.
- blisters (2) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.

Description of the drug approved by the manufacturer for the printed edition of 2015.

PHARMACHOLOGIC EFFECT

Valsartan is a selective antagonist of angiotensin II receptor (type AT 1 ) for oral administration, non-protein nature.

Has a selective antagonistic effect on the receptors of the subtype AT 1 .
The consequence of the blockade of AT 1 -receptors is an increase in the plasma concentration of angiotensin II, which can stimulate unlocked receptors of the AT2 subtype, which presumably regulates the effects of AT 1 -receptors. Valsartan has no agonistic activity against AT 1 -receptors. Its affinity for the receptors of the AT 1 subtype is approximately 20,000 times higher than that of the AT 2 receptor subtype.
Valsartan does not inhibit ACE, also known as kininase II, which converts angiotensin I into angiotensin II and breaks down bradykinin.
In connection with the lack of influence on ACE, the effects of bradykinin and substance P are not potentiated, therefore, when dry angiotensin II is administered, it is unlikely that dry cough will develop. Valsartan does not interact and does not block the receptors of other hormones or ion channels involved in the regulation of the functions of the cardiovascular system.
Arterial hypertension

When treating arterial hypertension, valsartan reduces blood pressure without affecting the heart rate.

After ingestion of a single dose of the drug, the antihypertensive effect develops within 2 hours, and the maximum decrease in blood pressure is achieved within 4-6 hours. The antihypertensive effect of the drug persists for 24 hours after its administration.
With repeated appointments of valsartan, the maximum decrease in blood pressure, regardless of the dose, is achieved after 2-4 weeks and is maintained at the achieved level during prolonged therapy. Combination with hydrochlorothiazide allows to achieve a significant additional reduction in blood pressure.
The sudden discontinuation of valsartan is not accompanied by a sharp rise in blood pressure or other undesirable phenomena.

In patients with arterial hypertension, type 2 diabetes and nephropathy, taking valsartan at a dose of 160-320 mg, a clinically significant decrease in proteinuria (albumin excretion) (36-44%) was observed.

Application after acute myocardial infarction

The use of valsartan in patients 12 to 10 days after the development of myocardial infarction complicated by chronic heart failure and / or left ventricular systolic dysfunction for 2 years reduces the overall mortality, cardiovascular mortality and lengthens the time until the first hospitalization exacerbation of the course of chronic heart failure (CHF), repeated myocardial infarction, sudden cardiac arrest and nonfatal stroke (without lethal outcome).

The safety profile of valsartan in patients with acute myocardial infarction is similar to that in other conditions.

Chronic heart failure

When valsartan is used against standard therapy (ACE inhibitors and / or diuretics and / or digoxin and / or beta-blockers) for 2 years in patients with NYHA functional class (FC) class II-IV CHF with a left ventricular ejection fraction LVEF) less than 40% and internal diastolic LV (LVDD) more than 2.9 cm / m 2 there is a significant reduction in the risk of primary hospitalization for worsening of CHF flow.

In patients who do not receive ACE inhibitors, the overall mortality, cardiovascular mortality and incidence associated with CHF are significantly reduced when treated with valsartan.
With the use of ACE inhibitors without a beta-adrenoblocker, the cardiovascular mortality and morbidity associated with CHF are reduced.Treatment with valsartan leads to a significant reduction in NYHA class and a decrease in the symptoms of heart failure (including dyspnea, fatigue, edema and wet wheezing in the lungs), significantly improves quality of life (Minnesota questionnaire for assessing the quality of life of patients with CHF), increases LVEF and significantly reduces left ventricular dysfunction.
PHARMACOKINETICS

Suction

Valsartan is rapidly absorbed after ingestion, C max is reached after 2-4 hours. The average absolute bioavailability of valsartan is 23%.

