Composition, form of production and packaging
The tablets covered with a film membrane of a reddish-brown color, oval, biconcave.
1 tab.
valsartan 160 mg
hydrochlorothiazide 12.5 mg
Excipients: microcrystalline cellulose, lactose monohydrate, magnesium stearate, croscarmellose sodium, povidone, silicon dioxide colloidal anhydrous.
The composition of the film shell: hypromellose, titanium dioxide (E171), iron dye red oxide (E172), macrogol 4000.
7 pcs. - blisters (4) - packs of cardboard.
7 pcs. - blisters (8) - packs of cardboard.
7 pcs. - blisters (14) - packs of cardboard.
14 pcs. - blisters (2) - packs of cardboard.
14 pcs. - blisters (4) - packs of cardboard.
14 pcs. - blisters (7) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2012.
PHARMACHOLOGIC EFFECT
Combined antihypertensive drug.
Valsartan is a selective antagonist of angiotensin II receptors, 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 unblocked receptors of the AT2 subtype, which balances the effects associated with the stimulation of AT 1 -receptors.
Valsartan does not have agonistic activity against AT 1 -receptors. Its affinity for the receptors of the AT1 subtype is approximately 20,000 times greater than that of the AT 2 subtype receptors. 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, so when taking antagonists of the receptors of apogiotenzin II, the development of dry cough is unlikely. Valsartan does not interact and does not block the receptors of other hormones or ion channels involved in the regulation of cardiovascular function.
When treating arterial hypertension, valsartan reduces blood pressure without affecting the heart rate.
After ingestion of a single dose of valsartan, the antihypertensive effect develops within 2 hours, and the maximum decrease in blood pressure is achieved within 4-6 hours.
The antihypertensive effect of valsartan persists for 24 hours. For repeated appointments of valsartan, the maximum decrease in blood pressure, regardless of dose, is achieved in 2-4 weeks and remains at the reached 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 withdrawal syndrome (sudden increase in BP or other undesirable clinical consequences).
Hydrochlorothiazide is a thiazide diuretic whose diuretic effect is associated with a disruption of the reabsorption of sodium, chlorine, potassium, magnesium, water in the distal nephron; delays the excretion of calcium ions, uric acid. Has hypotensive effect, which is due to the expansion of arterioles. Virtually no effect on normal BP.
Diuretic effect develops 1-2 hours after taking the drug inside, reaches a maximum after 4 hours and persists for 6-12 hours. Antihypertensive effect occurs in 3-4 days, but it may take 3-4 weeks to achieve the optimal therapeutic effect.
PHARMACOKINETICS
Valsartan
Suction
Valsartan is rapidly absorbed after ingestion, but the degree of absorption varies widely. The average absolute bioavailability of valsartan is 23%. The time required to achieve C max is 2 h.
When taking valsartan with food, the AUC is reduced by 48%. However, 8 hours after taking plasma concentrations of valsartan taken on an empty stomach or with food are the same. AUC reduction is not accompanied by a clinically significant decrease in the therapeutic effect of valsartan, so the drug can be used regardless of food intake.
Distribution
When taking the drug inside 1 time / day, its accumulation is insignificant. Plasma concentrations of valsartan are the same for men and women.
Valsartan actively binds to blood serum proteins (94-97%), mainly with serum albumin. The equilibrium V d of the preparation is small, about 17 liters. Plasma clearance is relatively low (approximately 2 l / h) when compared with hepatic blood flow (approximately 30 l / h).
Metabolism and excretion
It is metabolized by the CYP 2C9 isoenzyme. T 1/2 is 9 hours. It is excreted mainly unchanged through the intestine (70%) and kidneys (30%).
Pharmacokinetics in special clinical cases
Given that the renal clearance is only 30% of the total clearance, patients with impaired renal function do not require correction of the doses of the drug. Because the degree of binding of valsartap to plasma proteins is high, its excretion in hemodialysis is unlikely.
