Angiotensin II is the main vasoactive hormone in the renin-angiotensin aldosterone system and plays a major role in the pathophysiology of hypertension, heart failure and other cardiovascular disorders. Angiotensin II also plays an important role in the pathogenesis of target organ damage and hypertrophy. The main physiological effects of angiotensin II such as vasoconstriction, aldosterone stimulation, regulation of water and salt homeostasis, and stimulation of cell growth are via type I receptors (AT1).
Candesartan cilexetil is a prodrug used orally. The product changes to its active form, namely candesartan when absorbed in the digestive tract by hydrolysis of esters. Candesartan cilexetil is an angiotensin II receptor antagonist, which is selective towards the AT 1 receptor, the bond is very strong and is released from the receptor slowly. Candesartan does not have an agonist effect.
Candesartan does not inhibit ACE which converts angiotensin I to angiotensin II and alters bradykinin. Does not affect ACE and there is no potentiating effect on bradykinin or P substance. In a controlled clinical trial comparing Candesartan cilexetil with ACE inhibitors, the frequency of cough was lower in patients receiving Candesartan cilexetil. Candesartan does not bind or inhibit other hormone receptors or ion channels that are known to be important in cardiovascular settings.
Hypertension. Treatment of patients with heart failure and left ventricular systolic function impairment (LVEF ≤ 40%) when ACE inhibitors drug is not tolerated.
Hypertension: The initial dose of Candesartan cilexetil is 4 mg daily. The dose is increased according to the treatment response to a maximum of 16 mg daily. The maximum antihypertensive effect will be achieved within 4 weeks after treatment. Elderly: Adjustment does not need for initial dose if the patient is not over than 75 years old. In patients over 75 years, recommended initial dose is 2 mg once daily and the dose can be increased depends on the clinical response. Patients with renal failure: No dose adjustment is needed if given to patients with mild kidney failure. In patients with moderate and severe kidney failure, it is recommended, administration of Candesartan cilexetil with an initial dose of 2 mg once a day and the dose can be increased according to the response. Patients with liver failure: In patients with mild and moderate liver failure it is recommended that Candesartan cilexetil be given with an initial dose of 2 mg daily, and the dose can be increased according to the response. There is no experience of using Candesartan cilexetil in patients with severe liver disease. Candesartan cilexetil can be given along with other antihypertensive drugs.
Heart Failure: The recommended initial dose is 4 mg daily. The dose increases up to 32 mg once daily or the highest dose that can be tolerated, is done by doubling the dosage with a minimum interval of 2 weeks. Combination therapy: Cilexetil Candesartan can be administered with other heart failure treatments, including ACE inhibitors, beta-blocker, diuretics and digitalis or a combination of these drugs.
Symptoms: Based on pharmacological considerations, the main manifestations of excessive doses are likely to be hypotension and dizziness. In individual reports of cases of overdose (up to 672 mg candesartan cilexetil), patients can recover without causing symptoms.
Management: If symptoms of hypotension occur, symptomatic treatment must be carried out and monitor vital signs. The patient must be placed in the supine position with the legs elevated. If this is not enough, plasma volume is increased by infusion, such as: isotonic saline solution. Sympathomimetic drugs can be given if the above measures are considered insufficient. Candesartan cilexetil cannot be removed by hemodialysis.
Hypersensitivity. Pregnant and lactating women. Severe liver damage and/or cholestasis.
Renal failure: The administration of Candesartan cilexetil to hypertensive patients with renal failure is recommended to do along with regular checks of potassium levels and serum creatinine levels. The experience of using Candesartan cilexetil in patients with severe renal failure and already at the end (Clcr <15 ml/min) is still very limited. In patients like this a dose increase needs to be done carefully accompanied by a blood pressure check.
Combination therapy with ACE inhibitors in heart failure: The risk of unwanted effects, especially damage to kidney function and hyperkalemia, can be increased when Candesartan cilexetil is used in combination with an ACE inhibitor. Patients with this treatment must be monitored regularly and carefully.
