Description of the drug VALSARTAN PLUS
Lithium preparations -
with simultaneous use of lithium preparations with ACE inhibitors and angiotensin II receptor blockers or thiazide diuretics, a reversible increase in the concentration of lithium in the blood plasma and an associated increase in toxic manifestations were noted. The risk of toxicities associated with the use of lithium may be further increased during concomitant use of this combination since the renal clearance of lithium is reduced by thiazide diuretics. Concomitant use of the combination of valsartan + hydrochlorothiazide is contraindicated.
Antihypertensive drugs -
it is possible to enhance the antihypertensive effect when used together with other drugs that lower blood pressure (ACE inhibitors, beta-blockers, slow calcium channel blockers, guanethidine, methyldopa, vasodilators, direct renin inhibitors, angiotensin II receptor blockers).
Pressor amines -
the effect of pressor amines (norepinephrine, epinephrine) may be weakened, without requiring cessation of joint use.
NSAIDs, including selective COX-2 inhibitors -
may weaken the antihypertensive effect of both angiotensin II receptor antagonists and hydrochlorothiazide when taken simultaneously. The simultaneous use of a combination of valsartan + hydrochlorothiazide and NSAIDs can lead to impaired renal function and an increase in potassium levels in the blood serum. If it is necessary to use this combination and NSAIDs together, renal function should be assessed and fluid and electrolyte disturbances corrected before starting treatment.
Potassium-containing substitutes for table salt; other medicines that increase serum potassium levels (for example, heparin)
requires compliance with precautions (including frequent determination of potassium levels in the blood).
Medicines that can cause hypokalemia -
The risk of hypokalemia caused by diuretics may be increased with simultaneous use of corticosteroids, laxatives, ACTH, amphotericin B, carbenoxolone, penicillin, acetylsalicylic acid or its derivatives and antiarrhythmic drugs.
Double blockade of the RAAS -
When treated with drugs that affect the RAAS, especially when they are combined, a marked decrease in blood pressure, syncope, stroke, hyperkalemia and impaired renal function (including acute renal failure) have been reported in sensitive patients. Concomitant use of the combination of valsartan + hydrochlorothiazide is contraindicated.
Caution is required when combining angiotensin II receptor blockers, including valsartan, with other drugs that block the RAAS, such as ACE inhibitors or aliskiren. Concomitant use of angiotensin II receptor blockers, including valsartan, or ACE inhibitors with aliskiren in patients with type 2 diabetes mellitus or impaired renal function (GFR < 60 ml/min/1.73 m2) is contraindicated.
Transport proteins -
According to the results of an in vitro study on hepatocyte cultures, valsartan is a substrate for the transporter proteins OATP1B1 and MRP2. Co-administration of valsartan with inhibitors of the OATP1B1 transport protein (rifampicin, cyclosporine) and with an inhibitor of the MRP2 transport protein (ritonavir) may increase the systemic exposure of valsartan (Cmax and AUC). Simultaneous use is contraindicated.
Curare-like muscle relaxants -
thiazide diuretics, including hydrochlorothiazide, potentiate the effect of non-depolarizing muscle relaxants. Simultaneous use is contraindicated.
Medicines that affect sodium levels in the blood -
The hyponatremic effect caused by diuretics may be enhanced when used simultaneously with antidepressants, antipsychotic anticonvulsants (carbamazepine). Caution should be exercised during long-term co-administration of hydrochlorothiazide with the above drugs.
Medicines that can provoke polymorphic ventricular
tachycardia of the "pirouette" type -
class IA antiarrhythmic drugs (quinidine, hydroquinidine, disopyramide); class III antiarrhythmic drugs (amiodarone, dofetilide, ibutilide), sotalol; some antipsychotics (thioridazine, chlorpromazine, levomepromazine, trifluoperazine, cyamemazine, sulpiride, sultopride, amisulpride, tiapride, pioside, haloperidol, droperidol); other drugs (bepridil, cisapride, difemanil, erythromycin IV, halofantrine, ketanserin, mizolastine, pentamidine, sparfloxacin, terfenadine, vincamine IV). Due to the risk of hypokalemia, hydrochlorothiazide should be used with caution concomitantly with drugs that can cause torsade de pointes (TdP).
