Wikipedia:WikiProject Chemicals/Chembox validation/VerifiedDataSandbox and Valsartan: Difference between pages

{{Short description|Angiotensin II receptor antagonist}}

{{Use dmy dates|date=February 2024}}

{{cs1 config |name-list-style=vanc |display-authors=6}}

{{Infobox drug

| verifiedrevid = 470628341

| image = Valsartan skeletal.svg

| width =

| alt =

| image2 = Valsartan-from-xtal-3D-bs-17.png

| width2 =

| alt2 =

| caption =

<!-- Clinical data -->

| pronounce =

| tradename = Diovan, others

| DailyMedID = Valsartan

| pregnancy_AU = D

| pregnancy_AU_comment = <ref name="Drugs.com pregnancy">{{cite web | title=Valsartan Use During Pregnancy | website=Drugs.com | date=28 March 2019 | url=https://www.drugs.com/pregnancy/valsartan.html | access-date=12 February 2020}}</ref>

| pregnancy_category =

| routes_of_administration = [[Oral administration|By mouth]]

| class = [[Angiotensin II receptor antagonist]]

| ATCvet =

| ATC_prefix = C09

| ATC_suffix = CA03

| ATC_supplemental = {{ATC|C09|DX05}}, {{ATC|C09|DA03}}, {{ATC|C09|DX02}}, {{ATC|C09|DX01}}, {{ATC|C09|DB08}}, {{ATC|C09|DB01}}, {{ATC|C09|DX04}}, {{ATC|C10|BX10}}

<!-- Legal status -->

| legal_AU = S4

| legal_AU_comment = <ref>{{cite web | title=Diovan valsartan 40mg film-coated tablet blister pack | website=Therapeutic Goods Administration (TGA) | url=https://tga-search.clients.funnelback.com/s/search.html?collection=tga-artg&profile=record&meta_i=93165 | access-date=24 October 2021 | archive-date=25 October 2021 | archive-url=https://web.archive.org/web/20211025160457/https://tga-search.clients.funnelback.com/s/search.html?collection=tga-artg&profile=record&meta_i=93165 | url-status=dead }}</ref><ref>{{cite web | title=Diovan valsartan 80mg film-coated tablet blister pack | website=Therapeutic Goods Administration (TGA) | url=https://tga-search.clients.funnelback.com/s/search.html?collection=tga-artg&profile=record&meta_i=80868 | access-date=24 October 2021 | archive-date=25 October 2021 | archive-url=https://web.archive.org/web/20211025160419/https://tga-search.clients.funnelback.com/s/search.html?collection=tga-artg&profile=record&meta_i=80868 | url-status=dead }}</ref><ref>{{cite web | title=Diovan valsartan 160mg film-coated tablet blister pack | website=Therapeutic Goods Administration (TGA) | url=https://tga-search.clients.funnelback.com/s/search.html?collection=tga-artg&profile=record&meta_i=80871 | access-date=24 October 2021 | archive-date=25 October 2021 | archive-url=https://web.archive.org/web/20211025160608/https://tga-search.clients.funnelback.com/s/search.html?collection=tga-artg&profile=record&meta_i=80871 | url-status=dead }}</ref>

| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F-->

| legal_BR_comment =

| legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII -->

| legal_CA_comment =

| legal_DE = <!-- Anlage I, II, III or Unscheduled-->

| legal_DE_comment =

| legal_NZ = <!-- Class A, B, C -->

| legal_NZ_comment =

| legal_UK = POM

| legal_UK_comment = <ref>{{cite web | title=Valsartan 160 mg capsules - Summary of Product Characteristics (SmPC) | website=(emc) | date=19 February 2019 | url=https://www.medicines.org.uk/emc/medicine/30901 | access-date=12 February 2020 | archive-date=13 February 2020 | archive-url=https://web.archive.org/web/20200213034657/https://www.medicines.org.uk/emc/medicine/30901 | url-status=dead }}</ref>

| legal_US = Rx-only

| legal_US_comment = <ref name="Diovan FDA label" />

| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV-->

| legal_UN_comment =

| legal_status = <!--For countries not listed above-->

<!-- Pharmacokinetic data -->

| metabolism =

| metabolites =

| onset =

| duration_of_action =

| excretion = [[Kidney]] 30%, [[bile duct]] 70%

<!-- Identifiers -->

| index_label = <!-- parent -->

| index2_label = tritiated

| CAS_supplemental =

| IUPHAR_ligand = 3937

| IUPHAR_ligand2 = 593

| KEGG_Ref = {{keggcite|correct|kegg}}

| ChEBI_Ref = {{ebicite|correct|EBI}}

| NIAID_ChemDB =

| PDB_ligand =

| synonyms =

<!-- Chemical and physical data -->

| IUPAC_name = (''S'')-3-methyl-2-(''N''-<nowiki/>{[2'-(2''H''-1,2,3,4-tetrazol-5-yl)biphenyl-4-yl]methyl}pentanamido)butanoic acid

| C=24 | H=29 | N=5 | O=3

| SMILES = CCCCC(=O)N(Cc1ccc(-c2ccccc2-c2nn[nH]n2)cc1)C(C(=O)O)C(C)C

| StdInChI_comment =

| density =

| density_notes =

| melting_point =

| melting_high =

| melting_notes =

| boiling_point =

| boiling_notes =

| solubility =

| sol_units =

| specific_rotation =

<!-- Definition and medical uses -->

'''Valsartan''', sold under the brand name '''Diovan''' among others, is a [[medication]] used to treat [[hypertension|high blood pressure]], [[heart failure]], and [[diabetic kidney disease]].<ref name=AHFS2019/> It belongs to a class of medications referred to as [[angiotensin II receptor blocker]]s (ARBs). It is a reasonable initial treatment for high blood pressure.<ref name=AHFS2019/> It is taken [[Oral administration|by mouth]].<ref name=AHFS2019/>

