Olmesartan medoxomil
|
| Systematic (IUPAC) name |
| (5-methyl-2-oxo-2H-1,3-dioxol-4-yl)methyl 4-(2-hydroxypropan-2-yl)-2-propyl-1-({4-[2-(2H-1,2,3,4-tetrazol-5-yl)phenyl]phenyl}methyl)-1H-imidazole-5-carboxylate |
| Clinical data |
| Trade names |
Benicar, Olmetec, WinBP, Golme, Erastapex, Olsart. |
| AHFS/Drugs.com |
monograph |
| MedlinePlus |
a603006 |
| Pregnancy cat. |
- C (D if used in second or third trimester)
|
| Legal status |
|
| Routes |
Oral |
| Pharmacokinetic data |
| Bioavailability |
26% |
| Metabolism |
Hepatic (cannot be removed by hemodialysis) |
| Half-life |
13 hours |
| Excretion |
Renal 40%, biliary 60% |
| Identifiers |
| CAS number |
144689-63-4 Y |
| ATC code |
C09CA08
C09DA08 (with diuretics)
C09DB02 (with amlodipine) |
| PubChem |
CID 130881 |
| DrugBank |
DB00275 |
| ChemSpider |
115748 Y |
| UNII |
6M97XTV3HD Y |
| KEGG |
D01204 Y |
| ChEMBL |
CHEMBL1516 N |
| Chemical data |
| Formula |
C29H30N6O6 |
| Mol. mass |
558.585 g/mol |
SMILES
- O=C1O/C(=C(\O1)C)COC(=O)c2c(nc(n2Cc5ccc(c4ccccc4c3nnnn3)cc5)CCC)C(O)(C)C
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InChI
-
InChI=1S/C29H30N6O6/c1-5-8-23-30-25(29(3,4)38)24(27(36)39-16-22-17(2)40-28(37)41-22)35(23)15-18-11-13-19(14-12-18)20-9-6-7-10-21(20)26-31-33-34-32-26/h6-7,9-14,38H,5,8,15-16H2,1-4H3,(H,31,32,33,34) Y
Key:UQGKUQLKSCSZGY-UHFFFAOYSA-N Y
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| N (what is this?) (verify) |
Olmesartan medoxomil (trade names: Benicar in the US, Olmetec in EU, Canada and Japan, WinBP, Olsar, Golme in India, Erastapex in Egypt) is an angiotensin II receptor antagonist used to treat high blood pressure.It was developed by Sankyo in 1995 and it is an ester prodrug that is completely and rapidly hydrolyzed to the active acid form, olmesartan (RNH-6270). [1]
Contents
- 1 Indications
- 2 Contraindications
- 3 Cautions
- 4 Adverse effects
- 5 Structure
- 6 Mechanism of action
- 7 Interactions
- 8 Dosage and administration
- 9 Preparations
- 10 Research
- 11 See also
- 12 References
- 13 External links
Indications
Olmesartan is indicated for the treatment of hypertension. It may be used alone or in combination with other antihypertensive agents.[2] The U.S. Food and Drug Administration (FDA) has determined that the benefits of Benicar continue to outweigh its potential risks when used for the treatment of patients with high blood pressure according to the drug label.[3]
Contraindications
Contraindications for treatment with olmesartan include biliary obstruction (BNF). Another major contraindication is pregnancy; reports in the scientific literature reveal fetal malformations for pregnant women taking sartan-derived drugs.[4]
Cautions
Angiotensin-II receptor antagonists should be used with caution in renal artery stenosis. 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. Angiotensin-II receptor antagonists should be used with caution in aortic or mitral valve stenosis and in hypertrophic cardiomyopathy. Those with primary aldosteronism, and Afro-Caribbean patients (particularly those with left ventricular hypertrophy), may not benefit from an angiotensin-II receptor antagonist.
