Pharmacological properties of the drug Cardosal plus
Cardosal Plus is a combined antihypertensive drug that includes an angiotensin II receptor antagonist (olmesartan medoxomil) and a thiazide diuretic (hydrochlorothiazide). With the combined use of these substances, blood pressure levels decrease more significantly than with their separate use. Olmesartan medoxomil blocks the binding of angiotensin II to AT1 receptors in tissues, including vascular smooth muscle and adrenal glands, which leads to the elimination of its vasoconstrictor and aldosterone-secreting effects, an increase in renin activity in the blood plasma, the concentration of angiotensin I and II, as well as a slight a decrease in the concentration of aldosterone in the blood plasma. In hypertension (arterial hypertension), olmesartan medoxomil causes a prolonged dose-dependent decrease in blood pressure. There is no data on the development of arterial hypotension associated with taking the first dose of the drug, on tachyphylaxis with its prolonged use, or on hypertension when the drug is discontinued. Taking olmesartan medoxomil once a day causes an effective and uniform decrease in blood pressure over 24 hours. With continuous treatment, the maximum decrease in blood pressure levels is achieved 8 weeks after the start of therapy, while a significant hypotensive effect is noted after 2 weeks of treatment. Hydrochlorothiazide affects the reabsorption of electrolytes in the renal tubules, while the excretion of sodium and water increases almost equally. The diuretic effect of hydrochlorothiazide leads to a decrease in blood plasma volume, an increase in plasma renin activity, increased aldosterone secretion and, as a result, a decrease in urinary losses of potassium and bicarbonate ions, as well as a decrease in the level of potassium in the blood serum. Concomitant use of olmesartan medoxomil may prevent potassium losses associated with the action of the diuretic. After taking hydrochlorothiazide, diuresis increases after 2 hours, the maximum diuretic effect is observed within 4 hours, the effect lasts about 6–12 hours. Olmesartan medoxomil is a prodrug that, under the influence of esterases in the intestinal mucosa and in the blood of the portal vein, is converted into an active metabolite - Olmesartan. The absolute bioavailability of olmesartan averages 25.6%. After oral administration of olmesartan medoxomil, maximum plasma concentrations are achieved after approximately 2 hours; with increasing oral dose to 80 mg, the plasma concentration of olmesartan increases almost linearly. The effect of concomitant food intake on the bioavailability of olmesartan is minimal. Olmesartan is 99.7% bound to plasma proteins. Olmesartan is excreted through the kidneys (about 40%) and the hepatobiliary system (about 60%). With repeated oral administration, the terminal half-life of olmesartan ranges between 10 and 15 hours. The saturation stage was reached on the 14th day of administration and no further accumulation occurred. Hydrochlorothiazide. When taking the combination of olmesartan medoxomil and hydrochlorothiazide orally, the average time to reach the maximum concentration of hydrochlorothiazide is 1.5–2 hours. Hydrochlorothiazide is 68% bound to plasma proteins and is not metabolized in the human body. About 60% of an oral dose is eliminated within 48 hours. The terminal half-life of hydrochlorothiazide is 10–15 hours. The systemic bioavailability of hydrochlorothiazide with simultaneous use of olmesartan medoxomil is reduced by approximately 20%, but this is not clinically significant. Co-administration of hydrochlorothiazide does not affect the pharmacokinetics of olmesartan.
Instructions for use of Cardosal (Method and dosage)
Instructions for use of Cardosal prescribe taking the drug orally every day at the same time, once a day.
The recommended initial dose is 10 mg once daily. If the blood pressure reduction is not sufficient when taking 10 mg per day, it can be increased to 20 mg per day. If additional pressure reduction is required, the dosage is increased to a maximum of 40 mg per day or a diuretic (for example, hydrochlorothiazide ).
The highest daily dose is 40 mg.