About 83% of valsartan is excreted through the intestine, mostly unchanged. Valsartan does not undergo significant biotransformation, so its systemic effect does not correlate with the degree of impaired hepatic function. Therefore, patients with hepatic insufficiency of non-biliary origin and in the absence of cholestasis do not require a change in the dose of valsartan. In patients with biliary cirrhosis of the liver or obstruction of the biliary tract, the AUC of valsartan increases approximately 2-fold. Valsacor В® H160 is not recommended for patients with impaired liver function.
Some elderly patients have a slightly greater systemic effect of valsartan compared to young volunteers; However, it is not established whether these differences are of clinical significance. Systemic clearance of hydrochlorothiazide decreases in elderly patients, in comparison with the young.
Hydrochlorothiazide
Suction and distribution
After oral intake of hydrochlorothiazide is 60-80%. C max hydrochlorothiazide a in the blood is achieved 2 hours after ingestion. Connection with blood plasma proteins - 40-70%.
Metabolism and excretion
Hydrochlorothiazide is not metabolized and is quickly excreted in the urine (more than 95%). T 1/2 is 6 to 15 hours.
INDICATIONS
- Arterial hypertension (in patients who are shown combined therapy).
DOSING MODE
The drug is taken inside, regardless of food intake, the frequency of reception - 1 time / day.
Valsacor В® H160 can be combined with other antihypertensive agents. Treatment should be started with minimal doses of the drug.
Patients who did not achieve the target level of BP against monotherapy (valsartan 160 mg or hydrochlorothiazide at a dose of 12.5 mg) are recommended a fixed combination of doses - Valsacor В® H160 (160 / 12.5 mg) 1 time / day.
The maximum antihypertensive effect of the preparation Valsacor В® H160 (160 / 12.5 mg) develops within 2-4 weeks. If necessary (the level of diastolic blood pressure above 100 mm Hg on the background of monotherapy with valsartan), in order to achieve a more pronounced effect, it is possible to increase the dose of the drug to 160/25 mg (not earlier than 4-8 weeks) (Valsakor В® ND160 preparation may be used) 1 time / day.
Patients with impaired renal function (QC more than 30 ml / min (0.5 ml / s)) do not need to change the dose of the drug.
Valsacor В® H160 is not recommended for patients with impaired liver function . The maximum recommended daily dose of valsartan in patients with mild or moderate impairment of liver function of non-biliary origin is 80 mg (1 tablet / day of preparation ValsacorВ® H80).
Older patients are not required to adjust the dose.
SIDE EFFECT
Classification of the incidence of adverse events WHO:
very often> 1/10
often from> 1/100 to <1/10
sometimes from> 1/1000 to <1/100
rarely from> 1/10 000 to <1/1000
very rarely from <1/10 000, including individual messages.
The adverse effects were generally mild and transitory in nature.
From the side of the central nervous system and peripheral nervous system: often - general weakness; sometimes - increased fatigue, asthenia, dizziness, incl. postural, vertigo, insomnia; rarely - headache, depression, paresthesia, neuralgia; very rarely - fainting (when used after a heart attack).
From the respiratory system: often - nasopharyngitis; sometimes - infections of the upper respiratory tract, rhinitis, sinusitis, cough; very rarely - a respiratory distress syndrome with pneumonitis and pulmonary edema.
From the cardiovascular system: sometimes - chest pain; often - marked decrease in blood pressure and orthostatic hypotension; very rarely - arrhythmias; Potentially possible - peripheral edema.
On the part of the digestive system: often - diarrhea; sometimes - nausea, dyspepsia, abdominal pain; rarely - gastroenteritis, decreased appetite, constipation, hyperbilirubinemia, increased activity of hepatic transaminases; very rarely - pancreatitis, intrahepatic cholestasis, jaundice.
From the skin: rarely - skin rash, photosensitivity; very rarely - alopecia.
From the musculoskeletal system: sometimes - pain in the back, limbs, sprains and tears of ligaments and muscles or muscle tendons, arthritis, arthralgia; rarely - myalgia, muscle weakness, muscle cramps.
From the genitourinary system: sometimes - decreased libido, impotence (less than 1%), urinary tract infection, viral infections, increased frequency of urination;rarely - hypercreatininaemia, increased serum urea nitrogen concentration; very rarely - renal dysfunction.
