Atakand Plus - instructions for use, dose, side effects, contraindications

Carmellose calcium (carmellose calcium salt) 5.6 mg, giprolose 4.0 mg, lactose monohydrate 68 mg, magnesium stearate 1.3 mg, corn starch 20 mg, macrogol 2.6 mg, iron dye oxide yellow CI 77492 0.21 mg, iron dye oxide red CI 77491 0.050 mg.

Description:Pink oval biconvex tablet with a notch on both sides and engraved

on one side.

Pharmacotherapeutic group:Hypotensive combined agent (angiotensin II receptor blocker + diuretic)

ATX: & nbsp

C.09.D.A.06 Candesartan in combination with diuretics

Pharmacodynamics:

Angiotensin II is the main hormone of the renin-angiotensin-aldosterone system, which plays an important role in the pathogenesis of arterial 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. All these effects are mediated by the interaction of angiotensin II with angiotensin type 1 receptors (AT₁ receptors).

Candesartan is a selective antagonist of angiotensin II receptor type 1 (AT₁ receptors), does not inhibit the angiotensin converting enzyme (ACE), which converts angiotensin I into angiotensin II and breaks down bradykinin; does not affect the ACE and does not lead to the accumulation of bradykinin or P. In comparing candesartan with ACE inhibitors, the development of cough was less common in patients receiving candesartan cilexetil. Candesartan does not bind to the receptors of other hormones and does not block the ion channels involved in the regulation of the functions of the cardiovascular system. As a result of blocking AT₁ receptors of angiotensin II, a dose-dependent increase in renin activity, angiotensin I concentration, angiotensin II, and a decrease in aldosterone in the blood plasma.The clinical effect of candesartan cilexetil on morbidity and mortality at 8-16 mg (mean 12 mg) once daily was studied in a randomized clinical trial involving 4937 elderly patients (age 70 to 89 years, 21% of patients in age 80 years and older) with mild to moderate arterial hypertension who are receiving candesartan cilexetil therapy for an average of 3.7 years (SCOPE is a study of cognitive function and prognosis in elderly patients). Patients received candesartan cilexetil or placebo, if necessary, in combination with other antihypertensive agents. Both regimens showed an effective reduction in systolic and diastolic blood pressure (BP) (from 166/90 to 145/80 mm Hg in the group of patients who received candesartan, and from 167/90 to 149/82 mm Hg. in the control group) against a background of good tolerability. Cognitive function and quality of life were maintained at a good level in both groups of patients. Between these two groups of patients, there were no statistically significant differences in the incidence of cardiovascular events (cardiovascular mortality,the incidence of nonfatal myocardial infarction and nonfatal stroke). In the group of patients who received candesartan, 26.7 cases of cardiovascular complications for 1000 patients-years in comparison with 30.0 cases per 1000 patient-years in the control group (relative risk = 0.89, 95% confidence interval 0.75 - 1.06, p = 0.19) .

The table below shows the results of the assessment of the primary endpoint (cardiovascular complications) and its components.

	Number of patients with primary event		Relative risk (95% CI)	R
	Candesar tana cilex til * (N = 2477)	Control * (N = 2460)	Relative risk (95% CI)	R
Cardiovascular complications	242	268	0,89 (0,75-1,06)	0,19
- Cardiovascular mortality	145	152	0,95 (0,75-1,19)	0,63
-Mortal Stroke	68	93	0,72 (0,53-0,99)	0,04
-Intensive myocardial infarction	54	47	1,14 (0,77-1,68)	0,52

* Prior to randomization, any previous antihypertensive therapy was standardized to hydrochlorothiazide at a dose of 12.5 mg once daily. Another antihypertensive agent was added to the double-blind study drug (candesartan cilexetil 8-16 mg or placebo once a day) if systolic blood pressure remained ≥160 mm Hg and / or diastolic blood pressure ≥ 90 mmHg. 49% and 66% of patients in the candesartan cilexetil group and control group received this additional therapy, respectively.

Hydrochlorothiazide inhibits active reabsorption of sodium, mainly in the distal sections of the renal tubules and enhances the release of sodium, chlorine and water ions. The excretion of potassium and magnesium by the kidneys intensifies depending on the dose, while calcium begins to be reabsorbed in larger quantities than before. Hydrochlorothiazide reduces the volume of blood plasma and extracellular fluid and reduces the intensity of blood transport by the heart and blood pressure. During long-term treatment, the hypotensive effect develops due to the expansion of arterioles.

