VALSAR [Valsartan + Hydrochlorothiazide] 80 + 12.5 mg Tablets
VALSAR
instructions for medical use of the medicinal product
Tradename
Valsar; Valsar
International non-proprietary name
Valsartan + Hydrochlorothiazide, Valsarten + Hydrochlorothiazide
Composition
Each film-coated tablet contains:
active substances: valsartan 80 mg, hydrochlorothiazide 12.5 mg (for a dosage of 80/12.5 mg), valsartan 160 mg, hydrochlorothiazide 12.5 mg (for dosage 160/12.5 mg)
excipients: starch, dextrin, CMS - Na , hypromellose, silicon dioxide, magnesium stearate, talc
Dosage form
Tablets.
Pharmacotherapeutic group
Antihypertensive combined agent (angiotensin II receptor antagonist + diuretic).
Pharmacological properties
Pharmacodynamics
Combined antihypertensive drug, which includes an angiotensin II receptor blocker and a thiazide diuretic.
Angiotensin II is the active hormone of the RAAS and is formed from angiotensin I with the participation of ACE. Angiotensin II binds to specific receptors located on cell membranes in various tissues. It has a wide range of physiological effects, including primarily both direct and indirect participation in the regulation of blood pressure. Being a powerful vasoconstrictor, angiotensin II causes a direct pressor response. In addition, it stimulates the secretion of aldosterone and promotes the retention of sodium ions.
Valsartan is a selective angiotensin II receptor antagonist. Provides selective antagonistic effect on the AT1 subtype receptors responsible for the vasopressor action of angiotensin II. An increase in serum angiotensin II concentration due to blockade of AT1 receptors by valsartan can stimulate free AT2 subtype receptors, which balances the effects associated with stimulation of AT1 receptors. It does not have agonistic activity against AT1 receptors. Does not inhibit ACE. Valsartan does not interact with and does not block other hormone receptors or ion channels involved in the regulation of the functions of the cardiovascular system.
Hydrochlorothiazide is a thiazide diuretic. The point of action of thiazide diuretics is the distal convoluted renal tubules. Under the influence of thiazide diuretics on highly sensitive receptors of the distal tubules of the cortical layer of the kidneys, the reabsorption of sodium and chlorine ions is suppressed. The suppression of the co-transport system of sodium and chlorine, apparently, occurs due to competition for the binding sites of chlorine ions, as a result of which the excretion of sodium and chlorine ions increases approximately to the same extent. As a result of the diuretic action, there is a decrease in the volume of circulating blood (BCC), resulting in increased renin activity, secretion of aldosterone, excretion of potassium by the kidneys and, consequently, a decrease in the content of potassium in the blood serum.
Pharmacokinetics
Valsartan
Absorption of valsartan occurs rapidly, but the degree of absorption varies widely. The average bioavailability is 23%. The pharmacokinetic curve of valsartan has a descending multi-exponential character (T1 / 2 a < 1 h and T1 / 2 b about 9 h). The kinetics of valsartan is linear. With repeated use of the drug, no changes in kinetic parameters are noted. When taking the drug once a day, the cumulation is insignificant. Valsartan is 94-97% bound to serum proteins, predominantly to albumin. The equilibrium volume of distribution is low (about 17 liters). Compared to hepatic blood flow (about 30 l/h), plasma clearance of valsartan is relatively slow (about 2 l/h). Excretion of valsartan with feces is 70% (of the value taken orally dose). About 30% is excreted in the urine, mostly unchanged. When prescribing valsartan with food, the area under the concentration-time curve (AUC) decreases by 48%, although, starting from about the 8th hour after taking the drug, plasma concentrations of valsartan both in the case of taking it on an empty stomach and in the case of taking it with food are the same. A decrease in the area under the concentration-time curve is not accompanied by a clinically significant decrease in the therapeutic effect.