From the senses: sometimes - a blurred vision; rarely - noise in the ears, conjunctivitis.
Allergic reactions: very rarely - angioedema, urticaria, skin rash, itching, hypersensitivity reactions, including serum sickness and necrotizing vasculitis, toxic epidermal necrolysis (Lyell's syndrome), lupus-like reactions, exacerbation of SLE flow.
From the hemopoietic system: rarely - anemia, incl. hemolytic, leukopenia, agranulocytosis, bone marrow depression, decreased hemoglobin and hematocrit concentration, neutropenia, thrombocytopenia (sometimes with purpura).
On the part of laboratory indicators: often - hyperkalemia, hypokalemia, hyponatremia, hypomagnesemia, hypercalcemia.
Other: rarely - increased sweating; very rarely - epistaxis.
CONTRAINDICATIONS
- pronounced violations of the liver function;
- biliary cirrhosis of the liver and obstruction of the biliary tract (cholestasis);
- mild and moderate violations of the liver function of non-biliary origin (for a given dose of the drug);
- Anuria, expressed renal dysfunction (CC less than 30 ml / min (0.5 ml / sec));
- hemodialysis;
- hypokalemia, hyponatremia, hypercalcemia or hyperuricemia with clinical manifestations, refractory to adequate therapy;
- intolerance to galactose, lactase deficiency lapp or syndrome of impaired glucose / galactose absorption;
- age under 18 years (effectiveness and safety of valsartan in children is not installed);
- Pregnancy;
- lactation period;
- Hypersensitivity to valsartan, hydrochlorothiazide, sulfonamide derivative and to other components of the drug.
Caution should be applied to the drug with simultaneous intake of potassium preparations, potassium-sparing diuretics, potassium-containing substitutes for edible salt and other agents that can raise the level of potassium in the blood (for example, heparin), chronic heart failure IV functional class according to NYHA classification, renal failure (QC more than 30 ml / min (0.5 ml / sec)), mild liver function abnormalities, bilateral or unilateral stenosis of the renal arteries or stenosis of the single kidney artery, post-transplant condition (including diarrhea, vomiting), primary hyperaldosteronism, stenosis of aortic and mitral valves, hypertrophic obstructive cardiomyopathy (GOKMP), systemic lupus erythematosus, hypersensitivity to other receptor antagonists and kidneys, conditions accompanied by a decrease in bcc and / or sodium ions (including diarrhea, vomiting) angiotensin II, allergic reactions and bronchial asthma.
PREGNANCY AND LACTATION
The use of angiotensin II receptor antagonists is not recommended in the first trimester of pregnancy. The drug is contraindicated in the II and III trimesters of pregnancy, since the use of pregnancy in the II and III trimesters 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). If the drug was used in the II and III trimesters of pregnancy, it is necessary to carry out ultrasound of the kidneys and bones of the fetal skull.
When planning pregnancy, it is recommended that the patient be transferred to alternative antihypertensive therapy, taking into account the safety profile.
When confirming the pregnancy, the preparation Valsacor В® H160 must be canceled as soon as possible.
There is no data on the isolation of valsartan with breast milk. However, it is known that valsartan penetrates the milk of lactating rats. Hydrochlorothiazide is excreted in breast milk. Therefore, if you need therapy with the drug Valsacor В® H160 during lactation should be abolished breastfeeding.
APPLICATION FOR FUNCTIONS OF THE LIVER
Patients with impaired renal function (QC more than 30 ml / min (0.5 ml / s)) do not need to change the dose of the drug. With caution should be used in patients with renal insufficiency (CC <10 ml / min), incl. in patients on hemodialysis, with bilateral stenosis of the renal arteries or stenosis of the artery of a single kidney.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Valsacor В® H160 is not recommended for patients with impaired liver function . The maximum recommended daily dose of valsartan in patients with mild or moderate impairment of liver function of non-biliary origin is 80 mg (1 tablet / day of preparation ValsacorВ® H80).
APPLICATION FOR CHILDREN
Contraindicated: age under 18 years (effectiveness and safety of valsartan in children is not proven).
