Cardosal Plus tabs 12.5mg + 20mg #28

Cardosal Plus instruction

You can buy Cardosal Plus here

Composition

active ingredient: 1 tablet, coated, contains olmesartan medoxomil 20 mg and hydrochlorothiazide 12.5 mg olmesartan medoxomil 20 mg and hydrochlorothiazide 25 mg
Excipients: microcrystalline cellulose, low substituted hydroxypropyl cellulose, lactose, hydroxypropyl cellulose, magnesium stearate or shell Opadry O2A22352 O2A24576 (hypromellose, talc, titanium dioxide (E 171), yellow iron oxide (E172), red iron oxide (E172).

Dosage Form

Tablets, film coated.
Basic physico-chemical properties.
Cardosal plus 20 / 12,5: round tablets, film-coated, reddish-yellow in color, embossed with "C 22" on one side.
Cardosal plus 20/25: round tablets, film coated, pale pink color, with a stamping "C 24" on the one hand.

Pharmacological group

Angiotensin II antagonists and diuretics. ATC code C09D A08.

Pharmacodynamics

Cardosal Plus is a combination drug of the angiotensin II receptor blocker, olmesartan medoxomil and thiazide diuretic, hydrochlorothiazide. The combination of these components has an additive hypotensive effect, as a result of which the blood pressure is reduced more than when using each of the components separately.
Taking Cardosal plus once a day provides an effective and mild decrease in blood pressure for 24 hours until the next dose.