Hypoglycemic agents -
Thiazide diuretics may alter glucose tolerance, which may require dose adjustments of insulin and oral hypoglycemic agents. Metformin should be used with caution due to the risk of developing lactic acidosis caused by possible renal impairment associated with hydrochlorothiazide.
Beta blockers and diazoxide -
simultaneous use of thiazide diuretics, incl. hydrochlorothiazide, with beta-blockers may increase the risk of developing hyperglycemia. Thiazide diuretics, incl. hydrochlorothiazide may enhance the hyperglycemic effect of diazoxide.
Anti-gout drugs (probenecid, sulfinpyrazone and allopurinol) -
Dosage adjustment of uricosuric agents (probenecid or sulfinpyrazone) may be required as hydrochlorothiazide may increase serum uric acid concentrations. Concomitant use of thiazide diuretics, including hydrochlorothiazide, may increase the incidence of hypersensitivity reactions to allopurinol.
Cardiac glycosides -
Hypokalemia and hypomagnesemia (undesirable effects of thiazide diuretics) may contribute to the development of cardiac arrhythmias in patients receiving cardiac glycosides.
N- and m-anticholinergics
(including atropine, biperiden) can increase the bioavailability of hydrochlorothiazide, which is associated with a decrease in gastrointestinal motility and the rate of gastric emptying. Accordingly, gastrointestinal motility stimulants (cisapride) may reduce the bioavailability of hydrochlorothiazide.
Cholestyramine and colestipol
may interfere with the absorption of concomitantly used drugs. The interval between doses should be 4-6 hours.
Vitamin D and calcium salts -
simultaneous use of hydrochlorothiazide with vitamin D or calcium supplements can lead to hypercalcemia due to increased calcium reabsorption.
Cyclosporine -
with simultaneous use of hydrochlorothiazide and cyclosporine, the risk of developing hyperuricemia and exacerbation of gout increases.
Methyldopa -
Cases of hemolytic anemia have been reported with the simultaneous administration of hydrochlorothiazide and methyldopa.
Co-administration of thiazide diuretics, including hydrochlorothiazide, may lead to an increased risk of side effects from amantadine
;
reducing the excretion by the kidneys of drugs that have a cytotoxic effect (for example, cyclophosphamide, methotrexate
), to potentiate their myelosuppressive effect.
Ethanol, barbiturates and narcotic drugs -
combined use with hydrochlorothiazide may potentiate the development of orthostatic hypotension.
When taking iodine contrast agents
in high doses against the background of a reduced volume of blood volume due to the use of diuretics, there is an increased risk of developing acute renal failure.
Valsartan, 30 pcs., 80 mg, film-coated tablets
Active specific angiotensin II receptor antagonist, intended for oral administration. Selectively blocks receptors of the AT1 subtype, which are responsible for the effects of angiotensin II. The consequence of AT1 receptor blockade is an increase in the plasma concentration of angiotensin II, which can stimulate unblocked AT2 receptors. Valsartan does not have any pronounced antagonistic activity against AT1 receptors. The affinity of valsartan for receptors of the AT1 subtype is approximately 20,000 times higher than for receptors of the AT2 subtype.
Valsartan does not interact with or block other hormone receptors or ion channels that are important for regulating the function of the cardiovascular system.
The likelihood of coughing when using valsartan is very low, which is due to the lack of influence on the angiotensin converting enzyme (ACE), which is responsible for the degradation of bradykinin.
A comparison of valsartan with an ACE inhibitor showed that the incidence of dry cough was significantly (p < 0.05) lower in patients receiving valsartan than in patients receiving an ACE inhibitor (2.6% versus 7.9%, respectively). In the group of patients who had previously developed a dry cough during treatment with an ACE inhibitor, during treatment with Valsartan this complication was noted in 19.5% of cases, and during treatment with a thiazide diuretic - in 19% of cases, while in the group of patients receiving treatment ACE inhibitor, cough was observed in 68.5% of cases (p < 0.05).
Use for arterial hypertension in patients over 18 years of age
When treating patients with arterial hypertension with valsartan, a decrease in blood pressure (BP) is observed, not accompanied by a change in heart rate (HR).
After taking a single dose of the drug, in most patients, the onset of the antihypertensive effect is noted within 2 hours, and the maximum reduction in blood pressure is achieved within 4-6 hours. After taking the drug, the antihypertensive effect lasts more than 24 hours.
