Prosp Pharma
Full Prescribing Info
Candesartan cilexetil.
Each tablets contains Candesartan cilexetil 16 mg.
Pharmacology: Pharmacodynamics: Candesartan is an angiotensin II receptor antagonist, selective for the AT1 receptor. It blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT1 receptor subtype in many tissues (such as vascular smooth muscle, adrenal gland).
Pharmacokinetics: Absorption: Candesartan cilexetil is converted to active drug candesartan by rapidly and completely bioactive by ester hydrolysis during absorption from the GI tract. Peak plasma concentrations are reached in about 3-4 hours following oral administration. Bioavailability is approximately 15% and food not effect on bioavailability.
Distribution: Candesartan is highly bound to plasma protein (more than 99%). The volume of distribution is 0.13 L/kg.
Metabolism: Candesartan cilexetil is a prodrug which almost completes ester hydrolysis (99%) within intestinal wall to candesartan which is an active metabolite and minor hepatic metabolism by O-deethylation to an inactive metabolite.
Elimination: The plasma half-life elimination is about 5-9 hours. Candesartan approximately 26% of the dose is excreted unchanged in the urine and feces as candesartan.
Treatment of essential hypertension.
Treatment of patients with heart failure and impaired left ventricle systolic function (left ventricular ejection fraction ≤40%) as add-on therapy to ACE-inhibitor or when ACE-inhibitors are not tolerated.
Dosage/Direction for Use
Recommended dose: Dosage in Hypertension: The recommended initial dose and usual maintenance dose is 8 mg once daily. The dose can be increased to 16 mg once daily and to a maximum of 32 mg once daily if not sufficiently controlled after 4 weeks. If blood pressure control is not achieved with this dose, alternative strategies should be considered.
Therapy should be adjusted according to blood pressure response. Most of the antihypertensive effect is attained within 4 weeks of initiation of treatment.
In patients with less than optimal blood pressure reduction, combination with hydrochlorothiazide is recommend.
Use in elderly: No initial dosage adjustment is necessary in elderly patients.
Patients with intravascular volume depletion: An initial dose of 4 mg may be considered in patients at risk for hypotension, such as patients with possible volume depletion.
Use in impaired renal function: No initial dosage adjustment is necessary in patients with mild to moderate impaired renal function (creatinine clearance ≥ 30 ml/min/1.73m2 BSA). In patients with severe impaired renal function (creatinine clearance <30 ml/min/1.73m2 BSA), the clinical experience is limited and a lower initial dose of 4 mg should be considered.
Use in impaired hepatic function: In patients with mild to moderate impaired liver function, initial dose of 4 mg is recommended. Currently, no data are available in patients with severe impairment of liver function.
Concomitant therapy: Addition of thiazide-type diuretic such as hydrochlorothiazide has been shown to have an additive antihypertensive effect with candesartan tablet.
Use in children: The safety and efficacy of candesartan have not been established in children.
Dosage in Heart Failure: The usual recommended initial dose of candesartan is 4 mg once daily, Up-titration to the target dose of 32 mg once daily or the highest tolerated dose is done by doubling the dose at intervals of at least 2 weeks.
Special patient populations: No initial dose adjustment is necessary for elderly patients or in patients with intravascular volume depletion, renal impairment or mild to moderate hepatic impairment.
Concomitant therapy: Candesartan can be administered with other heart failure treatment, including ACE inhibitors, beta-blockers, diuretics and digitalis or a combination of these medicinal products.
Mode of administration: Candesartan should be orally once daily with or without food.
Symptoms: Based on pharmacological considerations, the main manifestation of an overdose is likely to be symptomatic hypotension and dizziness. In individual case reports of overdose (of up to 672 mg candesartan cilexetil), patient recovery was uneventful.
Management: If symptomatic hypotension should occur, supportive treatment should be instituted and vital signs monitored. The patient should be placed supine with the legs elevated. If this is not sufficient, plasma volume should be increased by infusion of, for example, isotonic saline solution. Sympathomimetic medicinal products may be administered if the previously mentioned measures are not sufficient.
Candesartan is not removed by haemodialysis.
Hypersensitivity to candesartan cilexetil or to any of the excipients of the formulation.
Pregnancy and lactation.
Severe hepatic impairment and/or cholestasis.
Special Precautions
Renal artery stenosis: Renal function may be worsen in patients with renal artery stenosis. Medicinal products that affect the renin-angiotensin-aldosterone system, including angiotensin II receptor antagonists (AIIRAs), may increase blood urea and serum creatinine in patients with bilateral renal artery stenosis or stenosis of the artery to a solitary kidney.
Intravascular volume depletion: The addition of up to 8 mg of candesartan cilexetil to patients pre-treated with 12.5 mg hydrochlorothiazide was well tolerated. Concomitant administration of up to 25 mg hydrochlorothiazide with 16 mg of candesartan cilexetil for 8 weeks also well tolerated.
In patients who are intravascularly volume depleted (such as those receiving high dose diuretics) symptomatic hypotension may occur. Correct these conditions prior to administration, or a lower initial dose of 4 mg should be considered.
Potassium-sparing diuretic: Concomitant of candesartan with potassium-sparing diuretics may increases in serum potassium levels.
Renal impairment: As with other agents inhibiting the renin-angiotensin-aldosterone system, changes in renal function may be anticipated in susceptible patients treated with Candesartan.
