Coded pills coated 160mg + 12.5mg N28
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Active ingredients
Valsartan + Hydrochlorothiazide
Release form
Pills
Composition
Active ingredient: Valsartan + Hydrochlorothiazide (Valsartan + Hydrochlorothiazide) Active ingredient concentration (mg): valsartan 160 mg, hydrochlorothiazide 12. 5 mg
Pharmacological effect
Antihypertensive drug, which consists of an angiotensin II receptor antagonist and thiazide diuretic. The active hormone of the renin-angiotensin-aldosterone system (RAAS) is angiotensin II, which 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 pressure response. In addition, it stimulates the secretion of aldosterone and contributes to sodium retention. Valsartan is an active and specific angiotensin II receptor antagonist, intended for oral administration. It acts selectively on the AT1 receptor subtype, which is responsible for the known effects of angiotensin II. Increased serum levels of angiotensin II due to blockade of AT1 receptors with valsartan can stimulate free AT2 receptors, which balances the effect of AT1 receptors. Valsartan does not show any pronounced agonistic activity against AT1 receptors. The affinity of valsartan to AT1 receptors is approximately 20,000 times higher than that to AT2 receptors. Valsartan does not inhibit ACE, also known as kininase II, which converts angiotensin I to angiotensin II and destroys bradykinin. No side effects due to bradykinin are observed. In clinical studies that compared valsartan with an ACE inhibitor, the incidence of dry cough was significantly (p <0.05) lower in patients who received valsartan than in patients who received an ACE inhibitor (2.6% versus 7.9%, respectively). In a clinical study that included patients who had previously developed a dry cough when treating with an ACE inhibitor, this complication was observed in 19.5% of cases in valsartan, and in 19% of cases in treatment with thiazide diuretic; while in the group of patients treated with an ACE inhibitor, cough was observed in 68.5% of cases (p <0.05).Valsartan does not interact and does not block the receptors of other hormones or ion channels that are important for regulating the functions of the cardiovascular system. When treating patients with arterial hypertension with valsartan, there is a decrease in blood pressure that is not accompanied by a change in heart rate. After ingestion of the drug in a single dose, In most patients, the onset of the antihypertensive effect is observed within 2 hours, and the maximum decrease in blood pressure is reached within 4-6 hours. After taking the drug, the antihypertensive effect remains tsya over 24 hours. The maximum reduction in blood pressure, regardless of the dose on repeated administration of the drug, typically achieved within 2-4 weeks and is maintained at that level during prolonged therapy. When combined with hydrochlorothiazide, a significant additional decrease in blood pressure is achieved. The application of the action of thiazide diuretics is the cortical section of the distal convoluted renal tubules, where the receptors are highly sensitive to the action of diuretics and where the transport of sodium and chlorine ions is suppressed. The mechanism of action of thiazides is associated with the suppression of the pump Na + Cl-, which, apparently, occurs due to competition for the place of transport of Cl-. As a result, the excretion of sodium ions and chlorine increases by about the same degree. As a result of the diuretic effect, a decrease in circulating plasma volume is observed, as a result of which renin activity increases, aldosterone secretion, potassium excretion with urine and, consequently, a decrease in serum potassium concentration. The relationship between renin and aldosterone is mediated by angiotensin II, so the appointment of an angiotensin II receptor antagonist will reduce the potassium loss associated with the use of thiazide diuretic.
