Azilsartan

Azilsartan
Names
Trade namesEdarbi, Azilva
Other namesAzilsartan medoxomil, TAK-536, TAK-491
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
Clinical data
Drug classAngiotensin II receptor blocker[1]
Main usesHigh blood pressure, diabetic kidney disease, heart failure[2]
Side effectsDiarrhea, dizziness[1][3]
WHO AWaReUnlinkedWikibase error: ⧼unlinkedwikibase-error-statements-entity-not-set⧽
Routes of
use		By mouth
Onset of actionWithin 2 wks[2]
External links
AHFS/Drugs.comMonograph
MedlinePlusa611028
Legal
License data
Legal status
  • UK: POM (Prescription only)
  • US: ℞-only
  • EU: Rx-only
  • In general: ℞ (Prescription only)
Pharmacokinetics
Bioavailability60%
MetabolismCYP2C9
Elimination half-life11 hrs
Excretion55% feces, 42% urine
Chemical and physical data
FormulaC25H20N4O5
Molar mass456.458 g·mol−1
3D model (JSmol)
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) ☒N
  • Key:KGSXMPPBFPAXLY-UHFFFAOYSA-N ☒N

  • as medoxomil: 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

Azilsartan, sold under the brand name Edarbi, is a medication used to treat high blood pressure.[1][3] Other uses may include diabetic kidney disease and heart failure.[2] It is taken by mouth.[2] Effects generally occur within 2 weeks.[2]

Common side effects include diarrhea and dizziness.[1][3] Other side effects may include angioedema, low blood pressure, and kidney problems.[2] Use in pregnancy may harm the baby.[4] It is an angiotensin II receptor blocker.[1]

Azilsartan was approved for medical use in the United States and Europe in 2011.[1][3] In the United Kingdom 4 weeks costs the NHS less than £20 as of 2021.[5] This amount in the United States is about 160 USD.[6]

Medical uses

Azilsartan is used for the treatment of hypertension in adults.[3][7][1] One of the benefits of the medication is that Azilsartan does not need dose adjustments for patients with renal or hepatic dysfunction.

It is also sold as a combination drug with chlortalidone under the brand name Edarbyclor.[8]

Dosage

It is generally taken at a dose of 40 to 80 mg once per day.[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.[3][1] Like other antihypertensive drugs acting on the renin–angiotensin system, it is contraindicated during the second and third trimesters of pregnancy.[3][7][9] It should not be used during pregnancy in the United States.[1][10]

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.[7][9]

Pharmacology

Mechanism of action

Main article: Angiotensin II receptor antagonist

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.[7]

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.[9]

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.[9] This ester is more lipophilic than azilsartan itself.

Like other ARBs, the azilsartan group has an extended diphenyl group within the structure. An interesting aspect of the molecule is that unlike other ARBs which have a tetrazole attached to the molecule, Azilsartan has an oxadiazole, which has an acidic proton at the nitrogen. The tetraziole represents a non-classical bio-isostere. The carboxylate seen in the molecule is the active moiety after the molecule has been metabolized. Azilsartan is a pro-drug.

History

In February 2011, the U.S. Food and Drug Administration (FDA) approved azilsartan medoxomil for the treatment of high blood pressure in adults.[11][12] 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.[13]

In December 2014, Valeant Canada acquired the marketing rights to Edarbi and Edarbyclor from Takeda Pharmaceutical.[14]

References

  1. 1 2 3 4 5 6 7 8 9 10 "Edarbi- azilsartan kamedoxomil tablet". DailyMed. 26 July 2019. Archived from the original on 7 February 2019. Retrieved 9 March 2020.
  2. 1 2 3 4 5 6 "Azilsartan Monograph for Professionals". Drugs.com. Archived from the original on 21 January 2021. Retrieved 17 January 2022.
  3. 1 2 3 4 5 6 7 8 "Edarbi EPAR". European Medicines Agency (EMA). 18 May 2018. Archived from the original on 24 March 2020. Retrieved 9 March 2020.
  4. ↑ "Azilsartan medoxomil (Edarbi) Use During Pregnancy". Drugs.com. Archived from the original on 26 November 2020. Retrieved 17 January 2022.
  5. ↑ BNF 81: March-September 2021. BMJ Group and the Pharmaceutical Press. 2021. p. 189. ISBN 978-0857114105.
  6. ↑ "Azilsartan Prices, Coupons & Savings Tips - GoodRx". GoodRx. Archived from the original on 1 November 2016. Retrieved 17 January 2022.
  7. 1 2 3 4 Haberfeld H, ed. (2015). Austria-Codex (in Deutsch). Vienna: Österreichischer Apothekerverlag. Edarbi-Tabletten.
  8. ↑ "Drug Approval Package:Edarbyclor (azilsartan medoxomil and chlorthalidone) NDA #202331". U.S. Food and Drug Administration (FDA). 16 August 2012. Archived from the original on 2 April 2021. Retrieved 11 March 2020.
  9. 1 2 3 4 Dinnendahl V, Fricke U, eds. (2012). Arzneistoff-Profile (in Deutsch). Vol. 2 (26 ed.). Eschborn, Germany: Govi Pharmazeutischer Verlag. ISBN 978-3-7741-9846-3.
  10. ↑ "Azilsartan medoxomil (Edarbi) Use During Pregnancy". Drugs.com. 28 February 2020. Archived from the original on 26 November 2020. Retrieved 9 March 2020.
  11. ↑ "Drug Approval Package: Edarbi (azilsartan medoxomil) NDA 200796". U.S. Food and Drug Administration (FDA). 4 April 2011. Archived from the original on 1 April 2021. Retrieved 9 March 2020.
  12. ↑ "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.
  13. ↑ "Summary Basis of Decision - Edarbi - Health Canada". Government of Canada. 26 June 2012. Archived from the original on 17 May 2019. Retrieved 6 March 2021.
  14. ↑ "Valeant Canada acquires rights to Edarbi and Edarbyclor for the Canadian market" (Press release). Valeant Canada. 17 December 2014. Archived from the original on 9 March 2020. Retrieved 9 March 2020 – via Cision.
External sites:
Identifiers:
  • "Azilsartan medoxomil". Drug Information Portal. U.S. National Library of Medicine. Archived from the original on 21 May 2021. Retrieved 31 October 2021.
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