Cardosal Plus pills 12.5 mg + 20 mg 28 pcs
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Active ingredients
Olmesartan medoximyl + Hydrochlorothiazide
Release form
Pills
Composition
Hydrochlorothiazide 12.5 mg; olmesartan medoxomil 20 mg
Pharmacological effect
Cardosal plus is a combination drug that contains the angiotensin II receptor antagonist (olmesartan medoxomil) and thiazide diuretic (hydrochlorothiazide). The combination of the two active substances has a combined anti-hypertensive effect, as a result of which the 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 decrease in blood pressure is achieved within 24 hours; Olmesartan medoxomil is a specific antagonist of angiotensin II receptors (such as 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 by influencing AT1 receptors. It is assumed that olmesartan medoxomil blocks all effects of angiotensin II mediated by the AT1 receptor, regardless of the source and route of synthesis of angiotensin II; medoxomil causes arterial hypertension of olmesartan and a dose-dependent prolonged 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 "withdrawal" syndrome (a sharp increase in blood pressure after discontinuation of the drug) .; Taking olmesartan medoxomil once a day provides an effective and mild decrease in blood pressure over 24 hours. The hypotensive effect of olmesartan medoxomil occurs, as a rule, after 2 weeks, and the maximum effect develops after about 8 weeks. after initiation of therapy. Hydrochlorothiazide, a thiazide diuretic, disrupts the reabsorption of sodium, chlorine and water ions in the renal tubules. Increases the excretion of potassium, magnesium, bicarbonate ions, retains calcium ions in the body. The diuretic effect occurs 2 hours after taking hydrochlorothiazide inside, reaches a maximum after 4 hours and lasts up to 12 hours. Helps reduce high blood pressure. With the combined use of olmesartan medoxomil and hydrochlorothiazide, there is a decrease in the loss of potassium ions caused by the action of a diuretic.The result of the combination therapy with olmesartan medoxomil and hydrochlorothiazide is the 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) remains, the development of the syndrome of "cancellation" is not observed.
Pharmacokinetics
Absorption and Distribution; Olmesartan Medoxomil is a prodrug. It quickly turns into a pharmacologically active metabolite of olmesartan under the action of enzymes in the intestinal mucosa and in peripheral blood during absorption from the gastrointestinal tract and circulates in the blood as a metabolite (olmesartan). The average bioavailability of olmesartan is 25.6%; Cmax of olmesartan in blood plasma is achieved on average 2 hours after ingestion and increases approximately linearly with an increase in a single dose up to 80 mg. can be taken regardless of food intake; no clinically significant differences in pharmacokinetic parameters of olmesargan medoxomil, depending on gender.; Olmesargan has a high degree of binding with plasma proteins (99.7%). With the simultaneous use of olmesartan medoxomil with other drugs, characterized by a high degree of binding to plasma proteins, there is no significant change of this magnitude (this is confirmed by the absence of clinically significant interaction between olmesartan medoxomil and warfarin). The connection of olmesartan with blood cells is insignificant. After ingestion of olmesartan medoxomil in combination with hydrochlorothi azide, the average time to reach Cmax of hydrochlorothiazide is 1.5-2 hours; Hydrochlorothiazide binds to plasma proteins by 68%. The systemic bioavailability of hydrochlorothiazide with simultaneous use with olmesartan medoxomil is reduced by about 20%, but this small decrease is not significant in clinical terms. The simultaneous appointment of hydrochlorothiazide, for its part, does not significantly affect the kinetics of olmesartan medoxomil.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.; Metabolism and elimination; The total plasma clearance of olmesartan is usually 1.3 l / h (variation coefficient - 19%) and is relatively low compared with hepatic blood flow (approximately 90 l / h). Renal excretion of olmesartan is approximately 40%, with bile through the intestine - about 60%; extrahepatic circulation is minimal. Since most of olmesartan medoxomil is metabolized in the liver, its use in patients with obstruction of the biliary tract is contraindicated. The half-life of olmesartan is 10-15 hours. The sustained effect of therapy is achieved during the first 14 days of daily administration of olmesartan medoxomil. Renal clearance is approximately 0.5–0.7 l / h and is not dose-dependent. Hydrochlorothiazide is not metabolized in the body and is almost completely excreted by the kidneys. After ingestion, about 60% of the accepted dose of hydrochlorothiazide is excreted unchanged within 48 hours. The renal clearance of hydrochlorothiazide is about 250-300 ml / min; T1 / 2 of the final phase is 10-15 hours; Pharmacokinetnka in different categories of patients; In patients aged 65-75 years with arterial hypertension, the area under the concentration-time curve (AUC) for olmesartan in the saturation stage increases compared with the group about 35% of patients younger than 65 years, about 44% of patients older than 75 years. Available data allow us to conclude that the systemic clearance of hydrochlorothiazide in both healthy elderly volunteers and elderly patients with arterial hypertension is reduced compared with volunteers of younger age. In patients with impaired renal function (CK = 30-60 ml / min.), The AUC for olmesartan in the saturation stage increases by approximately 62, 82 and 179% in the case of mild, moderate and severe impaired renal function, respectively, compared with healthy volunteers . For this category of patients, an increase in T1 / 2 of hydrochlorothiazide is possible. In patients with impaired mild and moderate liver function after a single oral administration, the AUC values for olmesartan were 6% and 65% higher, respectively, compared with healthy volunteers.The unbound fraction of olmesartan 2 h after administration of the drug dose in healthy volunteers, in patients with mild and moderate degrees of liver dysfunction was 0.26; 0.34 and 0.41%, respectively. The effect of impaired liver function on the pharmacokinetics of hydrochlorothiazide is insignificant.; For patients with severe impaired liver function (more than 9 points on the Child-Pugh scale), there are no data on the pharmacokinetics of olmesartan medoxomil.