<!-- Side effects and mechanisms -->

Common side effects include feeling tired, dizziness, [[high blood potassium]], diarrhea, and joint pain.<ref name=AHFS2019/> Other serious side effects may include [[kidney problems]], [[low blood pressure]], and [[angioedema]].<ref name=AHFS2019/> Use in [[pregnancy]] may harm the baby and use when [[breastfeeding]] is not recommended.<ref name=Preg2019>{{cite web |title=Valsartan Pregnancy and Breastfeeding Warnings |url=https://www.drugs.com/pregnancy/valsartan.html |website=Drugs.com |access-date=3 March 2019}}</ref> It is an [[angiotensin II receptor antagonist]] and works by blocking the effects of [[angiotensin II]].<ref name=AHFS2019>{{cite web |title=Valsartan Monograph for Professionals |url=https://www.drugs.com/monograph/valsartan.html |website=Drugs.com |publisher=American Society of Health-System Pharmacists |access-date=3 March 2019}}</ref>

<!-- Society and culture -->

Valsartan was patented in 1990, and came into medical use in 1996.<ref name=Fis2006>{{cite book | veditors = Fischer J, Ganellin CR |title=Analogue-based Drug Discovery |date=2006 |publisher=John Wiley & Sons |isbn=9783527607495 |page=470 |url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA470 }}</ref> It is available as a [[generic medication]].<ref name=BNF76>{{cite book|title=British national formulary : BNF 76|date=2018|publisher=Pharmaceutical Press|isbn=9780857113382|pages=179|edition=76}}</ref> In 2021, it was the 120th most commonly prescribed medication in the United States, with more than 5{{nbsp}}million prescriptions.<ref>{{cite web | title=The Top 300 of 2021 | url=https://clincalc.com/DrugStats/Top300Drugs.aspx | website=ClinCalc | access-date=14 January 2024 | archive-date=15 January 2024 | archive-url=https://web.archive.org/web/20240115223848/https://clincalc.com/DrugStats/Top300Drugs.aspx | url-status=live }}</ref><ref>{{cite web | title = Valsartan - Drug Usage Statistics | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/Valsartan | access-date = 14 January 2024}}</ref> Versions are available as the combinations [[valsartan/hydrochlorothiazide]],<ref>{{cite web | title=Valsartan and hydrochlorothiazide Advanced Patient Information | website=Drugs.com | date=29 January 2024 | url=https://www.drugs.com/cons/valsartan-and-hydrochlorothiazide.html | access-date=7 February 2024}}</ref> [[valsartan/amlodipine]],<ref>{{cite web | title=Amlodipine and valsartan Advanced Patient Information | website=Drugs.com | date=27 June 2023 | url=https://www.drugs.com/cons/amlodipine-and-valsartan.html | access-date=7 February 2024}}</ref> [[valsartan/amlodipine/hydrochlorothiazide]],<ref>{{cite web | title=Amlodipine, valsartan, and hydrochlorothiazide Advanced Patient Information | website=Drugs.com | date=2 December 2023 | url=https://www.drugs.com/cons/amlodipine-valsartan-and-hydrochlorothiazide.html | access-date=7 February 2024}}</ref> [[nebivolol/valsartan|valsartan/nebivolol]],<ref>{{cite web | title=Nebivolol and valsartan Advanced Patient Information | website=Drugs.com | date=14 October 2023 | url=https://www.drugs.com/cons/nebivolol-and-valsartan.html | access-date=7 February 2024}}</ref> and [[sacubitril/valsartan|valsartan/sacubitril]].<ref name=AHFS2019/><ref name="Entresto AHFS">{{cite web | title=Sacubitril and Valsartan Monograph for Professionals | website=Drugs.com | date=7 November 2019 | url=https://www.drugs.com/monograph/sacubitril-and-valsartan.html | access-date=12 February 2020}}</ref>

==Medical uses==

Valsartan is used to treat [[hypertension|high blood pressure]], [[heart failure]], and to reduce death for people with [[left ventricular dysfunction]] after having a [[myocardial infarction|heart attack]].<ref name=G&G>{{cite book | vauthors = Randa HD |chapter=Chapter 26. Renin and Angiotensin |title=Goodman & Gilman's The Pharmacological Basis of Therapeutics | veditors = Brunton LL, Chabner B, Knollmann BC |edition=12th |location=New York |publisher=McGraw-Hill |year=2011 |isbn=978-0-07-162442-8|title-link=Goodman & Gilman's The Pharmacological Basis of Therapeutics }}</ref><ref name="Diovan FDA label">{{cite web | title=Diovan- valsartan tablet | website=[[DailyMed]] | date=12 June 2019 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5ddba454-f3e6-43c2-a7a6-58365d297213 | access-date=12 February 2020}}</ref>