It is shown that with prolonged use of hydrochlorothiazide, the risk of cardiovascular diseases and mortality decreases.

Candesartan and hydrochlorothiazide have additive hypotensive effect.

In patients with hypertension, Atakand® Plus causes an effective and prolonged BP reduction without an increase in the heart rate (heart rate). Orthostatic hypotension with the first intake of the drug is not observed, as well as hypertension does not increase after the end of treatment. After a single dose of Atacand® Plus, the main antihypertensive effect develops within 2 hours.With prolonged treatment, a stable decrease in blood pressure occurs within 4 weeks after starting the drug and can be maintained with a long course of treatment. Atakand® Plus once a day is effective and gently reduces blood pressure within 24 hours with a slight difference between the maximum and average effect of action. In clinical trials, the incidence of side effects, especially cough, was lower with Atacand® Plus than with the combination of ACE inhibitors with hydrochlorothiazide. The efficacy of the combination of candesartan and hydrochlorothiazide does not depend on the sex and age of the patient. There is currently no data on the use of candesartan / hydrochlorothiazide in patients with renal failure / nephropathy, reduced left ventricular function / acute heart failure, and patients with myocardial infarction.

Pharmacokinetics:

The simultaneous use of candesartan cilexetil and hydrochlorothiazide does not have a clinically significant effect on the pharmacokinetics of any of these drugs.

Suction and distribution

Candesartan cilexetil

Candesartan cilexetil is a prodrug for oral administration. Quickly turns into an active substance - candesartan through ether hydrolysis when absorbed from the digestive tract, firmly binds to AT₁- receptors and dissociates slowly, does not have the properties of an agonist. Absolute bioavailability of candesartan after ingestion of a solution of candesartan cilexetil is about 40%. Relative bioavailability of the tablet preparation as compared to the oral solution is approximately 34%. Thus, the calculated absolute bioavailability of the tablet form of the drug is 14%. Maximum concentration in serum (C_m_Oh) is achieved through 3-4 hours after taking the tablet form of the drug. With an increase in the dose of the drug within the recommended limits, the concentration of candesartan rises linearly. Pharmacokinetic parameters candesartan do not depend on the sex of the patient. Food intake does not have a significant effect on the area under the curve "concentration - time" (AUC), those. food does not significantly affect the bioavailability of the drug. Candesartan actively binds to blood plasma proteins (more than 99%). Plasma volume distribution of candesartan is 0.1 l / kg.

Hydrochlorothiazide

Hydrochlorothiazide is rapidly absorbed from the gastrointestinal tract, bioavailability is approximately 70%. Concomitant ingestion increases absorption by about 15%.

Bioavailability can be reduced in patients with heart failure and severe swelling. The connection with plasma proteins is approximately 60%. The apparent volume of distribution is approximately 0.8 l / kg.

Metabolism and excretion

Candesartan

Candesartan, in general, is excreted from the body by the kidneys and through the intestines with bile in unchanged form and only marginally metabolized in the liver. The half-life of candesartan is approximately 9 hours. Cumulation of the drug in the body is not observed.

The total clearance of candesartan is about 0.37 ml / min / kg, with a kidney clearance of about 0.19 ml / min / kg. Renal excretion of candesartan is carried out by glomerular filtration and active tubular secretion. When ingestion of radio-labeled candesartan cilexetil, about 26% of the administered amount is excreted by the kidneys in the form of candesartan and 7% in the form of an inactive metabolite,whereas in feces 56% of the administered amount in the form of candesartan and 10% in the form of an inactive metabolite is detected.

Hydrochlorothiazide

Hydrochlorothiazide is not metabolized and is released almost completely as an active form of the drug by glomerular filtration and active tubular secretion in the proximal part of the nephron. The half-life is approximately 8 hours. Approximately 70% of the dose taken orally is excreted by the kidneys within 48 hours. The half-life does not change when taken together with candesartan. When using a combination of drugs, no additional accumulation of hydrochlorothiazide was found in comparison with monotherapy.