Pharmacokinetics
Valsartan Absorption After taking the drug inside the absorption of valsartan occurs quickly, however, the degree of absorption varies widely. The average bioavailability is 23%. The pharmacokinetic curve of valsartan has a descending multiexponential pattern (T1 / 2 in α-phase <1 h and T1 / 2 in β-phase about 9 h). In the range of doses studied, the kinetics of valsartan is linear. With repeated use of the drug changes in kinetic parameters were noted.When taking the drug 1 time / day, the accumulation is insignificant. The concentration of the drug in the blood plasma in women and men were the same. The distribution of Valsartan is largely (94-97%) associated with serum proteins, mainly albumin. Vss low (about 17 liters). Compared with hepatic blood flow (about 30 l / h), plasma clearance of valsartan is relatively slow (about 2 l / h). Excretion Excretion Valsartan is mainly excreted unchanged, excretion with feces is 70% of the absorbed dose), with urine output around 30%. When prescribing valsartan with food, the AUC is reduced by 48%, although starting from about the 8th hour after taking the drug, the concentration of valsartan in the plasma is the same as in the case of fasting and fasting. However, a decrease in AUC is not accompanied by a clinically significant decrease in therapeutic effect. Hydrochlorothiazide Absorption After oral administration, absorption of hydrochlorothiazide occurs quickly, the time to reach Cmax in plasma is about 2 hours. T1 / 2 in the final phase is 6-15 hours. When ingested, the bioavailability of hydrochlorothiazide is 60-80%. With simultaneous administration of hydrochlorothiazide with food, both increase and decrease in its systemic bioavailability were noted (compared to the corresponding indicator when taken on an empty stomach). The range of these changes is small and clinically insignificant. Distribution In the therapeutic dose range, the average AUC increases in direct proportion to the dose increase. With repeated prescriptions, the pharmacokinetics of hydrochlorothiazide do not change; when administered once a day, accumulation is insignificant. Excretion is excreted in the urine: more than 95% of the dose is unchanged and about 4% in the form of a hydrolyzate - 2-amino-4-chloro-m-benzedisulfonamide. Valsartan / hydrochlorothiazide The bioavailability of hydrochlorothiazide is reduced by approximately 30%. The simultaneous appointment of hydrochlorothiazide, for its part, has no significant effect on the kinetics of valsartan. The observed interaction does not affect the effectiveness of the combined use of valsartan and hydrochlorothiazide.In controlled clinical trials, a pronounced antihypertensive effect of this combination was identified, which exceeded the effect of each of the components separately, as well as the placebo effect. is clinically significant. A few data suggest that in elderly people (both healthy and suffering from arterial hypertension) systemic lirens of hydrochlorothiazide is lower than in healthy young volunteers. AUC of valsartan in patients with mild (n = 6) and moderately pronounced (n = 5) impaired liver function was 2 times more than in healthy volunteers.
Indications
Arterial hypertension.
Contraindications
Severe abnormal liver function, biliary cirrhosis and cholestasis; anuria, pronounced renal dysfunction (CC <30 ml / min); hypokalemia, hyponatremia, hypercalcemia, hyperuricemia with clinical manifestations, refractory to adequate therapy; pregnancy; hypersensitivity to the components of Co-Diovan. With caution, the drug should be used in patients with unilateral or bilateral stenosis of the renal artery or stenosis of the artery of a single kidney, since safety of Co-Diovan use in these cases has not been established.
Precautionary measures
Do not exceed the recommended dose. With caution, you should use the drug in patients with unilateral or bilateral stenosis of the renal artery or stenosis of the artery of a single kidney, since safety of Co-Diovan use in these cases has not been established.
Use during pregnancy and lactation
Given the mechanism of action of angiotensin II antagonists, the risk of negative effects on the fetus cannot be ruled out when using drugs of this group. It is known that the effect of ACE inhibitors on the uterus in the case of their appointment to pregnant women in the second and third trimesters, leads to damage or death of the developing fetus. The introduction of thiazide diuretic into the uterus led to the development of thrombocytopenia in the fetus or in the neonatal period, as well as the development of other undesirable effects, which are noted later in adults.Therefore, Co-Diovan, like any other drug that has a direct effect on the RAAS, should not be used during pregnancy and lactation. If pregnancy is detected during the period of treatment with Co-Diovan, the drug should be canceled as soon as possible. It is not known whether valsartan penetrates into human breast milk. Hydrochlorothiazide penetrates the placental barrier and is excreted in breast milk. Therefore, it is not recommended to use Co-Diovan in nursing mothers. In experimental studies, it was shown that valsartan is excreted in breast milk in rats.
