Ordiss, 32 mg tablets 30 pcs

Interaction

Dual RAAS blockade with angiotensin II receptor antagonists (ARA II), ACE inhibitors or aliskiren (direct renin inhibitor) may be associated with an increased risk of hypotension, syncope, hyperkalemia and renal dysfunction (including acute renal failure) compared to monotherapy. Regular monitoring of BP, renal function, and blood electrolytes is necessary in patients taking concomitantly candesartan and other drugs that affect the RAAS.

Candesartan is contraindicated concomitantly with aliskiren or aliskiren-containing drugs in patients with diabetes mellitus and/or with moderate to severe renal function impairment (GFR less than 60 ml/min/1.73 m2 body surface area) and is not recommended in other patients.

The concomitant use of angiotensin II receptor antagonists with ACE inhibitors is contraindicated in patients with diabetic nephropathy and is not recommended in other patients.

The simultaneous use of ACE inhibitors and dipeptidyl peptidase type 4 inhibitors (e.g., vildagliptin) may increase the risk of Quincke’s edema. No clinically significant drug interactions have been observed with candesartan concomitantly with hydrochlorothiazide, warfarin, digoxin, oral contraceptives (ethinylestradiol/levonorgestrel), glibenclamide, nifedipine and enalapril. Candesartan is slightly metabolized in the liver with participation of CYP2C9 isoenzyme. Interaction studies have shown no effect of candesartan on CYP2C9 and CYP3A4 isoenzymes, the effect on other cytochrome P450 isoenzymes has not been studied. Concomitant use of candesartan with other hypotensive agents increases the antihypertensive effect.

The experience with other drugs acting on RAAS shows that concomitant therapy with potassium-saving diuretics, potassium preparations, table salt substitutes containing potassium, and other agents that increase serum potassium (e.g., heparin) may lead to hyperkalemia.

When concomitant use of lithium preparations and ACE inhibitors a reversible increase in serum lithium concentration and development of toxic reactions occurs. These reactions may also occur with angiotensin II receptor antagonists, and therefore it is recommended that serum lithium levels be monitored.

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

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Special Instructions

The concomitant use of ACE inhibitors, ARA II or aliskiren increases the risk of hypotension, hyperkalemia and renal dysfunction (including acute renal failure). Dual RAAS blockade in concomitant use of ACE inhibitors, ARA II with drugs containing aliskiren is contraindicated in patients with diabetes and/or with moderate or severe renal insufficiency (glomerular filtration rate (GFR) less than 60 ml/min/1.73 m2 body surface area) and is not recommended in other patients, (see section “Interaction with other medicinal products”).

If dual RAAS blockade is considered absolutely necessary, the treatment should take place only under medical supervision and should be accompanied by careful and regular monitoring of renal function, electrolytes and blood pressure. Concomitant use of angiotensin II receptor antagonists with ACE inhibitors is contraindicated in patients with diabetic nephropathy and is not recommended in other patients.

Kidney function impairment. In some cases, renal dysfunction may develop with use of Ordiss®, as with other drugs that inhibit the RAAS.

When using Ordiss® in patients with severe arterial hypertension and renal insufficiency (GFR less than 30 ml/min/1.73 m2 body surface area), it is recommended to monitor regularly potassium and serum creatinine concentration. Clinical experience concerning this medicine use in patients with end-stage renal failure (FFR less than 15 ml/min/1.73 m2 of body surface area) is limited. When using Ordiss® in such patients, the dose of Ordiss® should be adjusted under BP control.

In patients with CHF, 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 that serum potassium and creatinine concentrations be monitored.

The use of Ordiss® in patients with chronic heart failure with creatinine greater than 265 µmol/L (greater than 3 mg/ml) is not known.

Hemodialysis. Simultaneous use with ACE inhibitors in CHF. Simultaneous use with ACE inhibitors increases the risk of side effects, especially renal dysfunction and hyperkalemia.Clinical status of patients and relevant laboratory values should be monitored.

Renal artery stenosis. The drugs affecting the RAAS (e.g., ACE inhibitors) may cause increased serum urea and creatinine concentrations in patients with bilateral renal artery stenosis or artery stenosis of the single kidney. A similar effect can be expected with angiotensin II receptor antagonists.

Kidney transplantation. There is no experience with the use of Ordiss® in patients who have recently undergone a kidney transplant.

Arterial hypotension. In patients with CHF, arterial hypotension may develop when Ordiss® is used. Hypotension is also possible in patients with circulatory blood pressure deficit, for example, when using high doses of diuretics. In this case, correction of the blood pressure before Ordiss® administration should be performed.

General anesthesia and/or surgical interventions. In patients receiving angiotensin II antagonists during general anesthesia and surgical interventions, arterial hypotension due to RAAS blockade may develop. In rare cases, arterial hypotension may be severe, requiring intravenous fluid administration and/or vasopressor agents.

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

Primary hyperaldosteronism. Patients with primary hyperaldosteronism are usually resistant to therapy with hypotensive agents affecting the RAAS, therefore Ordiss® is not recommended for this group of patients.

Hyperkalemia. Simultaneous use of Ordiss® with potassium-saving diuretics, potassium preparations or salt substitutes containing potassium, or other drugs that can increase serum potassium (e.g., heparin) may cause hyperkalemia in patients with arterial hypertension.

® Hyperkalemia may also develop in patients with CHF taking Ordiss. During therapy with Ordiss® in patients with CHF, periodic monitoring of serum potassium is recommended, especially if ACE inhibitors and potassium saving diuretics (spironolactone, triamterene, amiloride, eplerenone (spironolactone derivative) are used simultaneously.)

General. Patients in whom vascular tone and renal function are predominantly dependent on RAAS activity (e.g., patients with severe chronic heart failure, renal disease, including renal artery stenosis) are particularly sensitive to drugs acting on RAAS. The use of such drugs in these patients is accompanied by severe arterial hypotension, azotemia, oliguria and, less frequently, acute renal failure. The possibility of these effects is not excluded by the use of angiotensin II receptor antagonists. Sharp decrease of BP in patients with ischemic cardiopathy, cerebrovascular diseases of ischemic genesis while using any hypotensive agents may lead to myocardial infarction or stroke.

Pediatric use. The safety and effectiveness of the use of Ordiss® under 18 years of age has not been established.