Pharmacokinetics in special groups

Candesartan

In elderly patients (over 65 years) C_m_Ohand AUC candesartan increased by 50% and 80%, respectively, compared with young patients. However, the hypotensive effect and incidence of side effects with Atacand® Plus do not depend on the age of the patients. In patients with mild to moderate renal impairment, C_m_Oh and AUC candesartan increased by 50% and 70%, respectively, while the half-life of the drug does not change compared to patients with normal renal function.In patients with severe renal dysfunction C_m_Oh and AUC candesartan increased by 50% and 110%, respectively, and the period the half-life of the drug increased in 2 times. Patients on hemodialysis, the same pharmacokinetic parameters candesartan, as in patients with severe impaired renal function. In patients with mild to moderate a violation of liver function was noted increased AUC of candesartan by 23%.

Hydrochlorothiazide

Half-life is longer prolonged in patients with renal insufficiency.

Indications:Treatment of arterial hypertension in patients who are shown combined therapy.

Contraindications:

Hypersensitivity to the active or auxiliary components of the drug, derivatives of sulfonamides.

Pregnancy and the period of breastfeeding.

Severe liver dysfunction and / or cholestasis.

Severe renal impairment (creatinine clearance less than 30 mL / min / 1.73 m²surface area of the body).

Anuria.

Refractory hypokalemia and hypercalcemia.

Gout.

Age to 18 years (effectiveness and safety not established).

Lactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome.

The use of candesartan cilexetil in combination with drugs containing aliskiren, in patients with diabetes mellitus (type 1 or type 2) or with moderate or severe renal failure (glomerular filtration rate <60 ml / min / 1.73 m²).

Carefully:

Severe chronic heart failure, bilateral renal artery stenosis, single-kidney artery stenosis, hemodynamically significant stenosis of the aortic and mitral valve, in patients with cerebrovascular disease and coronary heart disease, hypertrophic obstructive cardiomyopathy, in patients with reduced circulatory blood volume, cirrhosis, hyponatremia, primary hyperaldosteronism, surgical intervention, in patients after kidney transplantation, kidney failure, diabetes mellitus, acute myopia.

Pregnancy and lactation:

Pregnancy

The use of Atakand® Plus during pregnancy is contraindicated (see section "Contraindications"). Patients taking Atakand® Plus should be warned about this before planning pregnancy so that they can discuss alternative therapies with their doctor.In case of pregnancy diagnosis, Atacand® Plus therapy should be immediately discontinued and, if necessary, an alternative treatment is prescribed.

Drugs that have a direct effect on the renin-angiotensin-aldosterone system can cause fetal developmental disorders or have a negative effect on the newborn, up to a lethal outcome, when the drug is used during pregnancy. It is known that therapy with angiotensin II receptor antagonists can cause fetal development disorders function kidney, oligohydramnion, slowing ossification of the skull bones) and development of complications in the newborn (renal failure, arterial hypotension, hyperkalemia).

The experience of using hydrochlorothiazide during pregnancy, especially in the first trimester, is limited. Data from studies in animals are also limited. Hydrochlorothiazide penetrates through placenta. Given the pharmacological mechanism of action of hydrochlorothiazide, its use during pregnancy can cause violations of the fetoplacental blood flow and undesirable effects in the fetus and newborn in the form of jaundice, violations of water-electrolyte balance and thrombocytopenia.

Breastfeeding period

At the present time, it is not known whether candesartan in breast milk. but candesartan is released from the milk of lactating rats. Hydrochlorothiazide penetrates into the mother's milk. Due to possible undesirable effects on infants, Atacand® Plus should not be used during breastfeeding.

Dosing and Administration:

Atakand® Plus should be taken once a day, regardless of food intake.

Dosage

The recommended dose is 1 tablet once a day.

It is recommended to titrate the dose of candesartan before transferring the patient from hydrochlorothiazide monotherapy to Atakand® Plus therapy. If necessary, patients are transferred from Atakand® monotherapy to Atakand® Plus therapy.

The main antihypertensive effect is achieved, as a rule, in the first 4 weeks after the start of treatment.

Elderly patients

In elderly patients, dose adjustment is not required.

Patients with impaired renal function

In patients with mild to moderate renal impairment (clearance Creatinine 30-80 ml / min / 1.73 m² body surface area), titration of the dose is recommended.

Atakand® Plus is contraindicated in patients with severe renal insufficiency (creatinine clearance <30 mL / min / 1.73 m² surface area of the body).

