candesartan

candesartan
Name	Candesartan
Tradename	Atacand, Amias, Blopress
Routes of administration	Oral, intravenous (prodrug as candesartan cilexetil)
Legal status	Prescription-only medicine
Bioavailability	15%
Metabolism	Ester hydrolysis to active candesartan
Elimination half-life	9 hours
Excretion	Renal and biliary

candesartan is an angiotensin II receptor antagonist used primarily to treat hypertension and heart failure. It is prescribed to reduce cardiovascular morbidity in patients with left ventricular dysfunction and to manage elevated blood pressure in adults. Clinical use is guided by randomized trials and guideline recommendations from cardiovascular and renal organizations.

Medical uses

Candesartan is indicated for essential hypertension, chronic heart failure with reduced ejection fraction, and reduction of cardiovascular risk after heart failure; major clinical trials and guideline panels from the European Society of Cardiology, American College of Cardiology, American Heart Association, and National Institute for Health and Care Excellence inform its use. It is used alone or combined with other antihypertensive agents such as thiazide diuretics endorsed by the Hypertension Canada recommendations and in combination strategies discussed in consensus documents from the World Health Organization, International Society of Hypertension, and regional cardiac societies. Off-label applications have been evaluated in randomized studies involving patients with diabetic nephropathy discussed by the American Diabetes Association and in meta-analyses published in journals associated with the European Renal Association.

Mechanism of action

Candesartan selectively blocks the angiotensin II type 1 (AT1) receptor, preventing angiotensin II–mediated vasoconstriction, aldosterone secretion, and sympathetic activation; mechanistic insights are elaborated by basic researchers affiliated with institutions such as the National Institutes of Health, Max Planck Society, and University of Cambridge. By antagonizing AT1 receptors expressed in vascular smooth muscle and adrenal cortex, it reduces systemic vascular resistance and cardiac afterload, a mechanism described in pharmacology texts used at the Johns Hopkins University School of Medicine and Harvard Medical School. Comparative receptor pharmacology studies from laboratories at the University of Oxford and Karolinska Institutet contrast its binding profile with other angiotensin receptor blockers evaluated in multinational trials coordinated by the European Medicines Agency.

Pharmacokinetics

Candesartan is administered as the prodrug candesartan cilexetil and is converted to active candesartan by esterases during absorption, a process characterized in pharmacokinetic studies from the Food and Drug Administration and academic centers such as the University of California, San Francisco. Oral bioavailability is low (~15%), but peak plasma concentrations are reached within 3–4 hours; elimination half-life is approximately 9 hours with steady state achieved within a few days, parameters reported in clinical pharmacology reports from the British Pharmacological Society and the European Federation of Pharmaceutical Industries and Associations. Excretion occurs via renal and biliary routes, and population pharmacokinetic analyses from the Mayo Clinic and Cleveland Clinic describe altered clearance in renal impairment.

Adverse effects

Common adverse effects include dizziness, hypotension, and hyperkalemia reported in post-marketing surveillance by regulatory agencies such as the Medicines and Healthcare products Regulatory Agency, the Pharmaceuticals and Medical Devices Agency, and the Therapeutic Goods Administration. Rare but serious events documented in case series and safety reviews published by the World Health Organization and in cardiology journals include angioedema and renal dysfunction; safety communications have been issued by the European Medicines Agency and the U.S. Food and Drug Administration. Pregnancy exposure is contraindicated because of teratogenic risk identified in registries overseen by perinatal research networks at the University of Toronto and Guy's and St Thomas' NHS Foundation Trust.

Interactions

Clinically significant interactions occur with potassium-sparing agents and potassium supplements noted in clinical guidelines from the American Society of Nephrology and with nonsteroidal anti-inflammatory drugs highlighted in position papers from the American College of Rheumatology. Concomitant use with aliskiren in patients with diabetes or renal impairment is discouraged by advisories from the European Medicines Agency and the U.S. Food and Drug Administration. Drug interaction databases curated by the U.S. Pharmacopeia and Lexicomp list additive hypotensive effects with other antihypertensives and altered pharmacokinetics when coadministered with agents affecting hepatic transporters described in pharmacology reviews from the Royal College of Physicians.

Dosage and administration

Adult hypertension dosing usually starts at 4–8 mg once daily with titration up to 32 mg once daily as tolerated; heart failure dosing often begins at 4 mg with upward titration guided by trials conducted by multinational cooperative groups including the Heart Failure Society of America and the European Society of Cardiology. Renal impairment and elderly dosing adjustments are recommended in product monographs reviewed by national formularies such as the British National Formulary and hospital guidelines from the Veterans Health Administration. Intravenous formulations are not standard; when converting from other agents clinicians reference dosing equivalence tables developed by expert committees at institutions like the National Heart, Lung, and Blood Institute.

Chemistry and formulations

Candesartan is a biphenyl-substituted tetrazole chemically synthesized and formulated as the isopropyl ester prodrug candesartan cilexetil; synthetic routes and structure–activity relationships have been reported by research groups at pharmaceutical companies and academic chemistry departments such as the Massachusetts Institute of Technology and the ETH Zurich. Commercial formulations include immediate-release oral tablets marketed under trade names approved by regulatory authorities including the European Medicines Agency and the U.S. Food and Drug Administration. Generic manufacturing, quality control, and stability data are governed by pharmacopeial standards from the United States Pharmacopeia, the European Pharmacopoeia, and quality audits by national agencies like the Pharmaceutical Inspection Co-operation Scheme.

Category:Angiotensin II receptor antagonists