Candecor H8 - instructions for use, dose, side effects, contraindications

Excipients: lactose monohydrate 76.90 mg, corn starch 20.00 mg, giprolose 4.00 mg, macrogol-8000 2.60 mg, carmellose calcium 5.60 mg, magnesium stearate 0.40 mg.

Description:Oval, biconvex white tablets with a risk on one side.

Pharmacotherapeutic group:Hypotensive drug combined (diuretic + angiotensin II receptor antagonist)

ATX: & nbsp

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

Pharmacodynamics:

Candesartan

Angiotensin II - the main hormone of the renin-angiotensin-aldosterone system (RAAS), taking part in the pathogenesis of arterial hypertension (AH) and other diseases of the cardiovascular system.

Candesartan is a selective angiotensin II receptor antagonist (APA II), subtype 1 (AT 1receptors). Does not exhibit the properties of an agonist.Does not affect the angiotensin-converting enzyme (ACE) and does not lead to the accumulation of bradykinin or substance P. When comparing candesartan with ACE inhibitors (ACE inhibitors), the development of cough was less common in patients who received candesartan. It does not bind to receptors of other hormones, does not affect the state of ion channels involved in the regulation of cardiovascular activity. As a result of blocking AT₁ -receptor angiotensin II compensatory dose-dependent increase in renin activity, angiotensin I concentration, angiotensin II, and a decrease in aldosterone in the blood plasma.

Hydrochlorothiazide

Hydrochlorothiazide inhibits active reabsorption of sodium mainly in the distal renal tubules and enhances the excretion of sodium, chlorine and water. Dose-dependent increases the excretion of potassium and magnesium by the kidneys; calcium is reabsorbed to a greater extent. Reduces the volume of blood plasma and extracellular fluid, reduces cardiac output and blood pressure (BP). With long-term therapy, the reduction in total peripheral vascular resistance (OPSS) develops due to the expansion of arterioles.Long-term therapy with hydrochlorothiazide reduces the risk of developing cardiovascular disease and mortality. Candesartan and hydrochlorothiazide have additive antihypertensive effect.

Arterial hypertension. In patients with AH candesartan causes a prolonged clinically significant decrease in blood pressure without a reflex increase in the heart rate (heart rate). There is no information on the development of severe arterial hypotension after taking the first dose and the development of the "withdrawal" syndrome with discontinuation of the drug. After a single dose of candesartan, the hypotensive effect usually develops after 2 hours. With continued therapy, a stable decrease in blood pressure is achieved within 4 weeks. The achieved level of blood pressure is maintained with prolonged therapy. With the use of Candecor® H 8, once a day, an effective and uniform decrease in blood pressure is ensured within 24 hours. The frequency of side effects, especially cough, when combined with hydrochlorothiazide / candesartan combination is lower than with hydrochlorothiazide / ACEI.

The efficacy of the combination hydrochlorothiazide / candesartan does not depend on the sex and age of the patient.

Pharmacokinetics:

Simultaneous use of the combination hydrochlorothiazide / candesartan does not have a clinically significant effect on the pharmacokinetics of hydrochlorothiazide and candesartan.

Suction and distribution

Candesartan

Candesartan cilexetil is a prodrug. After ingestion candesartan Cilexetil is rapidly converted into the active substance candesartan by ether hydrolysis. The absolute bioavailability of candesartan is approximately 40% after taking candesartan inward as a solution. The relative bioavailability of candesartan in the tablet dosage form as compared to the oral solution is approximately 34%. The mean maximum concentration in blood plasma (C_m_Oh) is achieved 3-4 hours after taking candesartan inside. The concentration of candesartan in the blood plasma increases linearly with increasing doses within the therapeutic range. The pharmacokinetics of candesartan does not depend on the sex of the patient. The intake of food does not significantly affect the area under the "concentration-time" curve (AUC). Actively binds to blood plasma proteins (more than 99%). The amount of candesartan distribution is 0.1 l / kg.

Hydrochlorothiazide

Hydrochlorothiazide is rapidly absorbed from the gastrointestinal tract (GIT). Bioavailability is approximately 70%. Simultaneous food intake increases suction by about 15%. In patients with chronic heart failure and severe edema, bioavailability can be reduced.