With repeated prescriptions of the drug, the maximum reduction in blood pressure, regardless of the dose taken, is usually achieved within 2-4 weeks and is maintained at the achieved level during long-term therapy.
When the drug is combined with hydrochlorothiazide, a significant additional reduction in blood pressure is achieved. Abrupt cessation of valsartan is not accompanied by a sharp increase in blood pressure or other undesirable consequences.
Use after acute myocardial infarction in patients over 18 years of age
When using the drug for 2 years in patients who began taking it from 12 hours to 10 days after acute myocardial infarction (complicated by left ventricular failure and/or left ventricular systolic dysfunction), the rates of overall mortality and cardiovascular mortality are reduced and the time until the first hospitalization for exacerbation of CHF, repeated myocardial infarction, sudden cardiac arrest and stroke (without death) increases. The safety profile of valsartan in patients with acute infarction is similar to that in other conditions.
CHF in patients over 18 years of age
The mechanism of action of valsartan in chronic heart failure (CHF) is based on its ability to eliminate the negative consequences of hyperactivation of the renin-angiotensin-aldosterone system (RAAS) and its main effector, angiotensin II, namely vasoconstriction; fluid retention in the body; cell proliferation leading to remodeling of target organs (heart, kidneys, blood vessels); stimulation of excess synthesis of hormones that act synergistically with the RAAS (catecholamines, aldosterone, vasopressin, endothelin, etc.).
With the use of valsartan for CHF, preload decreases, pulmonary capillary wedge pressure (PCWP) and diastolic pressure in the pulmonary artery decrease, and cardiac output increases. Along with hemodynamic effects, valsartan, due to indirect blockade of aldosterone synthesis, reduces sodium and water retention in the body.
It was found that the drug did not have a significant effect on the concentration of total cholesterol, uric acid, and also, when studied on an empty stomach, on the concentration of triglycerides and glucose in the blood plasma.
When using valsartan (in an average daily dose of 254 mg) for 2 years in patients with CHF II (62%), III (36%) and IV (2%) functional class according to the NYHA classification with left ventricular ejection fraction (LV) less than 40% and LV internal diastolic diameter more than 2.9 cm/m2, receiving standard therapy, including ACE inhibitors (93%), diuretics (86%), digoxin (67%) and beta-blockers (36%) there is a significant decrease (by 27.5%) risk of hospitalization due to exacerbation of CHF.
In patients not receiving ACE inhibitors, there was a significant reduction in overall mortality (by 33%), cardiovascular mortality and CHF-related morbidity (time to first cardiovascular event), assessed by the following indicators: death, sudden death with resuscitation, hospitalization for exacerbation of CHF, intravenous administration of inotropic and vasodilator drugs for 4 or more hours without hospitalization (44%). In the group of patients receiving ACE inhibitors (without beta-blockers), during treatment with valsartan there is no reduction in overall mortality, but cardiovascular mortality and morbidity associated with CHF decrease by 18.3%.
In general, the use of valsartan leads to a decrease in the number of hospitalizations for CHF, a slowdown in the progression of CHF, an improvement in the functional class of CHF according to the NYHA classification, an increase in LV ejection fraction, as well as a decrease in the severity of signs and symptoms of heart failure and an improvement in quality of life compared to placebo.
Use in patients over 18 years of age with arterial hypertension and impaired glucose tolerance
When using valsartan and changing lifestyle, there was a statistical reduction in the risk of developing diabetes mellitus in this category of patients. Valsartan had no effect on the incidence of deaths due to cardiovascular events, myocardial infarction and non-fatal ischemic attacks, hospitalizations due to heart failure or unstable angina, arterial revascularization, in patients with impaired glucose tolerance and arterial hypertension, differing in age, gender and race.
In patients receiving valsartan, the risk of developing microalbuminuria was significantly lower than in patients not receiving this therapy. The recommended initial dose of Valsartan in patients with arterial hypertension and impaired glucose tolerance is 80 mg once a day. If necessary, the dose can be increased to 160 mg.
Use in children and adolescents from 6 to 18 years of age with arterial hypertension
In children and adolescents from 6 to 18 years of age, valsartan provides a dose-dependent, smooth reduction in blood pressure. When using valsartan, the maximum reduction in blood pressure, regardless of the dose taken, is usually achieved within 2 weeks, and is maintained at this level during long-term therapy.