===High blood pressure===

Valsartan (and other ARBs) are an appropriate initial treatment option for most people with high blood pressure and no other coexisting conditions, as are [[ACE inhibitor]]s, [[thiazide diuretics]] and [[calcium channel blocker]]s.<ref>{{cite journal | vauthors = Ettehad D, Emdin CA, Kiran A, Anderson SG, Callender T, Emberson J, Chalmers J, Rodgers A, Rahimi K | title = Blood pressure lowering for prevention of cardiovascular disease and death: a systematic review and meta-analysis | journal = Lancet | volume = 387 | issue = 10022 | pages = 957–967 | date = March 2016 | pmid = 26724178 | doi = 10.1016/s0140-6736(15)01225-8 | s2cid = 8868485 | doi-access = free }}</ref> If patients have coexisting diabetes or kidney disease, ARBs or ACE inhibitors may be considered over other classes of blood pressure medicines.<ref>{{cite journal | vauthors = Brenner BM, Cooper ME, de Zeeuw D, Keane WF, Mitch WE, Parving HH, Remuzzi G, Snapinn SM, Zhang Z, Shahinfar S | title = Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy | journal = The New England Journal of Medicine | volume = 345 | issue = 12 | pages = 861–869 | date = September 2001 | pmid = 11565518 | doi = 10.1056/nejmoa011161 | hdl-access = free | hdl = 2445/122643 }}</ref><ref>{{cite journal | vauthors = Mancia G, Fagard R, Narkiewicz K, Redon J, Zanchetti A, Böhm M, Christiaens T, Cifkova R, De Backer G, Dominiczak A, Galderisi M, Grobbee DE, Jaarsma T, Kirchhof P, Kjeldsen SE, Laurent S, Manolis AJ, Nilsson PM, Ruilope LM, Schmieder RE, Sirnes PA, Sleight P, Viigimaa M, Waeber B, Zannad F, Redon J, Dominiczak A, Narkiewicz K, Nilsson PM, Burnier M, Viigimaa M, Ambrosioni E, Caufield M, Coca A, Olsen MH, Schmieder RE, Tsioufis C, van de Borne P, Zamorano JL, Achenbach S, Baumgartner H, Bax JJ, Bueno H, Dean V, Deaton C, Erol C, Fagard R, Ferrari R, Hasdai D, Hoes AW, Kirchhof P, Knuuti J, Kolh P, Lancellotti P, Linhart A, Nihoyannopoulos P, Piepoli MF, Ponikowski P, Sirnes PA, Tamargo JL, Tendera M, Torbicki A, Wijns W, Windecker S, Clement DL, Coca A, Gillebert TC, Tendera M, Rosei EA, Ambrosioni E, Anker SD, Bauersachs J, Hitij JB, Caulfield M, De Buyzere M, De Geest S, Derumeaux GA, Erdine S, Farsang C, Funck-Brentano C, Gerc V, Germano G, Gielen S, Haller H, Hoes AW, Jordan J, Kahan T, Komajda M, Lovic D, Mahrholdt H, Olsen MH, Ostergren J, Parati G, Perk J, Polonia J, Popescu BA, Reiner Z, Rydén L, Sirenko Y, Stanton A, Struijker-Boudier H, Tsioufis C, van de Borne P, Vlachopoulos C, Volpe M, Wood DA | title = 2013 ESH/ESC guidelines for the management of arterial hypertension: the Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) | journal = European Heart Journal | volume = 34 | issue = 28 | pages = 2159–2219 | date = July 2013 | pmid = 23771844 | doi = 10.1093/eurheartj/eht151 | doi-access = free | hdl = 1854/LU-4127523 | hdl-access = free }}</ref>

===Heart failure===

Valsartan has reduced rates of mortality and heart failure hospitalisations when used alone or in combination with [[beta blocker]]s in the treatment of heart failure.<ref name=":0">{{cite journal | vauthors = Cohn JN, Tognoni G | title = A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure | journal = The New England Journal of Medicine | volume = 345 | issue = 23 | pages = 1667–1675 | date = December 2001 | pmid = 11759645 | doi = 10.1056/NEJMoa010713 | doi-access = free }}</ref> Importantly, the combination of valsartan and [[ACE inhibitor]]s has not shown morbidity or mortality benefits but rather increases mortality risk when added to combination beta blocker and ACE inhibitor therapy, and increases the risk of adverse events like [[Hyperkalemia|hyperkalaemia]], [[hypotension]] and [[Renal Failure|renal failure]].<ref name=":0" /><ref>{{cite journal | vauthors = Makani H, Bangalore S, Desouza KA, Shah A, Messerli FH | title = Efficacy and safety of dual blockade of the renin-angiotensin system: meta-analysis of randomised trials | journal = BMJ | volume = 346 | issue = jan28 1 | pages = f360 | date = January 2013 | pmid = 23358488 | pmc = 3556933 | doi = 10.1136/bmj.f360 }}</ref> As shown in the PARADIGM-HF study, valsartan combined with sacubitril for the treatment of heart failure, significantly reduced all cause and cardiovascular mortality and hospitalisations due to heart failure.<ref>{{cite journal | vauthors = McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, Rouleau JL, Shi VC, Solomon SD, Swedberg K, Zile MR | title = Angiotensin-neprilysin inhibition versus enalapril in heart failure | journal = The New England Journal of Medicine | volume = 371 | issue = 11 | pages = 993–1004 | date = September 2014 | pmid = 25176015 | doi = 10.1056/NEJMoa1409077 | s2cid = 11383 | doi-access = free | hdl = 2445/178508 | hdl-access = free }}</ref>