The binding of hydrochlorothiazide to plasma proteins is approximately 60%. The volume of distribution is 0.8 l / kg.

Biotransformation and excretion

Candesartan

Candesartan is excreted mainly unchanged in kidneys, with bile through the intestine and only to a small extent is metabolized in the liver (isoenzyme CYP2C9). The results of the studies indicate the absence of clinically significant drug interaction with drugs that affect isoenzymes CYP2C9 and CYP3A4. According to research in vitro no drug interactions with drugs whose metabolism depends on cytochrome P450 isoenzymes are not expected: CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1 or CYP3A4. The half-life (T_1/2) candesartan is approximately 9 hours. When taking repeated doses, it does not accumulate in the body. T_1/2candesartan does not change (approximately 9 hours) after simultaneous application with hydrochlorothiazide.

The total plasma clearance of candesartan is 0.37 ml / min / kg, with renal clearance of about 0.19 ml / min / kg. The excretion of candesartan occurs via glomerular filtration and active tubular secretion. After oral administration of radiolabelled candesartan (¹⁴C-labeled candesartan) approximately 26% is excreted by the kidneys in the form of candesartan and 7% - in the form of an inactive metabolite, and 56% is excreted with bile through the intestine in the form of candesartan and 10% in the form of an inactive metabolite.

Hydrochlorothiazide

Hydrochlorothiazide is not metabolized and is excreted almost completely unchanged by glomerular filtration and active tubular secretion. T_1/2hydrochlorothiazide is approximately 8 hours. Approximately 70% of the ingested hydrochlorothiazide is excreted by the kidneys for 48 hours. T_1/2 hydrochlorothiazide does not change with simultaneous application with candesartan. Additional cumulation of hydrochlorothiazide after repeated use in combination with candesartan in comparison with monotherapy does not occur.

Pharmacokinetics in selected patient groups

Candesartan

Elderly patients

In patients older than 65 years of age, C_m_Oh and AUC candesartan compared with younger patients higher by about 50% and 80%, respectively. Nevertheless, the hypotensive effect and frequency of side effects are the same in both age groups.

Impaired renal function

In patients with mild or moderate impairment of renal function C_m_Oh and AUC candesartan upon repeated application increases by 50% and 70%, respectively, while T_1/2 does not change. Corresponding changes in patients with severe renal dysfunction are 50% and 110%. T_1/2 candesartan in patients with severe renal dysfunction is approximately twice as long. Pharmacokinetics in patients on hemodialysis is similar to that in patients with severe renal dysfunction.

Impaired liver function

In patients with mild or moderate hepatic impairment, the mean AUC candesartan increases by approximately 20% in one study and 80% in another study. No experience in patients with severe hepatic insufficiency.

Hydrochlorothiazide

T_1/2 Hydrochlorothiazide is increased in patients with impaired renal function.

Indications:Arterial hypertension (patients who are shown combined therapy).

Contraindications:

- Hypersensitivity to the active or auxiliary substances of the drug, as well as to other derivatives of the sulfonamide.

- Pregnancy and the period of breastfeeding.

- Severe renal function impairment (creatinine clearance (CK) less than 30 ml / min), incl. anuria.

- Severe liver dysfunction and / or cholestasis.

- Refractory hypokalemia or hypercalcemia.

- Gout.

- Simultaneous use with aliskiren in patients with diabetes mellitus or renal dysfunction (CC less than 60 ml / min).

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

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

Carefully:

Severe chronic heart failure, bilateral renal artery stenosis, single-kidney artery stenosis, hemodynamically significant stenosis of the aortic and / or mitral valve, cerebrovascular disease, coronary heart disease, hypertrophic obstructive cardiomyopathy, reduced circulating blood volume (bcc), liver cirrhosis,hyponatremia, primary hyperaldosteronism, surgical intervention, condition after recent kidney transplantation, kidney failure, hepatic insufficiency, diabetes mellitus, acute myopia, angle-closure glaucoma.

Pregnancy and lactation:

Pregnancy

The use of Candecor® H 8 during pregnancy is contraindicated. Patients taking Candecor® H 8 should be warned about this before planning a pregnancy so that they can discuss alternative therapies with the attending physician. In case of pregnancy, stop taking the drug Candecor® H 8 and, if necessary, transfer to alternative antihypertensive therapy.