Side effects of the drug Cardosal plus
To assess the frequency of side effects, the following gradation is used: very often (1/10), often (1/100, but ≤1/10), sometimes (1/1000, but ≤1/100), rarely (1/10,000 , but ≤1/1000), very rarely (≤1/10,000, including reports of isolated cases). Metabolic disorders Sometimes - hyperuricemia, hypertriglyceridemia. Nervous system disorders Often - dizziness, sometimes - syncope. Cardiovascular system disorders: Sometimes - tachycardia, arterial hypotension, orthostatic hypotension. Skin disorders Sometimes - skin rash, eczema. General disorders Often - increased fatigue. Sometimes it’s a general weakness. Indicators of laboratory tests Sometimes - a decrease in the level of potassium in the blood, an increase in the level of potassium, calcium, urea, lipids in the blood. A slight increase in blood levels of uric acid, urea nitrogen and creatinine, as well as a slight decrease in hemoglobin and hematocrit. When using both substances separately, the following side effects were noted. Olmesartan medoxomil Since the drug was marketed Very rarely - thrombocytopenia, dizziness, headache, cough, abdominal pain, nausea, vomiting, pruritus, rash, angioedema, allergic dermatitis, facial edema, urticaria, muscle cramps, myalgia, acute renal failure , impaired renal function, general weakness, fatigue, drowsiness, general malaise, increased levels of creatinine and urea in the blood, increased activity of liver enzymes. During clinical trials Often - dizziness, bronchitis, cough, laryngitis, rhinitis, abdominal pain, diarrhea, digestive disorders, nausea, gastritis, colitis, arthritis, back pain, bone pain, hematuria, urinary tract infections, pain in chest, fatigue, flu-like phenomena, peripheral edema, increased activity of CPK and liver enzymes, levels of lipids and uric acid in the blood; sometimes - attacks of dizziness, angina pectoris, skin rash; rarely - arterial hypotension, hyperkalemia. Hydrochlorothiazide Often - mild dizziness, dizziness, confusion, headache, fatigue. Sometimes - decreased or lack of appetite, orthostatic hypotension, gastric disorders, nausea, vomiting, diarrhea, flatulence, abdominal pain, photosensitivity, skin rash, urticaria, increased blood glucose levels, glycosuria, hyperuricemia, hyponatremia, hypokalemia, hypomagnesemia, hypochloremia, hypercalcemia, hypercholesterolemia, hypertriglyceridemia, increased levels of creatinine and urea in the blood. Rarely - inflammation of the salivary glands, leukopenia, neutropenia and/or agranulocytosis, thrombocytopenia, aplastic and hemolytic anemia, bone marrow damage, anxiety, depression, sleep disturbances, apathy, paresthesia, convulsions, xanthopsia, transient blurred vision, decreased formation of tear fluid, disorders heart rate, necrotizing angiitis, cutaneous vasculitis, thrombosis and embolism, shortness of breath, pneumonia and pulmonary edema, pancreatitis, jaundice, acute cholecystitis, lupus-like skin reactions, repeated manifestations of the cutaneous form of systemic lupus erythematosus, anaphylactic reactions, toxic epidermal necrolysis, muscle cramps, weakness in muscles, paresis, impaired renal function, acute renal failure, increased body temperature, impaired potency. Very rarely - paralytic intestinal obstruction.
Cardosal plus (tab. p.pl/vol. 12.5 mg + 20 mg No. 28)
A country
Germany
The country of production may vary depending on the batch of goods. Please check with the operator for detailed information when confirming your order.
Active substance
Hydrochlorothiazide + Olmesartan medoxomil
Compound
1 tablet contains: hydrochlorothiazide 12.5 mg, olmesartan medoxomil 20 mg
pharmachologic effect
Cardosal® plus is a combination drug that contains an angiotensin II receptor antagonist (olmesartan medoxomil) and a thiazide diuretic (hydrochlorothiazide). The combination of two active substances has a combined antihypertensive effect, as a result of which blood pressure decreases to a greater extent than when taking each of them separately. When taking the drug once a day, an effective and uniform reduction in blood pressure is achieved within 24 hours. Olmesartan medoxomil is a specific antagonist of angiotensin II receptors (type AT1). Angiotensin II is the primary vasoactive component of the renin-angiotensin-aldosterone system (RAAS) and plays a significant role in the pathophysiology of arterial hypertension through its effect on AT1 receptors. It is assumed that olmesartan medoxomil blocks all effects of angiotensin II mediated by AT1 receptors, regardless of the source and pathway of angiotensin II synthesis. In arterial hypertension, olmesartan medoxomil causes a dose-dependent, long-term decrease in blood pressure. There is no data on the development of arterial hypotension after taking the first dose of the drug and on the development of the “withdrawal” syndrome (a sharp increase in blood pressure after discontinuation of the drug). Taking olmesartan medoxomil once a day provides an effective and gentle decrease in blood pressure within 24 hours. The hypotensive effect of olmesartan medoxomil usually occurs after 2 weeks, and the maximum effect develops after approximately 8 weeks. after starting therapy. Hydrochlorothiazide, a thiazide diuretic, interferes with the reabsorption of sodium, chlorine and water ions in the renal tubules. Increases the excretion of potassium, magnesium, bicarbonate ions, and retains calcium ions in the body. The diuretic effect occurs 2 hours after taking hydrochlorothiazide orally, reaches a maximum after 4 hours and lasts up to 12 hours. Helps reduce high blood pressure. When olmesartan medoxomil and hydrochlorothiazide are taken in combination, the loss of potassium ions caused by the action of the diuretic decreases. The result of combination therapy of olmesartan with medoxomil and hydrochlorothiazide is a potentiation of the hypotensive effect, which depends on the dose of each component of the drug. Combination therapy is well tolerated by patients. With long-term treatment, the effectiveness of combination therapy (olmesartan medoxomil/hydrochlorothiazide) is maintained, and the development of withdrawal syndrome is not observed.