APPLICATION IN ELDERLY PATIENTS
Older patients are not required to adjust the dose.
SPECIAL INSTRUCTIONS
Patients with severe chronic heart failure in the stage of decompensation or other conditions accompanied by stimulation of RAAS
The use of the preparation Valsacor В® H160 in this group of patients is usually accompanied by a more pronounced decrease in blood pressure, however, if the recommendations for dosing are observed, treatment rarely requires cancellation due to hypotension. Therapy with Valsacor В® H160 should be performed with caution. Due to inhibition of RAAS activity, some patients may develop renal dysfunction. In severe chronic heart failure, it is possible to develop oliguria and / or progressive azotemia up to (in rare cases) acute renal failure and / or death (in rare cases).
Patients with chronic heart failure need regular monitoring of kidney function, with the simultaneous appointment of a combination of three classes of drugs - ACE inhibitors, beta-blockers and angiotensin II receptor antagonists (AT 1 ). It is possible to appoint in combination with other drugs prescribed after a myocardial infarction: thrombolytics, acetylsalicylic acid, beta-adrenoblockers and statins.
Patients with hyponatraemia and / or reduced BCC
In patients with severe hyponatraemia and / or reduced bcc, for example, due to taking large doses of diuretics, in rare cases early treatment with ValsacorВ® H160 can cause severe arterial hypotension. Before the beginning of treatment it is recommended to correct the disturbances of the water-electrolyte balance, in particular, by reducing the doses of diuretics. With the development of arterial hypotension with clinical manifestations, it is necessary to give the patient a horizontal position with raised legs, fill the BCC and correct the disturbances of the water-electrolyte balance. Therapy with Valsacor В® H160 can be continued only after the stabilization of blood pressure.
Stenosis of the renal artery
The safety of the use of the preparation Valsacor В® H160 in patients with bilateral or unilateral stenosis of the renal arteries, as well as stenosis of the artery of a single kidney is not established (it is possible to increase the serum concentrations of urea and creatinine).
Impaired renal function
In patients with impaired renal function (QC more than 30 ml / min (more than 0.5 ml / s)) no change in the doses of the drug is required. It is recommended to periodically monitor the content of potassium ions, the concentration of creatinine and uric acid in the blood serum. The experience of using the drug Valsacor В® H160 in patients with recent renal transplantation is absent.
Impaired liver function
Patients with impaired liver function are recommended to take no more than 80 mg of valsartan per day.
Primary hyperaldosteronism
Valsacor В® H160 is not recommended for patients with primary hyperaldosteronism.
Hard currency
There are reports of an exacerbation of SLE in the use of thiazide diuretics.
Other metabolic disorders
Thiazide diuretics can alter glucose tolerance and increase serum cholesterol, triglyceride and uric acid concentrations.
Valsacor В® H160 contains lactose, so the drug should not be given to patients with hereditary intolerance to galactose, a deficiency of lactase lapp or a syndrome of impaired absorption of glucose-galactose.
Impact on the ability to drive vehicles and manage mechanisms
Patients should be careful when managing transport and working with other complex mechanisms, requiring increased attention, because possibly the development of dizziness or weakness on the background of arterial hypotension.
OVERDOSE
Valsartan
Symptoms: marked decrease in blood pressure, which can lead to dizziness, collapse and / or shock with a fatal outcome.
Treatment: symptomatic, it is recommended to induce vomiting and rinse the stomach, the appointment of activated charcoal. With the development of arterial hypotension, it is necessary to give the patient a horizontal position with raised legs, replenish the BCC and correct the disturbances of the water-electrolyte balance.Hemodialysis is ineffective.
Hydrochlorothiazide
Symptoms: the most frequent symptoms are a consequence of deficiency of electrolytes (hypokalemia, hypochloraemia, hyponatremia) and dehydration due to excessive diuresis (nausea, drowsiness, arrhythmia, muscle spasm). With the simultaneous administration of cardiac glycosides, hypokalemia can aggravate the course of arrhythmias.
Treatment: symptomatic.