Adverse effects
The incidence of adverse effects with Benicar (the US trade name for olmesartan medoxomil) is reported as similar to placebo; the only adverse effect that occurred in >1% of patients treated with it and more frequently than placebo was dizziness (3% vs 1%). The full prescribing information for Benicar notes as with all drugs that act directly on the renin-angiotensin system, olmesartan is contraindicated in pregnancy and can cause injury and even death to the developing fetus. In studies of angiotensin II receptor antagonists such as olmesartan, patients with unilateral or bilateral renal artery stenosis, increases in serum creatinine or blood urea nitrogen have been reported. There has been no long-term use of olmesartan medoxomil in patients with unilateral or bilateral renal artery stenosis, but similar results may be expected.[5] Rarely, olmesartan can cause severe gastrointestinal issues. The symptoms, which include nausea, vomiting, diarrhea, weight loss, and electrolyte abnormalities, are common among those who have celiac disease.[6]
Structure
The olmesartan molecule includes one tetrazole group (a 5-member heterocyclic ring of four nitrogen and one carbon atom) and one imidazole group (a 5-membered planar heterocyclic aromatic ring of two nitrogen and three carbon atoms, classified as an alkaloid).
Mechanism of action
Olmesartan medoxomil is a prodrug, that is hydrolyzed to olmesartan during absorption from the gastrointestinal tract.
Metabolism of olmesartan medoxomil prodrug towards biologically active olmesartan
It works by blocking the binding of angiotensin II to the AT1 receptors in vascular muscle; it is therefore independent of angiotensin II synthesis pathways, unlike ACE inhibitors. By blocking the binding rather than the synthesis of angiotensin II, olmesartan inhibits the negative regulatory feedback on renin secretion. As a result of this blockage, olmesartan reduces vasoconstriction and the secretion of aldosterone. This lowers blood pressure by producing vasodilation, and decreasing peripheral resistance.
Interactions
Olmesartan may interact with nonprescription products that contain stimulants, including diet pills and cold medicines, and potassium supplements, including salt substitutes.
Dosage and administration
The usual recommended starting dose of olmesartan is 20 mg once daily. The dose may be increased to 40 mg after two weeks of therapy, if further reduction in blood pressure is desirable. Doses above 40 mg do not appear to have greater effect, and twice-daily dosing offers no advantage over the same total dose given once daily.[2] No adjustment of dosage is typically necessary for advanced age, renal impairment, or hepatic dysfunction. For patients with possible depletion of intravascular volume (e.g., patients treated with diuretics), olmesartan should be initiated with caution; consideration should be given to use of a lower starting dose in such cases.[2] If blood pressure is not controlled by Benicar alone, a diuretic may be added. Benicar may be administered with other antihypertensive agents. Benicar may be administered with or without food.[2]
Preparations
Olmesartan and Sevikar HCT is marketed worldwide by Daiichi Sankyo, in India by Abbott Healthcare Pvt. Ltd. under the trade name WinBP, by Zydus Cadila under the trade name Olmy, by Ranbaxy Laboratories Ltd. under the trade name Olvance, and in Canada by Schering-Plough as Olmetec. Benicar HCT is the brand name of a medication containing olmesartan medoxomil in combination with hydrochlorothiazide, a thiazide diuretic. Three dosage combinations are available: 20 mg or 40 mg of olmesartan medoxomil combined with 12.5 mg of hydrochlorothiazide, or 40 mg of olmesartan medoxomil combined with 25 mg of hydrochlorothiazide. Benitec H, another medication containing olmesartan medoxomil and hydrochlorothiazide, is marketed by GlaxoSmithKline in India. In Poland as Olesartan Medoxomil by TEVA, Olimestra and Co-Olimestra (with HCTZ) by Miklich Lab., Elestar (with amlodipine) and Elestar HCT (with amlodipine, HCTZ) by Menarini, Sevikar HCT (with amoldipine, HCTZ) by Aiichi Sankyo.
Research
Two clinical studies (MORE [7] and OLIVUS [8])[9] report that Benicar reduced arterial plaque during therapy for high-blood pressure (hypertension).