Patients with impaired hepatic function

Titration of a dose is recommended in patients with impaired liver function of mild or moderate severity. Atakand® Plus is contraindicated in patients with severe impairment of liver function and / or cholestasis.

Patients with reduced circulating blood volume

For patients at risk of arterial hypotension, for example, for patients with reduced circulating blood volume, titration of the dose of candesartan (via Atakand® monotherapy), starting at 4 mg, is recommended.

Application in children and adolescents

The safety and effectiveness of Atakand® Plus in children and adolescents (under the age of 18 years) have not been established.

Side effects:

Adverse events identified during clinical trials were of moderate and transient nature and were comparable in frequency with the placebo group. The overall incidence of side effects did not depend on the sex and age of the patients.The incidence of discontinuation due to side effects was similar with candesartan cilexitil / hydrochlorothiazide (2.3% -3.3%) and placebo (2.7% -4.3%).

In the combined analysis of the results of clinical trials, the following side effects associated with the appointment of candesartan / hydrochlorothiazide were noted.

The described side effects were observed with a frequency of at least 1% more than in the placebo group.

From the central nervous system: Circulation, weakness.

Candesartan

About the following side effects during the postmarketing use of the drug reported very rarely (<1/10000):

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

Disturbance of metabolism and diseases caused by a metabolic disorder: hyperkalemia, hyponatremia;

From the central nervous system: dizziness, headache;

On the part of the respiratory system, organs of the thorax and mediastinum: cough;

From the gastrointestinal tract: nausea;

From the liver and bile ducts: increased activity

"hepatic" enzymes, impaired liver function or hepatitis;

From the skin: angioedema, rash, hives, itching;

From the musculoskeletal system, connective tissue: back pain, arthralgia, myalgia;

From the side of the urinary system: impaired kidney function, including kidney failure in predisposed patients.

Hydrochlorothiazide

When hydrochlorothiazide was used, usually at a dose of 25 mg or more, the following side effects were noted, (> 1/100), infrequently (> 1/1000 and <1/100), rarely (<1/1000), unspecified frequency (insufficient data to establish the frequency).

From the blood and lymphatic system:

Rarely: leukopenia, neutropenia / agranulocytosis, thrombocytopenia, aplastic anemia, bone marrow depression, hemolytic anemia;

From the immune system:

Rarely: anaphylactic reactions;

Disturbance of metabolism and disease, caused by a metabolic disorder:

Often: hyperglycemia, hyperuricemia, hyponatremia and hypokalemia;

From the central nervous system:

Often: mild dizziness, headache pain;

Rarely: sleep disturbance, depression, anxiety, paresthesia;

From the side of the organ of vision:

Rarely: transient fuzziness Images;

Unspecified frequency: acute myopia, acute closed angle glaucoma;

From the side of cardiovascular system:

Infrequent: orthostatic hypotension;

Rarely: arrhythmia; necrotizing vasculitis, cutaneous vasculitis;

On the part of the respiratory system:

Rarely: respiratory distress syndrome (in including pneumonitis and pulmonary edema);

From the digestive tract:

Infrequent: loss of appetite, diarrhea, constipation;

Rarely: pancreatitis;

From the side of the liver:

Rarely: jaundice (intrahepatic cholestasis);

From the skin:

Infrequent: skin rash, urticaria, photosensitivity reactions;

Rarely: toxic epidermal necrolysis;

Unspecified frequency: system red lupus, cutaneous lupus erythematosus;

From the musculoskeletal and connective tissues:

Rarely: myalgia;

From the kidneys and genitourinary system:

Often: glucosuria;

Rarely: renal dysfunction and interstitial nephritis;

Common violations:

Often: weakness;

Rarely: a feeling of heat;

Laboratory indicators:

Often: hypercholesterolemia, hypertriglyceridemia;

Rarely: increased concentration creatinine.

Increase in the concentration of uric acid and activity of alanine aminotransferase (ALT) in blood plasma and concentration glucose in the blood were marked as side effects that occur when application of candesartan cilexetil (the approximate frequency of 1.1%, 0.9% and 1.0%, respectively) is slightly more frequent than when using placebo (0.4%, 0%, and 0.2% respectively). In individual patients, who took candesartan cilexetil / hydrochlorothiazide was observed a slight decrease in hemoglobin and increased activity aspartate aminotransferase (ACT) in the blood plasma.

There was also an increase in the concentration of creatinine, urea, hyperkalemia and hyponatremia.

