COMPOSITIONS :
Candesartan cilexetil Tablet 16 mg, each tablet contains : Candesartan cilexetil 16 mg.
DESCRIPTIONS :
Candesartan cilexetil with active ingredient Candesartan cilexetil is available in 8 mg and 16 mg tablet.
INDICATIONS :
Hypertension.
Treatment of patients with heart failure and left ventricular systolic function disorder (LVEF ≤ 40%) when ACE inhibitors are not tolerated.
DOSAGE AND ADMINISTRATIONS :
Dosage in hypertension :
Initial dose of Candesartan cilexetil is 4 mg daily. Increase of the dose is according to the therapy responses up to the limit of maximum dose 16 mg daily. Maximum antihypertensive effect will be achieved in 4 weeks after the therapy.
Usage in elderly :
No initial dose adjustment is necessary if given to patients whose age up to 75 years old.
For patients whose age > 75 years old, it is recommended to be given with initial dose 2 mg once daily and the dose may be increased according to the response.
Usage in patients with renal impairment :
No initial dose adjustment is necessary if given to patients with mild renal impairment.
For patients with moderate and severe renal impairment, it is recommended to give Candesartan cilexetil with initial dose 2 mg once daily and the dose may be increased according to the response.
Usage in patients with hepatic impairment :
For patients with mild and moderate hepatic impairment, it is recommended to give Candesartan cilexetil with initial dose 2 mg once daily and the dose may be increased according to the response.
There is no usage experience of Candesartan cilexetil in patients with severe hepatic impairment.
Candesartan cilexetil may be given concomitantly with other antihypertensive agents.
Usage in pediatrics :
There is no experience about safety and effectiveness of Candesartan cilexetil administrations in pediatrics.
Dosage in heart failure :
Recommended initial dose is 4 mg daily. Dose escalation up to 32 mg once daily or the highest dose that can be tolerated is done by doubling the dose with minimum interval 2 weeks.
Special patient populations :
No initial dosage adjustment is necessary for elderly patients or in patients with intravascular volume depletion, renal impairment and mild to moderate hepatic impairment.
Combination therapy :
Candesartan cilexetil can be administered concomitantly with other heart failure treatments, including ACE inhibitors, β-Blockers, Diuretics and Digitalis or combination of these drugs.
Usage in pediatrics and adolescents :
There is no experience about safety and effect of Candesartan cilexetil administration in pediatrics and adolescents (below 18 years old of age).
Method of administration :
Administer Candesartan cilexetil once daily before meal or after meal.
OVERDOSAGE :
Symptoms of overdosage :
According to pharmacology consideration, the main manifestation of overdosage is possibly hypotension and dizziness. In individual report of overdosage case (up to 672 mg of Candesartan cilexetil), the patient can recovers without raising any symptoms.
Treatments of overdosage :
If the symptoms of hypotension occur, symptomatic treatment must be conducted and monitor the vital signs. The patient must be placed in recumbent position with leg in lifted up position. If these are insufficient, the plasma volume can be boosted by infusion administration, such as : Isotonic Salt Solution. Sympathomimetic drugs may be given if treatments above considered insufficient. Candesartan cilexetil cannot be removed with hemodialysis.
CONTRAINDICATIONS :
Patients with hypersensitivity to any components of Candesartan cilexetil.
Pregnant and lactating women.
Severe hepatic impairment and/or cholestasis.
WARNINGS AND PRECAUTIONS :
Renal impairment
As in other renin-angiotensin-aldosterone system inhibitors, the changes of renal function can be anticipated in certain patients treated with Candesartan cilexetil. Usage of Candesartan cilexetil in hypertension patients with renal impairment, it is recommended to conduct serum potassium and serum creatinine concentration tests regularly. Experience about usage of Candesartan cilexetil in patients with severe and end-stage of renal impairment (creatinine clearance < 15 ml/minute) is still very limited. In these kinds of patients, the dose elevation must be done carefully, accompanied with blood pressure examination. Evaluation of heart failure patients must includes regular renal function test, particularly in elderly patients whose ages are 75 years old or more and patients with renal impairment. When increasing the dose of Candesartan cilexetil, it is recommended to conduct serum creatinine and serum potassium concentration tests.