DRUG INTERACTION
Valsartan
No clinically significant pharmacokinetic interactions with drugs cimetidine, warfarin, digoxin, atenolol, indomethacin, hydrochlorothiazide, amlodipine and glibenclamide were observed.
Since valsartan is not subjected to significant metabolism, it should not expect significant drug interactions associated with the induction or inhibition of cytochrome P450.
Simultaneous treatment with potassium-sparing diuretics (spironolactone, triamterene, amiloride), potassium-containing food additives, drugs that increase the level of potassium in blood serum (ACE inhibitors, heparin, cyclosporine) can cause hyperkalemia, and therefore required to be careful.
Simultaneous treatment with otherantihypertensive agents, in Vol. h. diuretics, leads to increased hypotensive effect.
When simultaneous administration of drugs lithium and angiotensin II receptor antagonists reported cases reversibly increasing the content of lithium ions in blood serum and increasing its toxicity. It is recommended to regularly monitor the content of the lithium ions in the blood.
Hydrochlorothiazide
With thiazide diuretic drugs such as ethanol, barbiturates , and opioid analgesics, can potentiate the risk of development of orthostatic hypotension.
Hypoglycemics (oral and insulin) may require correction dose hypoglycemic agents.
Other antihypertensive drugs: additive effect.
Anticholinergics (e.g., atropine, biperiden) increase the bioavailability of thiazide diuretics.
Cholestyramine and colestipol: in the presence of anionic exchange resins decreases absorption of hydrochlorothiazide.
Glucocorticosteroids, ACTH, laxatives, amphotericin B, carbenoxolone, benzathine benzylpenicillin, salicylic acid and salicylates:possible reduction of electrolytes, particularly hypokalemia, to regularly monitor the content of potassium ion in the blood.
Antiarrhythmics of class IA (quinidine, gidrohinidin, disopyramide), antiarrhythmics III class (amiodarone, dofetilide, ibutilide), sotalol, some neuroleptics (thioridazine, chlorpromazine, levomepromazine, trifluoperazine, tsiamemazin, sulpirid, sultopride, amisulpride, tiapride, pimozide, haloperidol , droperidol) and other drugs (bepridil, cisapride, difemanil, erythromycin, a / c, halofantrine, ketanserin, mizolastine, pentamidine, sparfloxacin, terfenadine, vincamine w / w): risk of arrhythmias such as "pirouette" on the background of a possible gipokalie AI and hypomagnesemia. Recommended control content of potassium ion in the blood.
Cardiac glycosides:the risk of arrhythmia in the background of hypokalemia and hypomagnesemia.
Beta-blockers and diazoxide: strengthening of hypoglycemic effect of these funds.
Uricosuric agents (probenecid, sulfinpyrazone, allopurinol) may increase the concentration of uric acid in blood, and increase the incidence of hypersensitivity reactions to allopurinol; if necessary - dosage adjustment of uricosuric agents.
Pressor amines (e.g., epinephrine, norepinephrine) may decrease the effect of pressor amines.
Amantadine: increased risk of side effects of amantadine.
Cytotoxic agents (e.g., cyclophosphamide, methotrexate):decreased excretion of cytotoxic agents and potentiate myelosuppressive action.
Muscle relaxants nondepolarizing mode of action (e.g., tubocurarine): strengthening muscle relaxant effect.
Cyclosporin: increased risk of hyperuricemia and podagropodobnyh complications.
Tetracyclines (doxycycline in addition to) the risk of increasing the concentration of urea in the blood serum.
Methyldopa: There are cases of hemolytic anemia.
Lithium: diuretics reduce the renal clearance of lithium and increase the risk of toxic action of lithium; recommended to control the lithium content in the blood.
NSAIDs (including COX-2 inhibitors, e.g., salicylic acid, indoleacetic acid derivatives):may reduce the diuretic, natriuretic and antihypertensive effect of diuretics, may develop acute renal failure.
Simultaneous treatment with calcium supplementation, vitamin D can lead to an increase in the content of calcium ions in the blood, which can distort the results of the research function of the parathyroid glands.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
List B. The drug should be kept out of the reach of children, dry, dark place at a temperature not higher than 30 В° C. Shelf life - 2 years.