When taking valsartan with food, AUC and C max decrease by 40% and 50%, respectively.
The decrease in AUC, however, is not accompanied by a clinically significant decrease in the therapeutic effect, so valsartan can be taken regardless of the time of ingestion.
Distribution

Binding to whey proteins, mainly with serum albumin, is 94-97%.
V ss - about 17 liters.
Metabolism

Valsartan is not subjected to a pronounced metabolism, about 20% of the dose is determined in the form of metabolites.
The hydroxyl metabolite is determined in the blood plasma at low concentrations (less than 10% of the valsartan AUC). This metabolite is pharmacologically inactive.
Excretion

Valsartan is biphasic: the β phase with T 1/2 is less than 1 hour and the β phase is T 1/2 for about 9 hours. Valsartan is excreted mostly unchanged with bile through the intestine (about 83%) and kidneys (about 13% ).
After IV introduction, the plasma clearance of valsartan is about 2 l / h, the renal clearance is 0.62 l / h (about 30% of the total clearance). T 1/2 of valsartan is 6 hours.
Pharmacokinetics in special clinical cases

In patients older than 65 years of age, the systemic bioavailability of valsartan is higher than that of young patients, but this is not clinically relevant.

Correlation between renal function and systemic bioavailability of valsartan is absent.
In patients with impaired renal function and KK more than 10 ml / min, dose adjustment is not required. Currently, there is no data on the use of the drug in patients on hemodialysis. Valsartan has a high degree of binding to blood plasma proteins, so its elimination in hemodialysis is unlikely.
In patients with mild and moderate impairment of liver function, the bioavailability (by AUC value) of valsartan is increased by a factor of 2 compared to healthy volunteers.
However, there is no correlation between the values ​​of AUC of valsartan and the degree of impaired hepatic function. The use of valsartan in patients with severe impairment of liver function has not been studied.
INDICATIONS

- arterial hypertension;

- chronic heart failure (NYHA class II-IV functional class) in patients receiving standard therapy with one or more drugs from the following groups: diuretics, cardiac glycosides, as well as ACE inhibitors or beta-blockers (the use of each of these drugs is not mandatory );

- increased survival of patients with acute myocardial infarction (12 to 10 days) complicated by left ventricular failure and / or left ventricular systolic dysfunction, with stable hemodynamic parameters.

DOSING MODE

The drug is administered orally, regardless of food intake, the frequency of intake is 1-2 times / day.

Arterial hypertension

The recommended initial dose is 80 mg 1 time / day, regardless of race, age and sex of the patient.
The hypotensive effect develops within 2 weeks and reaches its maximum after 4 weeks. In patients who can not achieve optimal BP control, the daily dose of Valsacor ® can be gradually increased to a maximum daily dose of 320 mg. Simultaneous use of diuretics, for example hydrochlorothiazide, allows achieving a significant additional reduction in blood pressure.
Chronic heart failure (NYHA class II-IV functional class)

The recommended initial dose is 40 mg 2 times / day.
It is possible to gradually increase (for at least 2 weeks) the dose to 80 mg 2 times / day, with good tolerability - up to 160 mg 2 times / day. The maximum daily dose is 320 mg divided into 2 doses.
With the simultaneous administration of diuretics, the dose should be reduced.
It is possible to use simultaneously with other drugs intended for the treatment of CHF.However, the combination of an ACE inhibitor, a beta-blocker and valsartan is not recommended. In patients with heart failure, renal function should always be evaluated.
Increased survival of patients with acute myocardial infarction

In patients with stable hemodynamics treatment should be started within 12 hours after the development of myocardial infarction.
After the appointment of an initial dose of 20 mg 2 times / day, the dose of the drug Valsacor ® should be increased by titration up to 40 mg, 80 mg 2 times / day for several weeks to reach the target dose of 160 mg 2 times / day. The maximum daily dose is 320 mg 2 times / day.
As a rule, taking into account the tolerability of therapy, it is recommended to increase the dose to 80 mg 2 times / day by the end of the second week of treatment and to the maximum target dose of 160 mg 2 times / day - by the end of the third month of therapy.
In the case of symptomatic arterial hypotension or renal dysfunction, it is advisable to consider the question of dose reduction.
The drug Valsacor ® can be used in patients after myocardial infarction against the background of therapy with other drugs, including thrombolytics, acetylsalicylic acid as antiplatelet agents, beta-blockers, inhibitors of HMG-CoA reductase (statins) and diuretics.
It is not recommended to use Valsacor ® simultaneously with ACE inhibitors.
In patients with myocardial infarction, renal function should always be evaluated.