Combination therapy with ACE inhibitor in heart failure
The risks of undesirable effects, particularly renal function disorder and hyperkalaemia can be increased when Candesartan cilexetil used concomitantly with ACE inhibitor. Patients with this kind of therapy must be monitored regularly with care.
Hemodialysis
During hemodialysis, the blood pressure may be become very sensitive to receptor AT1 inhibition because of depletion of plasma volume and activation of renin-angiotensin-aldosterone system. Therefore, titration of Candesartan cilexetil must be done with care and along with thorough blood pressure examination in hemodialysis patients.
Renal artery stenosis
Other drugs those affect renin-angiotensin-aldosterone system, such as : ACE inhibitors which can increases blood urea and serum creatinine in bilateral renal artery stenosis patients or one renal artery stenosis patients. The same effects can be anticipated with Angiotensin II inhibitor.
Renal transplantation
There is no experience related to administration of Candesartan cilexetil in patients with renal transplantation.
Hypotension
Hypotension can be occurs during therapy with Candesartan cilexetil in heart failure patients. As described in other drugs work on renin-angiotensin-aldosterone system, hypotension also can be occurs in hypertension patients with intravascular volume depletion as in patients receiving high dose diuretics. Therefore, it is necessary to be careful when starting therapy and the hypovolaemia must be resolved first before the administration of Candesartan cilexetil.
Anesthesia and surgery
Hypotension can occurs during anesthesia and surgery in patients given Angiotensin II inhibitor as a result of renin-angiotensin system inhibition. Very rarely to occur, severe hypertension can arise so that the intravenous solution and/or vasopressor needed.
Aorta and mitral valves stenosis (obstructive hypertrophic cardiomyopathy)
As in vasodilator usage, special attention aimed at suffering patients because of hemodynamic related to aorta and mitral valves stenosis or obstructive hypertrophic cardiomyopathy.
Primary hyperaldosteronism
Patients with primary hyperaldosteronism are generally will not give any response to antihypertension agents which are act by renin-angiotensin-aldosterone system inhibition. Therefore, usage of Candesartan cilexetil is not recommended.
Hyperkalaemia
Based on experiences in concomitant usage with other drugs affecting renin-angiotensin-aldosterone system, concomitant administration of Candesartan cilexetil with potassium sparing diuretics, potassium supplements, salt substitutes contain potassium or other drugs which can increases potassium concentration (such as : Heparin) may leads to increases of potassium concentration in hypertension patients. Hyperkalaemia can occurs in heart failure patients given Candesartan cilexetil and during therapy with Candesartan cilexetil, it is recommended to conduct serum potassium concentration test regularly, particularly when used concomitantly with ACE inhibitor and potassium sparing diuretics such as Spironolactone.
General
In patients whose renal function and vascular tone are very depend on the renin-angiotensin-aldosterone system (such as in patients with congestive heart failure or renal diseases, including renal artery stenosis), therapy with other drugs affecting this system is already associated with arousing of acute hypotension, azotemia, oliguria or rarely to occurs is acute renal impairment. The possibility of same effects cannot be separated with Angiotensin II inhibitor. As in other antihypertensive agents, excess lowering of the blood pressure in ischemic cardiomyopathy or ischemic cerebrovascular patients may leads to myocardial infarction or stroke. Patients with rare hereditary problem i.e., galactose intolerancy, The Lapp Lactase deficiency or glucose-galactose malabsorption should not use this drug.
Pregnancy and lactation
Usage in pregnant women :
The data about usage of Candesartan cilexetil in pregnant women are very limited. Those data are insufficient for concluding about potential risks in fetus when using Candesartan cilexetil during first trimester. In human, renal perfusion in fetus, which is depends on the development of renin-angiotensin-aldosterone system started at the second trimester. Therefore, risks in fetus are increased if Candesartan cilexetil given during the second and third trimester of pregnancy. Drugs acting directly to the renin-angiotensin-aldosterone system when given to pregnant women in second or third trimester may lead to abnormality in fetus and neonatus, hypotension, renal dysfunction, oliguria and/or anuria, oligohydramnion, skull hypoplasia, intrauterine growth retardation and causing death. Case such as lung hypoplasia, abnormal face and body parts contracture have been reported too. Study in animals with Candesartan cilexetil shown renal abnormality in fetus and neonatus. It mechanism is believed related to its pharmacological effects. Based on informations above, Candesartan cilexetil should not be used during pregnancy. If a woman known pregnant during the therapy, discontinue the usage of Candesartan cilexetil.
