Ordiss N, pills 16mg + 12.5mg 30pcs

Composition

1 tablet contains:

Active ingredient:

candesartan in tsileksetil was 8.0 mg/16,0 mg/32,0 mg;

excipients:

starch pregelatinization 3.75 mg/7.5 mg/15,0 mg;

poloxamer 188 0.5 mg/1.0 mg/2.0 mg;

povidone-the COA 4.0 mg/8.0 mg/16,0 mg;

dye iron oxide red (E 172) 0.075 mg/0.15 mg/0.3 mg;

calcium carmellose of 1.65 mg/3.3 mg/6.6 mg;

microcrystalline cellulose 17,5 mg/35,0 mg/70,0 mg;

lactose monohydrate 43,725 mg/87,45 mg/174,9 mg;

magnesium stearate 0.8 mg/1.6 mg/3,2 mg.

Pharmacological action

Angiotensin II is the main hormone of the renin-angiotensin-aldosterone system (RAAS), 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. The effects are mediated by the interaction of angiotensin II with angiotensin type 1 receptors (AT1 receptors).

Candesartan is a selective antagonist of angiotensin II AT1 receptors, does not inhibit the angiotensin – converting enzyme (ACE) that converts angiotensin I to angiotensin II, which destroys bradykinin, does not lead to the accumulation of bradykinin or substance P. As a result of blocking AT1 receptors of angiotensin II, there is a dose-dependent increase in the content of renin, angiotensin I, angiotensin II and a decrease in the concentration of aldosterone in the blood plasma.

When comparing candesartan with ACE inhibitors, the development of cough was less common in patients receiving candesartan.

Candesartan does not bind to the receptors of other hormones and does not block ion channels involved in regulating the functions of the cardiovascular system.

Hydrochlorothiazide is a thiazide-like diuretic that inhibits active sodium reabsorption, mainly in the distal renal tubules, and increases the release of sodium, chlorine, and water ions. The excretion of potassium and magnesium by the kidneys increases 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, reduces the intensity of blood transport by the heart, and lowers blood pressure (BP). During long-term treatment, the hypotensive effect develops due to the expansion of arterioles. Long-term use of hydrochlorothiazide reduces the risk of cardiovascular diseases and mortality.

Candesartan and hydrochlorothiazide have a combined antihypertensive effect. In patients with arterial hypertension, the use of candesartan / hydrochlorothiazide causes an effective and prolonged decrease in blood pressure without increasing the heart rate (HR). Orthostatic arterial hypotension is not observed at the first dose of the drug, after the end of treatment, arterial hypertension does not increase.

After a single dose of candesartan/hydrochlorothiazide, the main antihypertensive effect develops within 2 hours. Using the drug once a day effectively and gently reduces blood pressure for 24 hours with a slight difference between the maximum and average effect of action. With prolonged treatment, a stable decrease in blood pressure occurs within 4 weeks after the start of taking the drug and can be maintained with a long course of treatment.

In clinical studies, the incidence of side effects, especially cough, was less frequent with candesartan/hydrochlorothiazide than with the combination of ACE inhibitors with hypothiazide.

Currently, there are no data on the use of candesartan / hydrochlorothiazide in patients with renal insufficiency, nephropathy, reduced left ventricular function, acute heart failure, or who have suffered a myocardial infarction.

The effectiveness of candesartan / hydrochlorothiazide is independent of gender and age.

Indications

Arterial hypertension.

Chronic heart failure and impaired left ventricular systolic function (left ventricular ejection fraction (LVEF) not more than 40%) as adjunctive therapy with ACE inhibitors or in case of intolerance to ACE inhibitors.

