candesartan (Atacand)
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Introduction
Tradname: Atacand. (candesartan cilexetil) Generic Dec 2012[8]
Indications
- an ACE inhibitor is indicated, but not tolerated
- hypertension
- heart failure (see CHARM trials)
- diabetes mellitus*
- nondiabetic proteinuric nephropathy[8]
- stroke prevention[2]
- migraine prophylaxis[4]
- may improve executive function# after 1 year in elderly independent of antihypertensive effect[9]
* Only irbesartan (Avapro) & losartan (Cozaar) shown to have beneficial effects[3]; candesartan probably does as well
# measured by Trail Making Test Part B[9]
Contraindications
- pregnancy, trimesters 2 & 3, probably 1 as well
- angioedema with ACE inhibitor
Dosage
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
- drug adverse effects of renin-angiotensin-aldosterone system inhibitors (RAAS inhibitors)
- drug adverse effects of antihypertensive agents
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
- diabetes type 1:
More general terms
Additional terms
Component of
References
- ↑ Internal Medicine Alert 20(21):165 1998
- ↑ 2.0 2.1 Journal Watch 23(4):34, 2003 Tronvik E et al, JAMA 289:65, 2003
- ↑ 3.0 3.1 Prescriber's Letter 9(11):61 2002
- ↑ 4.0 4.1 Journal Watch 23(21):165, 2003
- ↑ 5.0 5.1 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: https://www.ncbi.nlm.nih.gov/pubmed/16219883
- ↑ 6.0 6.1 Geriatric Dosage Handbook, 6th edition, Selma et al eds, Lexi-Comp, Cleveland, 2001
- ↑ 7.0 7.1 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: https://www.ncbi.nlm.nih.gov/pubmed/18823656
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: https://www.ncbi.nlm.nih.gov/pubmed/18823658 - ↑ 8.0 8.1 8.2 Prescriber's Letter 19(4): 2012 CHART: Anticipated Availability of First-Time Generics Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=280401&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 9.0 9.1 9.2 Lou N ARB Slows Cognitive Decline in Trial... But How? - Consequence of lowered blood pressure, or perhaps a direct effect -- or just a fluke Mhttps://www.medpagetoday.com/neurology/dementia/87929
Hajjar I, Okafor M, McDaniel D et al ffects of Candesartan vs Lisinopril on Neurocognitive Function in Older Adults With Executive Mild Cognitive Impairment. A Randomized Clinical Trial. JAMA Netw Open. 2020;3(8):e2012252. August 6. PMID: https://www.ncbi.nlm.nih.gov/pubmed/32761160 Free article https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2769104