Angiacand (Tablets) Instructions for Use

Marketing Authorization Holder

Canonpharma Production, CJS (Russia)

ATC Code

C09CA06 (Candesartan)

Active Substance

Candesartan (Rec.INN registered by WHO)

Dosage Forms

	Angiacand	Tablets 8 mg: 10, 14, 28, 30, 56, 60 or 90 pcs.
		Tablets 16 mg: 10, 14, 28, 30, 56, 60 or 90 pcs.
		Tablets 32 mg: 10, 14, 28, 30, 56, 60 or 90 pcs.

Dosage Form, Packaging, and Composition

Tablets white or almost white, round, biconvex.

Excipients : pregelatinized corn starch – 20.3 mg, croscarmellose sodium – 3.5 mg, lactose monohydrate – 64.5 mg, magnesium stearate – 0.7 mg, povidone K30 – 3 mg.

7 pcs. – contour cell packs (2) – cardboard packs.
7 pcs. – contour cell packs (4) – cardboard packs.
7 pcs. – contour cell packs (8) – cardboard packs.
10 pcs. – contour cell packs (1) – cardboard packs.
10 pcs. – contour cell packs (3) – cardboard packs.
10 pcs. – contour cell packs (6) – cardboard packs.
30 pcs. – contour cell packs (1) – cardboard packs.
30 pcs. – contour cell packs (2) – cardboard packs.
30 pcs. – contour cell packs (3) – cardboard packs.

Tablets white or almost white, round, biconvex.

Excipients : pregelatinized corn starch – 23.8 mg, croscarmellose sodium – 5 mg, lactose monohydrate – 90 mg, magnesium stearate – 1 mg, povidone K30 – 4.2 mg.

7 pcs. – contour cell packs (2) – cardboard packs.
7 pcs. – contour cell packs (4) – cardboard packs.
7 pcs. – contour cell packs (8) – cardboard packs.
10 pcs. – contour cell packs (1) – cardboard packs.
10 pcs. – contour cell packs (3) – cardboard packs.
10 pcs. – contour cell packs (6) – cardboard packs.
30 pcs. – contour cell packs (1) – cardboard packs.
30 pcs. – contour cell packs (2) – cardboard packs.
30 pcs. – contour cell packs (3) – cardboard packs.

Tablets white or almost white, round, biconvex.

Excipients : pregelatinized corn starch – 27.5 mg, croscarmellose sodium – 7 mg, lactose monohydrate – 126 mg, magnesium stearate – 1.5 mg, povidone K30 – 6 mg.

7 pcs. – contour cell packs (2) – cardboard packs.
7 pcs. – contour cell packs (4) – cardboard packs.
7 pcs. – contour cell packs (8) – cardboard packs.
10 pcs. – contour cell packs (1) – cardboard packs.
10 pcs. – contour cell packs (3) – cardboard packs.
10 pcs. – contour cell packs (6) – cardboard packs.
30 pcs. – contour cell packs (1) – cardboard packs.
30 pcs. – contour cell packs (2) – cardboard packs.
30 pcs. – contour cell packs (3) – cardboard packs.

Clinical-Pharmacological Group

Angiotensin II receptor antagonist

Pharmacotherapeutic Group

Agents acting on the renin-angiotensin system, angiotensin II receptor antagonists

Pharmacological Action

Antihypertensive agent, angiotensin II receptor antagonist. It blocks AT₁ receptors, which leads to a decrease in the biological effects of angiotensin II (mediated by receptors of this type), including vasoconstrictive action, stimulating effect on the release of aldosterone, regulation of salt and water homeostasis, and stimulation of cell growth.

The antihypertensive effect is due to a decrease in total peripheral vascular resistance without a reflex increase in heart rate.

It does not inhibit ACE. It does not interact with or block receptors of other hormones or ion channels that are important for the regulation of the cardiovascular system functions.

Pharmacokinetics

C_max in blood plasma is reached within 3-4 hours. Plasma concentration increases linearly with increasing dose in the therapeutic range (up to 32 mg). V_d – 0.13 l/kg. Plasma protein binding – 99.8%. It is slightly metabolized in the liver (20-30%) with the participation of CYP2C to form an inactive metabolite.

Terminal T_1/2 – 9 hours. Does not accumulate. Total clearance – 0.37 ml/min/kg, with renal clearance – about 0.19 ml/min/kg. Candesartan is excreted by the kidneys (by glomerular filtration and active tubular secretion): 26% as candesartan and 7% as an inactive metabolite; with bile – 56% and 10%, respectively. After a single dose, more than 90% of the dose is excreted within 72 hours.