Contraindications

Hypersensitivity to candesartan, hydrochlorothiazide, other components of the drug and other sulfonamide derivatives; pregnancy; lactation; lactose intolerance; lactase deficiency; glucose-galactose malabsorption syndrome; primary hyperaldosteronism; gout; severe renal impairment (creatinine clearance less than 30 ml/min); severe hepatic impairment; cholestasis; refractory hypokalemia, hypercalcemia; condition after kidney transplantation, children under 18 years of age. With caution: Concomitant use with other antihypertensive drugs, potassium-sparing diuretics, amphotericin, carbenoxolone, penicillin G sodium, salicylic acid derivatives, cardiac glycosides, antiarrhythmic drugs, lithium preparations, nonsteroidal anti-inflammatory drugs (NSAIDs), colestipol, colestyramine, tubocurarin, beta-blockers, anticholinergic drugs, amantadine, cytotoxic drugs, glucocorticosteroids (corticosteroids), adrenocorticotropic hormone (ACTH), alcohol, barbiturates, general anesthetics, epinephrine, iodine-containing drugs; impaired renal function (creatinine clearance more than 30 ml/min), liver function failure; severe chronic heart failure; bilateral renal artery stenosis; single kidney artery stenosis; hemodynamically significant aortic and/or mitral stenosis heart disease; hypertrophic obstructive cardiomyopathy; decreased circulating blood volume (BCC); diabetes mellitus, cerebrovascular diseases; acute myopia; angle-closure glaucoma; systemic lupus erythematosus.

Side effects

the incidence of side effects is classified according to the recommendations of the world health organization: very often – at least 10%; often – not less than 1% but < 10%; infrequently – no more than 0.1% but < 1%; rarely – not less than 0.01%, but less than 0.1%; very rarely (including private messages) – less than 0.01%.

Candesartan

From the blood system: very rarely – leukopenia, neutropenia, agranulocytosis.

From the side of metabolism and nutrition: very rarely – hyperkalemia, hyponatremia.

From the central nervous system( CNS): often – dizziness; very rarely – headache.

From the gastrointestinal tract: very rarely-nausea.

From the respiratory system: very rarely – cough.

From the liver and biliary tract: very rarely-increased activity of “hepatic” transaminases, impaired liver function, hepatitis.

From the skin and subcutaneous tissues: very rarely-skin rash, pruritus, urticaria, angioedema.

Musculoskeletal and connective tissue disorders: very rare – back pain, arthralgia, myalgia.

From the side of the kidneys and urinary tract: very rarely-renal failure

Hydrochlorothiazide

From the blood system: rarely-leukopenia, neutropenia, agranulocytosis, thrombocytopenia, aplastic anemia, bone marrow suppression, hemolytic anemia, decreased hemoglobin.

From the immune system: rarely – anaphylactic reaction.

From the side of metabolism and nutrition: often-hyperglycemia, hyperuricemia, hyponatremia, hypokalemia.

From the central nervous system: often – dizziness, vertigo; rarely-sleep disorders, anxiety, depression, paresthesia.

From the side of the visual organ: rarely-decreased visual clarity, acute myopia, acute angle-closure glaucoma.

From the cardiovascular system: infrequently-postural hypotension; rarely-arrhythmia, vasculitis.

Respiratory, thoracic and mediastinal disorders: rarely – respiratory distress syndrome, pneumonitis, pulmonary edema.

From the digestive system: infrequently – anorexia, loss of appetite, constipation, diarrhea, irritation of the gastric mucosa; rarely-pancreatitis.

From the liver and biliary tract: rarely-intrahepatic cholestatic jaundice.

From the skin and subcutaneous tissues: infrequently-skin rash, urticaria, photosensitization reaction; rarely-toxic epidermal necrolysis, erythematous-like reactions, relapse of cutaneous erythematosis.

Musculoskeletal and connective tissue disorders: rarely-muscle spasm.

From the side of the kidneys and urinary tract: often-glucosuria; rarely-impaired renal function, interstitial nephritis.

Other: often-weakness, increased concentration of cholesterol, triglycerides in blood plasma; rarely-fever, increased concentration of creatinine, urea in blood plasma.

Interaction

No clinically significant drug interactions were observed when candesartan was co-administered with hydrochlorothiazide, warfarin, digoxin, oral contraceptives (ethinyl estradiol/levonorgesgrel), glibenclamide, nifedipine, and enalapril.

Concomitant use of candesartan with ACE inhibitors, other angiotensin II receptor antagonists, and aliskiren increases the risk of hyperkalemia, a sharp drop in blood pressure, and impaired renal function, including acute renal failure, which requires careful monitoring of blood pressure, renal function, and water-electrolyte balance.

Concomitant use of candesartan with aliskiren in patients with diabetes mellitus and impaired renal function (UC less than 60 ml / min) is not recommended.Candesartan is metabolized in the liver to a small extent with the participation of the CYP2C9 isoenzyme. The conducted interaction studies did not reveal the effect of candesartan on the isoenzymes CYP2C9 and CYP3A4, the effect on other isoenzymes of the cytochrome P 450 system was not studied.