Dosage and administration
Co-Diovan appoint 1 tab. 1 time / day Depending on the clinical situation, the recommended daily dose is 1 tablet 80 / 12.5 mg or 1 tablet 160 / 12.5 mg. If necessary, 1 tablet of 160/25 mg is prescribed. Patients with mild or moderate renal impairment (CC> 30 ml / min) do not require changes in the dose. Patients with mild or moderate hepatic insufficiency of nonbiliary genesis without concomitant cholestasis are also not required to change the dose of the drug.
Side effects
Adverse events Co-diovan n = 2066 (%) Placebo n = 93 (%) Headache 5.1 17.2 Headache (except for vertigo) 3.9 6.5 Nasopharyngitis 2.7 1.1 Feeling of fatigue 2.0 1.1 Back pain 1.5 3.2 Cough 1.4 0.0 Upper respiratory tract infections 1.4 2.2 Sinusitis 1.3 3.2 Diarrhea 1.2 0.0 Pain in the chest 1.1 1.1 Pain in the extremities 1.1 0.0 The nausea 1.0 1.1 With a frequency of less than 1%, adverse events such as abdominal pain, visual disturbances, anxiety, arthralgia, arthritis, bronchitis, dyspepsia, shortness of breath impotence, insomnia, cramps of the muscles of the lower extremities, frequent urination, palpitations, rashes, sprains, urinary tract infections, viral infections, edema, asthenia, vertigo. The causal relationship of these phenomena with the use of Co-Diovan has not been established. Postmarketing studies indicate very rare cases of angioedema, rash, itching and other hypersensitivity / allergic reactions, including serum sickness and vasculitis. In some cases, renal dysfunction was observed. From laboratory indicators: in 2.2% of patients who received Co-Diovan, serum potassium concentrations decreased by more than 20% (a decrease in this indicator in the group of patients who received placebo was 3.3%).In controlled clinical trials, an increase in serum creatinine concentration was observed in 1.4% of patients who received Co-Diovan (compared to 1.1% for the group of patients who received placebo). In those clinical studies where valsartan was used as monotherapy, others were also noted adverse events (the causal relationship of these phenomena with the use of valsartan has not been established): with a frequency of more than 1%, arthralgia; with a frequency of less than 1% - edema, asthenia, insomnia, rash, decreased libido, vertigo. Hydrochlorothiazide has been widely used for many years, and more often in doses exceeding that included in Co-Diovan. The following adverse reactions have been reported during monotherapy with thiazide diuretics, including hydrochlorothiazide. Often - urticaria and other types of rash, loss of appetite, nausea and vomiting, postural hypotension (the severity of which increases with alcohol intake, the use of drugs for anesthesia or sedatives), impotence. Rarely - photosensitization, abdominal pain, constipation, diarrhea, discomfort in the gastrointestinal tract, intrahepatic cholestasis, jaundice, arrhythmias, headache, dizziness, sleep disturbances, depression, paresthesia, visual disturbances, thrombocytopenia, sometimes with purpura. Very rarely - necrotizing vasculitides, toxic epidermal necrolysis, lupus reaction exacerbation of cutaneous manifestations of systemic lupus erythematosus, pancreatitis, leukopenia, agranulocytosis, inhibition of bone marrow hematopoiesis, hemolytic anemia, hypersensitivity reactions, disorders of the respiratory system (including pneumonitis and pulmonary edema). Water-electrolyte and metabolic disorders are possible.
Overdose
Symptoms: although at present there is no information about an overdose of Co-Diovan, the main manifestation that could be expected is severe arterial hypotension. Treatment: if the drug has been taken recently, it should induce vomiting. In case of arterial hypotension, the usual method of treatment is intravenous injection of saline. Valsartan cannot be removed from the body using hemodialysis due to its significant binding to plasma proteins. At the same time, hemodialysis is effective in removing hydrochlorothiazide from the body.