In elderly patients (over 65 years), C_max and AUC increase by 50% and 80%, respectively, compared to young patients.

In patients with mild to moderate renal impairment, C_max and AUC increase by 50% and 70%, respectively, while T_1/2 of the drug does not change compared to patients with normal renal function.

In patients with severe renal impairment, C_max and AUC increase by 50% and 110%, respectively, and T_1/2 increases 2-fold.

In patients with mild to moderate hepatic impairment, an increase in AUC by 23% was observed.

Indications

Arterial hypertension; chronic heart failure and impaired left ventricular systolic function (LVEF <40%) as an additional therapy to ACE inhibitors or in case of intolerance to ACE inhibitors.

ICD codes

Dosage Regimen

Take orally once or twice daily, with or without food.

For arterial hypertension, initiate therapy at 8 mg once daily.

Titrate the dose to 16 mg once daily and then to 32 mg once daily based on blood pressure response.

The usual maintenance dose is 8 mg to 32 mg once daily.

For chronic heart failure with impaired left ventricular systolic function (LVEF <40%), initiate at 4 mg once daily.

Double the dose at intervals of at least two weeks to the target maintenance dose of 32 mg once daily, or the highest tolerated dose.

In patients with intolerance to ACE inhibitors, start under close medical supervision; consider a lower initial dose.

For patients with severe renal impairment (CrCl <30 mL/min) or undergoing hemodialysis, initiate therapy with caution under close medical supervision.

In patients with mild to moderate hepatic impairment, consider initiating at a lower dose; dosage adjustment may be necessary.

For elderly patients over 65 years, no initial dosage adjustment is required, but monitor renal function periodically.

Periodically monitor serum potassium and creatinine levels, especially during dose titration, in the elderly, and in patients with renal impairment or heart failure.

Correct any volume depletion prior to administration to minimize the risk of symptomatic hypotension.

Adverse Reactions

Infections common – respiratory infections.

From the hematopoietic system: very rare – leukopenia, neutropenia, agranulocytosis.

From the metabolism: rare – hyperkalemia, hyponatremia.

From the nervous system uncommon – dizziness/vertigo, headache.

From the cardiovascular system: common – pronounced decrease in blood pressure.

From the digestive system: very rare – nausea.

From the liver and biliary tract very rare – increased levels of liver enzymes, impaired liver function, hepatitis.

From the respiratory system: very rare – cough.

From the skin and subcutaneous tissues: skin itching.

Allergic reactions very rare – angioedema, skin rash, urticaria.

From the musculoskeletal system uncommon – back pain; very rare – arthralgia, myalgia.

From the urinary system very rare – impaired renal function, including renal failure in predisposed patients.

From laboratory parameters possible – slight decrease in hemoglobin, increase in creatinine and urea concentration, increase in potassium content and decrease in sodium content.

General reactions common – weakness.

Contraindications

Hypersensitivity to candesartan; pregnancy, breastfeeding period; severe liver dysfunction and/or cholestasis; age under 18 years (efficacy and safety not established). Use of candesartan in combination with drugs containing aliskiren in patients with diabetes mellitus and/or with moderate or severe renal impairment (GFR less than 60 ml/min/1.73 m² body surface area). Simultaneous use with ACE inhibitors in patients with diabetic nephropathy.

With caution severe renal impairment (creatinine clearance less than 30 ml/min); bilateral renal artery stenosis or stenosis of the artery of a single kidney; hemodynamically significant stenosis of the aortic and/or mitral valves; history of kidney transplantation; hemodialysis; cerebrovascular disorders of ischemic origin and coronary artery disease; hyperkalemia; in patients with reduced blood volume; primary hyperaldosteronism; hypertrophic obstructive cardiomyopathy.

Use in Pregnancy and Lactation

Candesartan is contraindicated for use during pregnancy and during lactation (breastfeeding).

Use in Hepatic Impairment

Contraindicated in severe liver dysfunction and/or cholestasis.

Use in Renal Impairment

Contraindicated in patients with moderate or severe renal impairment (glomerular filtration rate less than 60 ml/min/1.73 m² body surface area). Use with caution in patients with renal impairment (creatinine clearance less than 30 ml/min); with bilateral renal artery stenosis or stenosis of the artery of a single kidney; with primary hyperaldosteronism; history of kidney transplantation; hemodialysis.

When used in patients with renal failure, plasma potassium and creatinine levels should be monitored periodically.

Pediatric Use

Contraindicated in children and adolescents under 18 years of age.