===Diabetic kidney disease===

In people with type 2 diabetes, antihypertensive therapy with valsartan decreases the rate of progression of albuminuria (albumin in urine), promotes regression to normoalbuminuria and may reduce the rate of progression to end-stage kidney disease.<ref>{{cite journal | vauthors = Viberti G, Wheeldon NM | title = Microalbuminuria reduction with valsartan in patients with type 2 diabetes mellitus: a blood pressure-independent effect | journal = Circulation | volume = 106 | issue = 6 | pages = 672–678 | date = August 2002 | pmid = 12163426 | doi = 10.1161/01.CIR.0000024416.33113.0A | s2cid = 5887738 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Galle J, Schwedhelm E, Pinnetti S, Böger RH, Wanner C | title = Antiproteinuric effects of angiotensin receptor blockers: telmisartan versus valsartan in hypertensive patients with type 2 diabetes mellitus and overt nephropathy | journal = Nephrology, Dialysis, Transplantation | volume = 23 | issue = 10 | pages = 3174–3183 | date = October 2008 | pmid = 18450829 | doi = 10.1093/ndt/gfn230 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Hollenberg NK, Parving HH, Viberti G, Remuzzi G, Ritter S, Zelenkofske S, Kandra A, Daley WL, Rocha R | title = Albuminuria response to very high-dose valsartan in type 2 diabetes mellitus | language = en-US | journal = Journal of Hypertension | volume = 25 | issue = 9 | pages = 1921–1926 | date = September 2007 | pmid = 17762658 | doi = 10.1097/HJH.0b013e328277596e | s2cid = 25150658 }}</ref>

==Contraindications==

The packaging for valsartan includes a warning stating the drug should not be used with the [[renin inhibitor]] [[aliskiren]] in people with diabetes. It also states the safety of the drug in severe renal impairment has not been established.<ref name="Diovan FDA label" />

Valsartan includes a [[black box warning]] for fetal toxicity.<ref name="Diovan FDA label" /><ref name=Preg2019 /> Discontinuation of these agents is recommended immediately after detection of [[pregnancy]] and an alternative medication should be started.<ref name="Diovan FDA label" /> Breastfeeding is not recommended.<ref name="Diovan FDA label" /><ref name="lexi">{{cite web|title = Diovan Product Monograph|publisher = Novartis Pharmaceuticals Canada Inc.|access-date = 5 November 2015|url = http://webprod5.hc-sc.gc.ca/dpd-bdpp/index-eng.jsp|website = Health Canada Drug Product Database|archive-date = 30 December 2012|archive-url = https://web.archive.org/web/20121230155541/http://webprod5.hc-sc.gc.ca/dpd-bdpp/index-eng.jsp|url-status = dead}}</ref><ref>{{cite web |date=12 May 2015 |title=Product Monograph - PrDIOVAN® (valsartan) |url=https://pdf.hres.ca/dpd_pm/00030565.PDF |website=pdf.hres.ca}}</ref>

==Side effects==

Side effects depend on the reason the medication is being used.

===Heart failure===

Adverse effects are based on a comparison versus [[placebo]] in people with heart failure.<ref name="Diovan FDA label" /> Most common side effects include [[dizziness]] (17% vs 9% ), [[hypotension|low blood pressure]] (7% vs 2%), and [[diarrhea]] (5% vs 4%).<ref name="Diovan FDA label" /> Less common side effects include [[arthralgia|joint pain]], fatigue, and back pain (all 3% vs 2%).<ref name="Diovan FDA label" />

===Hypertension===

Clinical trials for valsartan treatment for hypertension versus placebo demonstrate side effects like viral infection (3% vs 2%), fatigue (2% vs 1%) and abdominal pain (2% vs 1%). Minor side effects that occurred at >1% but were similar to rates from the placebo group include:<ref name="Diovan FDA label" />

* headache

* dizziness

* [[Upper respiratory tract infection|upper respiratory infection]]

* cough

* diarrhea

* [[rhinitis]]/[[sinusitis]]

* nausea

* [[pharyngitis]]

* [[edema]]

* arthralgia

===Kidney failure===

{{see also|Angiotensin II receptor blocker#Renal failure}}

People treated with ARBs including valsartan or [[diuretics]] are susceptible to conditions of developing low renal blood flow such as abnormal narrowing of blood vessels in the kidney, [[hypertension]], [[renal artery stenosis]], [[heart failure]], [[chronic kidney disease]], severe [[congestive heart failure]], or [[volume depletion]] whose renal function is in part dependent on the activity of the renin-angiotensin system like efferent arteriolar vasoconstriction done by angiotensin II are at high risk of deterioration of renal function comprising [[acute kidney failure]], [[oliguria]], worsening [[azotemia]] or heightened [[serum creatinine]].<ref name="Diovan FDA label" /> When blood flow to the kidneys is reduced, the kidney activates a series of responses that triggers angiotensin release to constrict blood vessels and facilitate blood flow in the kidney.<ref name="Robbins and Cotran">{{cite book|title=Pathologic Basis of Disease|year=2010|publisher=Saunders Elsevier|isbn=978-1-4160-3121-5|page=493| vauthors = Kumar A, Fausto A |edition=8th|chapter=11 }}</ref> So long as the nephron function degradation is progressive or reaches clinically significant levels, withholding or discontinuing valsartan is warranted.<ref name="Diovan FDA label" /><ref name="Smith Benjamin Bonow Braun pp. 2458–2473">{{cite journal | vauthors = Smith SC, Benjamin EJ, Bonow RO, Braun LT, Creager MA, Franklin BA, Gibbons RJ, Grundy SM, Hiratzka LF, Jones DW, Lloyd-Jones DM, Minissian M, Mosca L, Peterson ED, Sacco RL, Spertus J, Stein JH, Taubert KA | title = AHA/ACCF Secondary Prevention and Risk Reduction Therapy for Patients with Coronary and other Atherosclerotic Vascular Disease: 2011 update: a guideline from the American Heart Association and American College of Cardiology Foundation | journal = Circulation | volume = 124 | issue = 22 | pages = 2458–2473 | date = November 2011 | pmid = 22052934 | doi = 10.1161/cir.0b013e318235eb4d | publisher = Ovid Technologies (Wolters Kluwer Health) | doi-access = free }}</ref><ref>{{cite web| url= https://www.kdigo.org/clinical_practice_guidelines/pdf/CKD/KDIGO_2012_CKD_GL.pdf | archive-url= https://web.archive.org/web/20190206124008/https://www.kdigo.org/clinical_practice_guidelines/pdf/CKD/KDIGO_2012_CKD_GL.pdf | url-status= dead | archive-date= 6 February 2019 | title=KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease | publisher=KDIGO | volume= 3 | issue= 1 | date = January 2013 }}</ref><ref name="Zar Graeber Perazella pp. 217–219">{{cite journal | vauthors = Zar T, Graeber C, Perazella MA | title = Recognition, treatment, and prevention of propylene glycol toxicity | journal = Seminars in Dialysis | volume = 20 | issue = 3 | pages = 217–219 | date = 7 June 2007 | pmid = 17555487 | doi = 10.1111/j.1525-139x.2007.00280.x | publisher = Wiley | s2cid = 41089058 }}</ref>

