Candesartan

From Anvita Health Wiki

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

Introduction

• Tradname: Atacand. (candesartan cilexetil) Generic Dec 2012 [8]

Indications

• an ACE inhibitor is indicated, but not tolerated

• heart failure (see CHARM trials)
• diabetes mellitus*
• stroke prevention [2]
• migraine prophylaxis [4]

• * Only irbesartan ( Avapro) & losartan ( Cozaar) shown to have beneficial effects [3]; candesartan probably does as well

Contraindications

• pregnancy, trimesters 2 & 3, probably 1 as well
• angioedema with ACE inhibitor

Dosage

• start: 16 mg QD when used as monotherapy
• CHF: start 4-8 mg QD; max 32 mg QD
  

• Tabs: 4, 8, 16, 32 mg.
  
• Addition of 12.5 mg of HCTZ may improve BP response.

Dosage-adjustment-in-renal-failure

• No dose adjustment is required for elderly or patients with mild renal insufficiency or hepatic insufficiency

Pharmacokinetics

• bioavailability 15%, enhanced by foot
• onset of action 2-3 hours
• peak effect 6-8 hours
• 1/life 9 hours (dose-dependent)
• volume of distribution 0.13 L/kg
• protein binding 99%
• clearance 60% renal, 36% biliary

Adverse-effects

• cardiovascular: flushing, chest pain, peripheral edema, tachycardia, palpitations
• no increased risk of myocardial infarction in high-risk patients [5]
• CNS: dizziness, lightheadedness, drowsiness, fatigue, headache, vertigo, anxiety, depression, somnolence, fever
• dermatologic: rash, angioedema (occurs within 30 minutes-30 days of 1st dose)
• metabolic: hyperglycemia, hypertriglyceridemia, hyperuricemia small increases in serum K+ as with ACE inhibitors
• gastrointestinal: nausea, vomiting, diarrhea, dyspepsia, gastroenteritis
• musculoskeletal: back pain, arthralgia, increased CPK, myalgia weakness
• neurologic: paresthesia
• renal: hematuria
• respiratory: upper respiratory tract infection, pharyngitis, rhinitis, bronchitis, cough, sinusitis, epistaxis, dyspnea
• diaphoresis [6]
  
• drug adverse effects of angiotensin II receptor antagonists

Mechanism-of-action

• angiotensin II receptor antagonist
• BP reduction of 8-12/4-8 mm of Hg with 8-32 mg QD
• limited effectiveness for diabetic retinopathy [7]

• diabetes type 1:

• modest reduction in the incidence of retinopathy
• was no effect on progression of retinopathy.

• diabetes type 2

• may risk for progression of retinopathy
• may facilitate regression of early retinopathy

More General Terms

• angiotensin II receptor antagonist (ARB)

Additional Terms

• CHARM program (clinical trials)

Internet Database

PubChem: 2541
PubChem: 2540

References

1. Internal Medicine Alert 20(21):165 1998
2. Journal Watch 23(4):34, 2003 Tronvik E et al, JAMA 289:65, 2003
3. Prescriber's Letter 9(11):61 2002
4. Journal Watch 23(21):165, 2003
5. Demers C, McMurray JJ, Swedberg K, Pfeffer MA, Granger CB, Olofsson B, McKelvie RS, Ostergren J, Michelson EL, Johansson PA, Wang D, Yusuf S; CHARM Investigators. Impact of candesartan on nonfatal myocardial infarction and cardiovascular death in patients with heart failure. JAMA. 2005 Oct 12;294(14):1794-8. PMID: [1]
6. Geriatric Dosage Handbook, 6th edition, Selma et al eds, Lexi-Comp, Cleveland, 2001
7. Chaturvedi N et al, Effect of candesartan on prevention (DIRECT-Prevent 1) and progression (DIRECT-Protect 1) of retinopathy in type 1 diabetes: randomised, placebo-controlled trials Lancet. 2008 Oct 18;372(9647):1394-402. Epub 2008 Sep 25. PMID: &dopt=Abstract
   - Sjolie AK et al, Effect of candesartan on progression and regression of retinopathy in type 2 diabetes (DIRECT-Protect 2): a randomised placebo-controlled trial Lancet. 2008 Oct 18;372(9647):1361-3. PMID: [2]
8. Prescriber's Letter 19(4): 2012 CHART: Anticipated Availability of First-Time Generics Detail-Document#: [3] (subscription needed) [4]

candesartan (Atacand)