For patients of advanced age (over 65 years), dose adjustment is not required.

In patients with impaired renal function, dose adjustment is not required.

In patients with impaired liver function of mild and moderate severity of non-biliary origin without phenomena of cholestasis, the maximum daily dose should not exceed 80 mg.

SIDE EFFECT

The incidence of adverse events is comparable to placebo.
There is no data on the dependence of the frequency of development of adverse events on the dose or duration of treatment, as well as age, sex or race of patients.
Classification of the incidence of adverse events WHO: very often (> 1/10), often (> 1/100 to <1/10), infrequently from (> 1/1000 to <1/100), rarely (> 1 / 10 000 to <1/1000), very rarely (from <1/10 000), the frequency is unknown (can not be estimated based on available data).

All adverse events with valsartan, identified in clinical practice and in the analysis of laboratory parameters that can not be attributed to any frequency of occurrence, are classified as "frequency unknown."

Arterial hypertension

On the part of the hematopoiesis system: the frequency is unknown - a decrease in hemoglobin, hematocrit, neutropenia, thrombocytopenia.

From the side of the immune system: the frequency is unknown - the reactions of hypersensitivity, including serum sickness.

From the side of metabolism: the frequency is unknown - an increase in the content of potassium in the blood serum, hyponatremia.

From the senses: infrequently - vertigo.

From the cardiovascular system: the frequency is unknown - vasculitis.

From the respiratory system: infrequently - cough.

From the side of the digestive system: infrequently - pain in the abdomen;
frequency unknown - impaired liver function, including increased bilirubin concentration in blood plasma.
From the skin of the subcutaneous tissues: very rarely - angioedema, skin rash, skin itching.

From the musculoskeletal system: the frequency is unknown - myalgia.

From the side of the urinary system: the frequency is unknown - a violation of kidney function, an increase in the concentration of creatinine in the blood serum.

Other: infrequently - increased fatigue.

Also, in the course of clinical studies, the following adverse events were observed in patients with arterial hypertension (cause-and-effect relationship with the drug not established): arthralgia, asthenia, back pain, diarrhea, dizziness, insomnia, decreased libido, nausea, peripheral edema, pharyngitis, rhinitis, sinusitis, upper respiratory tract infections, viral infections.

In adult patients with a history of myocardial infarction and / or heart failure, the safety profile in clinical trials differs somewhat from that in patients with hypertension.
This may be due to the disease itself.
Chronic heart failure (NYHA class II-IV functional class) and survival of patients with acute myocardial infarction

On the part of the hematopoiesis system: the frequency is unknown - thrombocytopenia.

From the side of the immune system: the frequency is unknown - reactions of hypersensitivity, including serum sickness.

From the side of metabolism: infrequently - hyperkalemia;
frequency is unknown - an increase in serum potassium, hyponatremia.
From the nervous system: often - dizziness, orthostatic (postural) dizziness;
infrequently - a syncope, a headache.
From the senses: infrequently - vertigo.

From the side of the cardiovascular system: often - a marked decrease in blood pressure, orthostatic hypotension;
infrequently - increased symptoms of heart failure;frequency is unknown - vasculitis.
From the respiratory system: infrequently - cough.

