Valsartan

From Anvita Health Wiki

Contents 1 Introduction 2 Indications 3 Contraindications 4 Dosage 5 Pharmacokinetics 6 Monitor 7 Adverse-effects 8 Drug-interactions 9 Mechanism-of-action 10 Clinical-trials 11 More General Terms 12 Additional Terms 13 Internet Database 14 References

Introduction

• Tradname: Diovan. Generic Sept 2012 [9]

Indications

• heart failure
• hypertension
• post- myocardial infarction [5]

Contraindications

• pregnancy, trimesters 2 & 3, probably 1 as well
• angioedema with ACE inhibitor
• primary hyperaldosteronism
• bilateral renal artery stenosis
• biliary cirrhosis or biliary obstruction
  

• pregnancy category = d
• safety in lactation = ?

Dosage

• start 40 mg BID or 80 mg QD
• titrate* to 160 mg BID as tolerated
• CHF: start 20-40 mg BID; max 160 mg BID

• * antihypertensive effect enhanced by concurrent use of diuretic
• Tabs: 80, 160 mg.
• No dosage adjustment needed for creatinine clearance > 10 mL/min
• Use <= 80 mg/day if hepatic impairment

Pharmacokinetics

• food delays & inhibits absorption up to 50%
• bioavailability 23%
• volume of distribution 17 L
• peak serum levels reached 2 hours after oral dose
• maximal effect observed 4-6 hours after oral dose
• protein binding 94-97%
• metabolized to an inactive metabolite {minor}
• elimination 1/2 life 6 hours
• 83% excreted unchanged in feces
• 13% excreted unchange in urine
• antihypertensive effects observed in 1-2 weeks
• maximal effects observed in 4-6 weeks
  

• elimination via liver
• elimination via kidney

Monitor

• baseline & periodic electrolytes, urinalysis, renal function, liver function
  
• monitor with ARBs

Adverse-effects

• similar to placebo [4]
• fewer adverse effects than ACE inhibitors
• cardiovascular

• edema, chest pain, tachycardia

• central nervous system

• headache, dizziness, drowsiness, ataxia, insomnia, fatigue, anxiety, nervousness

• gastrointestinal

• diarrhea, abdominal pain, nausea, abnormal taste, dyspepsia, heartburn

• hematologic: anemia, neutropenia
• musculoskeletal

• arthralgia, muscle cramps, myalgia

• renal: polyuria, increased serum creatinine
• respiratory

• cough (2.6%), upper respiratory tract infection, rhinitis, sinusitis, nasal congestion, pharyngitis

• rash
• increased liver function tests
• decreased libido
• serum K+ increases of > 20% in 4% of patients [4]

• Toxicity:

• hypotension, tachycardia, bradycardia from vagal response
• treatment is supportive
  
• drug adverse effects of angiotensin II receptor antagonists

Drug-interactions

• increased mortality when used with ACE inhibitor & beta- blocker in patients with heart failure [3]
• increased effect when used with cimetidine
• decreased effect when used with phenobarbital, ketoconazole, troleandomycin
• use caution with concurrent administration of K+ or K+-sparing diuretics
  
• drug interaction(s) of renin-angiotensin inhibitors with trimethoprim-sulfamethoxazole
• drug interaction(s) of angiotensin II receptor antagonists with aliskiren
• drug interaction(s) of ACE inhibitors with angiotensin II receptor antagonists
• drug interaction(s) of diuretics with angiotensin II receptor antagonists
• drug interaction(s) of NSAIDs with ARBs
• drug interaction(s) of ACE inhibitors, angiotensin II receptor antagonists & beta-blockers
• drug interaction(s) of NSAIDs, diuretics & angiotensin II receptor antagonists

Mechanism-of-action

• angiotensin II receptor antagonist

• directly inhibits AT2 receptors
• displaces angiotensin II from AT1 receptors
• antagonizes AT1-induced:

• vasoconstriction
• aldosterone release
• catecholamine release
• arginine vasopressin release
• water intake
• hypertrophic responses

• more efficient antagonism of cardiovascular effects of angiotensin II than ACE inhibitors
• improves survival after myocardial infarction [5]
• valsartan clears beta-amyloid & improves spatial learning in a mouse model for Alzheimer's disease [7], (not a general feature of ARBs)

Clinical-trials

• Navigator study:

• valsartan modestly lowers the incidence of diabetes (14%), but not cardiovascular events

More General Terms

• angiotensin II receptor antagonist (ARB)

Additional Terms

• VALUE trial

Internet Database

PubChem: 60846
PubChem: 5284633
PubChem: 5650

References

1. The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
2. Prescriber's Letter 8(1):2 2001
3. Journal Watch 22(1):2, 2002 Cohn et al N Engl J Med 345:1667, 2001
4. Geriatric Dosage Handbook, 6th edition, Selma et al eds, Lexi-Comp, Cleveland, 2001
5. Prescriber's Letter 10(12):67 2003
6. Department of Veterans Affairs, VA National Formulary
   - non formulary drug request
7. Wang J et al Valsartan lowers brain b-amyloid protein levels and improves spatial learning in a mouse model of Alzheimer disease Journal of ClinicalInvestigation [1] [2] PMID: [3]
8. Califf RM for the NAVIGATOR Study Group Effect of Valsartan on the Incidence of Diabetes and Cardiovascular Events N Engl J Med. 2010 Mar 29. <PubMed> PMID: [4] <Internet> [5]
9. Prescriber's Letter 19(4): 2012 CHART: Anticipated Availability of First-Time Generics Detail-Document#: [6] (subscription needed) [7]

valsartan (Diovan)