Indications for use
Essential arterial hypertension (if monotherapy with olmesartan medoxomil is ineffective).
Mode of application
Cardosal® plus tablets are taken orally, regardless of meals. Before prescribing the combination drug Cardosal® plus, it is recommended to pre-select the dose of each of the active ingredients separately (i.e. olmesartan medoxomil and hydrochlorothiazide). Recommended dose: Daily, 1 tablet of Cardosal® plus containing 20 mg of olmesartan medoxomil and 12.5 mg of hydrochlorothiazide, in the absence of adequate blood pressure control during monotherapy with olmesartan medoxomil at a dose of 20 mg; In the absence of adequate blood pressure control while taking the drug Cardosal® plus, containing 20 mg of olmesartan medoxomil and 12.5 mg of hydrochlorothiazide, it is possible to use the drug Cardosal® plus, containing 20 mg of olmesartan medoxomil and 25 mg of hydrochlorothiazide daily, 1 tablet. The maximum dose of Cardosal® plus is 20 mg of olmesartan medoxomil and 25 mg of hydrochlorothiazide once a day. Elderly patients (over 65 years of age) with normal renal function (creatinine clearance more than 90 ml/min.) and patients with impaired renal function (creatinine clearance = 30-60 ml/min.) do not require dose adjustment.
Interaction
Olmesartan medoxomil Concomitant use with potassium-sparing diuretics, potassium preparations, salt substitutes containing potassium, or other drugs that can increase the concentration of potassium in the blood serum (for example, heparin) is not recommended - an increase in the concentration of potassium in the blood serum is possible. Nonsteroidal anti-inflammatory drugs (NSAIDs), including acetylsalicylic acid in doses greater than 3 g/day, as well as cyclooxygenase-2 (COX-2) inhibitors and angiotensin II receptor antagonists may act synergistically to reduce glomerular filtration. With the simultaneous use of NSAIDs and angiotensin II receptor antagonists, there may be a risk of developing acute renal failure, therefore monitoring of renal function at the beginning of treatment, as well as regular intake of sufficient fluids, is recommended. However, simultaneous treatment may reduce the antihypertensive effect of angiotensin II receptor antagonists, leading to a partial loss of their therapeutic effectiveness. When used simultaneously with antacids (magnesium and aluminum hydroxides), a moderate decrease in the bioavailability of olmesartan medoxomil is possible. There are reports of a reversible increase in serum lithium concentrations and toxicity during concomitant use of lithium preparations with angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor antagonists, therefore the use of olmesartan medoxomil in combination with lithium preparations is not recommended. If it is necessary to use appropriate combination therapy, regular monitoring of lithium concentrations in the blood serum is recommended. In rare cases, ACE inhibitors may enhance the hypoglycemic effect of insulin and oral hypoglycemic agents (for example, sulfonylureas) in patients with diabetes mellitus. In these cases, with simultaneous use of ACE inhibitors, it may be necessary to reduce the dose of the oral hypoglycemic agent and insulin. Hydrochlorothiazide Glucocorticosteroids, adrenocorticotropic hormone (ACTH), amphotericin B (parenteral), carbenoxolone, penicillin G sodium salt, salicylic acid derivatives: when taken simultaneously with hydrochlorothiazide, there may be an increase in electrolyte losses, especially the development of hypokalemia. Simultaneous use of ion exchange drugs (colesteramine, colestepol) reduces the absorption of hydrochlorothiazide. With the simultaneous use of hydrochlorothiazide with calcium salts, it is possible to increase the concentration of calcium in the blood serum due to a decrease in its excretion. If it is necessary to prescribe calcium supplements, its concentration in the blood serum should be monitored and its dose adjusted accordingly. With the simultaneous use of hydrochlorothiazide with cardiac glycosides, arrhythmias may occur. Medicines that can cause ari (“torsades des pointes”) (a special form of polymorphic ventricular tachycardia with a wave-, screw- or spindle-shaped configuration of the ventricular complexes in combination with an increase or decrease in the amplitude of the QRS waves, which can lead to ventricular fibrillation or asystole) : due to the risk of hypokalemia, caution is required when using hydrochlorothiazide simultaneously with certain antiarrhythmic drugs (quinidine, hydroquinidine, disopyramide, amiodarone, sotalol, dofetilide, ibutilide), antipsychotics (thioridazine, chlorpromazine, levomepromazine, trifluoperazine, cyamemazine, sulpiride, sultopride, amisulpride , tiapride, pimozide, haloperidol, droperidol) and others (bepridal, cisapride, difemanil methyl sulfate, erythromycin for intravenous administration, halofantrine, mizolastine, nentamidine, sparfloxacin, terfenadine, vincamine for intravenous administration), which are known to cause arari. When combined with hydrochlorothiazide and non-depolarizing muscle relaxants (including tubocurarine chloride), the effect of muscle relaxants is enhanced. Thiazides may increase the risk of side effects from amantadine. Treatment with thiazide diuretics may impair glucose tolerance. With the simultaneous use of M-anticholinergics (atropine) and thiazides, due to a decrease in gastrointestinal motility, the bioavailability of thiazide diuretics may increase. It may be necessary to reduce the dose of oral hypoglycemic agents and insulin. Antigout drugs (probenecid, sulfinpyrazone, allopurinol): It may