Kandecor® H 8, like other agents that directly affect RAAS, can cause fetotoxic effects (renal dysfunction, fetal skeletal fading, oligohydramnios), and neonatal toxic effects (renal failure, arterial hypotension, hyperkalemia). If nevertheless used the drug in the II-III trimesters of pregnancy, then it is necessary to perform ultrasound examination of the kidneys and bones of the fetal skull. Hydrochlorothiazide penetrates the placenta.With the use of thiazide diuretics in the II-III trimester of pregnancy, it is possible to reduce uteroplacental blood flow, the development of thrombocytopenia, jaundice, a violation of water-electrolyte balance in a fetus or newborn.

Newborns whose mothers took Candecor® H 8 during pregnancy should be monitored, it is possible to develop an arterial hypotension in a newborn.

Breastfeeding period

There is no data on the isolation of candesartan in breast milk. but candesartan is released from the milk of lactating rats.

Hydrochlorothiazide penetrates the breast milk of the mother in small amounts. Thiazide diuretics in high doses cause intense diuresis, thereby suppressing lactation. The drug Candecor® H 8 is not recommended during the period of lactation.

Dosing and Administration:

Inside, once a day, regardless of food intake. The bioavailability of candesartan is not dependent on food intake. Eating does not have a clinically significant effect on the bioavailability of hydrochlorothiazide. The recommended dose is 1 tablet once a day.

It is recommended to titrate the dose of candesartan and hydrochlorothiazide before switching the patient to therapy with Candecor® H 8.If necessary, the issue of transferring the patient from monotherapy with Kandecor® to Kandekor® H 8 can be considered. When transferring a patient with monotherapy with hydrochlorothiazide, titration of candesartan dose is recommended.

In most cases, the hypotensive effect is achieved within 4 weeks from the start of treatment.

Elderly patients

Correction of the dose is not required.

Impaired renal function

Patients with impaired renal function prefer to use "loop" diuretics in comparison with thiazide. Patients with mild to moderate renal impairment (QC greater than 30 mL / min) are advised to select a dose of candesartan by titration (via Kandecor® monotherapy), starting at a dose of 4 mg. The drug Candecor® H 8 is contraindicated in patients with severe renal dysfunction (CC less than 30 ml / min) (see section "Contraindications").

Impaired liver function

Patients with mild or moderate impairment of liver function are advised to select a dose of candesartan by titration (through monotherapy with Candecor®), starting at a dose of 4 mg.

The drug Candecor® H 8 is contraindicated in patients with severe impairment of liver function and / or cholestasis (see section "Contraindications").

Patients with reduced BCC

Patients with reduced BCC (risk of developing hypotension) are recommended to select a dose of candesartan by titration (through monotherapy with Candecor®), starting at a dose of 4 mg.

Children and teenagers under 18 years of age

The safety and effectiveness of the use of Candecor® H 8 in children and adolescents under 18 years of age have not been established.

Side effects:

The side effects observed in the clinical trials of the combination hydrochlorothiazide / candesartan were mild and transient and were comparable (2.3-3.3%) in frequency with the placebo group (2.7%).

The side effects of the hydrochlorothiazide / candesartan combination are limited to side effects previously recorded separately for candesartan and / or hydrochlorothiazide.

Classification of the frequency of development of side effects of the World Organization Health (WHO):

Often ≥1/10

often from ≥1 / 100 to <1/10

infrequently from ≥1 / 1000 to <1/100

rarely from ≥1 / 10000 to <1/1000

very rarely from <1/10000

the frequency of the unknown can not be estimated from the available data.

In each group, undesirable effects are presented in order of decreasing severity.

Candesartan

From the nervous system:

often: dizziness / vertigo, headache.

From the genitourinary system:

very rarely: renal dysfunction, including kidney failure in predisposed patients.

From the hematopoiesis:

very rarely: leukopenia, neutropenia and agranulocytosis.

From the digestive system:

very rarely: nausea, increased activity of "liver" transaminases, violation liver function or hepatitis.