Indications
- Essential arterial hypertension (with the ineffectiveness of olmesartan medoxomil monotherapy).
Contraindications
- hereditary lactose intolerance, lack 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), obstruction of the biliary tract and cholestasis; - pronounced renal dysfunction (CC less than 30 ml / min.); - refractory hypokalemia, hyponatremia, hypercalcemia and symptomatic hyperuricemia; - pregnancy; - lactation period; - age up to 18 years (efficacy and safety of the drug have not been studied); - hypersensitivity to olmesartan medoxomil, hydrochlorothiazide or other sulfonamide derivatives or to any of the excipients that make up the preparation (see the Composition section); with caution: - bronchial asthma; - Ischemic heart disease (CHD); - chronic heart failure in the stage of decompensation; - severe cerebrovascular disorders; - Aortic or mitral valve stenosis; - hypertrophic obstructive cardiomyopathy; - dysfunction of the liver mild and moderate (less than 9 points on the Child-Pugh scale); - impaired renal function (CC more than 30 ml / min, but less than 60 ml / min); - bilateral stenosis of the renal arteries or stenosis of the artery of a single kidney; - a condition after a recently transferred kidney transplantation (there is no experience with the use of the drug); - primary aldosteronism; - diabetes, gout; - violations of water and electrolyte balance, dehydration; - diseases of the connective tissue, including systemic lupus erythematosus; - patients on a salt-restricted diet or on hemodialysis; - in the suppression of bone marrow hematopoiesis; - conditions accompanied by a decrease in circulating blood volume; - (bcc) including diarrhea, vomiting, or previous diuretic therapy.
Use during pregnancy and lactation
Experience with olmesartan medoxomil in pregnant women is absent.However, in view of the existing reports of severe teratogenic effects of drugs acting on the RAAS, like any drug of this class, Cardosal plus is contraindicated for use in pregnancy. In the case of planning or the occurrence of pregnancy during drug therapy Cardosal plus the drug must be canceled as soon as possible. It is not known whether olmesartan medoxomil is excreted in breast milk, but thiazides are excreted in breast milk and can suppress lactation, therefore, if necessary, use Cardosal plus during lactation breastfeeding for the period of its administration should be stopped.
Dosage and administration
Cardosal pills are taken orally, regardless of the meal. Before prescribing the combined drug Cardosal plus, a preliminary selection of the dose of each of the active ingredients is recommended separately (ie, olmesartan medoxomil and hydrochlorothiazide) .; Recommended dose: Daily 1 tablet of the drug Cardosal plus containing 20 mg of olmesartan medoxomil and 12.5 mg of hydrochlorothiazide , in the absence of adequate blood pressure control on the background of monotherapy with olmesartan medoxomil at a dose of 20 mg; In the absence of adequate blood pressure control in patients receiving Cardosal Plus, containing 20 mg of olmesartan medoxomil and 12.5 mg of hydrochlorothiazide, it is possible to use Cardosal plus, containing 20 mg of olmesartan medoxomil and 25 mg of hydrochlorothiazide, 1 tablet each daily.; plus is 20 mg of olmesartan medoxomil and 25 mg of hydrochlorothiazide 1 time per day.; Elderly patients (over 65) with normal renal function (CC more than 90 ml / min) and patients with impaired renal function (CC = 30-60 ml / min.) Correction dose is not required.
