Composition, form of production and packaging
The tablets covered with a film membrane of pink color, oval, biconcave.
1 tab.
valsartan 80 mg
hydrochlorothiazide 12.5 mg
Excipients: microcrystalline cellulose - 41 mg, lactose monohydrate - 17.125 mg, magnesium stearate - 4.5 mg, croscarmellose sodium - 2.375, povidone - 1.5 mg, silicon colloidal dioxide - 1 mg.
Composition of the film coat: hypromellose - 2.8 mg, titanium dioxide (E171) - 0.86 mg, macrogol 4000 - 0.3 mg, iron oxide red oxide (E172) - 0.03 mg, ferric oxide yellow oxide (E172) - 0.01 mg.
14 pcs. - blisters (2) - 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 2014.
PHARMACHOLOGIC EFFECT
Combined antihypertensive drug, consisting of an angiotensin II receptor blocker and a thiazide diuretic.
Valsartan is a selective antagonist of angiotensin II receptors of non-protein nature. Has a selective antagonistic effect on the receptors of the subtype AT 1 . The consequence of blockade of AT 1 -receptors is an increase in the plasma concentration of angiotensin II, which can stimulate the unblocked receptors of the AT2 subtype, which balances the effects associated with the stimulation of AT 1 -receptors. Valsartan has no 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. Due to the lack of influence on the ACE, the effects of bradykinin and P substance are not potentiated, so when taking angiotensin II receptor antagonists, development of a 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 through 2-4 weeks and remains at the reached level during long-term 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 rise in blood pressure or other undesirable clinical consequences).
Hydrochlorothiazide is a thiazide diuretic. Reduces 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 and distribution
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 hours. When the drug is taken orally 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. V d of the drug is small, about 17 liters. Plasma clearance is relatively low (approximately 2 liters / hour) when compared with hepatic blood flow (approximately 30 liters / hour).
When taking valsartan with food, the AUC decreases 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.
Metabolism and excretion
Metabolised by the isoenzyme CYP2C9.
T 1/2 is 9 hours. It is excreted mainly unchanged through the intestine (70%) and kidneys (30%).
When taking valsartan with food, the AUC decreases 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.
Hydrochlorothiazide
Suction and distribution
After oral intake of hydrochlorothiazide is 60-80%. C max hydrochlorothiazide in the blood is achieved 2 hours after ingestion. Binding to plasma proteins is 40-70%.
Metabolism and excretion
Hydrochlorothiazide is not metabolized and is rapidly excreted through the kidneys (more than 95%). T 1/2 is 6 to 15 hours.
Pharmacokinetics in specific patient groups
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 valsartan to plasma proteins is high, 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.
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.
INDICATIONS
- Arterial hypertension (patients who are shown combined therapy).
DOSING MODE
The drug is taken orally, 1 time / day, regardless of food intake.
Valsacor В® H80 can be combined with other antihypertensive drugs.
Patients who do not achieve the target level of BP against monotherapy (valsartan or hydrochlorothiazide) recommend a fixed combination of doses - Valsacor В® H80 (80 / 12.5 mg) 1 time / day. If hypotensive effect is insufficient, the dose of the drug can be increased to the maximum daily dose - 2 tablets / day Valsacor В® H80 or 1 tab. / Day Valsakor В® ND160.
The maximum antihypertensive effect of the preparation Valsacor В® H80 (80 / 12.5 mg) develops within 2-4 weeks. If necessary (the level of diastolic blood pressure above 100 mm Hg against the background of monotherapy with valsartan), in order to achieve a more pronounced effect, it is possible to increase the dose of the drug up to 160/25 mg 1 time / day (not earlier than 4-8 weeks) Valsacor В® ND160).
Patients with impaired renal function (CK> 30 ml / min (0.5 ml / s)) do not require dose adjustment.
The maximum recommended daily dose of the preparation ValsacorВ® H80 in patients with impaired liver function of mild and moderate severity of non-biliary origin -1 tab. / Day .
Older patients are not required to adjust the dose.
SIDE EFFECT
Classification of the incidence of adverse events (WHO): very often (> 1/10), often (> 1/100 to <1/10), sometimes (> 1/1000 to <1/100), rarely (> 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 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; very rarely - pancreatitis, intrahepatic cholestasis, jaundice.