Overdose:

Symptoms

Analysis of the pharmacological properties of the drug suggests that the main manifestation of an overdose may be a clinically pronounced decrease in blood pressure and dizziness. Individual cases of drug overdose (up to 672 mg candesartan), which resulted in the recovery of patients without severe consequences, were described. The main manifestation of an overdose of hydrochlorothiazide is the acute loss of fluid and electrolytes. Symptoms such as dizziness, lowering of blood pressure, dry mouth, tachycardia, ventricular arrhythmia, loss of consciousness and muscle cramps were also observed.

Treatment

When developing a clinically pronounced BP reduction, symptomatic treatment and monitor the patient's condition. Lay the patient on his back and raise his legs. If necessary, increase the volume of circulating blood, for example, by intravenous administration of 0.9% sodium chloride solution. If necessary, sympathomimetic facilities.

Candesartan is not excreted by hemodialysis. The degree of excretion of hydrochlorothiazide in hemodialysis is unknown.

Interaction:

The use of candesartan cilexetil in combination with drugs containing aliskiren, is contraindicated in patients with diabetes mellitus (type 1 or type 2) or with moderate or severe renal failure (glomerular rate

filtration <60 ml / min / 1.73 m²) and is not recommended for other patients (see the sections "Contraindications" and "Special instructions").

In pharmacokinetic studies, the combined use of candesartan cilexetil with hydrochlorothiazide, warfarin, digoxin, oral contraceptives (ethinyl estradiol / levonorgestrel), glibenclamide, nifedipine, and enalapril.Clinically significant pharmacokinetic interaction was not revealed.

Candesartan is metabolized in the liver to an insignificant degree (isoenzyme CYP2C9). The conducted studies on the interaction did not reveal the effect of the drug on isozymes CYP2C9 and CYP3A4, the effect on other isoenzymes of the cytochrome P450 system has not been studied. Simultaneous use of Atakand® Plus with other antihypertensive drugs potentiates the hypotensive effect.

It should be expected that the action of hydrochlorothiazide, leading to loss of potassium, can be enhanced by other means leading to loss of potassium and hypokalemia (eg, diuretics, laxatives, amphotericin, carbenoxolone, penicillin G sodium, derivatives of salicylic acid). The experience of using 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 agents that can increase the serum potassium content (eg, heparin) may lead to the development of hyperkalemia.

Induced by diuretic hypokalemia and hypomagnesemia predispose to possible Cardiotoxic action of cardiac glycosides and antiarrhythmics. At reception of preparation Atakand® plus in parallel with such preparations control of the maintenance of a potassium in blood is required.

When combined prescription of lithium preparations with ACE inhibitors, a reversible increase in the concentration of lithium in serum and the development of toxic reactions were reported. Similar reactions may occur with the use of angiotensin receptor antagonists II, in connection with which it is recommended to monitor the concentration of lithium in the serum when combined use of these drugs.

With simultaneous use of angiotensin receptor antagonists II and non-steroidal anti-inflammatory drugs (NSAIDs), including selective inhibitors

cyclooxygenase-2, acetylsalicylic acid (more than 3 g / day), there may be a decrease in the hypotensive effect. As with the use of ACE inhibitors, simultaneous use of angiotensin receptor antagonists II and NSAIDs may increase the risk of impaired renal function,including acute renal failure, an increase in serum potassium, especially in patients with reduced renal function. Caution should be exercised when these drugs are used concomitantly, especially in elderly patients and in patients with reduced circulating blood volume. Patients need to compensate for fluid loss and regularly monitor kidney function after initiating combination therapy and periodically against such therapy. The bioavailability of candesartan is not dependent on food intake.

Diuretic, natriuretic and hypotensive action of hydrochlorothiazide is attenuated by non-steroidal anti-inflammatory drugs. The absorption of hydrochlorothiazide is weakened by the use of colestipol or colestyramine.

The action of nondepolarizing muscle relaxants (eg, tubocurarine) can be enhanced with hydrochlorothiazide. Thiazide diuretics can cause an increase in the calcium content in the blood due to a decrease in its excretion. If you need calcium supplements or vitamin D, should monitor the calcium content in the blood plasma and, if necessary,adjust the dose. Thiazides increase the hyperglycemic effect of beta-adrenoblockers and diazoxide.