Interaction with other drugs
It is possible to enhance the antihypertensive effect when used jointly with other antihypertensive drugs. When using potassium salts, potassium-saving diuretics, potassium-containing salt substitutes, or any other drugs that may cause an increase in the concentration of potassium in the blood (eg, heparin), caution and frequent determination are necessary. the concentration of potassium in the blood. In the simultaneous appointment of lithium preparations with ACE inhibitors or thiazide diuretics, reversible increasing the lithium concentration in the serum and increased therefore toxic effects. The experience of joint use of valsartan and lithium preparations is not yet available, therefore, in this case, it is recommended to control the concentration of lithium in the serum. No clinically significant interaction was noted during monotherapy with valsartan while using the following drugs: cimetidine, warfarin, furosemide, digoxin, atenolol, indomethacin hydrochlorothiazide, amlodipine, glibenclamide. Since Co-Diovan contains thiazide diuretic, the following drug interaction is potentially possible. Thiaz Ids potentiate the action of curare-like muscle relaxants. It is possible to reduce the diuretic and antihypertensive effects of hydrochlorothiazide, which is part of Co-Diovan, while being used with NSAIDs (for example, with salicylic acid derivatives, indomethacin). Concomitant hypovolemia can lead to the development of acute renal failure. The risk of developing hypokalemia increases with the appointment of salive drugs, corticosteroids, ACTH, amphotericin, carbenoxolone, penicillin G, and salicylic acid derivatives. in turn, they increase the risk of developing arrhythmia while using cardiac glycosides at the same time. You may need a dose adjustment of insulin or oral gi poglikemicheskogo drug. Simultaneous appointment of thiazide diuretics can increase the frequency of hypersensitivity reactions to allopurinol; increase the risk of side effects of amantadine; enhance the hyperglycemic effect of diazoxide; reduce the kidney excretion of cytotoxic drugs (eg, cyclophosphamide,methotrexate) and lead to the potentiation of their myelosuppressive action. An increase in the bioavailability of a thiazide diuretic is observed with the simultaneous administration of anticholinergics (for example, atropine, biperidine), which seems to be associated with a decrease in the gastrointestinal motility and slowing of gastric emptying. with simultaneous appointment of thiazide diuretic and methyldopa. Colestiramine reduces the absorption of thiazide diuretics. When combined use of thiazide diuretics with vi amine of D or calcium salts may potentiate increasing calcium concentration in syvorotke.Odnovremennoe cyclosporine may increase the risk for hyperuricemia and symptoms resembling exacerbation of gout.
special instructions
Changes in serum electrolyte balance Co-Diovan should be used with caution simultaneously with potassium salts, potassium-sparing diuretics, potassium-containing salt substitutes, as well as drugs that can cause an increase in potassium concentration in the blood (for example, heparin). There are reports of the development of hypokalemia during treatment thiazide diuretics. Frequent monitoring of the concentration of potassium in the blood is recommended. When using thiazide diuretics, hyponatremia and hypochloremic alkalosis may develop. Thiazides cause an increase in urinary magnesium excretion, which can lead to hypomagnesemia. Deficiency in sodium and / or OTsKU patients with severe deficiency in sodium and / or BCC, for example, receiving high doses of diuretics, in rare cases, at the beginning of treatment with Co-Diovan can to develop arterial hypotension with clinical manifestations. Before starting treatment with Co-Diovan, correction of the sodium content in the body and / or BCC should be carried out. If the patient develops hypotension, he should be laid down and, if necessary, IV saline should be given in / in the infusion. After stabilization of blood pressure, treatment with Co-diovan can be continued. Impaired renal function Patients with impaired renal function with QC more than 30 ml / min do not require dose adjustment. There are currently no data on the use of Co-Diovan in patients with severely impaired renal function (QC less than 30 ml / min) and in patientsthose on hemodialysis. Liver function impairment It is not necessary to change the dose of Co-Diovan in patients with mild or moderately impaired liver function in the absence of cholestasis, although in this category of patients the drug should be used with caution. Liver diseases do not have a significant effect on the pharmacokinetics of hydrochlorothiazide, therefore, a dose reduction is not required. Currently, there are no data on the use of valsartan in patients with severely impaired liver function. triglycerides and uric acid in serum. Use in pediatricsSafety and efficacy of using Co-Diovan in children to date not established. Impact on the ability to drive vehicles and control mechanisms. When appointing Co-Diovan, it is recommended to use caution when driving a car and controlling mechanisms.