Side effects
Possible side effects are listed below in descending frequency of occurrence: often (> 1/100, <1/10), infrequently (> 1/1000, <1/100), rarely (> 1/10000, <1/1000), very rarely (<1/10000), including individual reports.; Combination of olmesartan medoxomil and hydrochlorothiazide; CNS; Often: dizziness. Not often: syncope; Cardiovascular; Infrequent: heartbeat, marked decrease in blood pressure, orthostatic hypotension ; On the part of the skin; Infrequently: skin rash, eczema; On the part of the metabolism; Infrequently: hyper- or hypokalemia, hypercalcemia, ipertriglitseridemiya, hyperuricemia,elevation of blood lipids. On the laboratory side; Very rare: a slight increase in serum creatinine, uric acid and urea nitrogen, a slight decrease in hemoglobin and hematocrit.; Olmesartan Medoxomil (monotherapy); On the part of the hematopoietic system; Very rare : thrombocytopenia. From the side of the central nervous system; Very rarely: dizziness, headache. From the side of the cardiovascular system; Rarely: marked reduction in blood pressure. Not often: angina pectoris; From the respiratory system; Cha one hundred: bronchitis, pharyngitis, rhinitis.; Very rare: cough.; From the alimentary 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 rare: itchy skin, exanthema , angioedema, allergic dermatitis, urticaria.; From the exchange of things STV; Often: an increase in the activity of creatine phosphokinase, hypertriglyceridemia, hyperuricemia.; Rarely: hyperkalemia.; From laboratory indicators; Very rarely: an increase in the concentration of creatinine and urea in the serum.; Often: an increase in the activity of "hepatic" transaminases; : chest pain, flu-like symptoms, peripheral edema.; Very rare: weakness, fatigue, drowsiness, malaise.; Hydrochlorothiazide (monotherapy); From the hematopoietic system; Rarely: leukopenia, neutropenia I, agranulocytosis, thrombocytopenia, and plastic anemia, hemolytic anemia, inhibition of bone marrow hematopoiesis; From the central and peripheral nervous system; Often: dizziness, weakness, headache, fatigue.; Rarely: anxiety, sleep disturbance, confusion, apathy , depression, obnubilatsiya, paresthesia, convulsions. On the part of the organ of vision; Rarely: xantopsia, transient disturbance of accommodation, reduction of the formation of tears.; Of the cardiovascular system; Infrequent: orthostatism Essential hypotension; Rarely: arrhythmias, thrombosis,embolism.; On the part of the respiratory system; Rarely: dyspnea (including interstitial pneumonia and pulmonary edema) .; On the part of the digestive tract; Infrequently: anorexia, abdominal pain, nausea, vomiting, diarrhea, constipation, flatulence, inflammation of the salivary glands.; Rarely : pancreatitis, acute cholecystitis, intrahepatic cholestatic jaundice.; Very rare: paralytic intestinal obstruction.; From the urinary system; Rarely: impaired renal function, interstitial nephritis, acute renal failure, impaired potency.; From the locomotor rarely: muscle cramps, muscle weakness, paresis.; On the part of the skin; Infrequently: photosensitization, skin rash, urticaria; Rarely: the development of lupus-like syndrome (fever, arthralgia, myalgia, serositis, vasculitis, increased sedimentation rate ESR), leukocytosis, eosinophilia), activation of the skin form of systemic lupus erythematosus, anaphylactic reactions, toxic epidermal necrolysis. From the laboratory indicators; Often: hyperglycemia, glycosuria, hyperuricemia, increased concentration of cre tinina serum, disruption of water and electrolyte imbalance (including hyponatremia, hypomagnesemia, chloropenia, hypokalemia, and hypercalcemia), increasing the concentration of cholesterol and triglycerides in the blood; Other disorders; rare:. Fever.
Overdose
Symptoms: in case of overdose of olmesartan medoxomil, the most pronounced decrease in blood pressure, as well as tachycardia, bradycardia, nausea, drowsiness are most likely; in case of hydrochlorothiazide overdose - symptoms of electrolyte deficiency (hypokalemia, hypochloremia, hyponatremia) and dehydration due to excessive diuresis; Treatment: recommended gastric lavage and / or reception of activated charcoal; therapy aimed at correcting dehydration and impaired water and electrolyte balance. With a marked decrease in blood pressure, it is recommended to lay the patient in a horizontal position, raising his legs, and to conduct therapy aimed at replenishing the BCC. Hemodialysis is not effective.
