Candesartan Cilexetil

Candesartan cilexetil belongs to a medication class called angiotensin II receptor blocker, which treats high blood pressure in adults and children. It is also used to treat heart failure in adults. The combination formulations exist with low-dose hydrochlorothiazide, a thiazide diuretic. This combination helps to achieve the antihypertensive effect. In February 2005, the FDA approved using candesartan in adults with heart failure and in June 1998, FDA approved managing hypertension in adults.

BRAND NAMES:

Atacand - Atacand is available as oral tablets containing candesartan cilexetil as the main active ingredient with strengths 4mg, mg, 16mg, and 32mg.

Atancand Hct – The main active ingredients contained in Atcand Hct are 32mg of candesartan cilexetil and 25mg of hydrochlorothiazide available as oral tablets.

MECHANISM OF ACTION:

The liver releases angiotensinogen and then cleaved into angiotensin I by renin. Angiotensin I is converted into angiotensin II in the lungs by angiotensin-converting enzyme. Candesartan works by antagonizing the type 1 angiotensin II receptor. This activity blocks angiotensin II which affects and reduces blood pressure and fluid retention. Candesartan blocks the binding of angiotensin II to its target receptor, its action is independent of the upstream steps leading to angiotensin II biosynthesis.

PHARMACOKINETICS:

Absorption – Candesartan cilexetil undergoes rapid ester hydrolysis during absorption from the gastrointestinal tract, converting to candesartan. The bioavailability of candesartan is approximately 15%. The peak plasma concentration is attained in 3 to 4 hours.

Distribution – The mean volume of distribution of candesartan is 0.13L/Kg. Candesartan has high plasma protein binding(>99%).

Metabolism – Candesartan undergoes hepatic metabolism through CYP2C9. The potential drug-to-drug interactions with medications metabolized by this system are minimal. Candesartan undergoes minor hepatic metabolism by O-de-ethylation to an inactive metabolite.

Excretion - The mean elimination half-life of candesartan is approximately 9 hours. Candesartan is predominantly excreted unchanged in urine and feces.

PHARMACODYNAMICS:

Candesartan blocks the blood pressure-elevating effects of angiotensin II infusion in a dose-dependent manner. After one week of once-daily 8 mg doses of candesartan cilexetil, the pressor effect was reduced by approximately 90% at its peak, with about 50% inhibition still evident after 24 hours. Both single and repeated doses of candesartan cilexetil resulted in a dose-dependent increase in plasma concentrations of angiotensin I, angiotensin II, and plasma renin activity.

DOSAGE AND ADMINISTRATION:

Candesartan is administered orally and is available as 4mg, mg, 16mg, and 32mg tablets. Oral suspensions are also available based on the patient’s condition the dosage will be prescribed.

Hypertension

For adults and older patients, the recommended dosage is initially 16mg once daily, if the patient is volume depleted, the initial dose should be lowered to 8mg once daily.
Children, weighing over 50kg should receive an initial dose of 16mg once daily. If the patient is volume depleted the initial dose should be lowered to 4mg once daily.
If the children weigh less than 50kg, should receive an initial dose of 4 mg once daily. If the patient is volume-depleted, the initial dose should be lowered to 2mg once daily.
If the children are recommended for oral suspension the initial dose is 0.2mg/kg/d.
If the patient is prescribed for combinational tablets the dosage contains 6mg candesartan and hydrohlorothiazide 12.5mg. The dose can be increased to candesartan 32mg and hydrochlorothiazide 25mg.

DRUG INTERACTIONS:

Some drugs can interact with candesartan cilexetil and can cause adverse effects. Below are a few drugs mentioned that should be avoided while taking candesartan cilexetil.