Anticholinergics (for example, atropine, biperidene) can increase the bioavailability of diuretics based on thiazides due to decreased motility of the gastrointestinal tract. Thiazides may increase the risk of adverse effects of amantadine. Thiazides can slow down the excretion of cytostatic agents (such as cyclophosphamide, methotrexate) from the body and enhance their myelosuppressive effect. The risk of hypokalemia may increase with concomitant use of steroid medications or adrenocorticotropic hormone. Against the background of taking the drug may increase the frequency of orthostatic hypotension when taking ethanol, barbiturates or general anesthetics.

Treatment with thiazides can reduce glucose tolerance. Dose selection may be required hypoglycemic agents for oral administration and insulin.

Hydrochlorothiazide can reduce the effect of vasoconstrictive amines (eg, epinephrine (adrenaline)). Hydrochlorothiazide may increase the risk of developing acute renal failure, especially in combination with large doses of iodine-containing contrast agents.

Significant interactions hydrochlorothiazide with food was not detected.

Special instructions:Double blockade of the renin-angiotensin-aldosterone system when using preparations containing aliskiren

The double blockade of the renin-angiotensin-aldosterone system is not recommended by combining candesartan cilexetil and aliskiren, in view of the increased risk of developing arterial hypotension, hyperkalemia and changes in renal function.

The use of candesartan cilexetil in combination with aliskiren contraindicated in patients with diabetes mellitus (type 1 or type 2) or with moderate or severe renal failure (GFR <60 mL / min / 1.73 m²) (see the section "Contraindications").

Impaired renal function

Atakand® Plus, as with other agents that inhibit the renin-angiotensin-aldosterone system, renal dysfunction may be noted in susceptible patients (see "Contraindications").

Kidney transplantation

The clinical experience of Atacand® Plus in patients who underwent kidney transplantation is limited.

Stenosis of the renal artery

Other drugs that affect the renin-angiotensin-aldosterone system, such as ACE inhibitors, can lead to increased urea levels in the blood and serum creatinine concentrations in patients with bilateral renal artery stenosis or stenosis of the single kidney artery. A similar effect should be expected from angiotensin II receptor antagonists.

Decreased circulating blood volume

Patients with circulating blood and / or sodium deficiency may develop symptomatic arterial hypotension as described for other drugs that affect the renin-angiotensin-aldosterone system. Therefore, it is not recommended to use Atacand® Plus before correcting these violations.

General anesthesia and surgery

Patients receiving angiotensin II antagonists may develop arterial hypotension as a result of blockade of the renin-angiotensin aldosterone system during general anesthesia and during surgical interventions.Very rarely there can be cases of severe arterial hypotension, requiring intravenous administration of plasma-substituting solutions and / or vasopressors.

Liver failure

Patients with impaired liver function or progressive liver disease should use thiazides with caution because small fluctuations in fluid volume and electrolyte composition can cause hepatic coma. Data on the use of Atakand® Plus with patients with hepatic insufficiency are absent.

Stenosis of the aortic and mitral valve or hypertrophic obstructive cardiomyopathy

At the appointment of Atakand® Plus, as well as other vasodilators, patients with hypertrophic obstructive Caution should be exercised in cardiomyopathy or hemodynamically significant stenosis of the aortic or mitral valve.

Primary hyperaldosteronism

Patients with primary hyperaldosteronism usually resistant to therapy with antihypertensive drugs that affect the renin-angiotensin-aldosterone system. In this regard, it is not recommended to assign such patients Atakand® Plus.

Violation of the water-electrolyte balance

As in all cases of taking drugs that have a diuretic effect, the electrolyte content in the blood plasma should be monitored. Drugs based on thiazides, having a diuretic effect, can reduce the excretion of calcium ions in the urine and can cause abrupt changes and a slight increase in the content of calcium ions in the blood plasma. Thiazides, including hydrochlorothiazide, can cause disturbances in the water-electrolyte balance (hypercalcemia, hypokalemia, hyponatremia, hypomagnesemia and hypochloraemic alkalosis).

The revealed hypercalcemia can be a sign of latent hyperparathyroidism. Admission of thiazide drugs should be discontinued until the results of parathyroid gland testing are obtained.

