Valsartan-N

General characteristics. Structure:

Active ingredients: валсартан, hydrochlorothiazide.

The cardiological drug having anti-hypertensive, diuretic effect.

Pharmacological properties:

Pharmacodynamics. Valsartan contacts the specific AT1 receptors of angiotensin II located in vessels, heart, kidneys, a brain lungs and bark of adrenal glands and competitively blocks them. Suppresses all  receptors mediated through AT1 effects of angiotensin II, including vasoconstriction and secretion of Aldosteronum. Causes the decrease in the ABP which is not followed by pulse rate change. Reduces a myocardium hypertrophy at patients with arterial hypertension. Does not influence the content of the general cholesterol, triglycerides, glucose and uric acid.

Hydrochlorothiazide — thiazide diuretic of average force. Reduces Na reabsorption + at the level of a cortical segment of a Henle's loop. Blocks a karboangidraza in proximal department of gyrose tubules, strengthens removal with K+ urine  (in distal tubules of Na + exchanges on K+), hydrocarbonates and phosphates. Practically does not influence an acid-base state (Na + is removed either together with Cl-, or with a hydrocarbonate therefore at an alkalosis removal of a hydrocarbonate amplifies, at acidosis — Cl-). Increases removal of Mg2+, detains in an organism Ca2 ions + and urates.

Pharmacokinetics. The diuretic effect develops in 1–2 h, reaches a maximum in 4 h, proceeds 10–12 h. Action decreases at reduction of a glomerular filtration rate and stops at its size less than 30 ml/min. Lowers the ABP due to reduction of OTsK, change of reactivity of a vascular wall, decrease in pressor influence of vasoconstrictive HP (Epinephrinum, Norepinephrinum). The maximum hypotensive effect is observed in the first 2–4 weeks of treatment.

At combined use with valsartany system bioavailability of a hydrochlorothiazide decreases approximately by 30%, the hydrochlorothiazide has no significant effect on kinetics of a valsartan. Noted interaction does not exert impact on efficiency of the combined use.

Indications to use:

Arterial hypertension (at inefficiency of monotherapy valsartany), decrease in risk of cardiovascular incidence and mortality at patients with arterial hypertension and a hypertrophy of a left ventricle.

Route of administration and doses:

Inside, according to 1 tab. of 1 times a day, daily (80 mg of a valsartan and 12,5 mg of a hydrochlorothiazide; for those patients to whom further decrease in the ABP is shown — 160/12,5 mg respectively).

Features of use:

Use at pregnancy and feeding by a breast. Category of action on a fruit on FDA — D.

Before treatment carry out correction of contents Na + to blood and/or OTsK. Regular control of content in K+ plasma, glucose, uric acid, fats and creatinine is necessary. In case of approach of pregnancy during treatment drug should be cancelled.

During treatment it is necessary to be careful during the driving of motor transport and occupations other potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions.

Side effects:

According to the State registry, at the patients receiving a combination a valsartan-hydrochlorothiazide the following side effects were observed: dizziness, feeling of fatigue, diarrhea, abdominal pain, nausea, cough, rhinitis, pharyngitis, viral infections, decrease in a hematocrit, hyperpotassemia, giperkreatininemiya, arthralgia, stethalgia, allergic reactions, Quincke's disease, itch, serum disease, vasculitis, skin rash, renal failure.

Are potentially possible: caused valsartany — hypostases, sleeplessness, an adynamy, decrease in a libido (less than 1%); caused by a hydrochlorothiazide — disorder of water and electrolytic balance; often — urticaria, a loss of appetite, nausea, vomiting, orthostatic hypotension, decrease in a potentiality; seldom — a photosensitization, a lock or diarrhea, unpleasant feelings in a stomach, an intra hepatic cholestasia, jaundice, arrhythmia, a headache, a depression, paresthesia, a vision disorder, thrombocytopenia, sometimes with a purpura; very seldom — the necrotizing vasculitis, a toxic epidermal necrolysis (Lyell's disease), skin reactions reminding a system lupus erythematosus, an aggravation of skin manifestations of a system lupus erythematosus, pancreatitis, a leukopenia, an agranulocytosis, a marrow depression, hemolitic anemia, a pneumonitis, a fluid lungs.