Concomitant use of candesartan with other antihypertensive agents increases the antihypertensive effect.

Experience with other drugs that affect the RAAS shows that concomitant therapy with potassium-sparing diuretics, potassium preparations, salt substitutes containing potassium, and other agents that increase the content of potassium in the blood serum (for example, heparin) can lead to the development of hyperkalemia.

With the simultaneous use of lithium preparations and ACE inhibitors, there is a reversible increase in the concentration of lithium in the blood serum and the development of toxic reactions. Similar reactions may occur with the use of angiotensin II receptor antagonists, and therefore it is recommended to monitor the lithium content in the blood serum.

Concomitant use with non-steroidal anti-inflammatory drugs (NSAIDs), including selective cyclooxygenase-2 (COX-2) inhibitors, acetylsalicylic acid (more than 3 g/day) and non-selective NSAIDs, may reduce the antihypertensive effect of candesartan, and may also lead to an increased risk of renal dysfunction, including the development of acute renal failure and an increase in serum potassium. The combination of these drugs should be used with caution, especially in elderly patients.

How to take, course of use and dosage

Inside, regardless of food intake,1 time a day.

Arterial hypertension

The recommended starting dose of Ordiss® is 8 mg once daily. Patients who need a further reduction in blood pressure (BP), it is recommended to increase the dose to 16 mg once a day. The maximum antihypertensive effect is achieved within 4 weeks from the start of treatment. The maximum daily dose is 32 mg / day. If adequate blood pressure control is not achieved during treatment with NORDISS®, it is recommended to add a thiazide diuretic to therapy.

 In elderly patients, there is no need to adjust the initial dose of the drug.

In patients with reduced BCC, there is a risk of developing arterial hypotension, so you should start treatment with the drug at a dose of 4 mg / day (1/2 tablet of 8 mg).

In patients with renal insufficiency. When used in patients with mild or moderate renal insufficiency (creatinine clearance of at least 30 ml/min/1.73 m2 of body surface area), the initial dose is 4 mg / day (1/2 tablet of 8 mg).

Clinical experience with the drug in patients with severe renal insufficiency (creatinine clearance less than 30 ml / min/1.73 m2 of body surface area) is limited. In these cases, the possibility of starting treatment with a dose of 4 mg/day (1/2 tablet of 8 mg) should be considered.

In patients with impaired liver function. When using the drug in patients with mild to moderate hepatic impairment, an initial dose of 2 mg/day (1/4 tablet of 8 mg) is recommended. If necessary, it is possible to increase the dose. Clinical experience with the drug in patients with severe hepatic impairment and / or cholestasis is limited (see section “Contraindications”).

Ordiss® can be used in combination with thiazide diuretics (for example, hydrochlorothiazide), which leads to an increased hypotensive effect.

Chronic heart failure (CHF)

The recommended starting dose of Ordiss® is 4 mg once a day (1/2 tablet of 8 mg). Increasing the dose to 32 mg once a day or to the maximum tolerated dose is carried out by doubling it at intervals of at least 2 weeks.

Ordiss® can be used in combination with other medications used for CHF, such as ACE inhibitors, beta-blockers, diuretics, and cardiac glycosides.

Special patient groups

Elderly patients, patients with renal insufficiency or impaired liver function do not need to change the initial dose of the drug.

Overdose

Symptoms: analysis of the pharmacological properties of the drug suggests that the main manifestation of overdose may be a clinically pronounced decrease in blood pressure, dizziness. Individual cases of overdose of the drug (up to 672 mg of candesartan) were described, which resulted in recovery of patients without serious consequences.

The main manifestation of an overdose of hydrochlorothiazide is a decrease in BCC and a violation of the water-electrolyte balance. There were also symptoms such as dizziness, a marked decrease in blood pressure, dryness of the oral mucosa, tachycardia, ventricular arrhythmia, loss of consciousness and muscle cramps.

Treatment: with the development of a clinically pronounced decrease in blood pressure, it is necessary to conduct symptomatic treatment and monitor the patient’s condition. Place the patient on his back and lift his legs.

If necessary, the BCC should be increased, for example, by intravenous use of 0.9% sodium chloride solution. If necessary, sympathomimetic agents may be prescribed. Elimination of candesartan and hydrochlorothiazide by hemodialysis is unlikely.