Olmesartan medoxomil

Olmesartan medoxomil is a selective angiotensin II receptor blocker (type AT 1), intended for oral administration. Angiotensin II - the main vasoactive hormone renin-angiotensin-, which plays an important role in the pathophysiology of arterial hypertension. It causes vasoconstriction, induces the synthesis and secretion of aldosterone, stimulates cardiac activity and sodium reabsorption by the kidneys. Olmesartan suppresses the effects of angiotensin II, aimed at vasoconstriction and aldosterone secretion, blocking the AT 1 receptor in tissues, including vascular smooth muscle and in the adrenal glands. The action of olmesartan does not depend on the source or route of synthesis of angiotensin II. Selective binding of olmesartan to the angiotensin II receptor AT 1 leads to an increase in the level of renin and the concentration of angiotensin I and angiotensin II in the blood plasma, as well as to a slight decrease in the concentration of aldosterone in the blood plasma.
In patients with arterial hypertension of olmesartan, medoxomil has a steady decrease in blood pressure, the degree of which depends on the dose. There were no signs of arterial hypotension after the first use (the effect of the “first dose”), tachyphylaxis on the background of prolonged use and ricochet hypertension after abrupt discontinuation of Cardosal plus.
Reception once a day of olmesartan medoxomil provides an effective and mild decrease in blood pressure within 24 hours before the next reception. When using Cardosal plus 1 time per day, its antihypertensive effect was approximately the same as as a result of its use twice a day in the same dose.
In the case of continuous treatment, the maximum reduction in blood pressure is reached 8 weeks after the start of treatment; however, a significant antihypertensive effect is observed after 2 weeks of treatment.
The effect of olmesartan medoxomil on mortality and complication rates has not been established.
A randomized study of the use of olmesartan and the prevention of diabetic microalbuminuria (ROADMAP), conducted in 4447 patients with type 2 diabetes with a normal level of albuminuria and at least one additional risk factor for cardiovascular diseases, was carried out to determine whether olmesartan therapy can delay the time of occurrence of microalbuminuria .
During a mean follow-up period of 3.2 years, patients received olmesartan or placebo in addition to other antihypertensive drugs, with the exception of ACE or ARB.
At the primary endpoint, the study showed a significant reduction in the risk of the time of microalbuminuria in favor of olmesartan. After the adjustment, in the differences in the AO indicators, this risk reduction is no longer statistically significant. In 8.2% (in 178 out of 2160) patients in the olmesartan group and in 9.8% (in 210 out of 2139) microalbuminuria developed in the placebo group.
At the secondary endpoint, cardiovascular events were observed in 96 patients (4.3%) who received olmesartan, and in 94 patients (4.2%) who received placebo. Cardiovascular mortality rates were higher in the olmesartan group compared with the placebo group (15 patients (0.7%) and 3 patients (0.1%)), despite a similar incidence of stroke without death (14 patients ( 0.6%) and 8 patients (0.4%)), non-fatal myocardial infarction (17 patients (0.8%) and 26 patients (1.2%)), and non-cardiovascular mortality (11 patients (0.5%) and 12 patients (0.5%)). The overall mortality in the olmesartan group was numerically higher (26 patients (1.2%) and 15 patients (0.7%)), mainly due to the higher mortality from cardiovascular causes.
In the ORIENT trial (The Olmesartan Reducing Incidence of End-stage Renal Disease in Diabetic Nephropathy Trial), the effect of olmesartan on renal and cardiovascular disease outcomes in 577 randomized patients in Japan and in China with type 2 diabetes and pronounced nephropathy was studied. During a mean follow-up period of 3.1 years, patients received olmesartan or placebo in addition to other antihypertensive agents, including ACE inhibitors.
Primary pooled endpoint (time of first appearance of serum creatinine doubling, end-stage renal disease, death for all causes) was achieved in 116 patients in the olmesartan group (41.1%) and in 129 patients receiving placebo (45, 4%) (HR 0.97 (95% CI from 0.75 to 1.24) p = 0.791).
A secondary combined cardiovascular endpoint was achieved in 40 patients who received olmesartan (14.2%) and 53 patients who received placebo (18.7%). This combined cardiovascular endpoint included mortality from cardiovascular disease in 10 (3.5%) patients receiving olmesartan and in 3 (1.1%) patients receiving placebo; the overall mortality rate is 19 (6.7%) and 20 (7.0%), stroke without death - 8 (2.8%) and 11 (3.9%) and myocardial infarction without death 3 (1, 1%) and 7 (2.5%), respectively.
The combined use of ACE inhibitors and angiotensin II receptor blockers have been investigated in two large-scale randomized controlled trials (ONTARGET (ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial) and VA NEPHRON-D (The Veterans Affairs Nephropathy in Diabetes)).
ONTARGET was a study in patients with a history of cardiovascular or cerebrovascular disease, or type 2 diabetes, accompanied by signs of damage to the target organ. VA NEPHRON-D was a study conducted in patients with type 2 diabetes and diabetic nephropathy. These studies did not reveal a significant beneficial effect on the outcome of renal and / or cardiovascular diseases and on mortality from them, while compared with monotherapy there was an increased risk of developing hyperkalemia, acute kidney damage and / or hypotension. Given the similarity of pharmacodynamic properties, these results are also applicable to other ACE inhibitors and angiotensin II receptor blockers.
The combined use of ACE inhibitors and angiotensin II receptor blockers is contraindicated in patients with diabetic nephropathy.
ALTITUDE (Aliskiren Trial in Type 2 Diabetes Using Cardiovascular and Renal Disease Endpoints) was a study conducted to identify the positive effect of adding aliskiren to standard therapy with ACE inhibitors or angiotensin II receptor blockers in patients with type 2 diabetes and chronic kidney disease, cardio vascular diseases, or both diseases.
This study was previously interrupted due to an increased risk of adverse effects. Cardiovascular mortality and stroke were frequent in the group treated with aliskiren than in the placebo group, and reports of adverse events and serious adverse events (hyperkalemia, hypotension, and renal dysfunction) were frequent in the group that took aliskiren, than in the placebo group.

