Expiration date: 09/2025

The composition and form of issue:

Tablets. 1 tablet contains active substance: 

candesartan 16 mg

hydrochlorothiazide 12.5 mg

excipients: calcium carmellose of hyprolose lactose monohydrate magnesium stearate maize starch macrogol dye iron oxide yellow dye iron oxide red 

blistere in 14 PCs the paper cartons 2 blister.

Description pharmaceutical form:

Pink oval biconvex tablet with a notch on both sides and engraved A/CS on one side.

Indications:

Treatment of hypertension in patients' which shows the combined therapy.

Contraindications:

• hypersensitivity to the active or auxiliary components included in the composition of the drug, a derivative of sulfonamides
  
• the human liver and/or cholestasis
  
• the human kidney (Cl creatinine less than 30 ml/min/1.73 m2)
  
• anuria
  
• refractory hypokalemia and hypercalcemia
  
• gout
  
• pregnancy
  
• lactation
  
• the age of 18 years (efficacy and safety not established).
  

With caution: severe chronic heart failure, bilateral renal artery stenosis, stenosis of artery only kidneys, hemodynamically significant stenosis of the aortic and mitral valves, in patients with cerebrovascular diseases and ischemic heart disease, hypertrophic obstructive cardiomyopathy, in patients with reduced BCC, cirrhosis of the liver, in patients suffering from lactose intolerance, malabsorption of lactose and galactose, hyponatraemia, primary hyperaldosteronism, surgery, in patients after kidney transplantation, renal failure, diabetes.

Application of pregnancy and breast-feeding:

Pregnancy

Experience with the use of the drug in pregnant Atacand Plus limited.

These data are insufficient to judge the possible dangers to the fetus in the first trimester of pregnancy. The human embryo is the circulatory system of the kidney, which depends on the development of the renin-angiotensin-aldosterone system, begins to form in the second trimester of pregnancy. Thus, the risk to the fetus increases with the appointment of Atacand Plus in the last 6 months of pregnancy. Funds that have a direct impact on the renin-angiotensin-aldosterone system, can cause abnormalities of fetal development or to have a negative effect on the newborn (hypotension, impairment of renal function, oliguria and/or anuria, oligohydramnios, hypoplasia of skull bones, intrauterine growth retardation), or death with use of the drug in the last 6 months of pregnancy. Was also described cases of pulmonary hypoplasia, facial anomalies and contractions of limbs.

In studies on animals revealed kidney damage in the embryonic and neonatal periods with the use of candesartan in. It is assumed that the mechanism of damage due to the pharmacological effects of the drug on the renin-angiotensin-aldosterone system.

Hydrochlorothiazide can reduce plasma volume of blood and decrease utero-placental blood flow, may also cause thrombocytopenia in the newborn.

Based on this information, you should not use Atacand Plus during pregnancy. If pregnancy occurred during treatment with Atacand Plus, therapy should be discontinued (see section "Contraindications").

Lactation

At present it is not known whether candesartan penetrates in breast milk. However, candesartan is secreted from the milk of lactating rats. Hydrochlorothiazide passes into mother's milk.

In connection with possible adverse effects on infants, Atacand Plus should not be used during breast-feeding.

Side effects:

Side effects identified during clinical trials carried moderate and transient in nature and were comparable in frequency with the placebo group. The incidence of discontinuation of therapy due to side effects was similar when using candesartan in /hydrochlorothiazide (3.3%) and placebo (2.7 percent).

In the combined analysis of the results of clinical studies have reported the following side effects caused by candesartan in appointment/hydrochlorothiazide. Described adverse effects were observed with a frequency of at least 1% more than in the placebo group.

CNS: dizziness, weakness

Candesartan

About the following side effects during post-marketing use of the drug were reported very rarely (<1/10000):

From the blood and lymphatic system: leukopenia, neutropenia and agranulocytosis.

Violation of metabolism and diseases caused by metabolic: hyperkalemia, hyponatremia.

CNS: dizziness, headache.

Gastrointestinal: nausea.

The liver and biliary tract: increased liver enzymes, abnormal liver function or hepatitis.

With the skin: angioedema, rash, urticaria, pruritus.

From the musculoskeletal and connective tissue: back pain, arthralgia, myalgia.

From the side of urinary system: impaired renal function including renal failure in susceptible patients.

Hydrochlorothiazide

With hydrochlorothiazide monotherapy, usually in a dose of 25 mg or more were noted following side effects: often (>1/100); sometimes (>1/1000 and <1/100), rare (<1/1000).

From the hematopoietic and lymphatic system: rarely — leukopenia, neutropenia/agranulocytosis, thrombocytopenia, aplastic anemia, bone marrow depression, anemia.