From the skin and subcutaneous tissues: rarely - skin rashes, 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 urinary system: sometimes - urinary tract infections, viral infections, increased frequency of urination; very rarely - renal dysfunction.
On the part of the reproductive system: sometimes - decreased libido, impotence (less than 1%).
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.
Laboratory indicators: often - hyperkalemia, hypokalemia, hyponatremia, hypomagnesemia, hypercalcemia; rarely - anemia, incl. hemolytic, leukopenia, agranulocytosis, bone marrow depression, decreased hemoglobin and hematocrit concentration, neutropenia, thrombocytopenia (sometimes with purpura), hypercreatinemia, hyperbilirubinemia, increased activity of hepatic transaminases, increased serum urea nitrogen concentration.
Other: rarely - increased sweating; very rarely - epistaxis.
CONTRAINDICATIONS
- pronounced violations of the liver, biliary cirrhosis and obstruction of the biliary tract (cholestasis);
anuria;
- severe renal dysfunction (CK <30 ml / min (0.5 ml / sec));
- hemodialysis;
- hypokalemia, hyponatremia, hypercalcemia or hyperuricemia with clinical manifestations, refractory to adequate therapy;
- Pregnancy;
- lactation period;
- age under 18 years (effectiveness and safety of valsartan in children is not established);
- intolerance to galactose, lactase deficiency lapp or syndrome of impaired glucose / galactose absorption;
- Hypersensitivity to valsartan, hydrochlorothiazide, sulfonamide derivative and to other components of the drug.
With caution: simultaneous use 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 (NYHA functional class IV); renal failure (CK> 30 ml / min (0.5 ml / sec)); mild liver function abnormalities; bilateral or unilateral stenosis of the renal arteries or stenosis of the artery of a single kidney; condition after kidney transplantation; conditions, accompanied by a decrease in bcc and / or sodium ions (including diarrhea, vomiting); primary hyperaldosteronism; Stenosis of the aortic and mitral valves;hypertrophic obstructive cardiomyopathy; systemic lupus erythematosus (SLE), hypersensitivity to other angiotensin II receptor antagonists; 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, because it 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, ultrasound of the kidneys and bones of the fetal skull should be performed.
When planning pregnancy, it is recommended that the patient be transferred to alternative antihypertensive therapy, taking into account the safety profile. When establishing a pregnancy, the preparation Valsacor В® H80 should be discontinued 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® H80 during lactation should be abolished breastfeeding.
APPLICATION FOR FUNCTIONS OF THE LIVER
Patients with impaired renal function (CK> 30 ml / min (0.5 ml / s)) do not require dose adjustment.
Contraindicated use of the drug for severe renal dysfunction (KK <30 ml / min (0.5 ml / sec)).
With caution should be used in patients with renal insufficiency (CK> 30 ml / min (0.5 ml / sec)), 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
The maximum recommended daily dose of the preparation ValsacorВ® H80 in patients with impaired liver function of mild and moderate severity of non-biliary origin -1 tab. / Day .
The use of the drug is contraindicated in severe violations of liver function, biliary cirrhosis and obstruction of the biliary tract (cholestasis).
With caution should prescribe the drug with moderate violations of the liver.
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 drug Valsacor В® H80 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® H80 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.
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® H80 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® H80 can be continued only after the blood pressure has stabilized.
Stenosis of the renal artery
The safety of the use of the preparation Valsacor В® H80 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 (possibly an increase in serum concentrations of urea and creatinine).
Impaired renal function
In patients with impaired renal function (CK> 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® H80 in patients with recently transferred kidney transplantation is absent.
Impaired liver function
Patients with impaired liver function are recommended to take no more than 80 mg of valsartan per day. Valsartan is excreted mainly through the intestines with bile.In patients with obstructive diseases of the bile ducts, a decrease in the clearance of valsartan was observed, so in such cases, the preparation of ValsacorВ® H80 should be administered with caution.
Primary hyperaldosteronism
Valsacor В® H80 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 raise serum cholesterol, triglyceride and uric acid concentrations.
Valsacor В® H80 contains lactose, therefore, the drug should not be administered to patients with hereditary intolerance to galactose, lactase deficiency lapp or glucose-galactose malabsorption syndrome.