Hydrochlorothiazide

Hydrochlorothiazide is a thiazide diuretic. The mechanism of the antihypertensive effect of thiazide diuretics has not been fully studied. Thiazides affect electrolyte reabsorption in the renal tubules, thereby enhancing the excretion of sodium and chloride (approximately at the same level). Acting as a diuretic, hydrochlorothiazide reduces plasma volume, resulting in increased plasma renin activity and aldosterone secretion, increased potassium and bicarbonate losses in urine and decreases in serum concentration. Since the relationship between renin levels and aldosterone secretion is mediated by angiotensin II, the use of hydrochlorothiazide in combination with angiotensin II receptor blockers in urine may decrease with the action of thiazide diuretics. When using hydrochlorothiazide diuresis occurs approximately 2:00 after administration, the maximum effect is achieved after 4:00, and the effect lasts for 6-12 hours.
According to epidemiological studies, long-term use of hydrochlorothiazide as a monotherapy helps to reduce the risk of cardiovascular complications and death from them.
Combined therapy with olmesartan medoxomil and hydrochlorothiazide.
In combination therapy with olmesartan medoxomil and hydrochlorothiazide, the antihypertensive effect is additively enhanced and, as a rule, exceeds the effects of each of the components separately. According to the combined data of placebo-controlled studies, as a result of the use of olmesartan medoxomil / hydrochlorothiazide at a dose of 20 / 12.5 mg and 20/25 mg, the mean decrease in systolic / diastolic blood pressure at the end of the dosing interval (corrected for the placebo effect) was in accordance with 12/7 mm Hg and 16/9 mm Hg Age and gender did not have a clinically significant effect on the effectiveness of combination therapy with olmesartan medoxomil and hydrochlorothiazide.
When hydrochlorothiazide was used in a dose of 12.5 mg and 25 mg in patients who did not have sufficient efficacy of olmesartan medoxomil at a dose of 20 mg, there was an additional decrease in mean daily systolic / diastolic blood pressure measured using ambulatory blood pressure monitoring (by 7/5 mm Hg and 12/7 mm Hg compared with baseline values ​​that are achieved as a result of monotherapy with olmesartan medoxomil). When measuring blood pressure using the traditional method, an additional decrease in mean systolic / diastolic blood pressure at the end of the dosing interval was 11/10 mm Hg, respectively. and 16/11 mm Hg (Compared to initial values).
Combined therapy with olmesartan medoxomil and hydrochlorothiazide remained effective for a long period of treatment (1 year). In the case of the withdrawal of olmesartan medoxomil (which was used both in combination with hydrochlorothiazide, and separately), ricochet hypertension was not observed.
The effect of the combined drug olmesartan medoxomil and hydrochlorothiazide cardiovascular complications and mortality from them is currently not known.

Pharmacokinetics

Suction and distribution

Olmesartan medoxomil.
Olmesartan medoxomil is a prodrug. It quickly turns into a pharmacologically active metabolite of olmesartan under the influence of esterases in the intestinal mucosa and in the portal blood during absorption in the digestive tract. Neither in plasma nor in the excretion products of olmesartan medoxomil or the lateral medoxomile group in unchanged form appeared. The average bioavailability of olmesartan in tablet form was 25.6%. The maximum concentration (C o x) of olmesartan in the blood plasma is reached 2:00 after oral administration. In the case of a single oral dose of up to 80 mg, the concentration of olmesartan in plasma increases approximately in proportion to the dose. Food has a minimal effect on the bioavailability of olmesartan, therefore, olmesartan medoxomil can be used regardless of the meal. Clinically significant differences in the pharmacokinetics of olmesartan in individuals of different sexes were not found. Olmesartan is actively associated with plasma proteins (99.7%), but the risk of clinically significant interactions with other drugs due to competition for binding to plasma proteins is small (this is confirmed by the absence of clinically significant interaction between olmesartan medoxomil and warfarin). Olmesartan binds slightly to blood cells. The average volume of distribution after administration is small (16–29 l).
Hydrochlorothiazide.
In the case of oral administration of olmesartan medoxomil in combination with hydrochlorothiazide, the median time to achieve C max of hydrochlorothiazide in the blood plasma was 1.5-2 g. Hydrochlorothiazide is 68% bound to plasma proteins, and its mental distribution volume is 0.83-1, 14 l / kg