See also
- Discovery and development of angiotensin receptor blockers
References
- ^ Aulakh GK, Sodhi RK, Singh M (August 2007), "An update on non-peptide angiotensin receptor antagonists and related RAAS modulators", Life Sci. 81 (8): 615–39, doi:10.1016/j.lfs.2007.06.007, PMID 17692338
- ^ a b c d RxList Inc. (5 July 2007). "Benicar (olmesartan medoxomil)". RxList Inc. Retrieved 22 July 2010.
- ^ "FDA Alert: Benicar (olmesartan): Ongoing Safety Review". Drugs.com. Retrieved 2013-06-27.
- ^ Angiotensin II receptor blocker induced fetopathy: 7 cases. Hünseler C, Paneitz A, Friedrich D, Lindner U, Oberthuer A, Körber F, Schmitt K, Welzing L, Müller A, Herkenrath P, Hoppe B, Gortner L, Roth B, Kattner E, Schaible T. Klin Padiatr. 2011 Jan;223(1):10-4. Epub 2011 Jan 26.
- ^ "BENICAR Prescribing Information". Retrieved 2011-01-20.
- ^ De Petris G, Caldero SG, Chen L, et al. (May 2014). "Histopathological changes in the gastrointestinal tract due to medications: an update for the surgical pathologist (part II of II)". Int. J. Surg. Pathol. 22 (3): 202–11. doi:10.1177/1066896913502230. PMID 24021900.
- ^ as referenced in http://www.medicalnewstoday.com/releases/91285.php "Olmetec(R) Is First Angiotensin Receptor Blocker (ARB) To Suggest Atherosclerosis Regression (In Hypertensives With Cardiovascular Risk), UK"
- ^ Cardiovascular Research Foundation (2008, October 16). Drug May Reduce Coronary Artery Plaque. ScienceDaily. Retrieved January 5, 2013, from http://www.sciencedaily.com /releases/2008/10/081012121318.htm
- ^ (Review) R Preston Mason, Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, and Elucida Research, Beverly, MA, USA. Vascular Health and Risk Management, Dovepress, Published Date June 2011 Volume 2011:7 Pages 405 - 416. Optimal therapeutic strategy for treating patients with hypertension and atherosclerosis: focus on olmesartan medoxomil. Retrieved January 5, 2013, from http://www.dovepress.com/optimal-therapeutic-strategy-for-treating-patients-with-hypertension-a-peer-reviewed-article-VHRM
External links
- Daiichi-Sankyo Benicar page
- Benicar HCT from RXlist.com
- Mayo Clinic Proceedings vol.87 Issue 8, pages 732-738
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Antihypertensives: agents acting on the renin–angiotensin system (C09)
|
|
ACE inhibitors
("-pril") |
- Sulfhydryl-containing: Captopril
- Zofenopril
- Dicarboxylate-containing: Enalapril#
- Ramipril
- Quinapril (+HCT)
- Perindopril
- Lisinopril (+HCT)
- Benazepril
- Phosphonate-containing: Fosinopril (+HCT)
- Other/ungrouped: Alacepril
- Cilazapril
- Delapril
- Imidapril
- Moexipril
- Rentiapril
- Spirapril
- Temocapril
- Trandolapril
|
|
AIIRAs/
("-sartan") |
- Azilsartan
- Candesartan
- Eprosartan
- Irbesartan
- Losartan (+HCT)
- Olmesartan (+amlodipine)
- Tasosartan§
- Telmisartan (+HCT)
- Valsartan (+HCT, +amlodipine)
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Renin inhibitors/
("-kiren") |
- Aliskiren (+amlodipine, +amlodipine and HCT)
- Remikiren§
|
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- #WHO-EM
- ‡Withdrawn from market
- Clinical trials:
- †Phase III
- §Never to phase III
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anat (a:h/u/t/a/l,v:h/u/t/a/l)/phys/devp/cell/prot
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noco/syva/cong/lyvd/tumr, sysi/epon, injr
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proc, drug (C2s+n/3/4/5/7/8/9)
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