== Interactions ==

The US prescribing information lists the following drug interactions for valsartan:

* Other inhibitors of the renin-angiotensin system may increase the risks of low blood pressure, kidney problems, and hyperkalemia.

* Potassium-sparing diuretics, [[potassium]] supplements, [[salt substitute]]s containing potassium may increase the risk of [[hyperkalemia]].

* [[NSAID]]s may increase the risk of kidney problems and may interfere with blood pressure-lowering effects.

* Valsartan may increase the concentration of [[lithium (medication)|lithium]].<ref name="Diovan FDA label" />

* Valsartan and other angiotensin-related blood pressure medications may interact with the [[antibiotics]] [[co-trimoxazole]] or [[ciprofloxacin]] to increase risk of sudden death due to [[cardiac arrest]].<ref name="pmid25359996">{{cite journal | vauthors = Fralick M, Macdonald EM, Gomes T, Antoniou T, Hollands S, Mamdani MM, Juurlink DN | title = Co-trimoxazole and sudden death in patients receiving inhibitors of renin-angiotensin system: population based study | journal = BMJ | volume = 349 | pages = g6196 | date = October 2014 | pmid = 25359996 | pmc = 4214638 | doi = 10.1136/bmj.g6196 }}</ref>

===Food interaction===

With the tablet, food decreases the valsartan tablet taker's exposure to valsartan by about 40% and peak plasma concentration (Cmax) by about 50%, evidenced by AUC change.<ref name="Diovan FDA label" />

==Pharmacology==

===Mechanism of action===

Valsartan blocks the actions of [[Angiotensin|angiotensin II]], which include constricting blood vessels and activating [[aldosterone]], to reduce blood pressure.<ref name=":1" /> The drug binds to angiotensin type I receptors (AT1), working as an antagonist.<ref>{{cite journal | vauthors = Unger T | title = Significance of angiotensin type 1 receptor blockade: why are angiotensin II receptor blockers different? | journal = The American Journal of Cardiology | volume = 84 | issue = 10A | pages = 9S–15S | date = November 1999 | pmid = 10588089 | doi = 10.1016/s0002-9149(99)00728-6 }}</ref> This mechanism of action is different than that of the ACE inhibitor drugs, which block the conversion of angiotensin I to angiotensin II. As valsartan acts at the receptor, it can provide more complete angiotensin II antagonism since angiotensin II is generated by other enzymes as well as ACE. Also, valsartan does not affect the metabolism of bradykinin like ACE inhibitors do.<ref name=":1">{{cite book|title = Basic & Clinical Pharmacology| vauthors = Katzung BG, Trevor AJ |publisher = McGraw-Hill Education|year = 2015|isbn = 978-0071825054|chapter-url = http://accessmedicine.mhmedical.com/book.aspx?bookid=1193 |chapter = Chapter 11|edition = 13th }}</ref>

===Pharmacodynamics===

===Pharmacokinetics===

The peak concentration of valsartan in plasma occurs 2 to 4 hours after dosing.<ref name="Diovan FDA label" /> AUC and Cmax values of valsartan are observed to be approximately linearly dose-dependent over therapeutic dosing range. Owing to its relatively short elimination half life attribution, valsartan concentration in plasma does not accumulate in response to repeated dosing.<ref name="Diovan FDA label" />

==Society and culture==

===Economics===

In 2010, valsartan (trade name Diovan) achieved annual sales of $2.052{{nbsp}}billion in the United States and $6.053{{nbsp}}billion worldwide.<ref>{{cite web|url = https://www.novartis.com/sites/www.novartis.com/files/novartis-annual-report-2010-en.pdf|title = Novartis Annual Report 2010 }}</ref> The patents for valsartan and valsartan/hydrochlorothiazide expired in September 2012.<ref>{{cite news| title = Blockbuster Drugs That Will Go Generic Soon| date = 29 April 2011 | vauthors = Moeller P | work = [[U.S. News & World Report]] | url = http://money.usnews.com/money/blogs/the-best-life/2011/04/29/blockbuster-drugs-that-will-go-generic-soon}}</ref><ref>{{cite news | title = Novartis's Jimenez Has Blockbuster Plans For Diovan After Patent Expires| vauthors = Von Schaper E | date = 5 August 2011 | url = https://www.bloomberg.com/news/2011-08-05/novartis-has-blockbuster-diovan-plans-after-patent-expires-1-.html | publisher = Bloomberg}}</ref>