be necessary to adjust the dose of the hypouricemic drug (increasing the dose of probenecid or sulfinpyrazone) since hydrochlorothiazide may increase serum uric acid concentrations. Concomitant use with thiazide diuretics may increase the incidence of hypersensitivity reactions to allopurinol. The effect of sympathomimetics may be decreased when thiazide diuretics are taken concomitantly. Thiazide diuretics may reduce the renal excretion of cytotoxic drugs and enhance their myelosuppressive effect. When taking salicylates in high doses, hydrochlorothiazide may enhance their toxic effect on the central nervous system. There are reports of isolated cases of hemolytic anemia while taking methyldopa with hydrochlorothiazide. Concomitant use of cyclosporine with hydrochlorothiazide may increase the risk of hyperuricemia and exacerbation of gout. Concomitant use of tetracyclines with thiazide diuretics increases the risk of tetracycline-related increases in urea concentrations. This interaction does not apply to doxycycline. Olmesartan medoxomil/hydrochlorothiazide in combination Concomitant use of lithium preparations with thiazide diuretics may increase the already increased risk of lithium intoxication due to ACE inhibitors, therefore the combined use of Cardosal plus and lithium preparations is not recommended. If such a combination is still necessary, then careful monitoring of serum lithium concentrations is also necessary. With simultaneous use of the drug Cardosal* plus with baclofen and amifostine, the antihypertensive effect may be enhanced. With simultaneous use of other antihypertensive drugs, the hypotensive effect of Cardosal® plus may be enhanced. Ethanol, barbiturates, narcotic analgesics or antidepressants when used with Cardosal® plus may worsen orthostatic hypotension.
Side effect
Possible side effects are listed below in descending frequency of occurrence: often (> 1/100, 1/1000, 1/10000, Combination of olmesartan medoxomil and hydrochlorothiazide From the central nervous system Common: dizziness Uncommon: syncope Cardiovascular system Uncommon: palpitations , marked decrease in blood pressure, orthostatic hypotension. From the skin Uncommon: skin rash, eczema. From the metabolic side Uncommon: hyper- or hypokalemia, hypercalcemia, hypertriglyceridemia, hyperuricemia, increased concentration of lipids in the blood. From laboratory parameters Very rare: insignificant increased concentrations of creatinine, uric acid and urea nitrogen in the blood serum, a slight decrease in the concentration of hemoglobin and hematocrit Olmesartan Medoxomil (monotherapy) From the hematopoietic system Very rare: thrombocytopenia From the central nervous system Very rare: dizziness, headache From the cardiovascular system systems Rarely: marked decrease in blood pressure Uncommon: angina pectoris. From the respiratory system Often: bronchitis, pharyngitis, rhinitis. Very rare: cough. From the digestive tract Often: diarrhea, dyspepsia, gastroenteritis. Very rare: abdominal pain, nausea, vomiting. From the urinary system Often: hematuria, urinary tract infection. Very rare: acute renal failure. From the musculoskeletal system Often: arthritis, back pain. Very rare: muscle cramps, myalgia. From the skin Very rarely: skin itching, exanthema, angioedema, allergic dermatitis, urticaria. Metabolic disorders: Often: increased activity of creatine phosphokinase, hypertriglyceridemia, hyperuricemia. Rarely: hyperkalemia. From laboratory parameters Very rare: increased concentrations of creatinine and urea in the blood serum. Often: increased activity of liver transaminases. Other disorders Common: chest pain, flu-like symptoms, peripheral edema. Very rare: weakness, increased fatigue, drowsiness, malaise. Hydrochlorothiazide (monotherapy) From the hematopoietic system Rarely: leukopenia, neutropenia, agranulocytosis, thrombocytopenia, and plastic anemia, hemolytic anemia, suppression of bone marrow hematopoiesis. From the central and peripheral nervous system Often: dizziness, weakness, headache, increased fatigue. Rarely: anxiety, sleep disturbance, confusion, apathy, depression, numbness, paresthesia, convulsions. From the organ of vision Rarely: xanthopsia, transient disturbance of accommodation, decreased formation of tear fluid. From the cardiovascular system: Uncommon: orthostatic hypotension. Rarely: arrhythmias, thrombosis, embolism. From the respiratory system Rarely: dyspnea (including interstitial pneumonia and pulmonary edema). From the digestive tract: Uncommon: anorexia, abdominal pain, nausea, vomiting, diarrhea, constipation, flatulence, inflammation of the salivary glands. Rarely: pancreatitis, acute cholecystitis, intrahepatic cholestatic jaundice. Very rare: paralytic ileus. From the genitourinary system Rarely: impaired renal function, interstitial nephritis, acute renal failure, impaired potency. From the musculoskeletal system Rarely: muscle cramps, muscle weakness, paresis. From the skin Uncommon: photosensitivity, skin rash, urticaria. Rarely: development of lupus-like syndrome (fever, arthralgia, myalgia, serositis, vasculitis, increased erythrocyte sedimentation rate (ESR), leukocytosis, eosinophilia), activation of the cutaneous form of systemic lupus erythematosus, anaphylactic reactions, toxic epidermal necrolysis. From laboratory parameters Often: hyperglycemia, glucosuria, hyperuricemia, increased serum creatinine concentrations, water and electrolyte imbalance (including hyponatremia, hypomagnesemia, hypochloremia, hypokalemia and hypercalcemia), increased concentrations of cholesterol and triglycerides in the blood. Other disorders Rare: fever.