Metabolism and elimination

Olmesartan medoxomil.
The total clearance of olmesartan for blood plasma is approximately 1.3 l / h (coefficient of variation 19%) and is relatively low compared to hepatic blood flow (about 90 l / h). After a single oral administration of olmesartan medoxomil labeled with an 14 C isotope, 10–16% of the radioactive label was in the urine (most within 24 hours after ingestion); radioactive label remaining manifested in feces. Given that the systemic bioavailability of Cardosal plus is 25.6%, it can be calculated that the olmesartan absorbed is excreted both by the kidneys (approximately 40%) and by the hepatobiliary system (approximately 60%). All radioactive label, found in the products of excretion, was in the composition of olmesartan. No other significant metabolites were detected. In the gastro-hepatic circulation, olmesartan is practically not involved.
Since most of olmesartan is excreted in the bile, it is contraindicated for patients with obstruction of the bile duct. The final elimination half-life of olmesartan after repeated oral administration varies from 10 to 15 g. The steady state was reached after the first few doses; after 14 days of repeated use, no further accumulation of the drug was observed. Renal clearance is approximately 0.5-0.7 l / h and is not dependent on the dose of Cardosal plus.
Hydrochlorothiazide.
Hydrochlorothiazide in the human body is not metabolized and is almost completely excreted unchanged in the urine. After ingestion, about 60% of the dose is excreted unchanged within 48 hours. Renal clearance is approximately 250-300 ml / min. The final half-life is about 10-15 hours.
Combination of olmesartan medoxomil with hydrochlorothiazide.
In the case of the use of hydrochlorothiazide in combination with olmesartan medoxomil, the systemic bioavailability of the first decreases by approximately 20%, however, such a decrease has no clinical significance. The pharmacokinetics of olmesartan in the case of its use in combination with hydrochlorothiazide does not change.

Pharmacokinetics in certain groups of patients

Elderly patients (over 65 and older).
In elderly patients (65-75 years), patients with arterial hypertension, the area under the pharmacokinetic curve (AUC) of olmesartan in the hospital state was about 35% higher than in younger patients, and in very elderly patients (≥75 years) ) - about 44% higher.
Based on the available data, we can assume that the elderly (both healthy and patients with arterial hypertension) have a systemic clearance of hydrochlorothiazide lower than that of healthy volunteers.

Impaired renal function

In patients with impaired mild, moderate and severe renal function, the AUC of olmesartan in the steady state was, respectively, 62%, 82% and 179% higher than in healthy volunteers.
The half-life of hydrochlorothiazide in patients with impaired renal function is increased.

Liver dysfunction

After a single oral administration, the AUC of olmesartan in patients with mild and moderately impaired liver function was 6% and 65% higher, respectively, than in healthy volunteers from the control group with the same demographic indicators. In healthy volunteers and in patients with mild and moderately impaired liver function, the unbound fraction of olmesartan at 2:00 after administration was, respectively, up to 0.26%, 0.34% and 0.41%. After repeated use, the average AUC of olmesartan in patients with impaired liver function of moderate severity was 65% higher than in healthy volunteers from the control group with the same demographic indicators. The value of C x x olmesartan in patients with impaired liver function and healthy volunteers were similar. In patients with severe hepatic impairment, the efficacy of olmesartan medoxomil has not been determined. Liver dysfunction was not significantly affected by the pharmacokinetics of hydrochlorothiazide.

Interaction with other drugs

Drug wheels, which binds bile acids:
The simultaneous intake of 40 mg of olmesartan medoxomil and 3750 mg of wheels for hydrochloride in healthy subjects led to a decrease in C max by 28% and a decrease in AUC by 39% for the drug olmesartan. A smaller effect, a decrease in C max and AUC by 4% and 15%, respectively, was observed when olmesartan medoxomil was administered at 4:00 each time before taking the wheels of hydrochloride. The half-life of olmesartan was reduced by 50–52%, regardless of whether the drugs were prescribed together or taking olmesartan at 4:00 am to receive the wheels of hydrochloride.

Indications

Treatment of essential hypertension.
Cardosal plus combined preparation is intended for adult patients in whom the use of olmesartan medoxomil alone does not ensure that blood pressure is reduced to the required level.

Contraindications for Cardosal plus

Allergic reaction (sensitivity) to active ingredients, to any of the excipients or to other derivatives of sulfonamides (hydrochlorothiazide is also derived from sulfanilamides).
Severe renal dysfunction (creatinine clearance
Persistent hypokalemia, hypercalcemia, hyponatremia and clinically severe hyperuricemia.
Severe abnormal liver function, cholestasis and obstructive diseases of the biliary tract. Pregnant women or women who are planning to become pregnant.
The combined use of Cardosal plus and preparations containing aliskiren is contraindicated in patients with diabetes mellitus or renal dysfunction (GFR 2).