Special instructions

Impaired renal function. When using Ordiss®, as with other drugs that inhibit the RAAS, in some cases, renal function disorders may develop.

When using Ordiss® in patients with arterial hypertension and severe renal insufficiency (creatinine clearance less than 30 ml / min), it is recommended to regularly monitor the potassium content and serum creatinine concentration. Clinical experience with the drug in patients with end-stage renal failure (creatinine clearance less than 15 ml / min) is limited. When using Ordiss® in such patients, it is necessary to select the dose of Ordiss® under the control of blood pressure.

In patients with CHD, renal function should be monitored periodically, especially in patients over 75 years of age and in patients with impaired renal function. When increasing the dose, it is also recommended to monitor the potassium content and serum creatinine concentration.

There are no data on the use of Ordiss® in patients with CHF with a creatinine concentration of more than 265 mmol / l (more than 3 mg / ml).

Hemodialysis. During hemodialysis, blood pressure may be particularly sensitive to AT1-receptor blockade as a result of BCC reduction and RAAS activation. Therefore, patients undergoing hemodialysis should monitor their blood pressure and individually select the dose of Ordiss® in accordance with blood pressure indicators.

Concomitant use with ACE inhibitors in patients with CHF. When used concomitantly with ACE inhibitors, the risk of side effects increases, especially impaired renal function and hyperkalemia. Patients ‘ clinical condition and appropriate laboratory parameters should be monitored.

Renal artery stenosis. Drugs that affect the RAAS (for example, ACE inhibitors) can lead to increased serum urea and creatinine concentrations in patients with bilateral renal artery stenosis or stenosis of the artery of a single kidney. A similar effect can be expected with the use of angiotensin II receptor antagonists.

 There is no experience of using Ordiss® in patients who have recently undergone a kidney transplant.

Arterial hypotension. In patients with CHF when using the drug Ordiss® may cause hypotension. Hypotension may also occur in patients with BCC deficiency, for example, when using high doses of diuretics. In this case, BCC correction should be performed before using Ordiss®.

General anesthesia and / or surgery. Patients receiving angiotensin II antagonists may develop hypotension during general anesthesia and surgery as a result of RAAS blockade. In rare cases, hypotension may be severe, requiring intravenous fluids and / or vasopressors.

Aortic and/or mitral valve stenosis, HOCMP. Caution should be exercised when using Ordiss® in patients with HOCMP or hemodynamically significant aortic or mitral valve stenosis.

Primary hyperaldosteronism. Patients with primary hyperaldosteronism are usually resistant to therapy with antihypertensive agents that affect the RAAS, so the use of Ordiss® in this group of patients is not recommended. Hyperkalemia. Concomitant use of Ordiss® with potassium-sparing diuretics, potassium preparations or salt substitutes containing potassium, or other drugs that may increase the serum potassium content (for example, heparin) may lead to the development of hyperkalemia in patients with arterial hypertension.

Hyperkalemia may also occur in patients with CHF taking Ordiss®. During therapy with Ordiss® in patients with CHF, it is recommended to periodically monitor the serum potassium content, especially with the simultaneous use of ACE inhibitors and potassium-sparing diuretics (spironolactone, triamterene, amiloride).

Common.  Patients whose vascular tone and renal function are predominantly affected by RAAS activity (for example, patients with severe chronic heart failure, kidney diseases, including renal artery stenosis) are particularly sensitive to drugs acting on RAAS. The use of such drugs is accompanied in these patients by severe hypotension, azotemia, oliguria and, less often, acute renal failure. The possibility of developing these effects is not excluded with the use of angiotensin II receptor antagonists. A sharp decrease in blood pressure in patients with ischemic cardiopathy, cerebrovascular diseases of ischemic origin with the use of any antihypertensive agents can lead to the development of myocardial infarction or stroke.

Use in pediatrics: The safety and efficacy of Ordiss® in children under 18 years of age have not been established.

Form of production

Biconvex capsule-shaped tablets of light pink color with a risk on both sides. On one side there is an engraving “C” and “16” on different sides of the risk.

Storage conditions

  Store in a dry place, protected from light, at a temperature not exceeding 25 °C.

Shelf life

2 years

Active ingredient

Hydrochlorothiazide, Candesartan

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as directed by your doctor

Indications

Hypertension