Description

Simple

A medication used to lower blood pressure and to improve symptoms of heart failure.

Clinical

An angiotensin-receptor blocker used to manage hypertension alone or in combination with other antihypertensive agents and to manage heart failure in patients who are intolerant to ACE inhibitors.

Overview

Valsartan belongs to the angiotensin II receptor blocker (ARB) family of drugs, which also includes [telmisartan], [candesartan], [losartan], [olmesartan], and [irbesartan]. ARBs selectively bind to angiotensin receptor 1 (AT1) and prevent the protein angiotensin II from binding and exerting its hypertensive effects, which include vasoconstriction, stimulation and synthesis of aldosterone and ADH, cardiac stimulation, and renal reabsorption of sodium, among others. Overall, valsartan's physiologic effects lead to reduced blood pressure, lower aldosterone levels, reduced cardiac activity, and increased excretion of sodium.

Valsartan also affects the renin-angiotensin aldosterone system (RAAS), which plays an important role in hemostasis and regulation of kidney, vascular, and cardiac functions. Pharmacological blockade of RAAS via AT1 receptor blockade inhibits negative regulatory feedback within RAAS, which is a contributing factor to the pathogenesis and progression of cardiovascular disease, heart failure, and renal disease. In particular, heart failure is associated with chronic activation of RAAS, leading to inappropriate fluid retention, vasoconstriction, and ultimately a further decline in left ventricular function. ARBs have been shown to have a protective effect on the heart by improving cardiac function, reducing afterload, increasing cardiac output and preventing ventricular hypertrophy and remodelling.[Read more

Pharmacology

Indication

Valsartan is indicated for the treatment of hypertension to reduce the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. It is also indicated for the treatment of heart failure (NYHA class II-IV) and for left ventricular dysfunction or failure after myoc... Read more

Pharmacodynamic

Valsartan inhibits the pressor effects of angiotensin II with oral doses of 80 mg inhibiting the pressor effect by about 80% at peak with approximately 30% inhibition persisting for 24 hours. Removal of the negative feedback of angiotensin II causes a 2- to 3-fold rise in plasma renin and consequent... Read more

Mechanism of action

Valsartan belongs to the angiotensin II receptor blocker (ARB) family of drugs, which selectively bind to angiotensin receptor 1 (AT1) and prevent angiotensin II from binding and exerting its hypertensive effects. These include vasoconstriction, stimulation and synthesis of aldosterone and ADH, card... Read more

Absorption

After one oral dose, the antihypertensive activity of valsartan begins within approximately 2 hours and peaks within 4-6 hours in most patients.[F3139] Food decreases the exposure to orally administered valsartan by approximately 40% and peak plasma concentration by approximately 50%. AUC and Cmax v... Read more

Protein binding

Valsartan is highly bound to serum proteins (95%), mainly serum albumin.[F4607]

Volume of distribution

The steady state volume of distribution of valsartan after intravenous administration is small (17 L), indicating that valsartan does not distribute into tissues extensively.[F3139,F3607]

Clearance

Following intravenous administration, plasma clearance of valsartan is approximately 2 L/hour and its renal clearance is 0.62 L/hour (about 30% of total clearance).[F4607]

Half life

After intravenous (IV) administration, valsartan demonstrates bi-exponential decay kinetics, with an average elimination half-life of about 6 hours.[F4607]

Route of elimination

Valsartan, when administered as an oral solution, is primarily recovered in feces (about 83% of dose) and urine (about 13% of dose). The recovery is mainly as unchanged drug, with only about 20% of dose recovered as metabolites.[F4607]

Toxicity

Approximate LD50 >2000 mg/kg (Gavage, rat) [F3139]

**Reproductive Toxicology Studies**

No teratogenic effects were seen when valsartan was given to pregnant mice and rats at oral doses up to 600 mg/kg/day and to pregnant rabbits at oral doses reaching up to 10 mg/kg/day. Despite this, marked d... Read more