The immune system: rarely — anaphylactic reactions.

Violation of metabolism and the diseases caused by the metabolic: often — hyperglycemia, hyperuricemia, hyponatremia, and hypokalemia.

CNS: frequently — slight dizziness, headache, rarely — sleep disturbance, depression, anxiety, paresthesia.

From the body of the vision: rarely — transient blurring of the image.

From the CCC: sometimes — orthostatic hypotension rarely arrhythmias necrotizing vasculitis, cutaneous vasculitis.

From the side of respiratory system: rarely — shortness of breath (pneumonia and pulmonary edema).

From the digestive tract: sometimes — loss of appetite, diarrhoea, constipation rare pancreatitis.

Hepatic: rare intrahepatic cholestatic jaundice.

With the skin: sometimes — skin rash, urticaria, photosensitivity reaction, rarely — necrosis of the epidermis, the reaction is similar to skin erythematous, recurrence of erythematous skin.

From the musculoskeletal and connective tissue: rarely — myalgia.

The kidneys and urinary system: common — glycosuria rare — violation of the kidney and interstitial nephritis.

General disorders: often — the weakness of rarely — feeling of heat.

The laboratory parameters: often — hypercholesterolemia, hypertriglyceridemia rarely — increased creatinine.

The elevated levels of uric acid and ALT in plasma and the level of blood glucose was noted as a side effects encountered when using candesartan in has tsileksetil (approximate frequency of complaints of 1.1, 0.9 and 1% respectively) slightly more often than with placebo (0,4, 0 and 0.2%, respectively). Certain patients taking candesartan/hydrochlorothiazide, there was a slight decrease in hemoglobin concentration and increase in AST in the blood plasma.

Also saw an increase in the content of creatinine, urea, hyperkalemia, and hyponatremia.

Method of application and dose:

Inside, 1 times per day regardless of the meal.

Dosage

Recommended dose — 1 tab. 1 time per day.

It is recommended that the dose titration of candesartan in before putting the patient on therapy with Atacand Plus. If necessary, patients are transferred from monotherapy Atacando to therapy with Atacand Plus.

The main hypotensive effect is achieved, usually within the first 4 weeks after start of treatment.

Elderly patients

In patients older dose adjustment is not required.

Patients with impaired renal function

In patients with impaired renal function is preferable to the use of loop diuretics compared with the thiazide. Before the start of drug therapy Atacand Plus in patients with mild or moderate impaired renal function (Cl creatinine &ge30 ml/min/1.73 m2) including patients on hemodialysis, the recommended dose titration of candesartan in (through monotherapy drug Atacand), starting with 4 mg.

Drug Atacand Plus is contraindicated in patients with severe renal insufficiency (Cl creatinine <30 ml/min/1.73 m2 BSA).

Patients with reduced BCC

For patients with risk of hypotension, e.g. patients with reduced BCC, it is recommended that the dose titration of candesartan in (through monotherapy drug Atacand), starting with 4 mg.

The safety and efficacy of Atacand Plus in children and adolescents (under 18 years) is not installed.

Overdose:

Symptoms: analysis of pharmacological properties of the drug suggests that the main manifestation of an overdose may be clinically significant decrease in blood pressure and dizziness. Described isolated cases of overdose (up to 672 mg candesartan in), and ended with the recovery of patients without severe consequences.

The main manifestation of an overdose of hydrochlorothiazide is acute loss of fluid and electrolytes. Also observed other symptoms such as dizziness, decreased blood pressure, dry mouth, tachycardia, ventricular arrhythmia, loss of consciousness and muscle spasms.

Treatment: with the development of clinically expressed lower AD should be symptomatic treatment and monitor the patient's condition. To lay the patient on his back and lift his legs. If necessary, increase the volume for example by in/with the introduction of isotonic solution of sodium chloride. If necessary, can be assigned sympathomimetic means. Excretion of hydrochlorothiazide and candesartan in by hemodialysis is unlikely.

Special instructions:

Violation of kidney function

In this situation, the use of loop diuretics thiazide is preferable. For patients with renal insufficiency when using Atacand Plus is recommended to constantly monitor the level of potassium, creatinine and uric acid.

Kidney transplant

Data on the use of Atacand Plus patients who recently had a kidney transplant, no.

Renal artery stenosis

Other drugs that affect the renin-angiotensin-aldosterone system, such as ACE inhibitors, may lead to the increase of urea content in blood and in serum creatinine in patients with bilateral renal artery stenosis or stenosis of the artery to a solitary kidney. A similar effect should be expected from the antagonists of angiotensin II receptors.