Interaction with other drugs
Olmesartan medoxomil; Combined use with potassium-sparing diuretics, potassium preparations, salt substitutes containing potassium, or other drugs is not recommendedable to increase the concentration of potassium in the serum (eg, heparin) - it is possible to increase the concentration of potassium in the blood serum.; Non-steroidal anti-inflammatory drugs (NSAIDs), including acetylsalicylic acid in doses of more than 3 g / day, as well as cyclooxygenase-2 inhibitors (COX-2 ), and angiotensin II receptor antagonists can act synergistically, reducing glomerular filtration. With simultaneous use of NSAIDs and angiotensin II receptor antagonists, there may be a risk of developing acute renal failure, therefore, monitoring renal function at the beginning of treatment is recommended, as well as regular intake of a sufficient amount of fluid. However, simultaneous treatment can reduce the antihypertensive effect of angiotensin II receptor antagonists, leading to a partial loss of their therapeutic efficacy. With simultaneous use 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 concentration and manifestation of toxicity during simultaneous use of lithium preparations with angiotensin-converting enzyme inhibitors (ACE) and angiotensin II receptor antagonists, therefore, the use of olmesartan medoxomil in combination with lithium preparations is not recommended. If necessary, the use of appropriate combination therapy is recommended to regularly monitor the concentration of lithium in the serum. In rare cases, ACE inhibitors can enhance the hypoglycemic effect of insulin and hypoglycemic oral agents (for example, sulfonylurea derivatives) in diabetic patients. In these cases, with the simultaneous use of ACE inhibitors, it may be necessary to reduce the dose of the hypoglycemic agent for ingestion and insulin. when taken with hydrochlorothiazide, there may be an increase in electrolyte loss, in particular, the development of hypokalemia.; Simultaneous administration of ion-exchange drugs (colesteramine, wheels epol) reduces the absorption of hydrochlorothiazide;. In an application of hydrochlorothiazide with calcium salts may increase calcium concentration in serum, due to the reduction of its excretion.If it is necessary to prescribe calcium, its concentration in the serum should be monitored and its dose should be adjusted accordingly. With simultaneous use of hydrochlorothiazide with cardiac glycosides, arrhythmias may occur. Drugs that can cause a torsades des pointes ( a special form of polymorphic ventricular tachycardia with a wave, screw or spindle configuration of ventricular complexes in combination with an increase or decrease in the amplitude of the teeth of the QRS complex, It may result in ventricular fibrillation or asystole): due to the risk of hypokalemia, caution is required when using hydrochlorothiazide with some antiarrhythmic agents (quinidine, hydroquinidine, disopyramide, amiodarone, sotalol, dofetilide, ibutilide), neuroleptics (thyroid) zyneidiamine, tidyrididazine, thyroid, zyroidia, sothalol, dofetilide, ibutilide, neuroleptics (thyroid); trifluoperazine, cyamemazine, sulpiride, sultoprid, amisulpride, Tiapride, pimozide, haloperidol, droperidol and SIC, halofantrine, mizolastine, nentamidin, sparfloxacin, terfenadine, vincamine for intravenous administration), which are known that they can cause arrhythmia type "pirouette";. When combined with hydrochlorothiazide non-depolarizing muscle relaxants (including tubocurarine chloride) - increased action of muscle relaxants. Thiazides may increase the risk of side effects of amantadine. Treatment with thiazide diuretics may impair glucose tolerance. With the simultaneous use of M-anticholinergics (atropine) and thiazides, due to the reduced motility of the gastrointestinal tract, the bioavailability of thiazide diuretics may increase. : it may be necessary to adjust the dose of a hypouricemic agent (an increase in the dose of probenecid or sulfinpyrazone), since hydrochlorothiazide may increase the concentration of uric acid in serum. Simultaneous use with thiazide diuretics can increase the frequency of hypersensitivity reactions to allopurinol.The effect of sympathomimetics while taking thiazide diuretics can be weakened. Thiazide diuretics can reduce the excretion of cytotoxic drugs by the kidneys and increase their myelosuppressive effect. When taking salicylates in high doses, hydrochlorothiazide may increase their toxic effect on the CNS. simultaneous use of methyldopa with hydrochlorothiazide.; Simultaneous use of cyclosporine with hydrochlorothiazide may increase the risk of developing hyperuricemia and and exacerbation of gout.; The simultaneous use of tetracyclines with thiazide diuretics increases the risk of increasing the concentration of urea caused by tetracyclines. This interaction does not apply to doxycycline.; Olmesartan medoxomil / hydrochlorothiazide in combination; Simultaneous use of lithium preparations with thiazide diuretics may increase the already increased risk of lithium intoxication due to ACE inhibitors, therefore, combined use of the drug Cardosal plus and lithium preparations is not recommended. If this combination is still necessary, careful monitoring of the serum lithium concentration is also necessary. With the simultaneous use of the drug Cardosal * plus with baclofen and amifostine, the antihypertensive effect may be enhanced. With the simultaneous use of other antihypertensive drugs, the hypotensive effect of the drug Cardosal plus may be enhanced. Ethanol, barbiturates, narcotic analgesics, or antidepressants when used with Cardosal plus can lead to worsening orthostatic hypotension.