From the musculoskeletal system:

very rarely: back pain, arthralgia, myalgia.

From the respiratory system:

often: respiratory infections;

very rarely: cough.

From the skin:

very rarely: angioedema, skin rash, itching, hives.

Laboratory indicators:

very rarely: hyperkalemia, hyponatremia.

Hydrochlorothiazide

When monotherapy with hydrochlorothiazide, usually at a dose of 25 mg or more, were noted

following side effects:

From the nervous system:

often: mild dizziness, vertigo;

rarely: sleep disturbance, depression, anxiety, paresthesia.

From the cardiovascular system:

infrequently: orthostatic hypotension;

rarely: arrhythmia, necrotizing angiitis (vasculitis, cutaneous vasculitis).

From the respiratory system:

rarely: respiratory distress syndrome (including pneumonitis, pulmonary edema).

From the digestive system:

infrequently: anorexia, loss of appetite, stomach irritation, diarrhea, constipation; rarely: pancreatitis, intrahepatic cholestatic jaundice.

From the hematopoiesis:

rarely: leukopenia, neutropenia / agranulocytosis, thrombocytopenia, aplastic anemia, oppression of bone marrow hematopoiesis, hemolytic anemia.

From the sense organs:

rarely: transient impairment of visual perception;

frequency unknown: acute myopia, acute angle-closure glaucoma.

From the skin:

infrequently: skin rash, hives, photosensitization reactions;

rarely: toxic epidermal necrolysis, skin lupus-like reactions, exacerbation of cutaneous manifestations of systemic lupus erythematosus.

From the urinary system:

often: glucosuria;

rarely: renal dysfunction and interstitial nephritis.

From the musculoskeletal system:

rarely: muscle spasms.

Allergic reactions:

rarely: anaphylactic reactions.

Laboratory indicators:

often: hyperglycemia, hyperuricemia, disturbance of water-electrolyte balance (including hyponatremia and hypokalemia), increased cholesterol and triglyceride concentrations;

rarely: an increase in the concentration of residual nitrogen and creatinine in the blood plasma.

Other:

often: weakness;

rarely: a fever.

Overdose:

Given the pharmacological properties of the drug, we can assume that the main manifestation of an overdose can be a pronounced decrease in blood pressure and dizziness. Cases of drug overdose (up to 672 mg candesartan) are described, which culminated in the recovery of the patient without severe consequences. The main manifestation of an overdose of hydrochlorothiazide is the acute loss of fluid and electrolytes. Nevertheless, against the background of the use of Candecor® H 8, the following symptoms of an overdose: marked decrease in blood pressure, dizziness, thirst, disturbance of water-electrolyte balance, tachycardia, ventricular arrhythmia, oppression / loss of consciousness and muscle cramps.

Treatment: induce vomiting, carry out gastric lavage.Further - symptomatic therapy under the control of vital functions. The patient should be moved to a horizontal position and raise his legs, carry out activities aimed at increasing bcc (introduction of 0.9% sodium chloride solution intravenously). It is necessary to monitor the condition of water-electrolyte and acid-base balance of blood serum and, if necessary, to correct them. If necessary, symptomatic agents may be prescribed. Candesartan is not excreted by hemodialysis, the removal of hydrochlorothiazide is unlikely.

Interaction:

Clinically significant drug interaction candesartan with warfarin, digoxin, contraceptives for oral administration (ethinyl estradiol / levonorgestrel), glibenclamide and nifedipine has not been identified.

Diuretics, laxatives, amphotericin B and derivatives of salicylic acid, steroids and adrenocorticotropic hormone (ACTH)

With the simultaneous use of hydrochlorothiazide with furosemide, amphotericin B, salicylic acid derivatives, steroids and ACTH, or in case of abuse of laxatives it is possible to increase the excretion of potassium ions.

Simultaneous use of potassium supplements, potassium-sparing diuretics (triamterene, spironolactone, amiloride, eplerenone), potassium substitutes, or other agents that can increase the level of potassium in the blood plasma (eg, heparin), can lead to an increase in potassium in the blood serum. If necessary, monitor potassium levels in serum.

