Azilsartan

Azilsartan is an angiotensin II receptor antagonist used in the treatment of hypertension,[1] developed by Takeda. It is marketed in tablet form under the brand name Edarbi as the prodrug azilsartan medoxomil.[2]

Azilsartan

Clinical data
Trade names	Edarbi, Azilva
Other names	TAK-536, TAK-491
AHFS/Drugs.com	Monograph
MedlinePlus	a611028
License data	US DailyMed: Azilsartan US FDA: Azilsartan
Routes of administration	By mouth
ATC code	C09CA09 (WHO) C09DA09 (WHO)
Legal status
Legal status	UK: POM (Prescription only) US: ℞-only In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability	60%
Metabolism	CYP2C9
Elimination half-life	11 hrs
Excretion	55% feces, 42% urine
Identifiers
IUPAC name 2-Ethoxy-1-{[2'-(5-oxo-2,5-dihydro-1,2,4-oxadiazol-3-yl)-4-biphenylyl]methyl}-1H-benzimidazole-7-carboxylic acid
CAS Number	147403-03-0 863031-21-4
PubChem CID	135415867 135409642
IUPHAR/BPS	6901
DrugBank	DB08822
ChemSpider	8001032 9413866
UNII	F9NUX55P23 LL0G25K7I2
KEGG	D08864 D08067
ChEBI	CHEBI:68850 CHEBI:68845
ChEMBL	ChEMBL57242 ChEMBL2028661
CompTox Dashboard (EPA)	DTXSID70163712
ECHA InfoCard	100.235.975
Chemical and physical data
Formula	C25H20N4O5
Molar mass	456.458 g·mol^−1
3D model (JSmol)	Interactive image
SMILES CCOC1=NC2=CC=CC(=C2N1CC3=CC=C(C=C3)C4=CC=CC=C4C5=NOC(=O)N5)C(=O)O
InChI InChI=InChI=1S/C25H20N4O5/c1-2-33-24-26-20-9-5-8-19(23(30)31)21(20)29(24)14-15-10-12-16(13-11-15)17-6-3-4-7-18(17)22-27-25(32)34-28-22/h3-13H,2,14H2,1H3,(H,30,31)(H,27,28,32) Key:KGSXMPPBFPAXLY-UHFFFAOYSA-N InChI=1S/C30H24N4O8 /c1-3-38-28-31-23-10-6-9-22(27(35)39-16-24-17(2)40-30(37)41-24)25(23)34(28)15-18-11-13-19(14-12-18)20-7-4-5-8-21(20)26-32-29(36)42-33-26/h4-14H,3,15-16H2,1-2H3,(H,32,33,36) Key:QJFSABGVXDWMIW-UHFFFAOYSA-N
(what is this?)  (verify)

The most common adverse reaction in adults is diarrhea.[1]Some othere side effects includes Gastraointestinal disorders: nausea and Admininstration site conditions: asthenia, fatigue and musculoskeletal and Nervous Systems Disorders:Dizziness, respiratory.[3]

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

Medical uses

Azilsartan is used for the treatment of hypertension in adults.[2][5][1]

Contraindications

Azilsartan must not be used with aliskiren, a renin inhibitor, in patients with diabetes as this increases the risk of serious adverse effects.[2][1] Like other antihypertensive drugs acting on the renin–angiotensin system, it is contraindicated during the second and third trimesters of pregnancy.[2][5][6] It should not be used during pregnancy in the United States.[1][7]

Interactions

No relevant drug interactions have been found in studies. 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

Mechanism of action

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

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

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

In February 2011, the U.S. Food and Drug Administration (FDA) approved azilsartan medoxomil for the treatment of high blood pressure in adults.[8][9] In July 2011, azilsartan medoxomil was approved in the European Union for the treatment of essential hypertension.[2] In March 2012, Health Canada approved the drug for mild to moderate essential hypertension.[10]

In December 2014, Valeant Canada acquired the marketing rights to Edarbi and Edarbyclor from Takeda Pharmaceutical.[11]

References

1. "Edarbi- azilsartan kamedoxomil tablet". DailyMed. 26 July 2019. Retrieved 9 March 2020.
2. "Edarbi EPAR". European Medicines Agency (EMA). 18 May 2018. Retrieved 9 March 2020.
3. "Myotan (Azilsartan Medoxomil): Overview, Uses, Side Effects, Dosage". Medical Dialogues. 22 August 2020. Retrieved 22 August 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. Haberfeld, H, ed. (2015). Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag. Edarbi-Tabletten.
6. Dinnendahl, V; Fricke, U, eds. (2012). Arzneistoff-Profile (in German). 2 (26 ed.). Eschborn, Germany: Govi Pharmazeutischer Verlag. ISBN 978-3-7741-9846-3.
8. "Drug Approval Package: Edarbi (Azilsartan medoxomil) NDA 200796". U.S. Food and Drug Administration (FDA). 4 April 2011. Retrieved 9 March 2020.
9. "FDA approves Edarbi to treat high blood pressure" (Press release). U.S. Food and Drug Administration. 25 February 2011. Archived from the original on 18 January 2017. Retrieved 1 March 2011.
10. Notice of Decision for Edarbi
11. "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.

External links

• "Azilsartan". Drug Information Portal. U.S. National Library of Medicine.
• "Azilsartan medoxomil". Drug Information Portal. U.S. National Library of Medicine.