From the side of the digestive system: infrequently - nausea, diarrhea;
frequency unknown - impaired liver function.
From the skin and subcutaneous tissues: very rarely - angioedema;
frequency unknown - skin rash, skin itch.
From the musculoskeletal system: very rarely - rhabdomyolysis;
frequency is unknown - myalgia.
From the urinary system: often - a violation of kidney function;
infrequently - acute renal failure, increased serum creatinine concentration; frequency unknown - increased concentration of residual urea nitrogen in serum.
Other: infrequently - asthenia, increased fatigue.

CONTRAINDICATIONS

- Hypersensitivity to valsartan or other components of the drug;

- violations of liver function, biliary cirrhosis and cholestasis;

- violations of liver function of mild to moderate severity (for a dose of 320 mg);

- simultaneous use with aliskiren in patients with diabetes mellitus or renal dysfunction (CC <60 ml / min);

- lactase deficiency, lactose intolerance, glucose-galactose malabsorption syndrome;

- Pregnancy;

- the period of lactation (breastfeeding);

- Children and adolescents under 18 years of age (effectiveness and safety of valsartan in children is not proven).

With caution: severe renal dysfunction (CC <10 mL / min);
stenosis of the aortic and / or mitral valve; hypertrophic obstructive cardiomyopathy (GOKMP); chronic heart failure (NYHA class III-IV functional class); condition after kidney transplantation; hemodialysis; hyponatremia; diet with restriction of consumption of table salt;bilateral stenosis of the renal arteries or stenosis of the artery of a single kidney; hyperkalemia; primary hyperaldosteronism; conditions, accompanied by a decrease in BCC (including diarrhea, vomiting); hereditary angioedema, or edema on the background of previous therapy with angiotensin II receptor antagonists or ACE inhibitors.
PREGNANCY AND LACTATION

Given the mechanism of action of angiotensin II receptor antagonists, the risk to the fetus can not be ruled out.
The drug is contraindicated in the II and III trimesters of pregnancy, because its use during this period can cause fetotoxic effects (decreased kidney function, low blood pressure, slowing ossification of the fetal bones) and neonatal toxic effects (kidney failure, arterial hypotension, hyperkalemia). In case of using the drug in the II and III trimesters of pregnancy, it is necessary to carry out ultrasound of the kidneys and bones of the fetal skull.
Valsacor ® , like any other drug that directly affects RAAS, should not be used in pregnancy, as well as in women planning a pregnancy.
When planning pregnancy, it is recommended that the patient be transferred to alternative antihypertensive therapy, taking into account the safety profile.
When using drugs that affect RAAS, it is necessary to inform women of childbearing age about the potential risk of adverse effects of these drugs on the fetus during pregnancy.
When confirming the pregnancy, the preparation Valsacor ® should be canceled as soon as possible.
It is not known whether valsartan is excreted in breast milk.
If necessary, use Valsakor ® lactation discontinue breastfeeding.
Use of valsartan has no adverse effect on the reproductive function in male and female rats at doses up to 200 mg / kg / day when administered. This dose 6 times the maximum recommended human daily dose in terms of mg / m 2 (calculations were performed at the rate of 320 mg / day when administered and patient body weight 60 kg).
APPLICATION FOR FUNCTIONS OF THE LIVER

Precautions should be used drug with severe renal impairment (creatinine clearance <10 mL / min) condition after kidney transplantation, patients on hemodialysis, bilateral renal artery stenosis or artery stenosis only kidneys.
Concomitant use with aliskiren in patients with impaired renal function (creatinine clearance <60 mL / min).
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS

Do not use this drug in human liver, biliary cirrhosis and cholestasis (violations of mild to moderate severity - for the dose 320 mg).
APPLICATION FOR CHILDREN

Contraindicated: age of 18 years (effectiveness and safety of valsartan in children has not been proven).
APPLICATION IN ELDERLY PATIENTS

For elderly patients (over 65 years) dose adjustment is required.
SPECIAL INSTRUCTIONS