Cardiac glycosides and antiarrhythmics

Hypokalemia and hypomagnesemia against thiazide diuretic therapy may increase the cardiotoxicity of cardiac glycosides and antiarrhythmic agents. It is recommended to periodically monitor the potassium content in the blood serum with simultaneous use with cardiac glycosides and drugs that extend the interval QT (risk of developing ventricular tachycardia such as "pirouette"):

- I A class of antiarrhythmic drugs (for example, quinidine, disopyramide);

- III class of antiarrhythmic agents (eg, amiodarone, sotalol, dofetilide);

- some antipsychotics (for example, thioridazine, chlorpromazine, levomepromazine, trifluoperazine, sulpiride, amisulpride, tiapride, haloperidol, droperidol);

- other drugs (eg, cisapride, dipemanyl methyl sulfate, erythromycin for intravenous administration, halofantrine, ketanserin, misolastine, sparfloxacin, terfenadine, wincamine for intravenous administration).

Lithium

With the simultaneous use of lithium and ACE inhibitors or hydrochlorothiazide, cases of transient increase in the concentration of lithium in plasma and the development of toxic effects were noted. A similar effect is possible with simultaneous use of lithium and ARA II preparations. The simultaneous use of candesartan and hydrochlorothiazide with lithium preparations is not recommended. If simultaneous use is required, it is recommended that the serum concentrations of lithium be carefully monitored.

Non-steroidal anti-inflammatory drugs (NSAIDs)

Simultaneous application of NSAIDs (including selective inhibitors of cyclooxygenase-2, acetylsalicylic acid (more than 3 g / day) and nonselective NSAIDs) can weaken the hypotensive effect of ARA II.

As with the ACE inhibitor, the simultaneous use of ARA II and NSAIDs increases the risk of decreased renal function, up to the development of renal failure, leading to hyperkalemia, especially in patients with an existing impaired renal function.This combination should be used with caution, especially in elderly patients. All patients should receive a sufficient amount of fluid. It is necessary to monitor the function of the kidneys at the beginning of simultaneous therapy and periodically throughout the course of treatment.

NSAIDs can reduce the diuretic and hypotensive effects of thiazide diuretics.

Double blockade of RAAS

The double blockade of RAAS (simultaneous use of ACE inhibitors and ARA II) in patients with atherosclerosis, chronic heart failure or diabetes accompanied by affection of target organs is associated with a higher incidence of arterial hypotension, syncope, hyperkalemia, and renal dysfunction (including development acute renal failure) in comparison with application of the drug of one of the groups listed. Double blockade of RAAS is possible only in selected cases under careful control of kidney function. The simultaneous use of candesartan with aliskiren is contraindicated in patients with diabetes mellitus or renal dysfunction (KC less than 60 ml / min) and is not recommended in other patients.

Anion exchange resins (colestramine and colestipol)

The absorption of hydrochlorothiazide is significantly reduced in the presence of anion-exchange resins. A single dose of colestyramine or colestipol reduces the absorption of hydrochlorothiazide in the digestive tract by 85% and 43%, respectively.

Non-depolarizing muscle relaxants

Thiazide diuretics can enhance the effect of tubocurarine chloride.

Vitamin D and calcium salts

The simultaneous use of thiazide diuretics with vitamin D or calcium salts increases the serum calcium content, because it increases the amount of calcium in the blood. decreased excretion of calcium. If you need calcium or vitamin D, you should monitor the calcium level in the blood serum and, possibly, adjust the dose of these drugs.

The simultaneous use of hydrochlorothiazide with beta adrenoblockers and diazoxide potentiates their hyperglycemic effect.

Anticholinergic agents, for example, atropine, biperidine increase the bioavailability of thiazide diuretics due to a decrease in gastrointestinal motility. With simultaneous application amantadine the risk of side effects of amantadine increases due to decreased excretion.

Cytostatic drugs, for example, cyclophosphamide, methotrexate - increases mielopodavlivayuschee action by slowing the excretion from the body; At simultaneous reception with ethanol, barbiturates, narcotic analgesics the frequency of orthostatic hypotension may increase.

Hypoglycemic agents for oral administration and insulin

Simultaneous use of hypoglycemic agents for oral and insulin administration with Thiazide diuretics may require correction of their doses.