===Combinations===

{{see|amlodipine/valsartan|valsartan/hydrochlorothiazide|valsartan/hydrochlorothiazide/amlodipine|sacubitril/valsartan}}

[[File:Two boxes and a blister pack of Co-Diovan (Valsartan and hydrochlorothiazide), Singapore - 20150210.jpg|thumb|Co-Diovan (valsartan and [[hydrochlorothiazide]])]]

Valsartan is combined with [[amlodipine]] or [[hydrochlorothiazide]] (HCTZ) (or both) into single-pill formulations for treating hypertension with multiple drugs.<ref name=AHFS2019/><ref>{{cite web | title=Exforge- amlodipine besylate and valsartan tablet, film coated | website=DailyMed | date=12 June 2019 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d0caec89-96ec-411d-a933-63eda74a6da7 | access-date=12 February 2020}}</ref><ref>{{cite web | title=Diovan HCT- valsartan and hydrochlorothiazide tablet, film coated | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d76a0419-05ee-437e-884c-65807aea9569 | access-date=12 February 2020}}</ref><ref>{{cite web | title=Exforge HCT- amlodipine valsartan and hydrochlorothiazide tablet, film coated | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=18d7820d-471f-4ee2-9ec6-25d8d27c77de | access-date=12 February 2020}}</ref> Valsartan is also available as the combination [[valsartan/sacubitril]].<ref name="Entresto AHFS" /><ref>{{cite web | title=Entresto- sacubitril and valsartan tablet, film coated | website=DailyMed | date=1 September 2019 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=000dc81d-ab91-450c-8eae-8eb74e72296f | access-date=12 February 2020}}</ref><ref name="pmid26557227">{{cite journal | vauthors = Fala L | title = Entresto (Sacubitril/Valsartan): First-in-Class Angiotensin Receptor Neprilysin Inhibitor FDA Approved for Patients with Heart Failure | journal = American Health & Drug Benefits | volume = 8 | issue = 6 | pages = 330–334 | date = September 2015 | pmid = 26557227 | pmc = 4636283 }}</ref> It is used to treat heart failure with reduced ejection fraction.<ref name="pmid26557227"/><ref name="Entresto, a New Panacea for Heart Failure?">{{cite journal | vauthors = Khalil P, Kabbach G, Said S, Mukherjee D | title = Entresto, a New Panacea for Heart Failure? | journal = Cardiovascular & Hematological Agents in Medicinal Chemistry | volume = 16 | issue = 1 | pages = 5–11 | date = 2018 | pmid = 29532764 | doi = 10.2174/1871525716666180313121954 | s2cid = 3880750 }}</ref>

===Recalls===

{{Anchor|recalls}}

{{See also|Ranitidine#impurities}}

In July 2018, the [[European Medicines Agency]] (EMA) recalled certain batches of valsartan and valsartan/hydrochlorothiazide film-coated tablets distributed in 22 countries in the European Union.<ref name=":2">{{cite news | vauthors = Christensen J |title=Common heart drug recalled in 22 countries for possible cancer link |url=https://www.cnn.com/2018/07/06/health/valsartan-heart-drug-recall-intl/index.html |website=CNN |access-date=14 July 2018 }}</ref> {{ill|Zhejiang Huahai Pharmaceutical Co.|zh|華海藥業}} (ZHP) in [[Linhai|Linhai, China]] manufactured the bulk ingredient contaminated by [[N-nitrosodimethylamine]] (NDMA), a [[carcinogen]].<ref name="carcinogen">{{cite news | title=Carcinogens Have Infiltrated the Generic Drug Supply in the U.S. | work=Bloomberg News | date=12 September 2019 | url=https://www.bloomberg.com/news/features/2019-09-12/how-carcinogen-tainted-generic-drug-valsartan-got-past-the-fda | access-date=17 September 2019 | vauthors = Edney A, Berfield S, Yu E }}</ref> The [[active pharmaceutical ingredient]] was subsequently imported by a number of generic drugmakers, including [[Novartis]], and marketed in Europe and Asia under their subsidiary [[Sandoz]] labeling, and in the UK by Dexcel Pharma Ltd and Accord Healthcare.<ref name=":2" />

