Olmesartan

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 Olmecip.
AHFS/Drugs.com monograph
MedlinePlus a603006
Pregnancy
category
  • C (D if used in second or third trimester)
Routes of
administration		 Oral
Legal status
  • ℞ (Prescription only)
Pharmacokinetic data
Bioavailability 26%
Metabolism Hepatic (cannot be removed by hemodialysis)
Biological half-life 13 hours
Excretion Renal 40%, biliary 60%
Identifiers
CAS Number 144689-63-4 YesY
ATC code C09CA08 (WHO)
C09DA08 (with diuretics)
C09DB02 (with amlodipine)
PubChem CID 130881
IUPHAR/BPS 591
DrugBank DB00275 YesY
ChemSpider 115748 YesY
UNII 6M97XTV3HD YesY
KEGG D01204 YesY
ChEMBL CHEMBL1516 N
Chemical data
Formula C29H30N6O6
Molar mass 558.585 g/mol
 NYesY (what is this?)  (verify)

Olmesartan medoxomil is an angiotensin II receptor antagonist which has been used for the treatment of high blood pressure. It was developed by Sankyo in 1995, and is sold under the trade name Benicar Olmecip(Cipla)Olsar (Unichem Laboratories). An ester prodrug, it is completely and rapidly hydrolyzed to the active acid form, olmesartan (RNH-6270).[1]

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. 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] Recent studies suggested this form of sprue-like enteropathy could be caused by the inhibition of TGF-β, a polypeptide cytokine that maintains intestinal homeostasis. However, it is still unclear why this action was never observed with other ARBs.[7]

Structure

The olmesartan molecule includes one tetrazole group (a five-member heterocyclic ring of four nitrogen atoms and one carbon atom) and one imidazole group (a five-membered planar heterocyclic aromatic ring of two nitrogen and three carbon atoms, classified as an alkaloid).

Mechanism of action

Olmesartan medoxomil, a prodrug, is hydrolyzed to olmesartan during absorption from the gastrointestinal tract. 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.

Metabolism of olmesartan medoxomil prodrug towards biologically active olmesartan

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 combined 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, Olsar by Unichem Laboratories 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 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.

Research

Two clinical studies (MORE [8] and OLIVUS [9])[10] report that Benicar reduced arterial plaque during therapy for high blood pressure.

See also

References

  1. ↑ 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
  2. 1 2 3 4 RxList Inc. (5 July 2007). "Benicar (olmesartan medoxomil)". RxList Inc. Retrieved 22 July 2010. External link in |publisher= (help)
  3. ↑ "FDA Alert: Benicar (olmesartan): Ongoing Safety Review". Drugs.com. Retrieved 2013-06-27.
  4. ↑ 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 (Jan 2011). "Angiotensin II receptor blocker induced fetopathy: 7 cases". Klin Padiatr 223 (1): 10–4. doi:10.1055/s-0030-1269895.
  5. ↑ "BENICAR Prescribing Information" (PDF). Retrieved 2011-01-20.
  6. ↑ 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.
  7. ↑ Rubio-Tapia, Alberto; Herman, Margot L.; Ludvigsson, Jonas F.; Kelly, Darlene G.; Mangan, Thomas F.; Wu, Tsung-Teh; Murray, Joseph A. (2012-08-01). "Severe Spruelike Enteropathy Associated With Olmesartan". Mayo Clinic Proceedings 87 (8): 732–738. doi:10.1016/j.mayocp.2012.06.003. ISSN 0025-6196. PMC 3538487. PMID 22728033.
  8. ↑ 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"
  9. ↑ 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
  10. ↑ (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

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