Hydrochlorothiazide is dose-dependent increases the secretion of potassium, which can cause hypokalemia. This action of hydrochlorothiazide is less apparent if it is used in combination with candesartan cilexetil. The risk of hypokalemia is increased in patients with cirrhosis of the liver, in patients with severe diuresis, in patients not receiving enough electrolytes with food, and in patients taking concomitantly corticosteroids or adrenocorticotropic hormone.Based on the experience of using drugs that affect the renin- angiotensin-aldosterone system, the simultaneous use of Atakand® Plus and potassium-increasing diuretics can be compensated for by using dietary supplements containing potassium or other drugs that can increase the potassium content in the blood plasma. Based on the experience of using other drugs that affect the function of the renin-angiotensin-aldosterone system, the joint use of Atakand® Plus with ACE inhibitors, aliskiren, potassium-sparing diuretics, potassium preparations or salt substitutes containing potassium, can lead to an increase in the potassium content in the blood serum. It is shown that thiazides increase the excretion of magnesium, which can cause hypomagnesemia.

Influence on metabolism and endocrine system

Treatment with thiazides may interfere with glucose tolerance. It may be necessary to correct the dose of hypoglycemic agents, including insulin. During therapy with thiazide, the manifestation of latent-flowing diabetes mellitus. With treatment with thiazide, an increase in the concentration of cholesterol and triglycerides is also associated.However, with the use of the Atacand® Plus preparation containing a dose of 12.5 mg, minimal or no such effects were observed. Thiazide diuretics increase the concentration of uric acid in the blood plasma and can contribute to the occurrence of gout in predisposed patients.

Acute myopia and secondary closed-angle glaucoma

Hydrochlorothiazide derivative sulfonamide, can cause idiosyncratic reaction, leading to the development of acute transient myopia and acute closed-angle glaucoma. Symptoms include a sharp decrease in visual acuity or pain in the eye, and usually occur between a few hours to several weeks after starting the drug.

Untreated acute acute angle glaucoma can lead to persistent loss of vision. Primary treatment consists in the immediate discontinuation of hydrochlorothiazide. If there is no control of intraocular pressure, urgent medication or surgical treatment may be required. Risk factors for the development of acute angle-closure glaucoma may include the presence of an allergy to sulfonamide or penicillin in an anamnesis.

Are common

Patients who have vascular tone and renal function preferentially depend on the activity of the renin-angiotensin-aldosterone system (for example, patients with severe chronic 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 is accompanied in these patients by severe arterial hypotension, azotemia, oliguria and, more rarely, acute renal failure. The possibility of developing these effects can not be ruled out when angiotensin II receptor antagonists are used. A sharp decrease in blood pressure in patients with coronary heart disease or cerebrovascular diseases of atherosclerotic genesis, with the use of any antihypertensive drugs, can lead to the development of myocardial infarction or stroke. The occurrence of hypersensitivity reactions to hydrochlorothiazide is possible in patients who did not previously have allergic reactions and bronchial asthma (in the anamnesis), but it is more likely for patients with a weighed allergic anamnesis.With the use of thiazide diuretics, there are cases of exacerbation or symptoms of systemic lupus erythematosus. Hydrochlorothiazide refers to drugs banned by the World Anti-Doping Agency when participating in sports competitions. Against the background of taking Atacand® Plus, a positive doping test result can be obtained. The drug contains lactose, so it should not be taken to patients with lactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome.

Effect on the ability to drive transp. cf. and fur:Influence on the ability to drive a car or work with machinery has not been studied, but the pharmacodynamic properties of the drug indicate that such an effect is absent. Patients should be cautious when driving or working with machinery, as dizziness may occur during treatment and fatigue can occur.

Form release / dosage:Pills 16 mg + 12.5 mg.

Packaging:For 14 tablets in a blister of PVC / PVDC / aluminum, 2 blisters per cardboard pack with instructions for use.

Storage conditions:Store at a temperature not exceeding 30 ° C, out of the reach of children.

Shelf life:3 years. Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-001340/08

Date of registration:29.02.2008 / 29.01.2016

Expiration Date:Unlimited

The owner of the registration certificate:AstraZeneca ABAstraZeneca AB Sweden

Manufacturer: & nbsp

ASTRAZENECA, AB Sweden

Representation: & nbspAstraZeneca Pharmaceuticals Ltd.AstraZeneca Pharmaceuticals Ltd.

Information update date: & nbsp09.10.2017

Illustrated instructions

Instructions

Atacand® Plus (Atacand® Plus)