Atacand Plus 16mg pills + 12.5mg N28
Condition: New product
1000 Items
Rating:
Be the first to write a review!
More info
Active ingredients
Hydrochlorothiazide + Candesartan
Release form
Pills
Composition
Candesartan cilexetil 16 mg hydrochlorothiazide 12.5 mg Excipients: Carmellose calcium (carmellose calcium salt) - 5.6 mg, hyprolosis - 4 mg, lactose monohydrate - 68 mg, magnesium stearate - 1.3 mg, corn starch - 20 mg, macrogol - 2.6 mg, dye iron oxide yellow CI 77492 - 0.21 mg, iron dye red oxide CI 77491 - 0.05 mg.
Pharmacological effect
Combined antihypertensive drug. Angiotensin II is the main hormone of the RAAS, which plays an important role in the pathogenesis of hypertension, heart failure and other cardiovascular diseases. The main physiological effects of angiotensin II are vasoconstriction, stimulation of aldosterone production, regulation of the water-electrolyte state, and stimulation of cell growth. The effects are mediated by the interaction of angiotensin II with type 1 angiotensin receptors (AT1 receptors). Candesartan is a selective antagonist of angiotensin II receptor AT1, does not inhibit ACE (converts angiotensin I to angiotensin II, destroys bradykinin), does not result in the accumulation of bradykinin or substance R. As a result of blocking the angiotensin II AT1 receptor, a dose-dependent increase in renin level occurs, blocking rinine, gain, Rin, and rineinine do not result. I, angiotensin II and a decrease in the concentration of aldosterone in the blood plasma. When comparing candesartan with ACE inhibitors, the development of cough was less common in patients who received candesartan cilexetil. Candesartan does not bind to receptors of other hormones and does not block the ion channels involved in regulating the functions of the cardiovascular system. The clinical effect of candesartan cilexetil on morbidity and mortality when administered at a dose of 8–16 mg (average dose of 12 mg) was studied 1 time per day in a randomized clinical trial involving 4937 patients aged 70 to 89 years (21% of patients aged 80 years and older) with mild to moderate arterial hypertension, receiving Candesartan cilexetil therapy, on average, for 3.7 years (a SCOPE study - a study of cognitive functions and prognosis in elderly patients). Patients received candesartan or placebo, if necessary, in combination with other antihypertensive agents. In the group of patients who received candesartan, there was a decrease in blood pressure from 166/90 to 145/80 mm Hg. and in the control group from 167/90 to 149/82 mm Hg.There were no statistically significant differences in the incidence of cardiovascular complications (mortality due to cardiovascular diseases, the incidence of myocardial infarction and stroke, which did not lead to death) between the two groups of patients were not observed. Hydrochlorothiazide, a thiazide-like diuretic, inhibits the active reabsorption of sodium, mainly in the distal regions of the renal tubules and enhances the release of sodium, chlorine and water ions. The excretion of potassium and magnesium by the kidneys increases with the dose, while calcium begins to be reabsorbed in larger quantities than before. Hydrochlorothiazide reduces the volume of blood plasma and extracellular fluid, reduces the intensity of blood transport by the heart, reduces blood pressure. During long-term treatment, the hypotensive effect develops due to the expansion of arterioles. With prolonged use of hydrochlorothiazide decreases the risk of cardiovascular diseases and mortality. Candesartan and hydrochlorothiazide have a potent hypotensive effect. In patients with arterial hypertension, Atacand Plus causes an effective and prolonged decrease in blood pressure without an increase in heart rate. Orthostatic hypotension at the first dose of the drug is not observed, after the end of treatment arterial hypertension does not increase. After a single dose of the drug Atacand Plus, the main hypotensive effect develops within 2 hours. Using the drug 1 time / day effectively and gently reduces blood pressure within 24 hours with a slight difference between the maximum and average effect of the action. With prolonged treatment, a steady decrease in blood pressure occurs within 4 weeks after the start of the drug and can be maintained with a long course of treatment. In clinical studies, the incidence of side effects, especially cough, was less common with Atacand Plus than when taking a combination of ACE inhibitors with hypothiazide. Currently, there are no data on the use of the combination of candesartan / hydrochlorothiazide in patients with renal failure, nephropathy, reduced left ventricular function, acute heart failure, and after myocardial infarction. The effectiveness of the combination candesartan / hydrochlorothiazide does not depend on gender and age.