Metformin

Use with caution at the same time as metformin, since there is a risk of developing lactic acidosis, induced by renal failure against the background of hydrochlorothiazide.

Sympathomimetics (pressor amines, for example, epinephrine and norepinephrine)

Thiazide diuretics can reduce the effectiveness of adrenomimetov (epinephrine, norepinephrine).

Hydrochlorothiazide may increase the risk of developing acute renal failure, especially with the simultaneous use of high doses iodine containing contrast agents.

Simultaneous application cyclosporine increases the risk of hyperuricemia and exacerbation of gout.

Baclofen, amifostine, tricyclic antidepressants or antipsychotics increase the hypotensive effect, the risk of developing arterial hypotension.

Special instructions:

Impaired renal function

In patients with impaired renal function, it is preferable to use "loop" diuretics. If the drug Kandecor® H 8 is used in patients with impaired renal function, it is recommended to periodically monitor the potassium content and the concentration of creatinine and uric acid in the blood plasma.

Kidney Transplantation

The experience of using Candecor® H 8 in patients who have recently undergone kidney transplantation is absent.

Stenosis of the renal artery

In patients with bilateral stenosis of the renal artery, as well as stenosis of the artery of the only functioning kidney, drugs affecting the RAAS, incl. and ARA II, can increase urea and creatinine concentrations in the blood plasma.

Reduction of BCC (hypovolemia) and / or hyponatraemia

In patients with hypovolemia and / or hyponatremia, the symptomatic arterial hypotension may develop with the use of Candecor® H 8, as with other drugs that affect RAAS.Therefore, the use of Candecor® H 8 is not recommended until these conditions are eliminated.

General anesthesia / surgery

Before surgery (including dentistry), an anesthesiologist should be warned about the use of Candecor® H 8. When performing surgical procedures under general anesthesia, patients with ARA II may develop arterial hypotension due to RAAS blockade. Very rarely arterial hypotension can be pronounced and require intravenous fluid and / or vasopressors.

Impaired liver function

Thiazide diuretics should be used with caution in patients with impaired liver function or progressive liver disease, since even minimal disturbances of the water-electrolyte balance can contribute to the development of the hepatic coma. The experience of using Candecor® H 8 in patients with severe liver dysfunction is absent.

Stenosis of aortic and / or mitral valves, GOKMP

The drug Kandekor® H 8, like other vasodilators, should be used with caution in patients with hemodynamically significant stenosis of the aortic and / or mitral valves or with GOKMP.

Primary hyperaldosteronism

Patients with primary hyperaldosteronism are resistant to antihypertensive drugs that affect RAAS; therefore, in these patients, the use of Candecor® H 8 is not recommended.

Violations of the water-electrolyte balance

In all patients taking diuretics, it is necessary to periodically monitor the content of electrolytes in the blood plasma.

Thiazide diuretics, including hydrochlorothiazide, can cause a violation of the water-electrolyte balance (hypercalcemia, hypokalemia, hyponatremia, hypomagnesemia and hypokalemic alkalosis).

Thiazide diuretics can reduce the excretion of calcium by the kidneys and cause a temporary and insignificant increase in the calcium content in the blood plasma.

Expressed hypercalcemia may be a sign of latent hyperparathyroidism. Before the study of the function of parathyroid glands, thiazide diuretics should be discontinued.

Hydrochlorothiazide, depending on the dose, enhances the excretion of potassium and can cause hypokalemia. This effect of hydrochlorothiazide is less pronounced when applied simultaneously with candesartan. The risk of hypokalemia is increased in patients with cirrhosis of the liver, with hypovolemia or in patients who follow a salt-free diet, or who simultaneously take glucocorticosteroids or ACTH.

The use of Candecor® H 8 can provoke hyperkalemia, especially in patients with heart failure and / or renal insufficiency. Simultaneous use with potassium-sparing diuretics, potassium preparations, potassium substitutes or other agents capable of increasing the potassium content in blood plasma (eg, heparin), can lead to the development of hyperkalemia. If necessary, monitor potassium levels in serum. Thiazide diuretics increase the excretion of magnesium by the kidneys, which can lead to hypomagnesemia.

