Azilsartan

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Azilsartan
Azilsartan.svg
Clinical data
Trade namesEdarbi, Azilva
Other namesTAK-536, TAK-491, azilsartan kamedoxomil[2] (USAN US)
AHFS/Drugs.comMonograph
MedlinePlusa611028
License data
Pregnancy
category
  • US: D (Evidence of risk) [1]
Routes of
administration
By mouth
ATC code
Legal status
Legal status
  • UK: POM (Prescription only)
  • US: ℞-only
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability60%
MetabolismCYP2C9
Elimination half-life11 hrs
Excretion55% feces, 42% urine
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.235.975 Edit this at Wikidata
Chemical and physical data
FormulaC25H20N4O5
Molar mass456.46 g/mol g·mol−1
3D model (JSmol)
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Azilsartan is an angiotensin II receptor antagonist used in the treatment of hypertension,[2] developed by Takeda. It is marketed in tablet form under the trade name Edarbi as the prodrug azilsartan medoxomil (INN).[3]

The most common adverse reaction in adults is diarrhea.[2]

It is also sold as a combination drug with chlortalidone under the brand name Edarbyclor.[4]

Medical uses[edit]

Azilsartan is used for the treatment of hypertension in adults.[3][5][2]

Contraindications[edit]

Azilsartan must not be used with aliskiren, a renin inhibitor, in patients with diabetes as this increases the risk of serious adverse effects.[3][2] Like other antihypertensive drugs acting on the renin–angiotensin system, it is contraindicated during the second and third trimesters of pregnancy.[3][5][6] It should not be used during pregnancy in the United States.[2][1]

Interactions[edit]

No relevant drug interactions have been found in studies.[medical citation needed] Based on experiences with other drugs acting on the renin–angiotensin system, it is theorized that azilsartan could increase the toxicity of lithium and of other drugs increasing potassium levels, such as potassium sparing diuretics.[5][6]

Pharmacology[edit]

Mechanism of action[edit]

Azilsartan medoxomil lowers blood pressure by blocking the action of angiotensin II at the AT1 receptor, a hormone that contracts blood vessels and reduces water excretion through the kidneys.[5]

Pharmacokinetics[edit]

Azilsartan medoxomil is quickly absorbed from the gut, independently of food intake. Maximal blood plasma concentrations are reached after one to three hours. The liver enzyme CYP2C9 is involved in the formation of the two main metabolites, which are pharmacologically inactive; they are the O-deethylation and decarboxylation products of azilsartan. Elimination half life is about 11 hours. 55% are excreted via the feces, and 42% via the urine, of which 15% are present as azilsartan and the rest in form of the metabolites.[6]

Chemistry[edit]

Azilsartan medoxomil, the prodrug

The drug formulation contains the potassium salt of azilsartan medoxomil (codenamed TAK-491), an ester of azilsartan's carboxyl group with the alcohol (5-methyl-2-oxo-1,3-dioxol-4-yl)methanol.[6] This ester is more lipophilic than azilsartan itself.

History[edit]

In February 2011, the U.S. Food and Drug Administration (FDA) approved azilsartan medoxomil for the treatment of high blood pressure in adults.[7][8] In July 2011, azilsartan medoxomil was approved in the European Union for the treatment of essential hypertension.[3] In March 2012, Health Canada approved the drug for mild to moderate essential hypertension.[9]

In December 2014, Valeant Canada acquired the marketing rights to Edarbi and Edarbyclor from Takeda Pharmaceutical."Valeant Canada acquires rights to Edarbi and Edarbyclor for the Canadian market" (Press release). Valeant Canada. 17 December 2014. Retrieved 9 March 2020 – via Cision.</ref>

References[edit]

  1. ^ a b "Azilsartan medoxomil (Edarbi) Use During Pregnancy". Drugs.com. 28 February 2020. Retrieved 9 March 2020.
  2. ^ a b c d e f "Edarbi- azilsartan kamedoxomil tablet". DailyMed. 26 July 2019. Retrieved 9 March 2020.
  3. ^ a b c d e "Edarbi EPAR". European Medicines Agency (EMA). 18 May 2018. Retrieved 9 March 2020.
  4. ^ "Drug Approval Package:Edarbyclor (azilsartan medoxomil and chlorthalidone) NDA #202331". U.S. Food and Drug Administration (FDA). 16 August 2012. Retrieved 11 March 2020.
  5. ^ a b c d Haberfeld, H, ed. (2015). Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag. Edarbi-Tabletten.
  6. ^ a b c d Dinnendahl, V; Fricke, U, eds. (2012). Arzneistoff-Profile (in German). 2 (26 ed.). Eschborn, Germany: Govi Pharmazeutischer Verlag. ISBN 978-3-7741-9846-3.
  7. ^ "Drug Approval Package: Edarbi (Azilsartan medoxomil) NDA 200796". U.S. Food and Drug Administration (FDA). 4 April 2011. Retrieved 9 March 2020.
  8. ^ "FDA approves Edarbi to treat high blood pressure" (Press release). U.S. Food and Drug Administration. 25 February 2011. Retrieved 1 March 2011.[dead link]
  9. ^ Notice of Decision for Edarbi[permanent dead link]

External links[edit]