Adverse Effects

Contraindications

  • Regions: Canada
  • Patient Conditions:
      • Name: Diabetes Mellitus (DM)
      • Drugbank Id: DBCOND0063084
      • Name: Impaired Renal Function
      • Drugbank Id: DBCOND0038927
  • With Drugs Coadmin:
      • Name: Aliskiren
      • Drugbank Id: DB09026
  • Regions: Canada
  • Patient Conditions:
      • Name: Lactation
      • Drugbank Id: DBCOND0032213
  • Regions: Canada
  • Patient Conditions:
      • Name: Pregnancy
      • Drugbank Id: DBCOND0018394
  • Hypersensitivity:
    • true
  • Regions: US
  • Regions: US
  • Patient Conditions:
      • Name: Diabetes
      • Drugbank Id: DBCOND0022048
  • With Drugs:
      • Name: Aliskiren
      • Drugbank Id: DB09026

Food Interactions

  • Take with or without food. Co-administration with food slightly alters pharmacokinetics, but not to a clinically significant extent.

Interactions

Type in a drug name to check for interaction with Valsartan
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  • Paracetamol(acetaminophen)
  • Paxil(paroxetine)
  • Pamelor(nortriptyline)
  • Panadol(acetaminophen)
  • Patanol(olopatadine ophthalmic)
  • Pataday(olopatadine ophthalmic)
  • Parnate(tranylcypromine)
  • Pazeo(olopatadine ophthalmic)
(R)-warfarin
The metabolism of (R)-warfarin can be decreased when combined with Valsartan.
(S)-Warfarin
The metabolism of (S)-Warfarin can be decreased when combined with Valsartan.
1-benzylimidazole
1-benzylimidazole may decrease the antihypertensive activities of Valsartan.
2,5-Dimethoxy-4-ethylamphetamine
2,5-Dimethoxy-4-ethylamphetamine may decrease the antihypertensive activities of Valsartan.
2,5-Dimethoxy-4-ethylthioamphetamine
2,5-Dimethoxy-4-ethylthioamphetamine may decrease the antihypertensive activities of Valsartan.
4-Bromo-2,5-dimethoxyamphetamine
4-Bromo-2,5-dimethoxyamphetamine may decrease the antihypertensive activities of Valsartan.
4-Methoxyamphetamine
4-Methoxyamphetamine may decrease the antihypertensive activities of Valsartan.
5-methoxy-N,N-dimethyltryptamine
5-methoxy-N,N-dimethyltryptamine may decrease the antihypertensive activities of Valsartan.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline may increase the hypotensive activities of Valsartan.
Abatacept
The metabolism of Valsartan can be increased when combined with Abatacept.
Abediterol
Abediterol may decrease the antihypertensive activities of Valsartan.
Abiraterone
The metabolism of Valsartan can be decreased when combined with Abiraterone.
Acebutolol
The risk or severity of hyperkalemia can be increased when Valsartan is combined with Acebutolol.
Aceclofenac
The risk or severity of renal failure, hyperkalemia, and hypertension can be increased when Valsartan is combined with Aceclofenac.
Acemetacin
The risk or severity of renal failure, hyperkalemia, and hypertension can be increased when Valsartan is combined with Acemetacin.
Acenocoumarol
The metabolism of Acenocoumarol can be decreased when combined with Valsartan.
Acepromazine
Acepromazine may decrease the antihypertensive activities of Valsartan.
Acetohexamide
The metabolism of Acetohexamide can be decreased when combined with Valsartan.
Acetyl sulfisoxazole
The metabolism of Valsartan can be decreased when combined with Acetyl sulfisoxazole.
Acetylcysteine
The excretion of Valsartan can be decreased when combined with Acetylcysteine.
23 References