Usage in lactation :
It is not known if Candesartan cilexetil excreted in breast milk. But research in rat, Candesartan cilexetil excreted via rat breast milk. Because it potentially causing adverse effects in the breast feeded infants, so Candesartan cilexetil should not be given during lactation.
Effects on the ability of driving vehicle or operating machine
There is no study about Candesartan’s effect on ability to drive and operating machine, but based on pharmacodynamic characteristic, Candesartan does not give any effect on those ability. When driving vehicle or operating machine, it is important to be noticed that dizziness and fatigue can occur during the therapy.
DRUG INTERACTIONS :
There is no clinically significant drug interaction discovered.
Compounds which have been investigated in clinical pharmacokinetic studies including : Hydrochlorothiazide, Warfarin, Digoxin, oral contraceptives (such as Ethinylestradiol/ Levonorgestrel), Glibenclamide, Nifedipine and Enalapril.
Candesartan is eliminated in small number via hepatic metabolism (CYP2C9). Available interaction studies shown no effect on CYP2C9 and CYP3A4 but the effect on other cytochrome P450 isoenzymes is still unknown until now. Candesartan cilexetil’s antihypertensive effect can be enhanced with other antihypertensive drugs.
Reversible increases in serum lithium concentration and toxicity have been reported during concomitant administration of Lithium with ACE inhibitors. The same effect may occur in Angiotensin II Antagonist and it is recommended to monitor the serum lithium concentration during usage as combination.
As in other antihypertensive drugs, the antihypertensive effects of Candesartan cilexetil may be reduced by Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) such as Indomethacin.
The bioavailability of Candesartan cilexetil is not affected by meal.
ADVERSE REACTIONS :
Treatment of hypertension :
Nervous system disorders :
Dizziness/vertigo, headache.
Infection and infestation :
Respiratory infection.
Laboratory findings :
Generally, administration of Candesartan cilexetil does not affect results of any routine laboratory tests. As in other renin-angiotensin-aldosterone system inhibitor, there is slight decrease of haemoglobin. No routine laboratory test is necessary in patients receiving Candesartan cilexetil. However, periodical serum creatinine and potassium test are recommended for patients with renal impairment.
Treatment of heart failure :
Vascular disorder :
Hypotension.
Metabolism and nutrition disorder :
Hyperkalaemia.
Renal and urinary tract abnormality :
Renal impairment.
Laboratory findings :
Occur increases in creatinine, urea and potassium. It is recommended to conduct periodically creatinine serum and potassium level tests.
Very rarely :
Blood and lymphatic system disorders :
Leucopenia, neutropenia and agranulocytosis.
Metabolism and nutrition disorders :
Hyperkalaemia, hyponatraemia.
Neuromuscular system disorders :
Dizziness, headache.
Gastrointestinal disorder :
Nausea.
Hepato-biliary disorders :
Increases of hepatic enzyme, abnormality of liver function or hepatitis.
Skin and subcutaneous tissue disorders :
Angioedema, rash, urtikaria, pruritus.
Musculoskeletal, connective tissue and bone disorders :
Back pain, arthralgia, myalgia.
Renal and urinary tract disorders :
Renal disorders, including renal impairment in certain patients.
PRESENTATIONS :
Candesartan cilexetil Tablet 16 mg Box, 10 blisters @ 10 tablets Reg. No. GKL1502349710B1
STORAGE :
STORE BELOW 30ºC, PROTECT FROM LIGHT
ON MEDICAL PRESCRIPTION ONLY
Manufactured by :
BERNOFARM
Sidoarjo – Indonesia