Contraindications
- hereditary lactose intolerance, deficiency of lactase in the body or malabsorption syndrome of glucose and lactose;
- severe liver dysfunction (more than 9 points on the Child-Pugh scale) (risk of developing hepatic coma), biliary obstruction and cholestasis; - severe renal dysfunction (creatinine clearance less than 30 ml/min.); - refractory hypokalemia, hyponatremia, hypercalcemia and symptomatic hyperuricemia; - pregnancy; - lactation period; - age under 18 years (the effectiveness and safety of the drug have not been studied); - hypersensitivity to olmesartan medoxomil, hydrochlorothiazide or other sulfonamide derivatives or to any of the excipients included in the drug (see section Composition). With caution: - bronchial asthma; — coronary heart disease (CHD); — chronic heart failure in the stage of decompensation; - severe cerebrovascular disorders; - stenosis of the aortic or mitral valve; — hypertrophic obstructive cardiomyopathy; - mild to moderate liver dysfunction (less than 9 points on the Child-Pugh scale); - impaired renal function (creatinine clearance more than 30 ml/min., but less than 60 ml/min.); - bilateral renal artery stenosis or stenosis of the artery of a single kidney; — condition after a recent kidney transplant (no experience with the drug); - primary aldosteronism; - diabetes mellitus, gout; - water-electrolyte imbalance, dehydration; — connective tissue diseases, including systemic lupus erythematosus; - patients on a salt-restricted diet or on hemodialysis; - when bone marrow hematopoiesis is suppressed; - conditions accompanied by a decrease in circulating blood volume; — (OTSK) incl. diarrhea, vomiting or previous diuretic therapy. Use during pregnancy and lactation There is no experience with the use of olmesartan medoxomil in pregnant women. However, due to existing reports of severe teratogenic effects of drugs acting on the RAAS, like any drug of this class, Cardosal® plus is contraindicated for use during pregnancy. If pregnancy is planned or occurs during therapy with Cardosal® plus, the drug should be discontinued as soon as possible. It is not known whether olmesartan medoxomil is excreted in breast milk, but thiazides are excreted in breast milk and may suppress lactation, therefore, if it is necessary to use the drug Cardosal® plus during lactation, breastfeeding should be discontinued while taking it.
Use in elderly patients Elderly patients (over 65 years of age) with normal renal function (creatinine clearance more than 90 ml/min) do not require dose adjustment.
Overdose
Symptoms: - in case of an overdose of olmesartan medoxomil, a pronounced decrease in blood pressure is most likely, as well as tachycardia, bradycardia, nausea, drowsiness; - in case of an overdose of hydrochlorothiazide - symptoms of electrolyte deficiency (hypokalemia, hypochloremia, hyponatremia) and dehydration due to excessive diuresis. Treatment: - gastric lavage and/or intake of activated charcoal is recommended; - therapy aimed at correcting dehydration and water-electrolyte imbalances. If there is a pronounced decrease in blood pressure, it is recommended to place the patient in a horizontal position, raising his legs, and carry out therapy aimed at replenishing blood volume. Hemodialysis is not effective.
