Atakand Plus, tablets 16 mg+12, 5 mg 28 pcs.

Atacand Plus is a combined antihypertensive drug. Candesartan selectively blocks AT II receptors (AT subtype,). It prevents the effects of AT II – increase of BP due to vasoconstriction, stimulation of synthesis and release of aldosterone, renin, vasopressin, catecholamines, sodium reabsorption, increase of heart rate.

Creases OPPS, increases renal blood flow and glomerular filtration rate. Causes a compensatory increase in plasma renin activity, AT I and AT II concentrations.

Hydrochlorothiazide causes a moderately pronounced diuretic effect, increasing the excretion of sodium, chloride, potassium and water ions from the body, reducing the volume of plasma.blood and extracellular fluid.

Decreases the content of sodium ions in the vascular wall, reducing its sensitivity to vasoconstrictor effects and thereby increasing the hypotensive effect of candesartan. Atacand plus causes prolonged hypotensive effect without increasing HR.

There is no orthostatic arterial hypotension during the first administration; the AH does not increase after the end of treatment. The hypotensive effect develops gradually and lasts up to 24 hours.

The maximum therapeutic effect is usually achieved 4 weeks after the start of treatment. During absorption in the mucous membrane of the digestive tract it undergoes hydrolysis to form the active substance (candesartan).

Indications

Composition

One tablet contains:

The active ingredients:

candesartan cilexetil 16 mg,

hydrochlorothiazide 12.5 mg.

Excipients:

Calcium carmellose (carmellose calcium salt) 5.6 mg,

Hyprolose 4.0 mg,

lactose monohydrate 68 mg,

magnesium stearate 1.3 mg,

corn starch 20 mg,

macrogoal 2.6 mg,

iron oxide yellow dye CI 77492 0.21 mg,

iron oxide red dye CI 77491 0.050 mg.

How to take, the dosage

Overly, once a day regardless of meals. The recommended dose is 1 tablet once daily.

Titration of a dose of candesartan is recommended before transferring a patient to therapy with Atacandam Plus. If necessary, patients are transferred from Atacand monotherapy to therapy with Atacand Plus.

The main hypotensive effect is usually achieved in the first 4 weeks of treatment.

Interaction

In pharmacokinetic studies, co-administration of Atacanda Plus with hydrochlorothiazide, warfarin, digoxin, oral contraceptives (ethinylestradiol/levonorgestrel), glibenclamide, nifedipine and enalapril has been studied. No clinically significant drug interactions have been identified.

Candesartan is slightly metabolized in the liver (CYP2C9). The conducted studies on interaction showed no effect of the drug on CYP2C9 and CYP3A4, the effect on other isoenzymes of cytochrome P450 system has not been studied.

The co-administration of Atacanda Plus with other antihypertensive agents potentiates the hypotensive effect. The effect of hydrochlorothiazide leading to potassium loss may be enhanced by other drugs leading to potassium loss and hypokalemia (e.g., diuretics, laxatives, amphotericin, carbenoxolone, penicillin G sodium, salicylic acid derivatives).

The experience with other drugs acting on the renin-angiotensin-aldosterone system shows that concomitant therapy with potassium-saving diuretics, potassium preparations, salt substitutes containing potassium, and other agents that increase serum potassium levels (e.g., heparin) may lead to hyperkalemia.

Diuretic-induced hypokalemia and hypomagnesemia predispose to possible cardiotoxic effect of foxglove glycoside and antiarrhythmic agents. When taking Atakand® Plus concomitantly with such drugs it is required to control the blood potassium level.

When lithium preparations are combined with ACE inhibitors, reversible increase of lithium concentration in blood serum and development of toxic reactions occur. These reactions can also occur with angiotensin II receptor antagonists, therefore it is recommended that serum lithium levels be monitored when these drugs are used in combination.

The diuretic, natriuretic and hypotensive actions of hydrochlorothiazide are weakened by NSAIDs.

The absorption of hydrochlorothiazide is impaired when using colestipol, colestyramine.

The effects of nondepolarizing myorelaxants (e.g., tubocurarine) may be enhanced by hydrochlorothiazide.

Thiazide-like diuretics may increase blood calcium levels due to decreased calcium excretion. If it is necessary to use calcium-containing supplements or vitamin D, plasma calcium levels should be monitored and the dose should be adjusted if necessary.

Thiazide-like diuretics increase the hyperglycemic effect of beta-adrenoblockers and diazoxide.

The anticholinergic agents (e.g., atropine, biperidine) may 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 down the excretion of cytostatic agents (such as cyclophosphamide, methotrexate) from the body and increase their myelodepressant effect.

The risk of hypokalemia may increase with concomitant administration of GCS or ACTH.

The incidence of orthostatic arterial hypotension when taking alcohol, barbiturates or general anesthetics may increase with Atacand® Plus.

The treatment with thiazide-like diuretics may decrease glucose tolerance and may require adjusting the dose of hypoglycemic drugs (including insulin).

Hydrochlorothiazide may reduce the effect of vasoconstrictor amines (e.g., epinephrine).

Hydrochlorothiazide may increase the risk of acute renal failure, especially in combination with high doses of iodinated filler.

No significant interaction of hydrochlorothiazide with food has been found.

Special Instructions

Patients in whom vascular tone and renal function mainly depend on the activity of the renin-angiotensin-aldosterone system (e.g., patients with severe chronic heart failure, renal diseases, including renal artery stenosis) are particularly sensitive to drugs acting on the renin-angiotensin-aldosterone system. Prescription of such drugs in these patients is accompanied by severe arterial hypotension, azotemia, oliguria, and rarely – acute renal failure. The possibility of these effects is not excluded even when using angiotensin II receptor antagonists. Sharp decrease of BP in patients with ischemic cardiopathy, cerebrovascular diseases of ischemic genesis while using any antihypertensive agents may lead to myocardial infarction or stroke.

