Valsartan

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Valsartan
Systematic (IUPAC) name
(S)-3-methyl-2-(N-{[2'-(2H-1,2,3,4-tetrazol-5-yl)biphenyl-4-yl]methyl}pentanamido)butanoic acid
Clinical data
Trade namesDiovan
AHFS/Drugs.commonograph
MedlinePlusa697015
Licence dataUS FDA:link
Pregnancy cat.D (US)
Legal status-only (US)
Routesoral
Pharmacokinetic data
Bioavailability25%
Protein binding95%
Half-life6 hours
ExcretionRenal 30%, biliary 70%
Identifiers
CAS number137862-53-4 YesY
ATC codeC09CA03
PubChemCID 60846
IUPHAR ligand3937
DrugBankDB00177
ChemSpider54833 YesY
UNII80M03YXJ7I YesY
KEGGD00400 YesY
ChEBICHEBI:9927 YesY
ChEMBLCHEMBL1069 YesY
Chemical data
FormulaC24H29N5O3 
Mol. mass435.519 g/mol
 YesY (what is this?)  (verify)
 
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Valsartan
Systematic (IUPAC) name
(S)-3-methyl-2-(N-{[2'-(2H-1,2,3,4-tetrazol-5-yl)biphenyl-4-yl]methyl}pentanamido)butanoic acid
Clinical data
Trade namesDiovan
AHFS/Drugs.commonograph
MedlinePlusa697015
Licence dataUS FDA:link
Pregnancy cat.D (US)
Legal status-only (US)
Routesoral
Pharmacokinetic data
Bioavailability25%
Protein binding95%
Half-life6 hours
ExcretionRenal 30%, biliary 70%
Identifiers
CAS number137862-53-4 YesY
ATC codeC09CA03
PubChemCID 60846
IUPHAR ligand3937
DrugBankDB00177
ChemSpider54833 YesY
UNII80M03YXJ7I YesY
KEGGD00400 YesY
ChEBICHEBI:9927 YesY
ChEMBLCHEMBL1069 YesY
Chemical data
FormulaC24H29N5O3 
Mol. mass435.519 g/mol
 YesY (what is this?)  (verify)

Valsartan (Angiotan or Diovan) is an angiotensin II receptor antagonist (more commonly called an "ARB", or angiotensin receptor blocker), with particularly high affinity for the type I (AT1) angiotensin receptor. By blocking the action of angiotensin, valsartan dilates blood vessels and reduces blood pressure.[1] In the U.S., valsartan is indicated for treatment of high blood pressure, congestive heart failure (CHF), or post-myocardial infarction (MI).[2] In 2005, Valsartan was prescribed more than 12 million times in the United States[citation needed] and global sales were approximately $6.1 billion in 2010.[3] The patents for valsartan and valsartan/hydrochlorothiazide expired in September 2012.[4][5]

A study released in 2010, based on 819,491 cases in U.S. Department of Veterans Affairs database from 2002 to 2006, demonstrated a significant reduction in the incidence and progression of Alzheimer's disease and dementia.[6] An earlier study released by the Journal of Clinical Investigation in 2007 found some efficacy in the use of valsartan in the treatment and prevention of Alzheimer's disease (in a mouse model).[7]

Administration[edit]

Oral tablets, containing 40 mg (scored), 80 mg, 160 mg, or 320 mg of valsartan. Usual dosage ranges from 40–320 mg daily.

In some markets available as a hard gelatin capsule, containing 40 mg, 80 mg, or 160 mg of valsartan.

Diovan HCT contains a combination of valsartan and hydrochlorothiazide but, unlike Diovan, is only indicated for hypertension, not for CHF or post-MI.[citation needed] Diovan HCT is available in oral tablets, containing (valsartan/HCTZ mg) 80/12.5, 160/12.5, 160/25, 320/12.5, and 320/25.

Myocardial infarction controversy[edit]

Whether angiotensin receptor blockers may or may not increase the risk of myocardial infarction (heart attack) was announced in BMJ[8] and was debated in 2006 in the medical journal of the American Heart Association.[9][10] To date[when?], there is no consensus on whether ARBs have a tendency to increase MI, but there is also no substantive evidence to indicate that ARBs are able to reduce MI.

In the VALUE trial, the angiotensin II receptor blocker valsartan produced a statistically significant 19% (p=0.02) relative increase in the prespecified secondary end point of myocardial infarction (fatal and non-fatal) compared with amlodipine.[11]

The CHARM-alternative trial showed a significant +52% (p=0.025) increase in myocardial infarction with candesartan (versus placebo) despite a reduction in blood pressure.[12]

Indeed, as a consequence of AT1 blockade, ARBs increase Angiotensin II levels several-fold above baseline by uncoupling a negative-feedback loop. Increased levels of circulating Angiotensin II result in unopposed stimulation of the AT2 receptors, which are, in addition upregulated. Unfortunately, recent data suggest that AT2 receptor stimulation may be less beneficial than previously proposed and may even be harmful under certain circumstances through mediation of growth promotion, fibrosis, and hypertrophy, as well as proatherogenic and proinflammatory effects.[13][14][15]

Diabetes[edit]