Pharmacokinetics
Absorption and distribution of candesartan cilexetil Candesartan cilexetil is a prodrug for oral administration. When absorbed from the gastrointestinal tract, candesartan cilexetil is rapidly converted into active substance — candesartan by means of ether hydrolysis; it binds strongly to AT1 receptors and slowly dissociates and has no agonist properties. The absolute bioavailability of candesartan after ingestion of a solution of candesartan cilexetil is about 40%. The relative bioavailability of the tablet preparation compared to the oral solution is approximately 34%. Thus, the calculated absolute bioavailability of the tablet form of the drug is 14%. Eating does not have a significant effect on the area under the concentration-time curve (AUC), i.e. food does not significantly affect the bioavailability of the drug. Cmax in serum is reached 3-4 hours after taking the tablet form of the drug. With increasing doses of the drug in the recommended limits, the concentration of candesartan increases linearly. Binding of candesartan to plasma proteins - more than 99%. Plasma Vd candesartan is 0.1 L / kg. The pharmacokinetic parameters of candesartan do not depend on the sex of the patient. Hydrochlorothiazide Hydrochlorothiazide is rapidly absorbed from the gastrointestinal tract. Bioavailability is approximately 70%. Concomitant food intake increases absorption by approximately 15%. Bioavailability can be reduced in patients with heart failure and severe edema. Plasma protein binding is approximately 60%. Visible Vd is approximately 0.8 l / kg. Metabolism and elimination of Candesartan Cilexetil Candesartan is mainly excreted in the urine and bile in an unchanged form and is only slightly metabolized in the liver. T1 / 2 candesartan is approximately 9 hours. There is no cumulation of the drug in the body. The total clearance of candesartan is about 0.37 ml / min / kg, while the renal clearance is about 0.19 ml / min / kg. Renal excretion of candesartan is carried out by glomerular filtration and active tubular secretion. When administered radioactively-labeled candesartan cilexetil, about 26% of the injected amount is excreted in the urine as candesartan and 7% as an inactive metabolite, whereas 56% of the injected amount is detected in candesartan and 10% as an inactive metabolite.Hydrochlorothiazide Hydrochlorothiazide is not metabolized and is excreted almost completely as the active form of the drug by glomerular filtration and active tubular secretion in the proximal nephron. T1 / 2 is about 8 hours and does not change when taken together with candesartan. Approximately 70% of the dose taken orally is excreted in the urine within 48 hours. When using a combination of drugs, no additional accumulation of hydrochlorothiazide was found in comparison with monotherapy. Pharmacokinetics in special clinical situations Candesartan cilexetil Pharmacokinetic parameters of candesartan do not depend on the sex of the patient. In patients over 65 years of age, Cmax and AUC of candesartan are increased by 50% and 80%, respectively, compared with younger patients. However, the hypotensive effect and the frequency of side effects in the application of Atakanda Plus does not depend on the age of the patients. In patients with mild and moderate renal impairment, Cmax and AUC of candesartan increased by 50% and 70%, respectively, while the T1 / 2 of the drug does not change compared with patients with normal renal function. In patients with severe impaired renal function and / or on hemodialysis, Cmax and AUC of candesartan increased by 50% and 110%, respectively, and the T1 / 2 of the drug was increased 2-fold. In patients with mild and moderately impaired liver function, an increase in AUC of candesartan was noted by 23%. Hydrochlorothiazide T1 / 2 is more prolonged in patients with renal insufficiency.
Indications
- treatment of arterial hypertension in patients for whom combination therapy is indicated.