The manifestation of hypersensitivity reactions to hydrochlorothiazide is most likely in patients with bronchial asthma, history of allergic reactions; this does not exclude allergic symptoms in other patients.

When using thiazide-like diuretics, there have been cases of exacerbation or appearance of symptoms of congestive seborrhea.

The drug contains lactose; therefore, it should not be taken in patients with rare hereditary diseases manifested by lactose intolerance, lactose deficiency or impaired glucose and lactose absorption.

Pediatric use

The safety and effectiveness of Atacanda Plus in children and adolescents under the age of 18 years has not been established.

Impact on driving and operating machinery

The effect on the ability to drive or operate machinery has not been studied, but the pharmacodynamic properties of the drug indicate that there is no such effect. Patients should be cautious when driving or operating machinery, because dizziness and increased fatigue may occur during treatment.

Contraindications

Hypersensitivity, pregnancy, lactation, primary hyperaldosteronism (resistance to therapy).

With caution. Renal insufficiency, bilateral renal artery stenosis, renal artery stenosis of the sole kidney, hyperkalemia, aortic and mitral valve stenosis, GOCMP, decreased BOD, pediatric age.

Side effects

The side effects identified in the clinical trials were moderate and transient and were comparable in frequency to the placebo group. The incidence of discontinuation of therapy due to side effects was similar between candesartan/hydrochlorothiazide (3.3%) and placebo (2.7%).

In a pooled analysis of clinical trial results, the following side effects caused by the administration of candesartan/hydrochlorothiazide were noted. The side effects described were observed with a frequency of at least 1% greater than in the placebo group.

CNS side effects: dizziness, weakness

Candesartan

The following side effects were very rarely reported during postmarketing use of the drug

Hematological and lymphatic system side effects: Leukopenia, neutropenia, and agranulocytosis.

Metabolic disorders and diseases caused by metabolic disorders: hyperkalemia, hyponatremia.

CNS disorders: dizziness, headache.

Gastrointestinal disorders: nausea.

Hepatic and biliary tract disorders: increased activity of liver enzymes, impaired liver function or hepatitis.

Skin disorders: angioedema, rash, urticaria, itching.

Muscular and connective tissue disorders: back pain, arthralgia, myalgia.

Treatment of the urinary system: renal dysfunction, including renal failure in predisposed patients.

Hydrochlorothiazide

The following side effects have been reported with hydrochlorothiazide monotherapy, usually at a dose of 25 mg or more: frequently (>1/100), sometimes (>1/1000 and

Hematopoietic and lymphatic system disorders: rarely, leukopenia, neutropenia/agranulocytosis, thrombocytopenia, aplastic anemia, bone marrow depression, anemia.

Immune system disorders: rarely – anaphylactic reactions.

Metabolic disorders and diseases caused by metabolic disorders: often – hyperglycemia, hyperuricemia, hyponatremia and hypokalemia.

CNS disorders: frequently – light dizziness, headache; rarely – sleep disturbance, depression, anxiety, paresthesias.

As for the visual organ: rarely – transient blurred vision.

Systems: sometimes – orthostatic hypotension; rarely – arrhythmia; necrotizing vasculitis, cutaneous vasculitis.

Respiratory system disorders: rarely – difficulty in breathing (pneumonia and pulmonary edema).

Gastrointestinal tract: sometimes – loss of appetite, diarrhea, constipation; rarely – pancreatitis.

Hepatic disorders: rare – intrahepatic cholestatic jaundice.

Skin disorders: sometimes – skin rash, urticaria, photosensitization reactions; rarely – necrosis of epidermis, reactions similar to cutaneous erythematosis, relapse of cutaneous erythematosis.

Skeletal, muscular and connective tissue disorders: rarely – myalgia.

Kidney and urogenital system disorders: frequently – glucosuria; rarely – renal dysfunction and interstitial nephritis.

General disorders: often – weakness; rarely – fever.

Laboratory: frequently – hypercholesterolemia, hypertriglyceridemia; rarely – increase of creatinine level.

Elevated plasma uric acid and ALT and blood glucose levels have been reported as side effects occurring with candesartan cilexetil (approximate complaint rates of 1.1, 0.9, and 1%, respectively) slightly more frequently than with placebo (0.4, 0, and 0.2%, respectively). Individual patients taking candesartan/hydrochlorothiazide showed a slight decrease in hemoglobin concentration and an increase in plasma AST.

Elevated creatinine, urea, hyperkalemia and hyponatremia have also been observed.

Overdose

Symptoms: analysis of the pharmacological properties of the drug suggests that the main manifestation of overdose may be clinically pronounced BP decrease and dizziness. There have been individual cases of overdose (up to 672 mg of candesartan), which have resulted in recovery without serious sequelae.

The main manifestation of hydrochlorothiazide overdose is an acute loss of fluid and electrolytes. Symptoms such as dizziness, decreased BP, dry mouth, tachycardia, ventricular arrhythmia, loss of consciousness and muscle cramps have also been observed.

Treatment: if clinically pronounced BP decrease develops, symptomatic treatment should be administered and the patient’s condition monitored. Place patient on back and elevate legs. Increase the blood pressure, if necessary, e.g., by intravenous infusion of isotonic sodium chloride solution. Sympathomimetic agents may be administered if necessary. Excretion of candesartan and hydrochlorothiazide by hemodialysis is unlikely.

Pregnancy use