Losartan

From Anvita Health Wiki

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

Introduction

• Tradename: Cozaar. ( FDA-approved generic available)

Indications

• hypertension
• stroke prevention* [4,5,7]
• renal protection in patients with diabetes mellitus [6]

Contraindications

• pregnancy, trimesters 2 & 3, probably 1 as well
• angioedema with ACE inhibitor
• renal artery stenosis ? [3]

• * more effective than atenolol for similar reductions in blood pressure
  
• pregnancy category = d
• safety in lactation = ?

Dosage

• start 50 mg PO QD; max 100 mg/day
• CHF: 25-50 mg QD; max 50-100 mg/day
• 150 mg QD may be more effective than 50 mg QD at a cost of increased risk of adverse effects [8]

• Tabs: 25, 50 mg.

Pharmacokinetics

• well absorbed from GI tract
• time to peak concentration 1 hour; 3 hours for active metabolite
• plasma protein-binding 99%
• volume of distribution 34 L; active metabolite 12 L
• metabolized by cyt P450 2C9 & 3A4 to active metabolite

• significant 1st pass metabolism

• elimination 1/2 life 2 hours

• active metabolite 1/2life is 6-9 hours
  

• elimination via liver
• elimination via kidney
• 1/2life = 2 hours
• protein binding = 99 %
• elimination by hemodialysis = -

Adverse-effects

• well tolerated, adverse effects similar to placebo [3], 1-3%
• no effect in clinical trials on electrolytes, uric acid, triglycerides, glucose, cholesterol

• clinically minor effects on creatinine & BUN may be seen [3]

• hyperkalemia, hypotension, & renal impairment (dose-dependent)
• cardiovascular:

• flushing
• report of increased risk of heart failure with high dose losartan not confirmed [8,11]

• CNS: anxiety, ataxia, dizziness, insomnia, confusion, depression, memory impairment, nervousness, somnolence, vertigo, abnormal dreams, panic disorder
• dermatologic: rash, urticaria, pruritis, dermatitis, alopecia, erythema, photosensitivity, xerosis, angioedema (30 minutes-30 days of 1st dose)
• gastrointestinal: diarrhea, constipation, dyspepsia, anorexia, vomiting, flatulence, xerostomia, gastritis, dysgeusia
• genitourinary: nocturia, polyuria, impotence
• hematologic: anemia, hemolysis
• musculoskeletal: joint edema, muscle cramps, arthralgia, muscle weakness, arthritis, back pain, leg pain, myalgia
• neurologic: tremors, paresthesia, peripheral neuropathy
• ocular: burning eyes, blurred vision, conjunctivitis, decreased visual acuity
• otic: tinnitus
• respiratory: nasal congestion, cough, sinusitis, dyspnea, bronchitis, epistaxis, upper respiratory tract infection, rhinitis, lower airway congestion
• dental pain [3]
  
• drug adverse effects of angiotensin II receptor antagonists

Drug-interactions

• any drug which inhibits CYP2C9 or CYP3A4 can increase losartan levels
• any drug which induces CYP2C9 or CYP3A4 can diminish losartan levels
  
• 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
• may slow progression of atherosclerosis [4]
• slows progression of albuminuria in patients with diabetes mellitus[6]

More General Terms

• angiotensin II receptor antagonist (ARB)

Additional Terms

• ELITE II Study
• hydrochlorothiazide/losartan; HCTZ/losartan (Hyzaar)

Internet Database

PubChem: 3961
PubChem: 60771

References

1. The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
2. Prescriber's Letter 13(3): 2006 Cytochrome P450 drug interactions Detail-Document#: [1] (subscription needed) [2]
3. Geriatric Dosage Handbook, 6th edition, Selma et al eds, Lexi-Comp, Cleveland, 2001
4. Prescriber's Letter 9(4):19 2002
5. Journal Watch 22(10):76, 2002 Dahlof B et al, Lancet 359:995, 2002 Lindholm LH et al, Lancet 359:1004, 2002
6. Prescriber's Letter 9(11):61 2002
7. Prescriber's Letter 10(5):29 2003
8. Konstam MA et al Effects of high-dose versus low-dose losartan on clinical outcomes in patients with heart failure (HEAAL study): a randomised, double-blind trial The Lancet, Early Online Publication, 17 November 2009 PMID: [3] doi:10.1016/S0140-6736(09)61913-9 [4]
   - Krum H. Optimising management of chronic heart failure. Lancet 2009 Nov 17 [5]
9. FDA News Release April 7, 2010 FDA Approves First Generic Versions of Two Drugs for the Treatment of Hypertension [6]
10. Department of Veterans Affairs, VA National Formulary
    - restricted to patients who fail ACE inhibitor
11. Svanstrom H et al Association of Treatment With Losartan vs Candesartan and Mortality Among Patients With Heart Failure Association of Treatment With Losartan vs Candesartan and Mortality Among Patients With Heart Failure JAMA. 2012;307(14):1506-1512 <PubMed> PMID: [7] <Internet> [8]

losartan (Cozaar)