In applying the drug Valsakor ® in patients with hypertension do not require regular monitoring of laboratory parameters.
Hyponatremia and / or dehydration
in patients with severe hyponatremia and / or dehydration, for example by receiving large doses of diuretics, in rare cases, at the beginning of therapy with Valsakor ®may develop hypotension with clinical manifestations. Before treatment is recommended to recover the sodium content and / or make up the bcc in particular by reducing the doses of diuretics.
In developing hypotension with clinical manifestations of the patient must be given a horizontal position and, if appropriate, in / enter a 0.9% sodium chloride solution. Therapy with Valsakor® can continue only after stabilization of hemodynamic parameters.
Hyperkalemia
simultaneous use of potassium-sparing diuretics, potassium preparations, potassium-containing food additives or other agents capable to raise serum potassium content (e.g., heparin) is not recommended. It is necessary to control the content of potassium in the blood plasma.
Stenosis of the renal artery

Short use of valsartan in patients with renovascular hypertension, which developed secondary to unilateral renal artery stenosis only, was not accompanied by significant changes in parameters of renal hemodynamics, serum creatinine concentrations and blood urea nitrogen in serum. As other drugs acting on the RAAS, are capable of increasing the concentration of urea and serum creatinine in patients with bilateral renal artery stenosis or stenosis of the artery to a solitary kidney, these indicators are recommended to constantly monitor as a precaution.
Condition after undergoing a kidney transplant
Security drug Valsakor ® in patients who have recently had a kidney transplant, is not installed.
Primary hyperaldosteronism
Patients with primary hyperaldosteronism resistant to antihypertensive drugs affecting RAAS therefore such patients use Valsakor preparation ® not recommended.
Stenosis of the aortic and / or mitral valve, hypertrophic obstructive cardiomyopathy
drug Valsakor ® must be used with caution in patients with hemodynamically significant stenosis, aortic and / or mitral valves or with hypertrophic obstructive cardiomyopathy.
Impaired Renal Function
In patients with impaired renal function does not require change doses.
Because There are no data on the use of the drug in renal failure severe (creatinine clearance <10 mL / min or 0.167 ml / s) and in patients on hemodialysis, in such cases the drug is recommended to be used with caution.
The simultaneous use of the angiotensin II receptor antagonists, including valsartan, ACE inhibitors or with aliskiren is contraindicated in patients with impaired renal function (creatinine clearance <60 mL / min).
Abnormal liver function
Patients with impaired liver function mild to moderate severity nebiliarnogo genesis without signs of cholestasis preparation Valsakor ® at a dosage of 320 mg contraindicated because the maximum daily dose should not exceed 80 mg.
Angioedema history
Among patients with angioedema (swelling of the larynx and the vocal cords, causing obstruction of the airway and / or swelling of the face, lips, pharynx and / or language) against drug therapy Valsakor ® , observed cases of angioedema history, including and ACE inhibitors. With the development of angioedema should stop the drug immediately and eliminate the possibility of re-use.
Hypertension
In hypertension drug Valsakor ® can be used as monotherapy or in conjunction with other antihypertensives, in particular diuretics.
CHF / improving survival in patients with acute myocardial infarction
is possible to use the drug Valsakor ®in combination with other drugs used in acute myocardial infarction (thrombolytics, aspirin as antiplatelet drugs, beta-blockers and inhibitors MMC-CoA reductase inhibitors (statins)). Simultaneous use of the drug Valsakor ® and ACE inhibitors in such patients not recommended because this combination therapy does not lead to additional clinical effect and is accompanied by an increased risk of adverse events compared with therapy with two separate drugs.
In patients with CHF triple combination therapy: drug Valsakor ®, An ACE inhibitor and a beta-blocker is not recommended as It does not lead to additional clinical effect and is accompanied by an increased risk of adverse events.
Use of the drug Valsakor ® in patients with heart failure or myocardial infarction is often leads to a small reduction in blood pressure, usually without drug withdrawal when the dosing instructions.
In patients whose renal function may depend on the activity of the RAAS (e.g., severe chronic heart failure), treatment with ACE inhibitors is accompanied by oliguria and / or increase of azotemia, and in rare cases - acute renal failure and / or death. Since valsartan is an antagonist of angiotensin II receptors, can not exclude the possibility of deterioration of renal function in its application. To begin therapy in patients with chronic heart failure or myocardial infarction should be cautious.In a study of patients should always evaluate kidney function.
Specific information on excipients
drug Valsakor ® It contains lactose, and the drug is contraindicated in patients with lactase deficiency, lactose intolerance syndrome glucose-galactose malabsorption.
Impact on the ability to drive vehicles and manage mechanisms

