Candesartancilexetil

Candesartancilexetil Uses, Dosage, Side Effects, Food Interaction and all others data.

Candesartancilexetil is an ester prodrug that is hydrolysed in the body to the active form Candesartan during absorption from the gastro-intestinal tract. Candesartan is angiotensin II receptor (type AT1) antagonist. Candesartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT1 receptor in many tissues (eg, vascular smooth muscle, adrenal gland).

Candesartan cilexetil is an ARB prodrug that is rapidly converted to candesartan, its active metabolite, during absorption from the gastrointestinal tract. Candesartan confers blood pressure lowering effects by antagonizing the hypertensive effects of angiotensin II via the RAAS. RAAS is a homeostatic mechanism for regulating hemodynamics, water and electrolyte balance. During sympathetic stimulation or when renal blood pressure or blood flow is reduced, renin is released from granular cells of the juxtaglomerular apparatus in the kidneys. Renin cleaves circulating angiotensinogen to angiotensin I, which is cleaved by angiotensin converting enzyme (ACE) to angiotensin II. Angiotensin II increases blood pressure by increasing total peripheral resistance, increasing sodium and water reabsorption in the kidneys via aldosterone secretion, and altering cardiovascular structure. Angiotensin II binds to two receptors: type-1 angiotensin II receptor (AT1) and type-2 angiotensin II receptor (AT2). AT1 is a G-protein coupled receptor (GPCR) that mediates the vasoconstrictive and aldosterone-secreting effects of angiotensin II. Studies performed in recent years suggest that AT2 antagonizes AT1-mediated effects and directly affects long-term blood pressure control by inducing vasorelaxation and increasing urinary sodium excretion. Angiotensin receptor blockers (ARBs) are non-peptide competitive inhibitors of AT1. ARBs block the ability of angiotensin II to stimulate pressor and cell proliferative effects. Unlike ACE inhibitors, ARBs do not affect bradykinin-induced vasodilation. The overall effect of ARBs is a decrease in blood pressure.

Candesartancilexetil
Uses
Dosage
Side Effect
Precautions
Interactions
Uses during Pregnancy
Uses during Breastfeeding
Accute Overdose
Food Interaction
Half Life
Volume of Distribution
Clearance
Interaction With other Medicine
Contradiction
Storage

Trade Name	Candesartancilexetil
Generic	Candesartan Cilexetil
Candesartan Cilexetil Other Names	Candesartan cilexetil
Type
Formula	C₃₃H₃₄N₆O₆
Weight	Average: 610.671 Monoisotopic: 610.253982839
Protein binding	Candesartan is highly bound to plasma proteins (>99%) and does not penetrate red blood cells.
Groups	Approved
Therapeutic Class	Angiotensin-ll receptor blocker
Manufacturer
Available Country	Netherlands
Last Updated:	September 19, 2023 at 7:00 am

Uses

Candesartancilexetil is used for hypertension, heart failure with impaired left ventricular systolic function.

Candesartancilexetil is also used to associated treatment for these conditions: Diabetic Nephropathy, High Blood Pressure (Hypertension), Migraine, Chronic heart failure with reduced ejection fraction (NYHA Class II), Chronic heart failure with reduced ejection fraction (NYHA Class III), Chronic heart failure with reduced ejection fraction (NYHA Class IV)

How Candesartancilexetil works

Candesartan selectively blocks the binding of angiotensin II to AT1 in many tissues including vascular smooth muscle and the adrenal glands. This inhibits the AT1-mediated vasoconstrictive and aldosterone-secreting effects of angiotensin II and results in an overall decrease in blood pressure. Candesartan is greater than 10,000 times more selective for AT1 than AT2. Inhibition of aldosterone secretion may increase sodium and water excretion while decreasing potassium excretion.

Dosage

Candesartancilexetil dosage

Hypertention: initially 8 mg (hepatic impairment 2 mg, renal impairment or intravascular volume depletion 4 mg) once daily, increased if necessary at intervals of 4 weeks to max 32 mg once daily; usual maintenance dose 8 mg once daily.

Heart failure: initially 4 mg once daily, increased at intervals of at least 2 weeks to target dose of 32 mg once daily or to max tolerated dose.

Side Effects

Side-effects are usually mild. Symptomatic hypotension including dizziness may occur, particularly in patients with intravascular volume depletion (e.g. those taking high dose diuretics). Hyperkalemia occurs occassionally; angioedema has also been reported with some angiotension II receptor antagonist. Also vertigo, headache; rarely hepatitis, blood disorders, hyponatraemia, back pain, arthralgia, myalgia, rash, urticaria, pruritous.

Toxicity

No lethality was observed in acute toxicity studies in mice, rats and dogs given single oral doses of up to 2000 mg/kg of candesartan cilexetil or in rats given single oral doses of up to 2000 mg/kg of candesartan cilexetil in combination with 1000 mg/kg of hydrochlorothiazide. In mice given single oral doses of the primary metabolite, candesartan, the minimum lethal dose was greater than 1000 mg/kg but less than 2000 mg/kg.

Precaution

Candesartan should be used with caution in renal artery stenosis, aortic or mitral valve stenosis and in obstructive hypertropic cardiomyopathy. Monitoring of plasma-potassium concentration is advised, particularly in the elderly and in patients with renal impairment; lower initial doses may be appropriate in these patients.

Interaction

No significant drug interactions have been reported in studies of Candesartancilexetil given with other drugs such as glyburide, nifedipine, digoxin, warfarin, hydrochlorothiazide and oral contraceptives in healthy volunteers. Because candesartan is not metabolised by the cytochrome P-450 system and has no effects on P-450 enzymes, interactions with drugs that inhibit, or are metabolised by, those enzymes could not be expected.

Food Interaction

Take at the same time every day.
Take with or without food. The absorption is unaffected by food.

Volume of Distribution

0.13 L/kg

Elimination Route

Following administration of the candesartan cilexetil prodrug, the absolute bioavailability of candesartan was estimated to be 15%. Food with a high fat content has no effect on the bioavailability of candesartan from candesartan cilexetil.

Half Life

Approximately 9 hours.

Clearance

0.37 mL/min/kg

Elimination Route

When candesartan is administered orally, about 26% of the dose is excreted unchanged in urine. Candesartan is mainly excreted unchanged in urine and feces (via bile).