Metabolic and endocrine effects

Caution is needed in all patients receiving treatment with hypoglycemic agents for ingestion or insulin, since hydrochlorothiazide can weaken their action. Against the background of therapy with thiazide diuretics latent-flowing diabetes mellitus can manifest.

Against the background of treatment with thiazide diuretics, it is possible to increase the concentration of cholesterol and triglycerides in the blood serum. However, when using a combination of hydrochlorothiazide / candesartan containing hydrochlorothiazide 12.5 mg, there was minimal or no such effects.

Therapy with thiazide diuretics in some patients can aggravate hyperuricemia and / or aggravation of gout.

Photosensitivity

The cases of development of photosensitivity against hydrochlorothiazide are described. In the case of development of photosensitivity manifestations, it is recommended to stop therapy. If it is necessary to continue therapy, it is recommended to protect open areas of the body from exposure to sunlight and ultraviolet rays.

Anti-doping test

Hydrochlorothiazide, which is part of Candecor® H 8, may be the cause of a positive anti-doping test.

Acute myopia and secondary acute closed angle glaucoma

Hydrochlorothiazide is a sulfonamide that can cause an idiosyncratic reaction leading to the development of transient acute myopia and acute closed-angle glaucoma. Symptoms include: sudden reduction in visual acuity or eye pain, which usually appears within a few hours or weeks of initiating hydrochlorothiazide therapy.In the absence of treatment, acute closed-angle glaucoma can lead to persistent loss of vision.

Treatment: stop hydrochlorothiazide as soon as possible. If intraocular pressure remains uncontrolled, immediate medical treatment or surgery may be required. Risk factors for the development of acute closed-angle glaucoma are: an allergic reaction to sulfonamide or benzylpenicillin in the anamnesis.

Are common

In patients whose renal function depends on the state of RAAS (eg, in chronic heart failure III-IV functional class by classification NYHA, kidney disease, including renal artery stenosis), therapy with drugs that affect RAAS may be accompanied by severe arterial hypotension, oliguria and / or progressive azotemia, and in rare cases acute renal failure. It is impossible to exclude the development of these disorders due to the suppression of RAAS activity against the background of taking ARA II. A sharp decrease in blood pressure in patients with ischemic cardiomyopathy or cerebrovascular diseases of ischemic genesis with the use of any antihypertensive drugs can lead to the development of myocardial infarction or stroke.

In patients taking thiazide diuretics, hypersensitivity reactions can develop both in the presence and in the absence of a history of an allergic reaction or bronchial asthma, but are more likely if there are any in the history. There are reports of an exacerbation of the systemic lupus erythematosus with the use of thiazide diuretics.

The simultaneous use of other antihypertensive drugs potentiates the hypotensive effect Kandekor® H 8 formulation.

Special information on excipients

Preparation Kandekor® H 8 contains lactose, and the drug is contraindicated in patients with lactase deficiency, lactose intolerance syndrome glucose-galactose malabsorption.

Effect on the ability to drive transp. cf. and fur:Effect of drug Kandekor® H 8 to drive vehicles and work with complex technical devices has not been studied, but the pharmacodynamic properties of the drug indicate that this effect is absent. Nevertheless, care must be taken when driving vehicles and engaging in other potentially hazardous activities,in connection with the possibility of developing side effects (dizziness, etc.).

Form release / dosage:

Tablets 12.5 mg + 8 mg.

Packaging:For 14 tablets in a blister of the combined material OPA / Al / PVC and foil aluminum or PVC / PVDC and foil aluminum.

For 2 or 4 blisters together with instructions for use are placed in a pack of cardboard.

Storage conditions:At a temperature of no higher than 25 ° C, in the original packaging. Keep out of the reach of children.

Shelf life:

2 years. Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-002221

Date of registration:06.09.2013 / 16.06.2014

Expiration Date:06.09.2018

Date of cancellation:2018-09-06

The owner of the registration certificate:KRKA-RUS, LLC KRKA-RUS, LLC Russia

Manufacturer: & nbsp

KRKA, d.d. Slovenia

Representation: & nbspKRKA, dd, Novo mesto, AOKRKA, dd, Novo mesto, AO

Information update date: & nbsp22.11.2017

Illustrated instructions

Instructions

Candecor® H8 (Candecor® N8)