special instructions
Symptomatic arterial hypotension, especially after taking the first dose of the drug, can occur in patients with reduced BCC and / or reduced sodium concentration due to intensive diuretic therapy, restriction of salt intake with food in the diet, and also due to diarrhea or vomiting. Relevant factors should be eliminated before the use of the drug Cardosal Plus. Thiazide diuretics, including hydrochlorothiazide, can cause a violation of the BCC or the water-electrolyte balance of blood serum (including hypokalemia, hyponatremia and hypochloramic alkalosis).Symptoms of precursors are: dryness of the oral mucosa, thirst, weakness, drowsiness, anxiety, myalgia or convulsions, muscle weakness, arterial hypotension, oliguria, tachycardia, nausea and vomiting (see the Side Effects section); Highest risk of developing hypokalemia occurs in patients with cirrhosis of the liver, in patients during forced diuresis, and in those patients who also take glucocorticosteroids or ACTT (see the section on Interaction with Other Medicines). Conversely, due to the antagonism of the cardosal plus olmesartan medoxomil contained in the drug against angiotensin II (AT1), hyperkalemia can occur - primarily in patients with reduced kidney function and / or chronic heart failure, as well as in patients with diabetes mellitus. In patients with risk factors, regular monitoring of serum potassium concentrations is recommended. There is no data on whether olmesartan medoxomil can reduce hyponatremia caused by diuretics or interfere with its development. In hot weather patients with prone to edema may be dilutional hyponatremia. 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 without a history of metabolic disturbances. Hypercalihemia may indicate latent hyperparathyroidism. Before examining the function of the parathyroid glands, thiazides should be canceled. Thiazide diuretics have been proven to increase the excretion of magnesium ions by the kidneys, which can lead to hypomagnesemia. In patients whose vascular tone and kidney function depend to a large extent on the activity of the RAAS (for example, in patients with severe chronic heart failure or renal dysfunction, including renal artery stenosis), treatment with other drugs that affect the RAAS is associated with the possibility of developing acute arterial hypotension, nitrogen Mii, oliguria or, in rare cases, acute renal failure. The possibility of a similar action cannot be excluded when using angiotensin P. receptor antagonists. There is an increased risk of developing severe arterial hypotension and renal failure in the event thatif a patient with bilateral renal artery stenosis or arterial stenosis of a single functioning kidney is receiving 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 olmesartan medoxomil in patients with recent kidney transplantation or in patents with the last stage of renal dysfunction. In patients with renal impairment, thiazide diuretics may be associated with azotemia. With obvious progression of renal failure, it is necessary to review the therapy and decide on the elimination of diuretics. As in the case of any antihypertensive drug, an excessive decrease in blood pressure in patients with coronary artery disease or with cerebrovascular insufficiency can lead to myocardial infarction or stroke. glucose, as well as increasing the concentration of cholesterol, triglycerides and uric acid in the serum. In patients with diabetes mellitus, it may be necessary to adjust the dose of insulin or a hypoglycemic agent for oral administration (see the section on Interaction with Other Drugs). In the treatment of thiazide diuretics, latent diabetes mellitus may manifest.; There are reports that thiazide diuretics may contribute to the onset of a gout attack and cause an exacerbation of systemic lupus erythematosus. Reactions of hypersensitivity to hydrochlorothiazide may be more likely to occur in patients with a history of allergic or bronchial asthma (history). The effect on the ability to drive vehicles and control mechanisms; The effect of the drug Cardosal plus on the ability to drive vehicles and control mechanisms specifically studied, therefore, during the period of treatment with Cardosal plus, care should be taken when driving vehicles and practicing potentially dangerous species. activities that require high concentration and speed of psychomotor reactions.