Geriatric Use

Elderly patients should be prescribed with caution to avoid worsening of concomitant diseases. Renal function should be monitored periodically, especially in patients aged 75 years and older.

Special Precautions

When using candesartan in patients with arterial hypertension and severe renal impairment (creatinine clearance less than 30 ml/min), it is recommended to periodically monitor serum potassium and creatinine levels. In patients with creatinine clearance less than 15 ml/min, the dose should be carefully selected under careful blood pressure control.

In patients with chronic heart failure, renal function should be monitored periodically, especially in patients aged 75 years and older, as well as in patients with impaired renal function.

When increasing the dose of candesartan, it is recommended to monitor potassium and creatinine levels.

When candesartan is used concomitantly with ACE inhibitors in chronic heart failure, the risk of adverse effects, especially impaired renal function and hyperkalemia, may increase. In these cases, careful patient monitoring and control of laboratory parameters are necessary.

During hemodialysis, blood pressure may be particularly sensitive to AT₁ receptor blockade due to decreased plasma volume and activation of the renin-angiotensin-aldosterone system. In this regard, patients on hemodialysis require careful dose titration of candesartan under careful blood pressure control.

In patients with bilateral renal artery stenosis or stenosis of the artery of a single kidney, drugs affecting the renin-angiotensin-aldosterone system, in particular ACE inhibitors, may cause an increase in serum urea and creatinine concentrations. Similar effects can be expected with the use of angiotensin II receptor antagonists.

In patients with chronic heart failure, arterial hypotension may develop during therapy with candesartan. At the beginning of therapy, special caution should be exercised and, if necessary, hypovolemia should be corrected.

In patients receiving angiotensin II receptor antagonists, arterial hypotension may develop during general anesthesia and surgical interventions as a result of blockade of the renin-angiotensin-aldosterone system. Very rarely, cases of severe arterial hypotension may occur, requiring intravenous administration of plasma substitutes and/or vasopressors.

Patients in whom vascular tone and renal function predominantly 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 especially sensitive to drugs acting on the renin-angiotensin-aldosterone system. The prescription of such agents in these patients is accompanied by a sharp arterial hypotension, azotemia, oliguria and, less frequently, acute renal failure. The possibility of developing these effects cannot be excluded when using angiotensin II receptor antagonists. A sharp decrease in blood pressure in patients with coronary artery disease or cerebrovascular diseases of atherosclerotic origin, when using any antihypertensive agents, can lead to the development of myocardial infarction or stroke.

Effect on ability to drive vehicles and mechanisms

During treatment with candesartan, patients should exercise caution when driving vehicles and engaging in other activities that require high concentration and speed of psychomotor reactions, since Candesartan may cause dizziness and weakness.

Drug Interactions

Concomitant use of candesartan with aliskiren and aliskiren-containing drugs is contraindicated in patients with diabetes mellitus and/or with moderate or severe renal failure (glomerular filtration rate less than 60 ml/min/1.73 m² body surface area) and is not recommended in other patients.

There is evidence that concomitant use of ACE inhibitors and angiotensin II receptor antagonists may lead to an increase in adverse reactions, such as hypotension, hyperkalemia and impaired renal function, particularly in patients with diabetic nephropathy. Therefore, simultaneous use of angiotensin II receptor antagonists with ACE inhibitors is contraindicated in patients with diabetic nephropathy and is not recommended in other patients.

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

Concomitant use with potassium preparations, potassium-sparing diuretics, dietary supplements containing potassium, or potassium salt substitutes may lead to the development of hyperkalemia.

Candesartan increases serum lithium concentration and increases the risk of toxic reactions.

When angiotensin II receptor antagonists and NSAIDs are used concomitantly, including selective cyclooxygenase-2 inhibitors, acetylsalicylic acid (more than 3 g per day), a decrease in the antihypertensive effect may be noted.

As with the use of ACE inhibitors, concomitant use of angiotensin II receptor antagonists and NSAIDs may increase the risk of impaired renal function, including acute renal failure, increased serum potassium concentration, especially in patients with reduced renal function. Caution should be exercised when using these drugs concomitantly, especially in elderly patients and in patients with reduced blood volume. Patients should compensate for fluid loss and carefully monitor renal function after starting combination therapy and periodically during such therapy.

Drugs affecting the RAAS may increase blood urea and creatinine concentrations in patients with bilateral renal artery stenosis or artery of a single kidney. Concomitant use of diuretics and other antihypertensive agents increases the risk of arterial hypotension.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.