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 therapy; artificial vomiting and gastric lavage, the reception of activated charcoal. With the development of arterial hypotension should be given to the patient horizontal position with a low headboard; arrange for volume replacement and correction of violations of water-electrolyte balance. Hemodialysis is ineffective.
Hydrochlorothiazide
Symptoms: The most common symptoms are a consequence of electrolyte deficiency (hypokalemia, chloropenia, hyponatremia) and dehydration due to excessive diuresis (nausea, somnolence, arrhythmia, muscle spasm). With simultaneous use of cardiac glycosides may aggravate hypokalemia during arrhythmia.
Treatment: symptomatic therapy.
DRUG INTERACTION
Valsartan
No clinically significant pharmacokinetic interaction with cimetidine, warfarin, digoxin, atenolol, indomethacin, hydrochlorothiazide, amlodipine, and glibenclamide.
Since valsartan is not subjected to significant metabolism, it should not expect significant drug interaction associated with the induction or inhibition of cytochrome P450.
The simultaneous use of 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 otherantihypertensives , including diuretics leads to increased antihypertensive effect.
With simultaneous use of drugs lithium and angiotensin II receptor antagonists reported cases of reversible increase lithium content in serum and increasing its toxicity. Recommended regular monitoring of lithium in the blood.
Hydrochlorothiazide
While the use of thiazide diuretics , ethanol, barbiturates and means of anesthesia may potentiate the risk of orthostatic hypotension.
While the use of hypoglycemic drugs (oral and insulin) may require correction of the last dose.
In combination with other antihypertensive drugs - additive effect.
Anticholinergics (e.g., atropine, biperiden) increase the bioavailability of thiazide diuretics.
In the presence of anionic exchange resins (cholestyramine and colestipol) hydrochlorothiazide absorption decreases.
Corticosteroids, ACTH, laxatives, amphotericin B, carbenoxolone, benzathine benzylpenicillin, salicylic acid and salicylates can reduce the content of electrolytes, leading in particular to hypokalemia. It is recommended to regularly monitor the content of potassium in the blood.
Antiarrhythmic drugs of class Ia (quinidine, gidrohinidin, disopyramide), antiarrhythmics III class (amiodarone, dofetilide, ibutilide), sotalol, some neuroleptics (thioridazine, chlorpromazine, levomepromazine, trifluoperazine, tsiamemazin, sulpiride, sultopride, amisulpride, tiapride, pimozide, haloperidol , droperidol) other drugs (bepridil, cisapride, difemanil, erythromycin and vincamine to / v administration, halofantrine, ketanserin, mizolastine, pentamidine, sparfloxacin, terfenadine)while the use of hydrochlorothiazide increase the risk of arrhythmias such as "pirouette" on the background of a possible hypokalemia and hypomagnesemia. Should regularly monitor the content of potassium in the blood.
Cardiac glycosides increase the risk of arrhythmias in the background of hypokalemia and hypomagnesemia.
Hydrochlorothiazide increases the hypoglycemic effect of beta-blockers and diazoxide .
While the use of uricosuric drugs (probenecid, sulfinpyrazone, allopurinol) may increase the concentration of uric acid in blood, and increase the incidence of hypersensitivity reactions to allopurinol; may require dose adjustment of uricosuric agents.
Hydrochlorothiazide may reduce the effect of pressor amines (e.g., epinephrine, norepinephrine).
While the use of hydrochlorothiazide increases the risk of side effects of amantadine .
While the use of cytotoxic drugs (e.g., cyclophosphamide, methotrexate ) and reduced excretion of the last possible potentiation myelosuppressive action.
Hydrochlorothiazide may enhance the effect of muscle relaxants nondepolarizing mode of action (e.g., tubocurarine ).
At simultaneous application with cyclosporine increases the risk of hyperuricemia and podagropodobnyh complications.
While the use oftetracyclines (except doxycycline) may increase the concentration of urea in the blood serum.
With simultaneous application of methyldopa and hydrochlorothiazide described cases of hemolytic anemia.
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 derivatives, indole acetic acid) can reduce the diuretic, natriuretic and antihypertensive effect of diuretics; may develop acute renal failure.
The simultaneous use of calcium preparations, vitamin D may lead to increased calcium 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
The drug should be stored out of reach of children, dry, protected from light at a temperature of no higher than 30 В° C. Shelf life - 2 years.