Interaction with other drugs and other types of interactions

Potentially possible interactions are associated with the use of both olmesartan medoxomil and hydrochlorothiazide.
Simultaneous use is not recommended:
Lithium preparations.
With simultaneous use of lithium preparations with ACE inhibitors and, sometimes, with angiotensin II receptor blockers, a reversible increase in serum lithium concentration and its toxic action was observed. In addition, in the presence of thiazides, renal clearance is reduced, so the risk of its toxic action during the use of hydrochlorothiazide may increase. In this regard, the use of the drug Cardosal plus in combination with lithium is not recommended. In patients for whom these drugs should be prescribed simultaneously, during treatment it is recommended to carefully monitor the concentration of lithium in the blood plasma.
Simultaneous use, which requires caution:
Baclofen
The hypotensive effect may be enhanced.
Nonsteroidal anti-inflammatory drugs (NPLD).
NPLDs (for example, acetylsalicylic acid (> 3 g / day), COX-2 inhibitors, and non-selective NPLDs) can weaken the hypotensive effect of thiazide diuretics and angiotensin II receptor blockers. In some patients with impaired renal function (for example, in dehydrated or elderly patients with kidney disease), with the use of angiotensin II receptor blockers simultaneously with drugs that inhibit cyclooxygenase, these disorders may worsen, in particular, acute renal failure may occur, which however, in most cases is reversible.
Therefore, these drugs in combination with each other should be prescribed with caution, especially in elderly patients. Patients with this should drink enough liquid. In addition, after initiation of combination therapy and then at regular intervals, renal function in patients should be monitored.
Simultaneous application that requires special attention:
Amifostine.
May increase antihypertensive effect.
Other antihypertensives.
The antihypertensive effect of Cardosal Plus can be enhanced if it is used simultaneously with other drugs that lower blood pressure.
Ethyl alcohol, barbiturates, narcotic analgesics and antidepressants.
Can enhance manifestations of orthostatic hypotension.
Potential possible interactions with olmesartan medoxomil.
Simultaneous use is not recommended:
Double blockade of renin-angiotensin-.
Data from clinical trials show that double blockade of renin-angiotensin- (RAAS), associated with the general use of ACE inhibitors and angiotensin II receptor blockers or aliskiren, leads to an increase in the incidence of adverse events, such as hypotension, hyperkalemia and reduced kidney function (including including acute renal failure), compared with the use of a single agent acting on the RAAS.
Drugs that affect the concentration of potassium in the blood.
Given the experience of using other drugs that inhibit the renin-angiotensin system, serum potassium concentration may increase with simultaneous use of potassium-saving diuretics, potassium preparations, potassium-containing salt substitutes and other drugs that can increase the concentration of potassium in the blood (for example, heparin, ACE inhibitors ). When prescribing Cardosal plus, along with drugs that affect the level of potassium, it is recommended to control the serum concentration of potassium.
Drug wheels, which binds bile acids.
The combined use of Cardosal plus wheels on hydrochloride, which binds bile acids, reduces systemic exposure and peak plasma concentration of olmesartan, and also reduces the half-life.
Reception of olmesartan medoxomil at least 4:00 before taking the wheel hydrochloride reduced the effect of drug interactions. You should consider the possibility of taking olmesartan medoxomil at least 4:00 before taking the wheel hydrochloride.