special instructions
Symptomatic arterial hypotension, especially after taking the first dose of the drug, may occur in patients with reduced blood volume and/or reduced sodium concentration due to intensive diuretic therapy, restricted dietary salt intake during dietary nutrition, and also due to diarrhea or vomiting. Relevant factors should be eliminated before starting the use of Cardosal® plus. Thiazide diuretics, including hydrochlorothiazide, may cause disturbances in the blood volume or water-electrolyte balance of the blood serum (including hypokalemia, hyponatremia and hypochloremic alkalosis). Precursor symptoms are: dryness of the oral mucosa, thirst, weakness, drowsiness, anxiety, myalgia or cramps, muscle weakness, arterial hypotension, oliguria, tachycardia, nausea and vomiting (see section Side effects). The highest risk of developing hypokalemia exists in patients with liver cirrhosis, in patients undergoing forced diuresis, and in those patients who are simultaneously taking glucocorticosteroids or ACTT (see section Interaction with other drugs). Conversely, due to the antagonism of the angiotensin II (AT1) receptors contained in Cardosal plus olmesartan medoxomil, hyperkalemia may occur, especially in patients with decreased renal function and/or chronic heart failure, as well as patients with diabetes. In patients with risk factors, regular monitoring of serum potassium concentration is recommended. There are no data on whether olmesartan medoxomil can reduce or prevent diuretic-induced hyponatremia. In hot weather, dilution hyponatremia may occur in patients prone to edema. The decrease in chloride concentration is generally insignificant and usually does not require treatment. Thiazides can reduce the excretion of calcium ions by the kidneys and also lead to a transient slight increase in the concentration of calcium in the blood serum in the absence of a history of disturbances in its metabolism. Hyperkalygemia may indicate latent hyperparathyroidism. Before studying the function of the parathyroid glands, thiazides should be discontinued. It has been proven that thiazide diuretics increase the excretion of magnesium ions by the kidneys, which can lead to hypomagnesemia. In patients in whom vascular tone and renal function depend to a large extent on the activity of the RAAS (for example, in patients with severe chronic heart failure or impaired renal function, including renal artery stenosis), treatment with other drugs affecting the RAAS is associated with the possibility of developing acute arterial hypotension, azotemia, oliguria or, in rare cases, acute renal failure. The possibility of a similar effect cannot be excluded when using angiotensin P receptor antagonists. There is an increased risk of developing severe arterial hypotension and renal failure if a patient with bilateral renal artery stenosis or arterial stenosis of a single functioning kidney receives therapy with drugs that affect the RAAS. When using the drug Cardosal® plus in patients with impaired renal function, it is recommended to periodically monitor the concentration of potassium ions, creatinine and uric acid in the blood serum. There is no experience with the use of olmesartan medoxomil in patients with recent kidney transplantation or in patients with end-stage renal impairment. In patients with limited renal function, taking thiazide diuretics may be accompanied by azotemia. With obvious progression of renal failure, it is necessary to reconsider therapy and decide on the abolition of diuretics. As with any antihypertensive drug, excessive reduction of blood pressure in patients with coronary artery disease or cerebrovascular insufficiency can lead to myocardial infarction or stroke. Thiazide diuretics may cause impaired glucose tolerance, as well as increased serum concentrations of cholesterol, triglycerides and uric acid. In patients with diabetes mellitus, it may be necessary to adjust the dose of insulin or oral hypoglycemic agent (see section Interactions with other drugs). When treated with thiazide diuretics, latent diabetes mellitus can manifest itself. There are reports that thiazide diuretics may precipitate an attack of gout and cause exacerbation of systemic lupus erythematosus. Hypersensitivity reactions to hydrochlorothiazide may be more likely to occur in patients with a history of allergies or bronchial asthma (history). Effect on the ability to drive vehicles and operate machinery The effect of the drug Cardosal® plus on the ability to drive vehicles and operate machinery has not been specifically studied, therefore, during treatment with Cardosal® plus, caution should be exercised when driving vehicles and engaging in potentially hazardous activities that require increased concentration attention and speed of psychomotor reactions.