Valsartan was recalled in Canada.<ref>{{cite web|url=http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2018/67202a-eng.php|title=Several drugs containing valsartan being recalled due to contamination with a potential carcinogen|website=[[Health Canada]]|date=9 July 2018|access-date=15 July 2018}}</ref><ref>{{cite web|url=http://valsartanclassaction.com/|title=Valsartan Class Action|website=valsartanclassaction.com|access-date=15 July 2018}}</ref> Authorities believe the degree of contamination is negligible.<ref>{{cite web | title=Nitrosamine impurities in medications: Guidance | website=[[Health Canada]] | date=4 April 2022 | url=https://www.canada.ca/en/health-canada/services/drugs-health-products/compliance-enforcement/information-health-product/drugs/nitrosamine-impurities/medications-guidance.html }}</ref> In July 2018, The [[National Agency of Drug and Food Control of Indonesia|National Agency of Drug and Food Control]] (NA-DFC or Badan POM Indonesia) announced voluntary recalls for two products containing valsartan produced by Actavis Indonesia and Dipa Pharmalab Intersains.<ref>{{cite web|url=https://www.pom.go.id/new/view/more/klarifikasi/88/PENJELASAN-BPOM-RI--TENTANG--PENARIKAN-OBAT-ANTIHIPERTENSI-YANG-MENGANDUNG-ZAT-AKTIF-VALSARTAN.html|title=Penjelasan BPOM RI Tentang Penarikan Obat Antihipertensi Yang Mengandung Zat Aktif Valsartan|website=[[National Agency of Drug and Food Control of Republic of Indonesia]] (Badan POM)|language=id|access-date=18 July 2018|archive-date=13 November 2019|archive-url=https://web.archive.org/web/20191113101348/https://www.pom.go.id/new/view/more/klarifikasi/88/PENJELASAN-BPOM-RI--TENTANG--PENARIKAN-OBAT-ANTIHIPERTENSI-YANG-MENGANDUNG-ZAT-AKTIF-VALSARTAN.html|url-status=dead}}</ref> In July 2018, the US [[Food and Drug Administration]] (FDA) announced voluntary recalls of certain supplies of valsartan and [[valsartan/hydrochlorothiazide]] in the US distributed by Solco Healthcare LLC, Major Pharmaceuticals, and [[Teva Pharmaceutical Industries]].<ref>{{cite news|url=https://www.cnn.com/2018/07/13/health/valsartan-recall-fda-bn/index.html|title=FDA joins 22 countries' recall of common heart drug| vauthors = Christensen J |work=CNN|access-date=15 July 2018 }}</ref><ref name="carcinogen" /> Hong Kong's Department of Health initiated a similar recall.<ref>{{cite web|url=https://www.scmp.com/news/hong-kong/health-environment/article/2154171/hong-kong-health-department-issues-recall-five|title=Hong Kong health department issues recall for five heart drugs containing valsartan that was made in China|website=South China Morning Post|date=20 July 2018|access-date=20 July 2018}}</ref> In August 2018, the FDA published two lengthy, updated lists, classifying hundreds of specific US products containing valsartan into those included versus excluded from the recall.<ref>{{cite web|url=https://www.fda.gov/Drugs/DrugSafety/ucm613916.htm|title=FDA updates on valsartan recalls|website=[[Food and Drug Administration]] (FDA) |date=2 August 2018|access-date=8 August 2018}}</ref><ref name="FDA ARB Updates">{{cite web | title=FDA Updates and Press Announcements on Angiotensin II Receptor Blocker (ARB) Recalls (Valsartan, Losartan, and Irbesartan) | website=[[Food and Drug Administration]] (FDA) | date=20 August 2018 | url=https://www.fda.gov/drugs/drug-safety-and-availability/fda-updates-and-press-announcements-angiotensin-ii-receptor-blocker-arb-recalls-valsartan-losartan | access-date=17 September 2019}}</ref> A week later, the FDA cited two more drugmakers, Zhejiang Tianyu Pharmaceuticals of China and [[Hetero Drugs|Hetero Labs Limited]] of India, as additional sources of the contaminated valsartan [[active ingredient|ingredient]].<ref>{{cite web|url=https://www.webmd.com/heart-disease/news/20180813/more-drug-makers-tagged-as-valsartan-recall-grows|title=More Drug Makers Tagged as Valsartan Recall Grows|website=WebMD| vauthors = Wendling P |date=13 August 2018|access-date=13 August 2018}}</ref><ref name="FDA ARB Updates" />

In September 2018, the FDA announced that retesting of all valsartan supplies had found a second carcinogenic impurity, [[N-nitrosodiethylamine]] (NDEA), in the recalled products made by ZHP in China and marketed in the US under the [[Torrent Pharmaceuticals]] (India) brand.<ref>{{cite press release |url=https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm620499.htm|website=[[Food and Drug Administration]] (FDA) |title=FDA provides update on its ongoing investigation into valsartan products; and reports on the finding of an additional impurity identified in one firm's already recalled products|date=13 September 2018|access-date=14 September 2018}}</ref>

According to a 2018 [[Reuters]] analysis of national medicines agencies' records, more than 50 companies around the world have recalled valsartan mono-preparations or combination products manufactured from the tainted valsartan ingredient. The contamination has likely been present since 2012 when the manufacturing process was changed and approved by [[European Directorate for the Quality of Medicines|EDQM]] and FDA authorities. Based on inspections in late 2018, both agencies have suspended the Chinese and Indian manufacturers' certificates of suitability for the supply of valsartan in the EU and the US.<ref>{{cite news | vauthors = Harney A, Hirschler B | title=Toxin at heart of drug recall shows holes in medical safety net | website=Reuters | date=22 August 2018 | url=https://www.reuters.com/article/us-health-pharmaceuticals-china-insight-idUSKCN1L71D8 | access-date=23 November 2018 }}</ref>

In 2019, many more preparations of valsartan and its combinations were recalled due to the presence of the contaminant NDMA.<ref>{{cite journal | vauthors = Abdin AY, Yeboah P, Jacob C | title = Chemical Impurities: An Epistemological Riddle with Serious Side Effects | journal = International Journal of Environmental Research and Public Health | volume = 17 | issue = 3 | pages = 1030 | date = February 2020 | pmid = 32041209 | pmc = 7038150 | doi = 10.3390/ijerph17031030 | doi-access = free }}</ref><ref>{{cite web | title=ARB Recalls: Valsartan, Losartan and Irbesartan | website=U.S. [[Food and Drug Administration]] (FDA) | date=3 February 2020 | url=http://www.fda.gov/drugs/drug-safety-and-availability/recalls-angiotensin-ii-receptor-blockers-arbs-including-valsartan-losartan-and-irbesartan | access-date=12 February 2020}}</ref>