Contraindications
- abnormal liver function and / or cholestasis; - renal dysfunction (CC <30 ml / min / 1.73 m2); - anuria; - refractory hypokalemia and hypercalcemia; - gout; - pregnancy; - lactation period (breastfeeding); - children's and teenage age up to 18 years (efficiency and safety are not established); - Hypersensitivity to the active or auxiliary components of the drug; - hypersensitivity to sulfonamide derivatives. With careful use of medication for severe chronic cardiac insufficiency, bilateral renal artery stenosis, stenosis of the artery only kidneys, hemodynamically significant stenosis, aortic and mitral valves, in patients with cerebrovascular disease, ischemic heart disease, hypertrophic obstructive cardiomyopathy, with reduced BCC, cirrhosis with lactose intolerance , violation of the absorption of lactose and galactose,hyponatremia, primary hyperaldosteronism, surgery, kidney transplantation, renal failure, and diabetes mellitus.
Use during pregnancy and lactation
Experience with the use of the drug Atacand Plus in pregnant women is limited. These data are not enough to judge the possible danger to the fetus in the first trimester of pregnancy. In the human embryo, the kidney blood supply system, which depends on the development of the RAAS, begins to form in the second trimester of pregnancy: the risk to the fetus increases with the appointment of Atakanda Plus in the last 6 months of pregnancy. Funds that have a direct effect on the RAAS can cause abnormal fetal development or have a negative effect on the newborn (arterial hypotension, renal dysfunction, oliguria and / or anuria, oligohydramnion, hypoplasia of the skull bones, intrauterine growth retardation), up to fatal outcome, use of the drug in the last six months of pregnancy. Cases of lung hypoplasia, facial abnormalities and contractures of the extremities were also described. In animal studies, kidney damage was detected in the embryonic and neonatal periods when candesartan was used. It is assumed that the damage mechanism is due to the pharmacological effects of the drug on the RAAS. Hydrochlorothiazide is able to reduce the volume of blood plasma, uteroplacental blood flow and cause thrombocytopenia in the newborn. Based on the information received, Atacand Plus should not be used during pregnancy. If pregnancy occurs during the period of treatment with Atacandom, therapy should be discontinued. It is currently unknown if candesartan passes into breast milk. However, candesartan is released from the milk of lactating rats. Hydrochlorothiazide penetrates the mother's milk. Due to the possible undesirable effect on infants, Atacand Plus should not be used during breastfeeding.
Dosage and administration
Atacand Plus should be taken 1 time / day, regardless of the meal. The recommended dose - 1 tab. 1 time / day It is recommended to titrate the dose of candesartan before transferring the patient to therapy with Atacandom Plus. If necessary, patients are transferred from Atacand monotherapy to Atacand Plus therapy.The main hypotensive effect is achieved, as a rule, in the first 4 weeks after the start of treatment. In patients with impaired renal function, the use of loop diuretics is preferable to thiazide. Prior to the initiation of therapy with Atacand Plus, patients with mild or moderate renal dysfunction (CC> 30 ml / min / 1.73 m2), including patients on hemodialysis, candesartan dose titration is recommended (using monotherapy with Atacand) starting at 4 mg. Atacand Plus is contraindicated in patients with severe renal insufficiency (CC <30 ml / min / 1.73 m2). For patients with a risk of arterial hypotension (for example, with a reduced BCC), candesartan dose titration is recommended (through monotherapy with Atacand), starting at 4 mg. Elderly patients dose adjustment is not required.