Hemodialysis: During dialysis, blood pressure can be very sensitive to inhibition of the AT11 receptor as the result of decreased plasma volume and activation of the renin-angiotensin-aldosterone system. Therefore, titration of Candesartan cilexetil must be done carefully by checking the blood pressure closely in hemodialysis patients.
Renal artery stenosis: Other drugs that affect the renin-angiotensin-aldosterone system, for example: ACE inhibitors can increase serum blood urea and creatinine in patients with bilateral renal artery stenosis or one kidney artery stenosis. The same effect can be anticipated with the angiotensin II receptor inhibitor.
Hypotension: Hypotension may occur during treatment with Candesartan cilexetil in heart failure patients. As described in other drugs acting on the renin-angiotensin-aldosterone system, hypotension can also occur in hypertensive patients with reduced intravascular volume as in patients receiving high-dose diuretics. Therefore, it is necessary to be careful when starting treatment and hypovolemia must be treated first before giving Candesartan cilexetil.
Anesthesia and surgery: Hypotension may occur during anesthesia and surgery in patients given angiotensin II inhibitors due to inhibition of the renin-angiotensin system. Very rarely, severe hypotension can arise which requires intravenous fluids and/or vasopressors.
Obstructive hypertrophic cardiomyopathy: As with the use of vasodilators, special attention to patients with hemodynamics associated with aortic and mitral valve stenosis, or obstructive hypertrophic cardiomyopathy need to be done.
Primary hyperaldosterone: Patients with primary hyperaldosterone generally will not respond to antihypertensive agents acting through inhibition of the renin-angiotensin-aldosterone system. Therefore, the use of Candesartan cilexetil is not recommended.
Hyperkalemia: Based on experience with using other drugs that affect the renin-angiotensin-aldosterone system, giving Candesartan cilexetil along with potassium-sparing diuretics, potassium supplements, salt substitutes containing potassium or other drugs that can increase potassium levels (such as: heparin) can cause an increase in potassium levels in serum in hypertensive patients. Hyperkalemia may occur in patients with heart failure who are given Candesartan cilexetil and during treatment with Candesartan cilexetil it is recommended to carry out regular checks of serum potassium, especially when in conjunction with ACE inhibitors and potassium-sparing diuretics such as spironolactone.
General: In patients whom the kidney function and vascular tone are highly dependent on the activity of the renin-angiotensin-aldosterone system (such as patients with congestive heart failure or kidney disease, including renal artery stenosis), treatment with other drugs that affect this system has been associated with the onset of acute hypotension, azotemia, oliguria or, rarely, acute renal failure. The same possible effect cannot be separated from the angiotensin II receptor inhibitors. As with other antihypertensive agents, excessive blood pressure reduction in ischemic or cerebrovascular ischemic patients can cause myocardial infarction or stroke. Patients with hereditary problems, which are rare, namely intolerant galactose, deficiencies of "The Lapp lactase" or glucose-galactose malabsorption may not use this drug.
Nerve system disorders:
Dizziness / vertigo, headache.
Infection and Infestation:
Metabolic and nutritional disorders:
Kidney and urinary tract disorders:
Blood and lymph system disorders:
Leukopenia, neutropenia and agranulocytosis.
Metabolic and nutritional disorders:
Nervous system disorders:
Increased liver enzymes, abnormal liver function or hepatitis.
Skin and subcutaneous tissue disorders:
Angioedema, reddish skin, urticaria, pruritus.
Musculoskeletal, connective tissue and bone disorders:
Back pain, arthralgia, myalgia.
Kidney and urinary tract disorders:
Kidney disorders, including kidney failure in certain patients.
There is no clinically significant drug interactions were found.
Store in the temperature 30°C or below. Protected from light.
C09CA06 - candesartan ; Belongs to the class of angiotensin II receptor blockers (ARBs). Used in the treatment of cardiovascular disease.
Tab 8 mg x 3 x 10's. 16 mg x 3 x 10's.