Dispensing conditions in pharmacies
On prescription
Special instructions for the use of the drug Cardosal plus
The use of the drug in the first trimester of pregnancy is not recommended. When planning pregnancy, it is necessary to transfer the patient to appropriate alternative drugs. The safety and effectiveness of the drug in children and adolescents under 18 years of age have not been confirmed, so its use is not recommended. There is little experience with the use of the drug in patients with impaired liver function, so it is not recommended for use in this situation. In patients with impaired renal function, thiazide diuretics can cause the development of azotemia, therefore, if renal failure is clearly progressing, the issue of prescribing diuretics should be reconsidered. The drug is used with caution in patients with decompensated heart failure, kidney disease, renovascular hypertension due to the possibility of developing acute hypotension, azotemia, oliguria, and in rare cases, acute renal failure. Particular caution is also required when using Cardosal Plus in patients with aortic or mitral stenosis, obstructive hypertrophic cardiomyopathy. The use of the drug in patients with primary hyperaldosteronism is inappropriate. To prevent the development of symptomatic hypotension, before using Cardosal Plus, it is necessary to eliminate the deficiency of blood volume and/or sodium, if any. When using the drug in patients with mild or moderate impaired renal function (creatinine clearance - 30-60 ml/min), no dose adjustment is required, however, regular monitoring of renal function and the level of potassium and uric acid in the blood serum is recommended. Treatment with thiazide diuretics may impair glucose tolerance and lead to the manifestation of latent diabetes mellitus, and in patients with diabetes mellitus, dose adjustment of insulin or oral antidiabetic drugs may be required. When using the drug Cardosal Plus, it is recommended to periodically monitor the level of potassium and other electrolytes in the blood serum. This medicine contains lactose and should not be used by patients with hereditary galactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome. The presence of hydrochlorothiazide in the drug may cause a positive doping test. In people of the Negroid race, the severity of the hypotensive effect of ACE inhibitors, including olmesartan medoxomil, may be less than in representatives of other races. No special studies have been carried out on the ability of the drug to influence the reaction rate when driving vehicles or working with machinery. It should be taken into account that patients using antihypertensive drugs may sometimes experience drowsiness, dizziness or fatigue.
Contraindications
- Renal failure , a condition after a kidney transplant.
- Obstruction of the biliary tract.
- Lactase deficiency , malabsorption or galactosemia.
- Age less than 18 years.
- Pregnancy and lactation .
- Hypersensitivity to the components of the drug.
It is recommended to use the drug with caution in the following diseases and conditions:
- obstructive hypertrophic cardiomyopathy;
- heart valve stenosis
- primary aldosteronism;
- mild renal failure
- hyperkalemia or hyponatremia;
- chronic cardiac failure;
- cardiac ischemia;
- bilateral renal artery stenosis
- cerebrovascular disorders;
- decreased volume of circulating fluid due to diet , vomiting or diarrhea;
- liver dysfunction;
- elderly age;
- combined use with diuretics.
Interactions of the drug Cardosal plus
Combination of olmesartan medoxomil with hydrochlorothiazide Combinations whose use is not recommended Lithium - increases its concentration in the blood serum and increases toxicity. Combinations the use of which requires caution Baclofen - may enhance the antihypertensive effect. NSAIDs, including acetylsalicylic acid - decreased antihypertensive activity; in patients with kidney pathology, renal function may deteriorate up to the development of acute renal failure. Amifostine - may enhance the antihypertensive effect. Other antihypertensive drugs - enhance the antihypertensive effect. Alcohol, barbiturates, narcotic drugs, antidepressants - the appearance or intensification of orthostatic hypotension. Olmesartan medoxomil Use with drugs that increase the level of potassium in the blood plasma (potassium-sparing diuretics, heparin, ACE inhibitors) is not recommended - hyperkalemia may develop. With the simultaneous use of non-absorbable antacids (aluminum-magnesium hydroxide), a slight decrease in the bioavailability of olmesartan medoxomil was noted. The latter does not affect the pharmacokinetics or pharmacodynamics of warfarin or the pharmacokinetics of digoxin. The combined use of olmesartan medoxomil and pravastatin in healthy probands did not affect their pharmacokinetics. In vitro, olmesartan medoxomil does not have an inhibitory effect on cytochrome P450 enzymes. Hydrochlorothiazide Combinations whose use is not recommended Concomitant use with drugs that reduce the level of potassium in the blood (other diuretics that remove potassium from the body, laxatives, corticosteroids, ACTH, amphotericin, carbenoxolone, penicillin G sodium salt, salicylates) is not recommended - hypokalemia may develop. Combinations the use of which requires caution Calcium salts - increase the level of calcium in the blood. Cholestyramine and colestipol reduce the absorption of hydrochlorothiazide. Digitalis glycosides may cause hypokalemia and hypomagnesemia with the development of arrhythmia. Drugs whose side effects are more likely to occur with hypokalemia (class Ia and III antiarrhythmic drugs, antipsychotics, e.g. thioridazine, chlorpromazine, levomepromazine, trifluoperazine, cyamemazine, sulpiride, sultopride, amisulpride, tiapride, pimozide, haloperidol, droperidol; other drugs, e.g. bepridil , cisapride, difemanil, erythromycin for intravenous administration, halofantrine, mizolastine, pentamidine, sparfloxacin, terfenadine, vincamine for intravenous administration) - the development of severe cardiac arrhythmia, up to ventricular fibrillation, is possible. Non-depolarizing muscle relaxants (tubocurarine) - enhance the effect of muscle relaxants. Anticholinergic drugs (atropine) - increase the bioavailability of thiazide diuretics. Antidiabetic drugs (insulin and oral hypoglycemic agents) - Dosage adjustments of these drugs may be necessary due to the effect of hydrochlorothiazide on glucose tolerance. Metformin is a risk of developing lactic acidosis due to possible renal failure under the influence of hydrochlorothiazide. β-adrenergic receptor blockers and diazoxide-thiazides can enhance their hyperglycemic effect. Sympathomimetics (norepinephrine) - the effect of sympathomimetics may be reduced. Drugs for the treatment of gout (probenecid, sulfinpyrazone, allopurinol) - dose adjustment of these drugs may be required due to an increase in serum uric acid levels under the influence of hydrochlorothiazide, an increase in the frequency of hypersensitivity reactions to allopurinol under the influence of hydrochlorothiazide. Amantadine increases the risk of side effects. Cytotoxic drugs (cyclophosphamide, methotrexate) - thiazides can reduce their excretion by the kidneys and thereby increase their myelosuppressive effect. Salicylates - increasing their toxic effect on the central nervous system when used in high doses. Methyldopa - possible development of hemolytic anemia. Cyclosporine increases the risk of developing hyperuricemia and gout-like complications. Tetracyclines, including doxycycline - increases the likelihood of increased urea levels in the blood.