Side effects
Side effects identified during clinical studies were moderate and transient in nature and were comparable in frequency with the placebo group. The incidence of discontinuation due to side effects was similar when using a combination of candesartan / hydrochlorothiazide (3.3%) and placebo (2.7%). In a pooled analysis of the results of clinical studies, the following side effects were noted, caused by prescribing a combination of candesartan and hydrochlorothiazide. The described side effects were observed with a frequency of at least 1% more than in the placebo group. From the side of the central nervous system: dizziness, weakness. Candesartan Cilexetil The following side effects during the post-marketing use of the drug were reported very rarely (<1 / 10.000). On the part of the blood system: leukopenia, neutropenia and agranulocytosis. From the side of the central nervous system: dizziness, headache. On the part of the digestive system: nausea, increased activity of liver enzymes, abnormal liver function, hepatitis. On the part of the musculoskeletal system: back pain, arthralgia, myalgia. On the part of the urinary system: impaired renal function (including renal failure in susceptible patients). Metabolism: hyperkalemia, hyponatremia. Allergic reactions: angioedema, rash, urticaria, pruritus. Hydrochlorothiazide In monotherapy with hydrochlorothiazide at a dose of 25 mg or more, the following side effects were noted with a frequency: often (> 1/100), sometimes (> 1/1000 and <1/100), rarely (<1/1000).On the part of the blood system: rarely - leukopenia, neutropenia, agranulocytosis, thrombocytopenia, aplastic anemia, bone marrow depression, anemia. From the side of the central nervous system and peripheral nervous system: often - slight dizziness, headache; rarely - sleep disturbance, depression, anxiety, paresthesia. On the part of the senses: rarely - transient image blur. Since the cardiovascular system: sometimes - orthostatic hypotension; rarely - arrhythmia, necrotic vasculitis, skin vasculitis. On the part of the respiratory system: rarely - shortness of breath (pneumonia and pulmonary edema). On the part of the digestive system: sometimes - loss of appetite, diarrhea, constipation; rarely, pancreatitis, intrahepatic cholestatic jaundice. On the part of the musculoskeletal system: rarely - myalgia. From the urinary system: often - glycosuria; rarely - impaired renal function, interstitial nephritis. Metabolism: often - hyperglycemia, hyperuricemia, hyponatremia, hypokalemia, hypercholesterolemia, hypertriglyceridemia; rarely, increased creatinine levels. Allergic reactions: sometimes - skin rash, urticaria, photosensitivity; rarely, anaphylactic reactions, epidermal necrosis, recurrence of cutaneous erythematosus, reactions similar to cutaneous erythematosis. Others: often - weakness; seldom - feeling hot. An increase in plasma uric acid and ALT and blood glucose levels were noted as side effects occurring when using candesartan cilexetil (approximate complaint frequency 1.1%, 0.9% and 1%, respectively) slightly more often than when using placebo (0.4% , 0% and 0.2% respectively). In some patients taking the combination of candesartan / hydrochlorothiazide, there was a slight decrease in hemoglobin concentration and an increase in ACT in the blood plasma. An increase in creatinine, urea, hyperkalemia and hyponatremia was also observed.
Overdose
Symptoms Analysis of the pharmacological properties of the drug suggests that the main manifestation of overdose may be a clinically pronounced decrease in blood pressure, dizziness. Individual cases of drug overdose (up to 672 mg of candesartan), which ended in the recovery of patients without serious consequences, were described. The main manifestation of hydrochlorothiazide overdose is an acute loss of fluid and electrolytes.Also, symptoms such as dizziness, decreased blood pressure, dry mouth, tachycardia, ventricular arrhythmia, loss of consciousness and muscle cramps were observed. Treatment With the development of a clinically pronounced decrease in blood pressure, it is necessary to carry out symptomatic treatment and monitor the patient's condition. Lay the patient on his back and lift his legs. If necessary, increase the bcc, for example, by IV injection of isotonic sodium chloride solution. If necessary, sympathomimetic agents may be prescribed. Removal of candesartan and hydrochlorothiazide with hemodialysis is unlikely.