The decrease in BCC

In patients with a deficit intravascular volume and/or sodium may develop symptomatic hypotension, as described for other drugs that affect the renin-angiotensin-aldosterone system. Therefore it is not recommended to apply the Plus Atacand to the disappearance of these symptoms.

General anesthesia and surgical intervention

Patients receiving antagonist of angiotensin II, during anesthesia and during surgery may develop hypotension due to the blockade of the renin-angiotensin system. Very rarely observed cases of severe hypotension requiring I/V administration of fluids and/or vasopressors.

Liver failure

Patients with hepatic impairment or progressive liver disease thiazides should be used with caution in view of the fact that slight variations in fluid volume and electrolyte composition can cause hepatic coma. Data on the use of Atacand Plus in patients with hepatic insufficiency are absent.

Stenosis of the aortic and mitral valve (hypertrophic obstructive cardiomyopathy)

When you assign Atacand Plus, as with other vasodilators patients with obstructive hypertrophic cardiomyopathy or hemodynamically significant aortic stenosis or mitral valve should be used with caution.

Primary hyperaldosteronism

Patients with primary hyperaldosteronism is usually resistant to treatment with antihypertensive agents affecting the renin-angiotensin-aldosterone system. In this regard, it is not recommended to assign such patients Atacand Plus.

Violation of water-salt balance

As in all cases of reception of drugs with diuretic action, you should control of electrolytes in the blood plasma.

Preparations on the basis of thiazides, having diuretic effect, can reduce the secretion of calcium ions with urine and can cause abrupt changes and a slight increase in the concentration of calcium ions in the blood plasma.

Thiazides, including hydrochlorothiazide, may cause a violation of water-salt balance (hypercalcemia, hypokalemia, hyponatremia, hypomagnesemia, and gipohloremichesky alkaloz).

Revealed hypercalcemia may be a sign of hidden hyperthyroidism. Receiving thiazide should be discontinued prior to receiving results of the analyses of the study parathyroid glands.

Hydrochlorothiazide dose-dependently increases the secretion of potassium and can cause hypokalemia. Such action of hydrochlorothiazide is manifested less if you use it in combination with candesartan in cilexetil. The risk of hypokalemia is increased in patients with liver cirrhosis, with an increased diuresis, in patients receiving fluid with a reduced content of salts, and running parallel to the course of treatment with corticosteroids or ACTH the host.

Based on the experience of use of drugs affecting the renin-angiotensin-aldosterone system, parallel application Atacand Plus and increasing the allocation of potassium of diuretics may be compensated for use of food additives containing potassium, or other drugs that can increase potassium levels in the blood plasma.

Application Atacand Plus with ACE inhibitors or angiotensin II receptor can cause hypokalemia, especially if patient is suffering from cardiac insufficiency or renal insufficiency, although such cases was not documented.

It is shown that thiazides increase the excretion of magnesium, which can cause hypomagnesemia.

Effect on the metabolism and endocrine system

Treatment of thiazide-can disturb the glucose levels in the blood. May be required dose of hypoglycemic agents, including insulin. During therapy tiazida possible manifestation of latent flowing of diabetes. With treatment with thiazides also attributed the increase level of cholesterol and triglycerides. However, when using Atacand Plus contains a dose of hydrochlorothiazide 12.5 mg was observed a minimal amount or absence of such effects. Thiazide diuretics increase the concentration of uric acid in the blood plasma and may contribute to the development of gout in predisposed patients.

Common

Patients in whom vascular tone and renal function depend predominantly on the activity of the renin-angiotensin-aldosterone system (e.g. patients with severe congestive heart failure or kidney disease, including renal artery stenosis), are particularly sensitive to drugs acting on the renin-angiotensin-aldosterone system. The appointment of such drugs in these patients is accompanied by an abrupt arterial hypotension, azotemia, oliguria and rarely acute renal failure. The possibility of the development of the listed effects may not be excluded and the use of antagonists of angiotensin II receptors. A sharp decrease in blood pressure in patients with ischaemic cardiopathy or cerebrovascular diseases ischemic in the use of any antihypertensive drugs, can lead to the development of myocardial infarction or stroke.

The manifestation of hypersensitivity reactions to hydrochlorothiazide possible and patients who have no previous allergies or asthma, but it is more likely for patients who had similar symptoms.

If you are using a thiazide diuretic there were cases of aggravation or appearance of symptoms of seborrhea.

The drug contains lactose, therefore it should not be taken by patients suffering from rare genetic diseases which manifests itself in the lack of tolerance to lactose, lactase deficiency or malabsorption of glucose and lactose.

Effects on ability to drive or operate machinery. Not studied, but the pharmacodynamic properties of the drug indicate that such influence is absent. Patients should be careful when driving or operating machinery, because during the treatment may occur dizziness and may notice increased fatigue.