Additional Information

It was noted a moderate decrease in the bioavailability of olmesartan medoxomil after treatment with antacids (magnesium-aluminum hydroxide). Olmesartan medoxomil does not have a significant effect on the pharmacokinetics and pharmacodynamics of warfarin or digoxin pharmacokinetics. In healthy volunteers who took olmesartan medoxomil concurrently with pravastine, there were no clinically significant changes in the pharmacokinetics of these drugs. In in vitro studies, no clinically significant inhibition by Olmesartan of the activity of the isoenzymes IA1 / 2, IIA6, IIC8 / 9, IIC19, IID6, IIE1, and IIIA4 of human P450 was not found; regarding cytochrome P450 isoenzymes in animals, olmesartan either had a slight inducing effect, or did not have any. Thus, clinically significant interactions between olmesartan and drugs that are metabolized with the participation of these isoenzymes of the cytochrome P450 family are not expected.
Potentially possible hydrochlorothiazide interactions.
Simultaneous use is not recommended:
Drugs that affect the concentration of potassium in the blood.
The hypokalemic effect of hydrochlorothiazide may be enhanced while being used with other drugs that cause potassium loss and hypokalemia (for example, while prescribing diuretics, laxatives, corticosteroids, ACTH, amphotericin, carboxolone, penicillin G sodium and salicylic acid derivatives). Therefore, the use of hydrochlorothiazide simultaneously with these drugs is not recommended.
Simultaneous use, which requires caution:
Calcium salts.
By slowing calcium excretion, thiazide diuretics can increase its concentration in serum.
If it is necessary to use calcium preparations, the level of its concentration in serum should be controlled, and the corresponding dose of calcium should be adjusted.
Cholestyramine and colestipol.
The use of anion-exchange resins slows down the absorption of hydrochlorothiazide
Cardiac glycosides.
The use of cardiac glycosides leads to the fact that hypokalemia and hypomagnesemia, which are caused by thiazides, increase the risk of developing arrhythmias.
Drugs whose effectiveness depends on changes in the concentration of potassium in the serum. In the case of the use of the drug Cardosal plus simultaneously with drugs, the effectiveness of which depends on changes in the concentration of potassium in the blood serum (for example, cardiac glycosides and antiarrhythmic drugs), as well as with drugs that cause arrhythmia of the pirouette type (ventricular tachycardia), including Some antiarrhythmic drugs, it is recommended to regularly monitor the concentration of potassium in the serum and ECG:
    Class Ia antiarrhythmic drugs (for example, quinidine, hydroquinidine, disopyramide)
    Class IIIa antiarrhythmic drugs (amiodarone, sotalol, dofetilide, ibutilide)
    some antipsychotic drugs (for example, thioridazine, chlorpromazine, levomepromazine, trifluoroperazine, cyamemazine, sulpiride, sultopridom, amisulpride, tiaprid, pimozide, haloperidol, droperidol)
    others (for example, bepridil, cisapride, diphemanil, erythromycin i.v., halofantrine, mizolastine, pentamidine, sparfloxacin, terfenadine, vincamine i.v.).
Non-depolarizing skeletal muscle relaxants (for example, tubocurarine).
Hydrochlorothiazide may enhance the effectiveness of non-depolarizing skeletal muscle relaxants.
Anticholinergics (for example, atropine and biperidine).
By reducing gastrointestinal motility and the rate of gastric emptying, anticholinergics can increase the bioavailability of thiazide diuretics.
Antidiabetic drugs (oral medication and insulin).
Thiazide therapy may affect glucose tolerance. Correction of the dose of glucose-lowering drugs may be necessary.
Metformin.
Metformin should be used with caution because of the risk of lactic acidosis, which is caused by functional renal failure, which sometimes results from the use of hydrochlorothiazide.
Beta blockers and diazoxide.
Hyperglycemic efficacy of beta-blockers and diazoxide may be enhanced under the influence of thiazides.
Pressor amines (for example, norepinephrine).
The effectiveness of pressor amines may decrease.
Drugs used to treat gout (probenecid, sulfinpirazon and allopurinol).
Since hydrochlorothiazide sometimes causes an increase in serum uric acid concentration, a dose adjustment of uricosuric drugs for treating gout may be necessary. In addition, it is sometimes necessary to increase the dose of probenecid or sulfinpyrazone. In the case of using allopurinol simultaneously with thiazides, the frequency of allergic reactions to allopurinol may increase.
Amantadine.
Thiazides may increase the risk of adverse reactions, amantadine.
Cytotoxic agents (for example, cyclophosphamide, methotrexate).
Thiazides can reduce the excretion of anticancer drugs by the kidneys and increase their inhibitory effect on the bone marrow.
Salicylates In the case of receiving high doses of salicylates, hydrochlorothiazide may increase their toxic effects on the central nervous system.
Methyldopa
The literature describes isolated cases of hemolytic anemia as a result of the use of hydrochlorothiazide in combination with methyldopha.
Cyclosporine.
The simultaneous use of thiazides with cyclosporine increases the risk of hyperuricemia and complications similar to gout.
Tetracycline.
The use of thiazides simultaneously with tetracycline increases the risk of uraemia caused by tetracycline. This interaction probably does not concern doxycycline.