When Candesartan is used in hypertensive patients with renal impairment, periodic monitoring of serum potassium and creatinine levels is recommended. There is limited experience in patients with very severe or end-stage renal impairment (Creatinine < 15 ml/min). In these patients Candesartan should be carefully titrated with thorough monitoring of blood pressure.
Evaluation of patients with heart failure should include periodic assessments of renal function, especially in elderly patients 75 years or older, and patients with impaired renal function. During dose titration of Candesartan, monitoring of serum creatinine and potassium is recommended. Clinical trials in heart failure did not include patients with serum creatinine >265 μmol/L (>3 mg/dL).
Concomitant therapy with an ACE inhibitor in heart failure: The risk of adverse reactions, especially renal function impairment and hyperkalaemia, may increase when candesartan is used in combination with an ACE inhibitor. Patients with such treatment should be monitored regularly and carefully.
Haemodialysis: During dialysis the blood pressure may be particularly sensitive to AT1-receptor blockade as a result of reduced plasma volume and activation of the renin-angiotensin-aldosterone system. Therefore Candesartan should be carefully titrated with thorough monitoring of blood pressure in patients on haemodialysis.
Kidney transplantation: There is no experience regarding the administration of Candesartan in patients with a recent kidney transplantation.
Hypotension: Hypotension may occur during treatment with candesartan in heart failure patients. It may also occur in hypertensive patients with intravascular volume depletion such as those receiving high dose diuretics. Caution should be observed when initiating therapy and correction of hypovolemia should be attempted.
Hyperkalaemia: Concomitant use of candesartan with potassium-sparing diuretics, potassium supplements, salt substitutes containing potassium, or other medicinal products that may increase potassium levels (e.g. heparin) may lead to increases in serum potassium in hypertensive patients. Monitoring of potassium should be undertaken as appropriate.
In heart failure patients treated with candesartan, hyperkalaemia may occur. Periodic monitoring of serum potassium is recommended. The combination of an ACE inhibitor, a potassium-sparing diuretic (e.g. spironolactone) and candesartan is not recommended and should be considered only after careful evaluation of the potential benefits and risks.
General: In patients whose vascular tone and renal function depend predominantly on the activity of the renin-angiotensin aldosterone system (e.g. patients with severe congestive heart failure or underlying renal disease, including renal artery stenosis), treatment with other medicinal products that affect this system has been associated with acute hypotension, azotemia, oliguria or, rarely, acute renal failure. The possibility of similar effects cannot be excluded with AIIRAs. As with any antihypertensive agent, excessive blood pressure decreases in patients with ischaemic cardiopathy or ischaemic cerebrovascular disease could result in a myocardial infarction or stroke.
Use In Pregnancy & Lactation
Pregnancy: Pregnancy category D.
The use of renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal excretion and increase fetal and neonatal morbidity and death.
Lactation: The renin-angiotensin system were present in rat milk. It is not known whether candesartan is excreted in human milk. Because of the potential for adverse effect on the breast-feeding infant.The use candesartan is considered essential.
Adverse Reactions
Blood and lymphatic system disorders: Leukopenia, neutropenia and agranulocytosis.
Metabolism and nutrition disorders: Hyperkalaemia, hyponatraemia.
Nervous system disorders: Dizziness, headache.
Gastrointestinal disorders: Nausea.
Hepato-biliary disorders: Increased liver enzymes, abnormal hepatic function or hepatitis.
Skin and subcutaneous tissue disorders: Angioedema, rash, urticaria, pruritus.
Musculoskeletal, connective tissue and bone disorders: Back pain, arthralgia, myalgia.
Renal and urinary disorders: Renal impairment, including renal failure in susceptible patients.
Drug Interactions
Candesartan is eliminated only to a minor extent by hepatic metabolism (CYP2C9). Available interaction studies indicate no effect on CYP2C9 and CYP3A4 but the effect on other cytochrome P450 isoenzymes is presently unknown.
Concomitant use of potassium-sparing diuretics, potassium supplements, salt substitutes containing potassium, or other medicinal products (such as, heparin) may increase potassium levels. Monitoring of potassium should be undertaken as appropriate.
Reversible increases in serum lithium concentrations and toxicity have been reported during concomitant administration of lithium with ACE inhibitors. A similar effect may occur with AIIRAs. Use of candesartan with lithium is not recommended. If the combination proves necessary, careful monitoring of serum lithium levels is recommended.
When AIIRAs are administered simultaneously with non-steroidal anti-inflammatory drugs (NSAIDs) (i.e. selective COX-2 inhibitors, acetylsalicylic acid (>3g/day) and non-selective NSAIDs), attenuation of the antihypertensive effect may occur.
As with ACE inhibitors, concomitant use of AIIRAs and NSAIDs may lead to an increased risk of worsening of renal function, including possible acute renal failure, and an increase in serum potassium, especially in patients with poor preexisting renal function. The combination should be administered with caution, especially in the elderly. Patients should be adequately hydrated and consideration should be given to monitoring renal function after initiation of concomitant therapy, and periodically thereafter.
Store below 30 °C.
ATC Classification
C09CA06 - candesartan ; Belongs to the class of angiotensin II receptor blockers (ARBs). Used in the treatment of cardiovascular disease.
Tab 16 mg (pink, round, flat, engraved with "16" on one side and scored on the other) x 3 x 10's.
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