Interaction with other drugs
In pharmacokinetic studies, the combined use of Atacanda Plus with hydrochlorothiazide, warfarin, digoxin, oral contraceptives (ethinyl estradiol / levonorgestrel), glibenclamide, nifedipine and enalapril was studied. No clinically significant drug interactions have been identified. Candesartan is metabolized to the liver to an insignificant degree (CYP2C9). Studies on the interaction did not reveal the effect of the drug on CYP2C9 and CYP3A4, the effect on other isoenzymes of the cytochrome P450 system has not been studied. The combined use of Atacanda Plus with other antihypertensive agents potentiates the hypotensive effect. The action of hydrochlorothiazide, leading to the loss of potassium, may be enhanced by other means leading to the loss of potassium and hypokalemia (for example, diuretics, laxatives, amphotericin, carbenoxolone, penicillin g sodium, salicylic acid derivatives). Experience with other drugs acting on the renin-angiotensin-aldosterone system shows that concomitant therapy with potassium-sparing diuretics, potassium preparations, salt substitutes containing potassium, and other means that increase serum potassium levels (eg heparin) can lead to the development of hyperkalemia. Induced by diuretics, hypokalemia and hypomagnesemia predispose to the possible cardiotoxic action of digitalis glycoside and antiarrhythmic drugs. When taking Atacand Plus along with such drugs requires monitoring the level of potassium in the blood.In the combined prescription of lithium preparations with ACE inhibitors, there is a reversible increase in the concentration of lithium in the blood serum and the development of toxic reactions. Such reactions can also occur when using angiotensin II receptor antagonists, and therefore it is recommended to control the level of lithium in the blood serum with the combined use of these drugs. The diuretic, natriuretic and hypotensive actions of hydrochlorothiazide are weakened by NSAIDs. Hydrochlorothiazide absorption is weakened by the use of colestipol, Kolestiramine. The action of non-depolarizing muscle relaxants (for example, tubocurarine) can be enhanced by hydrochlorothiazide. Thiazide-like diuretics can cause an increase in calcium levels in the blood due to a decrease in its excretion. If you need to use calcium supplements or vitamin D, you should monitor the level of calcium in the blood plasma and, if necessary, adjust the dose. Thiazide-like diuretics enhance the hyperglycemic effect of beta-blockers and diazoxide. Anticholinergics (for example, atropine, biperidine) can increase the bioavailability of thiazide-like diuretics due to decreased GI motility. Thiazide-like diuretics may increase the risk of adverse effects of amantadine. Thiazide-like diuretics can slow the elimination of cytostatic drugs (such as cyclophosphamide, methotrexate) from the body and increase their myelo-suppressive effect. The risk of hypokalemia may increase with concomitant use of GCS or ACTH. Against the background of the use of the drug Atacand Plus, the incidence of orthostatic hypotension may increase when taking alcohol, barbiturates or general anesthetics. In the treatment of thiazide-like diuretics, glucose tolerance may decrease, and therefore it may be necessary to select a dose of hypoglycemic drugs (including insulin). Hydrochlorothiazide may reduce the effects of vasoconstricting amines (eg, epinephrine). Hydrochlorothiazide may increase the risk of developing acute renal failure, especially when combined with large doses of iodinated vehicle. Significant interaction of hydrochlorothiazide with food was not detected.
special instructions
Impaired renal function In this situation, the use of "loop" diuretics is preferable to thiazide-like ones. For patients with renal insufficiency with Atacandom therapy, it is recommended to constantly monitor the level of potassium, creatinine and uric acid. Kidney Transplantation There are no data on the use of Atacanda Plus in patients who have recently had a kidney transplant. Renal artery stenosis Other drugs that affect the RAAS (for example, ACE inhibitors) can lead to an increase in blood urea and creatinine in the serum of patients with bilateral renal artery stenosis or arterial stenosis of a single kidney. A similar effect should be expected from angiotensin II receptor antagonists. Reduction of BCC In patients with a deficiency of intravascular volume and / or sodium, symptomatic arterial hypotension may develop: Atacand Plus is not recommended until these symptoms disappear. General anesthesia and surgery In patients receiving angiotensin II antagonists, during anesthesia and during surgery, arterial hypotension may develop as a result of the renin-angiotensin system blockade. Very rarely, there may be cases of severe arterial hypotension, requiring IV fluids and / or vasoconstrictor