According to PDR, at the patients receiving a combination a valsartan-hydrochlorothiazide when carrying out controlled clinical tests the following adverse effects (which had frequency more than 2% and meeting more often against the background of HP — the first figure in brackets, than in group of placebo — the second figure in brackets are noted): dizziness (9%/7%), viral infections (3%/1%), fatigue (5%/1%), pharyngitis (3%/1%), cough (3%/0%), diarrhea (3%/0%).

The headache, upper respiratory tract infections, sinusitis, dorsodynia and stethalgia were observed more than at 2% of patients, but approximately with an identical frequency in control group and in group of placebo.

Dozozavisimy orthostatic effects were noted less than at 1% of patients. Dozozavisimy increase in frequency of dizzinesses was observed at reception of doses of a combination a valsartan-hydrochlorothiazide of 80/12,5 mg (6%) and 160/25 mg (16%).

Other side effects observed more than at 0,2% of patients when carrying out controlled clinical tests irrespective of a causal relationship with reception of a combination:

From a nervous system and sense bodys: the adynamy, alarm, a depression, an insomniya, paresthesia, drowsiness, вертиго, tinnit, a vision disorder.

From cardiovascular system and blood (a hemopoiesis, a hemostasis): heartbeat, syncope, tachycardia.

From respiratory system: bronchospasm, диспноэ, nasal bleeding.

From bodies of a GIT: increase in appetite, a lock, dyspepsia, a meteorism, dryness in a mouth, an abdominal pain, nausea, vomiting.

From a musculoskeletal system: arthralgia, spasms of muscles, muscular weakness, hand pain, scelalgia.

From urinogenital system: dysuria, increase of an urination, infection of urinary tract.

Allergic reactions: rash, anaphylaxis.

Others: peripheral hypostases, rushes of blood to the person, an erythema, the increased sweating, dehydration, gout, decrease in a libido, impotence.

Interaction with other medicines:

Strengthens a neurotoxicity of salicylates, side effects of cardiac glycosides, cardiotoxic and neurotoxic effect of drugs of lithium, efficiency of kurarepodobny muscle relaxants.

Reduces quinidine removal, weakens action of peroral hypoglycemic HP, Norepinephrinum, Epinephrinum and antigouty HP.

Increases the frequency of allergic reactions to Allopyrinolum; reduces removal by kidneys of cytotoxic HP (cyclophosphamide, a methotrexate) and leads to strengthening of their myelosuppressive action.

The HP which are intensively contacting blood proteins (indirect anticoagulants, Clofibratum, NPVS), strengthen diuretic effect.

The hypotensive effect is strengthened by vazodilatator, beta adrenoblockers, barbiturates, fenotiazina, tricyclic antidepressants, ethanol.

At a concomitant use Methyldopums hemolysis development is possible; Colestyraminum reduces absorption.

Contraindications:

Hypersensitivity; biliary cirrhosis, impassability of bilious ways; anury, chronic renal failure (creatinine Cl).

Overdose:

Symptoms: decrease in the ABP.

Treatment: gastric lavage, introduction to 0,9% of solution of sodium of chloride. The hemodialysis is effective concerning a hydrochlorothiazide.

Storage conditions:

To store at a temperature of 15-25 °C, in dry, protected from light and the place, unavailable to children. Period of validity 3 years. Not to use after the expiry date specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Tablets of 80 mg + 12,5 mg, 160 mg + 12,5 mg, 160 mg + 25 mg. 10 tablets in each blister, on one, two or three blisters together with the application instruction in cardboard packaging.