Hydrochlorothiazide
Absorption of hydrochlorothiazide occurs quickly (Tmax - about 2 hours). The half-life of the final phase is 6-15 hours. In the therapeutic dose range, the average AUC increases in direct proportion to the increase in dose. With repeated appointments, the pharmacokinetics of hydrochlorothiazide does not change; when administered once a day, cumulation is negligible. The bioavailability of hydrochlorothiazide is 60-80%. Excretion occurs in the urine: more than 95% of the dose is unchanged and about 4% is in the form of a hydrolyzate - 2-amino-4-chloro-m-benzenedisulfonamide.
Valsartan/hydrochlorothiazide
When combined with valsartan, the systemic bioavailability of hydrochlorothiazide is reduced by approximately 30%. The simultaneous administration of hydrochlorothiazide, for its part, does not significantly affect the kinetics of valsartan. The noted interaction does not affect the effectiveness of the combined use of valsartan and hydrochlorothiazide. A distinct antihypertensive effect of this combination was revealed, which exceeds the effect of each of the components separately.
Indications for use
Arterial hypertension (in patients who are indicated for combination therapy).
Contraindications
• hypersensitivity to valsartan, hydrochlorothiazide, sulfonamides or any other component of the drug;
• pregnancy and lactation;
• severe liver dysfunction, biliary cirrhosis and cholestasis;
• severe renal failure (GFR <30 ml/min/1.73 m2), anuria;
• refractory hypokalemia, hyponatremia, hypercalcemia and symptomatic hyperuricemia;
• simultaneous use with aliskiren in patients with type 2 diabetes mellitus ;
• children and adolescents up to 18 years of age.
Dosage and administration
Taken orally, regardless of the meal. Tablets are swallowed whole, without chewing, drinking plenty of water.
Before starting therapy, it is necessary to correct water and electrolyte disturbances.
It is recommended to select the dose of the combination depending on the individual antihypertensive effect. To reduce the risk of a sharp decrease in blood pressure and the manifestation of other adverse events, it is recommended to gradually increase the dose of the combination at each stage of dose selection.
In cases where this is acceptable, in patients with inadequate blood pressure control on monotherapy with valsartan or hydrochlorothiazide, it is possible to switch to a combination with fixed doses of active components with a previous step of titrating the doses of valsartan and hydrochlorothiazide.
The initial dose is 80 mg of valsartan + 12.5 mg of hydrochlorothiazide 1 time / day. With insufficient effectiveness, a combination of 160 mg + valsartan + 12.5 mg hydrochlorothiazide can be used. In the absence of adequate blood pressure control, the dose of the combination may be gradually increased. The maximum daily dose is 320 mg of valsartan + 12.5 mg of hydrochlorothiazide or 320 mg of valsartan + 25 mg of hydrochlorothiazide.
The maximum reduction in blood pressure is usually achieved within 2-4 weeks of therapy. However, some patients may require 4 to 8 weeks of treatment. This should be taken into account when titrating the dose.
Special patient groups
Patients with impaired renal function
Dose adjustment is not required in patients with mild to moderate renal insufficiency (GFR >30 ml/min/1.73 m2). Contraindicated in patients with severe renal insufficiency (GFR <30 ml / min / 1.73 m2) and anuria, since it contains hydrochlorothiazide.
Patients with diabetes
The simultaneous use of valsartan with aliskiren is contraindicated in patients with diabetes mellitus.
Patients with impaired liver function
In patients with mild to moderate hepatic impairment without cholestasis, the dose of valsartan should not exceed 80 mg. Dose modification of hydrochlorothiazide is not required in patients with mild to moderate hepatic impairment. Contraindicated in patients with severe hepatic impairment, biliary cirrhosis and patients with cholestasis because it contains valsartan.
Special instructions and precautions
Before treatment, the content of Na + is corrected . in blood and/or bcc . Regular monitoring of plasma K + , glucose, uric acid, fat and creatinine is necessary.