Interaction
Concomitant use with potassium supplements, potassium-sparing diuretics or other drugs that can increase potassium in the blood is not recommended.
The antihypertensive effect of treatment with olmesartan is enhanced when used in combination with other antihypertensive drugs.
Nonsteroidal anti-inflammatory drugs, cyclooxygenase type 2 inhibitors, and angiotensin type 2 receptor blockers may interact synergistically to inhibit glomerular filtration. In this case, there is a possibility of acute renal failure . To avoid such phenomena, it is recommended to monitor kidney function at the beginning of therapy, as well as timely intake of a sufficient volume of fluid.
When used together with antacids , a moderate decrease in the bioavailability of olmesartan is possible.
The use of olmesartan together with lithium preparations is dangerous due to an increase in the concentration of the latter in the blood.
Overdose of the drug Cardosal plus, symptoms and treatment
There is no data on an overdose of Cardosal Plus. The most likely symptoms of an overdose of olmesartan medoxomil may be hypotension, tachycardia or bradycardia. In case of an overdose of hydrochlorothiazide, nausea, drowsiness, muscle cramps and heart rhythm disturbances are observed, especially with the combined use of cardiac glycosides or certain antiarrhythmic drugs. In case of overdose, gastric lavage is performed, activated charcoal is used, symptomatic and supportive therapy is carried out. There is no data on the effectiveness of dialysis.
Cardosal price, where to buy
In Russia, the price of Cardosal 10 No. 28 is 460-570 rubles, the price of Cardosal 20 No. 28 is 505-660 rubles, and Cardosal 40 with the same number is 670-715 rubles.
In Ukraine, prices for the drug in the same release forms are close to 248, 328 and 374 hryvnia, respectively.
- Online pharmacies in RussiaRussia
- Online pharmacies in UkraineUkraine
ZdravCity
- Cardosal tablets p.p.o.
10 mg 28 pcs. Daichi Sankyo Europe GmbH RUR 594 order - Cardosal Plus tablets p.p.o. 12.5 mg+20 mg 28 pcs. Daichi Sankyo Europe GmbH
RUR 794 order
- Cardosal tablets p.p.o. 20 mg 28 pcs. Daichi Sankyo Europe GmbH
RUR 762 order
Pharmacy Dialogue
- Cardosal plus (tab. p.pl/vol. 12.5 mg + 20 mg No. 28) Daiichi Sankyo
RUB 816 order
- Cardosal (tab.p/vol.10mg No. 28)Berlin-Chemie AG/Menarini
RUR 576 order
- Cardosal (tab.p/vol.40mg No. 28)Berlin-Chemie AG/Menarini
RUB 816 order
- Cardosal (tablet p/o 20 mg No. 28)Berlin-Chemie AG/Menarini
RUR 744 order
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Pharmacy24
- Cardosal plus 20/12.5 No. 28 tablets Daichie Sankio Europe GmbH/Berlin Chemie AG (Menarini Group), Nimechchina/Nimechchina
380 UAH.order - Cardosal 40 mg No. 28 tablets Berlin Chemi AG, /Daichi Sankio Europe GmbH/Labor.Menarini S.A., Nimechchina
427 UAH. order
- Cardosal plus 20/25 No. 28 tablets Berlin Chemi AG, Nimechchina
380 UAH. order
- Cardosal 20 mg No. 28 tablets Berlin Chemi AG, /Daichi Sankio Europe GmbH/Labor.Menarini S.A., Nimechchina
388 UAH order
- Cardosal 10 mg N28 tablets Berlin Chemi AG, /Daichi Sankio Europe GmbH/Labor.Menarini S.A., Nimechchina
312 UAH. order