agents. Hepatic failure Patients with impaired liver function or progressive liver disease should use thiazide-like diuretics with caution: slight fluctuations in fluid volume and electrolyte composition may cause hepatic coma. Data on the use of Atacand Plus patients with hepatic insufficiency are not available. Aortic and mitral valve stenosis (hypertrophic obstructive cardiomyopathy) When prescribing Atacanda Plus patients with obstructive hypertrophic cardiomyopathy or hemodynamically significant stenosis of the aortic or mitral valve, caution should be exercised. Primary Hyperaldosteronism Patients with primary hyper aldosteronism are usually resistant to antihypertensive treatment with anti-RAAS. In this regard, it is not recommended to prescribe such patients Atacand Plus.Violation of water-salt balance As in all cases of taking drugs that have a diuretic effect, electrolytes in blood plasma should be monitored. Thiazide-based drugs with a diuretic effect can reduce the excretion of calcium ions in the urine and can cause abrupt changes and a slight increase in the concentration of calcium ions in the blood plasma. Thiazides, incl. and hydrochlorothiazide, can cause disturbances in water-salt balance (hypercalcemia, hypokalemia, hyponatremia, hypomagnemia and hypochloraemic alkalosis). Revealed hypercalcemia may be a sign of latent hyperthyroidism. The use of thiazide-like diuretics should be discontinued before obtaining the results of the parathyroid gland analysis. Hydrochlorothiazide increases potassium excretion in a dose-dependent manner, which can cause hypokalemia. This effect of hydrochlorothiazide is less pronounced when used in combination with candesartan cilexetil. The risk of hypokalemia is increased in patients with cirrhosis of the liver, increased diuresis, receiving a liquid with a low salt content, undergoing parallel treatment of GCS or ACTH. Based on the experience of using drugs that affect the renin-angiotensin-aldosterone system, parallel use of Atacand Plus and increasing potassium excretion of diuretics can be compensated by using dietary supplements containing potassium or other drugs that can increase plasma potassium. The use of Atacand Plus can cause hypokalemia, especially in patients with cardiac or renal failure (such cases have not been documented). Thiazide-like diuretics increase magnesium excretion, which can cause hypomagnesemia. Impact on metabolism and endocrine system The use of thiazide-like diuretics can change the level of glucose in the blood, up to the manifestation of latent diabetes mellitus. It may be necessary to adjust the dose of hypoglycemic agents, including insulin. Thiazide-like diuretics are associated with an increase in plasma cholesterol and triglyceride levels. However, when using Atacand Plus at a dose of 12.5 mg, there was a minimal amount or absence of similar effects.Thiazide-like diuretics increase plasma concentrations of uric acid and may contribute to the occurrence of gout in susceptible patients. General Patients in whom vascular tone and renal function depend primarily on the activity of the RAAS (for example, patients with severe chronic heart failure, kidney disease, including renal artery stenosis) are particularly sensitive to drugs acting on the RAAS. In these patients, the administration of such drugs is accompanied by severe arterial hypotension, azotemia, oliguria and, less commonly, acute renal failure. The possibility of the development of these effects is not excluded when using angiotensin II receptor antagonists. A sharp decrease in blood pressure in patients with ischemic cardiopathy, cerebrovascular diseases of ischemic genesis when using any antihypertensive drugs can lead to the development of myocardial infarction or stroke. The manifestation of hypersensitivity reactions to hydrochlorothiazide is most likely in patients with bronchial asthma, a history of allergic reactions; which does not exclude the appearance of allergic symptoms in other patients. When using thiazide-like diuretics, there have been cases of exacerbation or the appearance of symptoms of congestive seborrhea. The drug contains lactose, so it should not be taken in patients with rare hereditary diseases, manifested in the absence of lactose tolerance, lactose deficiency or impaired glucose absorption and lactose. Use in Pediatrics The safety and efficacy of Atacanda Plus in children and adolescents under the age of 18 years have not been established. The effect on the ability to drive motor vehicles and control mechanisms The effect on the ability to drive or work with equipment has not been studied, but the pharmacodynamic properties of the drug indicate that there is no such effect. Patients should be cautious when driving vehicles or working with equipment, as dizziness may occur during treatment and increased fatigue may occur.