In patients with impaired glucose tolerance, valsartan may decrease the incidence of developing diabetes mellitus type 2.[16] However, the absolute risk reduction is small (less than 1 percent per year) and diet, exercise or other drugs, may be more protective.[citation needed] In the same study, no reduction in the rate of cardiovascular events (including death) was shown.[citation needed]

Side effects[edit]

There is a case report of a stillbirth in which valsartan is implicated.[18]

Brands[edit]

In the US, UK and Australia, valsartan is marketed by Novartis under the trade name Diovan. In Pakistan, it is marketed by Efroze under the trade name Angiotan. In India, it is marketed by Cipla under the trade name Valtan and by Torrent Pharmaceuticals under the trade name Valzaar. In Egypt and in France, it is marketed by Novartis under the name of Tareg. In Ukraine, it is marketed by Фарма Старт under the trade name Диокор, Диокор Соло

See also[edit]

References[edit]

  1. ^ Marks JW (2007-02-15). "Valsartan, Diovan". MedicineNet. Retrieved 2010-03-04. 
  2. ^ "Diovan prescribing information". Novartis. 
  3. ^ "Novartis Annual Report". Novartis. 2010. Retrieved June 15, 2011.
  4. ^ Philip Moeller (April 29, 2011). "Blockbuster Drugs That Will Go Generic Soon". U.S.News & World Report. 
  5. ^ Eva Von Schaper (August 5, 2011). "Novartis's Jimenez Has Blockbuster Plans For Diovan After Patent Expires". Bloomberg. 
  6. ^ Li NC, Lee A, Whitmer RA, et al. (January 2010). "Use of angiotensin receptor blockers and risk of dementia in a predominantly male population: prospective cohort analysis". BMJ 340: b5465. doi:10.1136/bmj.b5465. PMC 2806632. PMID 20068258. 
  7. ^ Wang J, Ho L, Chen L, et al. (November 2007). "Valsartan lowers brain β-amyloid protein levels and improves spatial learning in a mouse model of Alzheimer disease" (PDF). J. Clin. Invest. 117 (11): 3393–402. doi:10.1172/JCI31547. PMC 2040315. PMID 17965777. Retrieved 2009-11-11. 
  8. ^ Verma S, Strauss M (November 2004). "Angiotensin receptor blockers and myocardial infarction: These drugs may increase myocardial infarction—and patients may need to be told". BMJ 329 (7477): 1248–9. doi:10.1136/bmj.329.7477.1248. PMC 534428. PMID 15564232. 
  9. ^ Strauss MH, Hall AS (August 2006). "Angiotensin receptor blockers may increase risk of myocardial infarction: unraveling the ARB-MI paradox". Circulation 114 (8): 838–54. doi:10.1161/CIRCULATIONAHA.105.594986. PMID 16923768. 
  10. ^ Tsuyuki RT, McDonald MA (August 2006). "Angiotensin receptor blockers do not increase risk of myocardial infarction". Circulation 114 (8): 855–60. doi:10.1161/CIRCULATIONAHA.105.594978. PMID 16923769. 
  11. ^ Julius S, Kjeldsen SE, Weber M, et al. (June 2004). "Outcomes in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine: the VALUE randomised trial". The Lancet 363 (9426): 2022–31. doi:10.1016/S0140-6736(04)16451-9. PMID 15207952. 
  12. ^ Granger CB, McMurray JJ, Yusuf S, et al. (September 2003). "Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function intolerant to angiotensin-converting-enzyme inhibitors: the CHARM-Alternative trial". The Lancet 362 (9386): 772–6. doi:10.1016/S0140-6736(03)14284-5. PMID 13678870. 
  13. ^ Levy BI (September 2005). "How to explain the differences between renin angiotensin system modulators". Am. J. Hypertens. 18 (9 Pt 2): 134S–141S. doi:10.1016/j.amjhyper.2005.05.005. PMID 16125050. 
  14. ^ Levy BI (January 2004). "Can angiotensin II type 2 receptors have deleterious effects in cardiovascular disease? Implications for therapeutic blockade of the renin-angiotensin system". Circulation 109 (1): 8–13. doi:10.1161/01.CIR.0000096609.73772.C5. PMID 14707017. 
  15. ^ Reudelhuber TL (December 2005). "The continuing saga of the AT2 receptor: a case of the good, the bad, and the innocuous". Hypertension 46 (6): 1261–2. doi:10.1161/01.HYP.0000193498.07087.83. PMID 16286568. 
  16. ^ McMurray JJ, Holman RR, Haffner SM, et al. (April 2010). "Effect of valsartan on the incidence of diabetes and cardiovascular events" (PDF). The New England Journal of Medicine 362 (16): 1477–90. doi:10.1056/NEJMoa1001121. PMID 20228403. 
  17. ^ Haberfeld, H, ed. (2009). Austria-Codex (in German) (2009/2010 ed.). Vienna: Österreichischer Apothekerverlag. ISBN 3-85200-196-X. 
  18. ^ Briggs GG, Nageotte MP (2001). "Fatal fetal outcome with the combined use of valsartan and atenolol". The Annals of Pharmacotherapy 35 (7–8): 859–61. doi:10.1345/aph.1A013. PMID 11485133. 

External links[edit]