Caution should be exercised when driving and classes of potentially hazardous activities that require high concentration and speed of psychomotor reactions, because may develop dizziness or weakness in the arterial hypotension.
OVERDOSE

Symptoms: marked reduction of blood pressure, which can lead to a violation of consciousness, collapse and / or shock .
Treatment: symptomatic, the nature of which depends on the time elapsed since administration of the drug, and the degree of severity of symptoms. In case of accidental overdose, induce vomiting (if the drug was recently adopted) or to gastric lavage. In marked decrease in blood pressure is necessary to transfer the patient to the horizontal position with a low headboard, followed conduct activities aimed at maintaining the functions of the cardiovascular and respiratory systems, bcc (administering 0.9% sodium chloride solution w / w) and control daily diuresis. Hemodialysis is ineffective.
DRUG INTERACTION

The simultaneous use is contraindicated
simultaneous use of the angiotensin II receptor antagonists, including valsartan, ACE inhibitors or with aliskiren is contraindicated in patients with diabetes mellitus and renal dysfunction (creatinine clearance <60 mL / min).
Simultaneous application is not suitable for
simultaneous use with lithium therapy is not recommended because possibly reversible increase the concentration of lithium in blood plasma and the development of intoxication. The simultaneous use of valsartan with diuretics and drugs lithium can contribute to further increase the concentration of lithium and increase the risk of toxicity. If necessary, the simultaneous application of lithium preparations should carefully monitor the concentration of lithium in the blood plasma.
While the use of potassium-sparing diuretics, potassium supplements, potassium-containing food additives and other drugs and substances that can increase the content of potassium in the serum (e.g., heparin) is recommended to control the content of potassium in the blood plasma.
Concomitant use with caution
Some patients dual blockade of the RAAS accompanied by the development of hypotension, syncope, hyperkalemia, and renal dysfunction (including acute renal failure). Requires caution while the use of angiotensin II receptor antagonists, including valsartan, with drugs that affect the RAAS, such as ACE inhibitors or aliskiren.
While the use of NSAIDs, including selective COX-2 inhibitors, acetylsalicylic acid in a dose of 3 g / day and non-selective NSAIDs may weaken the hypotensive effect, an increase in the risk of developing renal dysfunction and increasing potassium content in the blood plasma. At the start of therapy it is recommended to evaluate renal function, as well as adjust the violations of water-electrolyte balance.
According to the study in vitro of valsartan is a substrate for hepatic transporter proteins OATR1V1 / OATR1VZ efflux and MRP2 transporter. The clinical significance of this is unknown fact. The simultaneous use of inhibitors of transporter proteins OATR1V1 / OATR1VZ (e.g., rifampicin, cyclosporin) and efflux transporter MRP2 (such as ritonavir) can increase the systemic exposure of valsartan (CCmax and AUC). This should be considered at the beginning and at the end of concurrent therapy.
The lack of drug interaction
is not clinically significant interaction with the following drugs: cimetidine, warfarin, furosemide, digoxin, atenolol, indomethacin, hydrochlorothiazide, amlodipine and glibenclamide.
TERMS OF RELEASE FROM PHARMACY

The drug is released by prescription.

TERMS AND CONDITIONS OF STORAGE

The drug should be stored in reach of children, in the original package, at a temperature not higher than 30 ° C. Shelf life Valsakor ® 80 mg, 160 mg - 3 years;Valsakor ® 320 mg - 2 years.
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