If pregnancy occurs during treatment, the drug should be discontinued.
The drug is not used in patients with severe (more than 9 points on the Child-Pugh scale) impaired liver function, in the presence of biliary tract obstruction and cholestasis should be used with caution.
Influence on the ability to drive vehicles and mechanisms
When driving vehicles or working with mechanisms, the possibility of dizziness or weakness should be considered. As with the appointment of other antihypertensive drugs, care must be taken when driving and working with moving mechanisms.
Use during pregnancy and during breastfeeding
Use during pregnancy and during breastfeeding is contraindicated.
Interaction with other drugs
It enhances the neurotoxicity of salicylates, the side effects of cardiac glycosides, the cardiotoxic and neurotoxic effects of lithium preparations, the effectiveness of curare-like muscle relaxants. Reduces the excretion of quinidine, weakens the effect of oral hypoglycemic drugs, norepinephrine, epinephrine and anti-gout drugs. Increases the frequency of allergic reactions to allopurinol; reduces the excretion of cytotoxic drugs by the kidneys (cyclophosphamide, methotrexate) and leads to an increase in their myelosuppressive effect. Drugs that bind extensively to blood proteins (indirect anticoagulants, clofibrate, NSAIDs) increase the diuretic effect. The hypotensive effect is enhanced by vasodilators, beta-blockers, barbiturates, phenothiazines, tricyclic antidepressants, ethanol. With the simultaneous administration of methyldopa, hemolysis may develop; cholestyramine reduces absorption.
Side effect
Valsartan/hydrochlorothiazide combination
From the side of metabolism and nutrition: infrequently - dehydration.
From the nervous system: often - headache; infrequently - paresthesia; very rarely - dizziness; frequency unknown - fainting.
On the part of the organ of vision: infrequently - decreased visual acuity.
On the part of the organ of hearing and labyrinth disorders: rarely - tinnitus.
From the side of the vessels: infrequently - a pronounced decrease in blood pressure, peripheral edema.
From the respiratory system, chest organs and mediastinum: infrequently - cough; frequency unknown - non-cardiogenic pulmonary edema.
From the gastrointestinal tract: infrequently - nausea; very rarely - diarrhea.
From the musculoskeletal and connective tissue: infrequently - myalgia; very rarely - arthralgia.
From the side of the kidneys and urinary tract: the frequency is unknown - impaired renal function.
General disorders and disorders at the injection site: infrequently - increased fatigue.
Laboratory and instrumental data: the frequency is unknown - an increase in the concentration of uric acid in the blood serum, an increase in the concentration of bilirubin in the blood serum, an increase in serum creatinine, hypokalemia, hyponatremia, neutropenia, an increase in blood urea nitrogen.
Allergic reactions: rarely - angioedema.
General disorders and disorders at the injection site: infrequently - increased fatigue; very rarely - epistaxis, viral infection, fever.
If any of the side effects listed in the instructions get worse, or if you notice any other side effects not listed in the instructions, tell your doctor.
Overdose
Symptoms: severe arterial hypotension, which can lead to loss of consciousness, collapse and (or) shock. In addition, due to an overdose of the hydrochlorothiazide component, the following signs and symptoms may occur: nausea, drowsiness, hypovolemia and electrolyte disturbances associated with cardiac arrhythmia and muscle spasm.
Treatment: if the drug has been taken recently, induce vomiting. Hypotension is usually treated with intravenous saline.
Valsartan cannot be removed from the body by hemodialysis due to its significant binding to plasma proteins. At the same time, hemodialysis is effective for removing hydrochlorothiazide from the body.
Storage conditions
Store in a cool and dry place, at a temperature not exceeding 30º C. Keep out of the reach of children.
Best before date
3 years. Do not use after the expiry date stated on the packaging.
Holiday conditions
Released by prescription.
Release form
10 tablets in an aluminum foil blister. 3 blisters with instructions for use in a cardboard box.