Valsartan
2398993
224805550
2008-07-10T14:23:44Z
75.37.209.244
/* Myocardial Infarction: the controversy */
{{drugbox
| IUPAC_name = 3-methyl-2- [pentanoyl-[ [4-[2-(2''H''-tetrazol-5-yl) phenyl] phenyl] methyl]amino] -butanoic acid
| image = Valsartan.svg
| CAS_number = 137862-53-4
| ATC_prefix = C09
| ATC_suffix = CA03
| ATC_supplemental =
| PubChem = 60846
| DrugBank = APRD00133
| C = 24 | H = 29 | N = 5 | O = 3
| molecular_weight = 435.519 g/mol
| smiles = CCCCC(=O)N(Cc1ccc(cc1)c1ccccc1c1n[nH]nn1)[C@@H](C(C)C)C(=O)O
| bioavailability = 25%
| protein_bound = 95%
| metabolism =
| elimination_half-life = 6 hours
|excretion = [[Renal]] 30%, [[biliary]] 70%
| pregnancy_category = D
| legal_status = Rx-only
| routes_of_administration = oral
}}
'''Valsartan''' is an [[angiotensin II receptor antagonist]] (more commonly called an "ARB", which stands for Angiotensin Receptor Blocker), acting on the [[angiotensin receptor|AT<sub>1</sub>]] subtype. In the U.S., valsartan is indicated for treatment of [[hypertension|high blood pressure]], of [[congestive heart failure]] (CHF), and post-[[myocardial infarction]] (MI). It is marketed by [[Novartis]] under the trade name '''Diovan'''. In India, it is marketed by [[Cipla|CIPLA]] under the trade name '''Valtan''' and by [[Torrent Pharmaceuticals|Torrent Pharmaceuticals]] under the trade name '''Valzaar'''. In 2005, Diovan was prescribed more than 12 million times in the [[United States]]. A 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 although such use is considered to be highly experimental.<ref>"Valsartan lowers brain β-amyloid protein levels and improves spatial learning in a mouse model of Alzheimer disease." http://content.the-jci.org/articles/view/31547 . 2007.</ref> According to the Diovan Package Insert (PI), Diovan loses 40% of its efficacy when ingested with food.
==Administration==
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 40mg, 80mg, or 160mg 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.
==Myocardial Infarction Controversy==
Whether Angiotensin II Receptor Blockers may increase or not the risk of [[Myocardial Infarction]] was announced in the BMJ <ref name="BMJ1">Verma S, Strauss M. Angiotensin receptor blockers and myocardial infarction. BMJ. 2004 Nov 27; 329(7477):1248-9. PMID: 15564232</ref> and was more recently debated in the medical journal of the [[American Heart Association]]: Circulation <ref name="Circ1">Strauss MH, Hall AS. Angiotensin receptor blockers may increase the risk of myocardial infarction: unravelling the ARB-MI paradox. Circulation. 2006 Aug 22; 114(8):838-54. PMID: 16923768</ref> <ref name="Circ2">Tsuyuki RT, McDonald MA. Angiotensin receptor blockers do not increase the risk of myocardial infarction. Circulation. 2006 Aug 22; 114(8):855-60. PMID: 16923769</ref>.
To date, 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]] <ref name="Lancet1">Julius S et al. Outcomes in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine: the VALUE randomised trial. Lancet. 2004 Jun 19;363(9423):2022-31. PMID: 15207952</ref>.
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 <ref name="Lancet2">Granger CB et al. 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. Lancet 2003 Sep 6;362(9386):772-6. PMID: 13678870</ref>.
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 <ref name="AJH1">Levy Bl. How to explain the differences between renin angiotensin system modulators. Am J Hypertens. 2005;18(pt2):134S-141S. PMID: 16125050</ref> <ref name="Circ23">Levy Bl. Can angiotensin II type 2 receptors have deleterious effects in cardiovascular disease? Implications for therapeutic blockade of the renin-angiotensin system. Circulation. 2004;109:8-13</ref> <ref name="CircHyp43">Reudelhuber TL et al. The continuing saga of the AT2 receptor: a case of the good, the bad, and the innocuous. Hypertension. 2005;46:1261-1262. PMID: 16286568</ref>.
==Side effects==
Most commonly, [[headache]] and [[dizziness]].
==References==
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==External links==
*{{PubMed|Valsartan}}
*[http://www.diovan.com Official Diovan Site]
{{Angiotensin II receptor antagonists}}
[[Category:Angiotensin II receptor antagonists]]
[[Category:Novartis]]
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