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  2. 2 . Fogari R, Zoppi A: A drug safety evaluation of valsartan. Expert Opin Drug Saf. 2011 Mar;10(2):295-303. doi: 10.1517/14740338.2011.543416. Epub 2010 Dec 11.PubMed: 21142805
  3. 3 . McInnes GT: Clinical advantage of valsartan. Cardiology. 1999;91 Suppl 1:14-8. doi: 10.1159/000047283.PubMed: 10449890
  4. 4 . Chiolero A, Burnier M: Pharmacology of valsartan, an angiotensin II receptor antagonist. Expert Opin Investig Drugs. 1998 Nov;7(11):1915-25. doi: 10.1517/13543784.7.11.1915 .PubMed: 15991938
  5. 5 . Akazawa H, Yabumoto C, Yano M, Kudo-Sakamoto Y, Komuro I: ARB and cardioprotection. Cardiovasc Drugs Ther. 2013 Apr;27(2):155-60. doi: 10.1007/s10557-012-6392-2.PubMed: 22538956
  6. 6 . Zhou G, Cheung AK, Liu X, Huang Y: Valsartan slows the progression of diabetic nephropathy in db/db mice via a reduction in podocyte injury, and renal oxidative stress and inflammation. Clin Sci (Lond). 2014 May;126(10):707-20. doi: 10.1042/CS20130223.PubMed: 24195695
  7. 7 . Suzuki K, Souda S, Ikarashi T, Kaneko S, Nakagawa O, Aizawa Y: Renoprotective effects of low-dose valsartan in type 2 diabetic patients with diabetic nephropathy. Diabetes Res Clin Pract. 2002 Sep;57(3):179-83.PubMed: 12126767
  8. 8 . Currie G, Bethel MA, Holzhauer B, Haffner SM, Holman RR, McMurray JJV: Effect of valsartan on kidney outcomes in people with impaired glucose tolerance. Diabetes Obes Metab. 2017 Jun;19(6):791-799. doi: 10.1111/dom.12877. Epub 2017 Mar 17.PubMed: 28093841
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  11. 11 . Lee VC, Rhew DC, Dylan M, Badamgarav E, Braunstein GD, Weingarten SR: Meta-analysis: angiotensin-receptor blockers in chronic heart failure and high-risk acute myocardial infarction. Ann Intern Med. 2004 Nov 2;141(9):693-704. doi: 10.7326/0003-4819-141-9-200411020-00011.PubMed: 15520426
  12. 12 . Brenner BM, Cooper ME, de Zeeuw D, Keane WF, Mitch WE, Parving HH, Remuzzi G, Snapinn SM, Zhang Z, Shahinfar S: Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med. 2001 Sep 20;345(12):861-9. doi: 10.1056/NEJMoa011161.PubMed: 11565518
  13. 13 . Yusuf S, Teo KK, Pogue J, Dyal L, Copland I, Schumacher H, Dagenais G, Sleight P, Anderson C: Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med. 2008 Apr 10;358(15):1547-59. doi: 10.1056/NEJMoa0801317. Epub 2008 Mar 31.PubMed: 18378520
  14. 14 . Pfeffer MA, McMurray JJ, Velazquez EJ, Rouleau JL, Kober L, Maggioni AP, Solomon SD, Swedberg K, Van de Werf F, White H, Leimberger JD, Henis M, Edwards S, Zelenkofske S, Sellers MA, Califf RM: Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both. N Engl J Med. 2003 Nov 13;349(20):1893-906. doi: 10.1056/NEJMoa032292. Epub 2003 Nov 10.PubMed: 14610160
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  16. 16 . Nakashima A, Kawashita H, Masuda N, Saxer C, Niina M, Nagae Y, Iwasaki K: Identification of cytochrome P450 forms involved in the 4-hydroxylation of valsartan, a potent and specific angiotensin II receptor antagonist, in human liver microsomes. Xenobiotica. 2005 Jun;35(6):589-602.PubMed: 16192110
  17. 17 . Bader, M. (2004). Renin-angiotensin-aldosterone system. In Encyclopedic reference of molecular pharmacology (pp. 810-814). Berlin: Springer.
  18. 18 . FDA Approved Drug Products: Diovan (valsartan) oral tablets Link
  19. 19 . NZ Data Sheet, Valsartan and sacubitril File
  20. 20 . Valsartan and Sacubitril FDA label File
  21. 21 . Valsartan and Amlodipine FDA label File
  22. 22 . Valsartan and Nevibolol FDA label File
  23. 23 . Health Canada Monograph - Valsartan File