Application features

Decreased circulating blood volume.
Patients with a reduced circulating blood volume and / or low sodium levels due to intensive diuretic therapy, a low-salt diet, diarrhea, or vomiting may experience clinically severe hypotension, especially after the first dose of Cardosal plus. Before the use of the drug Cardosal plus the above phenomena should be eliminated.
Double renin-angiotensin-blockade (RAAS).
The simultaneous use of ACE inhibitors, angiotensin II receptor blockers or aliskiren increases the risk of arterial hypotension, hyperkalemia and reduced renal function (including acute renal failure). Therefore, a double blockade of RAAS against the background of simultaneous use of ACE inhibitors, angiotensin II receptor blockers or aliskiren is not recommended.
If therapy with double blockade is absolutely necessary, then it should be carried out only under the supervision of a specialist, as well as against the background of careful monitoring of kidney function, electrolyte levels and blood pressure.
The simultaneous use of ACE inhibitors and angiotensin II receptor blockers is contraindicated in patients with diabetic nephropathy.
Other phenomena accompanied by stimulation of renin-angiotensin-. Patients in whom vascular tone and kidney function are largely dependent on renin-angiotensin-activity (for example, patients with severe congestive heart failure or kidney pathology, including renal artery stenosis) may respond to other drugs that affect this system. experiencing acute hypotension, azotemia, oliguria, or, in some cases, acute renal failure.
Renovascular hypertension.
The use of drugs that affect the renin-angiotensin-aldosterone system in patients with bilateral renal artery stenosis or single kidney artery stenosis is associated with an increased risk of severe arterial hypotension and renal failure.
Impaired renal function and kidney transplantation.
Patients with severe impaired renal function (creatinine ® plus clearance should not be used. Patients with mild or moderate renal dysfunction (creatinine clearance ³30 ml / min, but ® plus should be used with caution, it is recommended to periodically monitor the concentration of potassium, creatinine and urinary serum acids. Patients with impaired renal function may experience azotemia caused by thiazide diuretics. If progressive renal failure becomes evident, a careful There is no clinical experience with Cardosal plus patients who have recently had a kidney transplant.
Liver dysfunction.
The experience of using olmesartan medoxomil in patients with severely impaired liver function is still lacking. In addition, in patients with impaired liver function or progressive liver disease, minor disturbances in water and electrolyte balance during thiazide therapy can cause hepatic coma. For this reason, in patients with mild to moderate hepatic impairment, the drug should be used with caution. Cardosal plus is contraindicated in patients with severe renal dysfunction, cholestasis and bile duct obstruction.
Aortic stenosis and mitral stenosis, hypertrophic obstructive cardiomyopathy.
As in the case of other vasodilators, olmesartan medoxomil is carefully prescribed for stenosis of the aortic or mitral stenosis, as well as for obstructive hypertrophic cardiomyopathy.
Primary aldosteronism.
Patients with primary aldosteronism usually do not respond to antihypertensive agents that suppress the renin-angiotensin system. Therefore, Cardosal plus is not recommended for such patients.
Metabolic and endocrine effects.
Preparations of the thiazide group can cause impaired glucose tolerance. Patients with diabetes need to adjust the dose of insulin or oral hypoglycemic agents. The use of thiazides may contribute to the development of latent diabetes.
While taking thiazide diuretics, side effects can occur, such as an increase in cholesterol and triglycerides. In some cases, the use of thiazides may contribute to the development of hyperuricemia or gout. Hydrochlorothiazide is able to increase the level of free bilirubin in the serum.
Electrolyte disturbances.
As in the case of any diuretics, when using hydrochlorothiazide should be monitored with a certain interval serum concentrations of electrolytes. Preparations of the thiazide group, including hydrochlorothiazide, can cause impaired water-electrolyte balance (including hypokalemia, hyponatremia and hypochloraemic alkalosis). Symptoms of water and electrolyte balance are symptoms such as dry mouth, thirst, weakness, prolonged sleep, drowsiness, anxiety, muscle pain or cramps, muscle fatigue, hypotension, oliguria, tachycardia, and disorders of the digestive tract, in particular nausea and vomiting. The risk of hypokalemia is highest with liver cirrhosis, with a sharp increase in diuresis, with insufficient consumption of electrolytes inside, as well as with the use of corticosteroids and ACTH as concomitant medications.

Terms of sell

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