Atacand^® (Tablets) Instructions for Use

ATC Code

C09CA06 (Candesartan)

Active Substance

Candesartan (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Angiotensin II receptor antagonist

Pharmacotherapeutic Group

Angiotensin II receptor antagonist

Pharmacological Action

Antihypertensive agent, angiotensin II receptor antagonist. It blocks AT₁ receptors, which leads to a reduction in the biological effects of angiotensin II (mediated by this type of receptor), including its vasoconstrictive action, stimulatory effect on aldosterone release, regulation of salt and water homeostasis, and stimulation of cell growth. The antihypertensive effect is due to a reduction in total peripheral resistance without a reflex increase in heart rate.

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

Pharmacokinetics

C_max in plasma is reached within 3-4 hours. Plasma concentration increases linearly with increasing dose within the therapeutic range (up to 32 mg). V_d – 0.13 L/kg. Plasma protein binding – 99.8%. It is minimally metabolized in the liver (20-30%) via 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 being about 0.19 mL/min/kg. Candesartan is excreted by the kidneys (via glomerular filtration and active tubular secretion): 26% as candesartan and 7% as the inactive metabolite; via bile – 56% and 10%, respectively. More than 90% of the dose is excreted within 72 hours after a single dose.

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 the 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 doubles.

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

Indications

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

ICD codes

Dosage Regimen

Administer tablets orally once or twice daily with or without food. The dosage must be individualized based on therapeutic response and patient tolerance.

For arterial hypertension, initiate therapy at 8 mg once daily. Titrate to 16 mg once daily based on blood pressure response. For insufficient control, consider a twice-daily regimen or increasing the dose to a maximum of 32 mg daily.

For chronic heart failure (LVEF <40%), initiate at 4 mg once daily. Double the dose at intervals of no less than two weeks, as tolerated by the patient, to the target maintenance dose of 32 mg once daily.

In patients with volume depletion, correct this condition prior to initiation or use a lower starting dose to mitigate the risk of symptomatic hypotension.

For elderly patients (over 65 years), no initial dose adjustment is typically required. Exercise caution and consider a lower starting dose due to potential age-related decreases in renal function.

In patients with mild to moderate hepatic impairment, initiate therapy with caution. The recommended initial dose is 4 mg. Do not use in severe hepatic impairment or cholestasis.

In patients with severe renal impairment (CrCl <30 mL/min) or on hemodialysis, initiate therapy with a lower dose and titrate carefully under close medical supervision. Monitor blood pressure, serum potassium, and creatinine closely.

Adverse Reactions

Infections and infestations: Common – respiratory infections.

Blood and lymphatic system disorders: Very rare – leukopenia, neutropenia, agranulocytosis.

Metabolism and nutrition disorders: Rare – hyperkalemia, hyponatremia.

Nervous system disorders: Uncommon – dizziness/vertigo, headache.

Cardiac disorders: Common – pronounced decrease in blood pressure.

Gastrointestinal disorders: Very rare – nausea.

Hepatobiliary disorders: Very rare – increased levels of liver enzymes, impaired liver function, hepatitis.

Respiratory, thoracic and mediastinal disorders: Very rare – cough.

Skin and subcutaneous tissue disorders: Pruritus.

Immune system disorders: Very rare – angioedema, skin rash, urticaria.

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

Renal and urinary disorders: Very rare – impaired renal function, including renal failure in predisposed patients.

Investigations: Possible – slight decrease in hemoglobin, increased concentration of creatinine and urea, increased potassium and decreased sodium levels.

General disorders and administration site conditions: Common – asthenia.

Contraindications

Hypersensitivity to candesartan; pregnancy, breastfeeding period; severe hepatic impairment 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). Concurrent 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 valve; history of kidney transplantation; hemodialysis; cerebrovascular disorders of ischemic origin and coronary artery disease; hyperkalemia; in patients with reduced circulating blood volume; primary hyperaldosteronism; hypertrophic obstructive cardiomyopathy.

Use in Pregnancy and Lactation

Candesartan is contraindicated during pregnancy and lactation (breastfeeding).

Use in Hepatic Impairment

Contraindicated in severe hepatic impairment 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. For patients with creatinine clearance less than 15 ml/min, the dose should be carefully titrated under close blood pressure monitoring.

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.

Concomitant use of candesartan with ACE inhibitors in chronic heart failure may increase the risk of adverse effects, especially impaired renal function and hyperkalemia. 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 reduced plasma volume and activation of the renin-angiotensin-aldosterone system. Therefore, patients on hemodialysis require careful dose titration of candesartan under close blood pressure monitoring.

In patients with bilateral renal artery stenosis or stenosis of the artery of a single kidney, drugs affecting the renin-angiotensin-aldosterone system, particularly ACE inhibitors, may cause an increase in serum urea and creatinine levels. 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. Special caution should be exercised at the beginning of therapy, and correction of hypovolemia should be performed if necessary.

In patients receiving angiotensin II receptor antagonists, arterial hypotension may develop during general anesthesia and surgery 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 depend predominantly on the activity of the renin-angiotensin-aldosterone system (e.g., 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. Administration of such agents in these patients is accompanied by sharp arterial hypotension, azotemia, oliguria, and less frequently, acute renal failure. The possibility of these effects cannot be excluded when using angiotensin II receptor antagonists. A sharp decrease in blood pressure in patients with coronary artery disease or atherosclerotic cerebrovascular disease, when using any antihypertensive agents, may lead to myocardial infarction or stroke.

Effect on ability to drive vehicles and operate machinery

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, as 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 impairment (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 hyperkalemia.

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

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

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, and increased 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 should compensate for fluid loss and renal function should be carefully monitored after initiation of combination therapy and periodically during such therapy.

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

Storage Conditions

Store at 2°C (36°F) to 30°C (86°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.