CANSARTAN is available for oral use as tablets containing either 4mg , 8mg , 16mg or 32mg of candesartan cilexetil.

Candesartan cilexetil, a prodrug, is hydrolyzed to the active drug candesartan, at the ester link, during absorption from the gastrointestinal tract.

Candesartan is a selective AT₁ subtype angiotensin Π receptor antagonist.

- Mechanism of Action & Pharmacodynamics:
Candesartan blocks the vasoconstrictor and aldosterone secreting effects of angiotensin Π by selectively blocking the binding of angiotensin Π to the AT1 receptor in many tissues such as vascular smooth muscle and the adrenal gland. Its action is therefore independent of the pathways for angiotensin Π synthesis.

Candesartan cilexetil is rapidly and completely bioactivated by ester hydrolysis during absorption from the gastrointestinal tract to candesartan.

Candesartan is mainly excreted unchanged in urine and feces ( via bile ).It undergoes minor hepatic metabolism by O-deethylation to an inactive metabolite, The elimination half-life of candesartan is approximately 9 hours. After single and repeated administration the pharmacokinetics of candesartan are linear for oral doses up to 32mg of candesartan cilexetil. Candesartan and its inactive metabolite do not accumulate in serum upon repeated once daily dosing. Following administration of candesartan cilexetil the absolute bioavailability of candesartan is estimated to be 15%. After tablet ingestion, the peak serum concentration (C_max) is reached after 3 – 4 hours.

CANSARTAN is indicated for the treatment of hypertension. It may be used alone or in combination with other antihypertensive agents.

CANSARTAN is contraindicated in patients who are hypersensitive to any component of this product.

In general treatment with CANSARTAN is well tolerated, the most common adverse reactions are: headache, dizziness, back pain, upper respiratory tract infection, pharyngitis, and rhinitis.

When used in pregnancy during the second and third trimesters; drugs that act directly on renin angiotensin system can cause injury and even death to the developing fetus. When pregnancy is detected, product should be discontinued as soon as possible, Since it has been associated with fetal and neonatal injury, including hypotension, neonatal skull hypoplasia, anuria, reversible or irreversible renal failure and death.

Oligohydramnios has also been reported, presumably resulting from decreased fetal renal function.

Infants with histories of in utero exposure to an angiotensin Π receptor antagonist should be closely observed for hypotension, oliguria, and hyperkalemia. The product should not be used in nursing women.

In patients with an activated renin angiotensin system such as volume-and / or salt-depleted patients (e.g., those being treated with diuretics) symptomatic hypotension may occur. These conditions should be corrected prior to administration of product, or the treatment should start under close medical supervision.

If hypotension occurs, the patients should be placed in the supine position and, if necessary, given an intravenous infusion of normal saline. A transient hypotensive response is not a contraindication to further treatment, which usually can be continued without difficulty once the blood pressure has stabilized.

As a consequence of inhibiting the renin angiotensin aldosterone system, changes in renal function may be anticipated in susceptible individuals treated with candesartan cilexetil.

In patients whose renal function may depend upon the activity of the renin angiotensin aldosterone system (e.g., patients with severe congestive heart failure), treatment with angiotensin converting enzyme inhibitors and angiotensin receptor antagonists has been associated with oliguria and / or progressive azotemia and rarely with acute renal failure and / or death. Similar results may be anticipated in patients treated with the product.  
   

Minor increases in blood urea nitrogen (BUN) and serum creatinine were observed infrequently. Small decreases in hemoglobin and hematocrit were observed in patients treated with candesartan alone, but were rarely of clinical importance. A small increase in potassium was observed in patients treated with CANSARTAN alone but was rarely of clinical importance.

Elevations of liver enzymes and / or serum bilirubin were observed infrequently.

Dosage must be individualized, blood pressure response is dose related over the range of 2- 32mg.

-   The usual recommended starting dose of CANSARTAN is 16mg once daily when it is used as monotherapy in patients who are not volume depleted.

CANSARTAN can be administered once or twice daily with total daily doses ranging from 8mg to 32mg. Most of the antihypertensive effect is present within 2 weeks and maximal blood pressure reduction is generally obtained within four to six weeks of initiating the treatment with the product.

For patients with possible depletion of intravascular volume (e.g., patients treated with diuretics particularly those with impaired renal function), CANSARTAN should be initiated under close medical supervision and consideration should be given to administration of lower dose. If blood pressure is not controlled by CANSARTAN alone, a diuretic may be added.

CANSARTAN may be administered with other antihypertensive agents.