In August 2020, the [[European Medicines Agency]] (EMA) provided guidance to marketing authorization holders on how to avoid the presence of nitrosamine impurities in human medicines and asked them to review all chemical and biological human medicines for the possible presence of nitrosamines and to test the products at risk.<ref name="EMA Nitrosamine impurities">{{cite web | title=Nitrosamine impurities | website=European Medicines Agency | date=23 October 2019 | url=https://www.ema.europa.eu/en/human-regulatory/post-authorisation/referral-procedures/nitrosamine-impurities | access-date=6 August 2020}} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref>

===Shortages===

Since July 2018, numerous recalls of [[losartan]], valsartan and [[irbesartan]] drug products have caused marked shortages of these life saving medications in North America and Europe, particularly for valsartan. In March 2019, the FDA approved an additional generic version of Diovan™ to address the issue.<ref>{{cite web | last=Clanton | first=Nancy | title=FDA OKs generic blood pressure drug in wake of recalls | website=ajc | date=21 March 2019 | url=https://www.ajc.com/lifestyles/health/fda-approves-generic-blood-pressure-drug-alleviate-shortages-caused-numerous-recalls/VWLrNx4u7vOGaKNFlvvZlO/ | access-date=13 July 2020}}</ref> According to the agency, the shortage of valsartan was resolved in April 2020,<ref>[https://www.accessdata.fda.gov/scripts/drugshortages/dsp_ActiveIngredientDetails.cfm?AI=Valsartan+Tablets&st=r&tab=tabs-3&i=4&panel=4# Current and Resolved Drug Shortages and Discontinuations Reported to FDA] U.S. [[Food and Drug Administration]] (FDA). Retrieved 13 July 2020.</ref> but the availability of the generic form remained unstable into July 2020. Pharmacies in the European Union were notified that the supply of the drug, particularly for higher dosage forms, would remain unstable well into December 2020.<ref>[https://www.gelbe-liste.de/lieferengpaesse/lieferengpass-valsartan-ct-160mg Lieferengpass Valsartan-CT 160mg ]. ''Gelbe Liste'' (in German). ''Pharmindex''. Retrieved 13 July 2020.</ref>

==Research==

{{see also|Discovery and development of angiotensin receptor blockers}}

In people with impaired glucose tolerance, valsartan may decrease the incidence of developing [[diabetes mellitus type 2]]. However, the absolute risk reduction is small (less than 1&nbsp;percent per year) and diet, exercise or other drugs, may be more protective. In the same study, no reduction in the rate of cardiovascular events (including death) was shown.<ref>{{cite journal | vauthors = McMurray JJ, Holman RR, Haffner SM, Bethel MA, Holzhauer B, Hua TA, Belenkov Y, Boolell M, Buse JB, Buckley BM, Chacra AR, Chiang FT, Charbonnel B, Chow CC, Davies MJ, Deedwania P, Diem P, Einhorn D, Fonseca V, Fulcher GR, Gaciong Z, Gaztambide S, Giles T, Horton E, Ilkova H, Jenssen T, Kahn SE, Krum H, Laakso M, Leiter LA, Levitt NS, Mareev V, Martinez F, Masson C, Mazzone T, Meaney E, Nesto R, Pan C, Prager R, Raptis SA, Rutten GE, Sandstroem H, Schaper F, Scheen A, Schmitz O, Sinay I, Soska V, Stender S, Tamás G, Tognoni G, Tuomilehto J, Villamil AS, Vozár J, Califf RM | title = Effect of valsartan on the incidence of diabetes and cardiovascular events | journal = The New England Journal of Medicine | volume = 362 | issue = 16 | pages = 1477–1490 | date = April 2010 | pmid = 20228403 | doi = 10.1056/NEJMoa1001121 | s2cid = 18710004 | doi-access = free | hdl = 2381/21817 | hdl-access = free }}</ref>

In one study of people without diabetes, valsartan reduced the risk of developing diabetes mellitus over [[amlodipine]], mainly for those with hypertension.<ref name="pmid18608200">{{cite journal | vauthors = Kjeldsen SE, McInnes GT, Mancia G, Hua TA, Julius S, Weber MA, Coca A, Girerd X, Jamerson K, Larochelle P, Macdonald T, Schmieder RE, Anthony Schork M, Viskoper R, Widimsky J, Zanchetti A | title = Progressive effects of valsartan compared with amlodipine in prevention of diabetes according to categories of diabetogenic risk in hypertensive patients: the VALUE trial | journal = Blood Pressure | volume = 17 | issue = 3 | pages = 170–177 | date = 2008 | pmid = 18608200 | doi = 10.1080/08037050802169644 | s2cid = 3426921 }}</ref>

A prospective study demonstrated a reduction in the incidence and progression of Alzheimer's disease and dementia.<ref name="pmid20068258">{{cite journal | vauthors = Li NC, Lee A, Whitmer RA, Kivipelto M, Lawler E, Kazis LE, Wolozin B | title = Use of angiotensin receptor blockers and risk of dementia in a predominantly male population: prospective cohort analysis | journal = BMJ | volume = 340 | pages = b5465 | date = January 2010 | pmid = 20068258 | pmc = 2806632 | doi = 10.1136/bmj.b5465 }}</ref>

== References ==

{{reflist}}

{{Angiotensin II receptor antagonists}}

{{Angiotensin receptor modulators}}

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{{Authority control}}

[[Category:Angiotensin II receptor antagonists]]

[[Category:Biphenyls]]

[[Category:Carboxamides]]

[[Category:Carboxylic acids]]

[[Category:Drugs developed by Novartis]]

[[Category:Wikipedia medicine articles ready to translate]]

[[Category:Tetrazoles]]