irbesartan (Avapro)
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Introduction
Tradename: Avapro. Generic 2012[8]
* FDA issues recall(s) due to potential carcinogen N-nitrosodiethylamine (NDEA)[9]
Indications
- treatment of hypertension, especially those who would benefit from an ACE inhibitor, but have had intolerable side effects
- renal protection in patients with diabetes mellitus[5]
- nondiabetic proteinuric nephropathy
- chronic heart failure
Contraindications
- pregnancy, trimesters 2 & 3, probably 1 as well
- angioedema with ACE inhibitor
- primary hyperaldosteronism
- bilateral renal artery stenosis
- biliary cirrhosis or biliary obstruction
Dosage
- usual dose is 150 mg PO QD
- 75 mg PO QD in volume or salt-depleted patients
- max dose 300 mg QD; no benefit to larger doses
- effect may be enhanced in combination with diuretic
Tabs: 150, 300 mg
Pharmacokinetics
- oral bioavailability is 60-80%
- 90% is bound to plasma proteins
- oxidized by cyt P450 2C9
- elimination 1/2life is 11-15 hours
- 20% of the drug is recovered in the urine
- no dose adjustment for renal or hepatic insufficiency is necessary
- volume of distribution 53-93 L
Adverse effects
- similar to placebo[6]
- fewer adverse effects than ACE inhibitors
- cardiovascular
- central nervous system
- gastrointestinal
- hematologic: anemia, neutropenia
- musculoskeletal
- renal: polyuria, increased serum creatinine
- respiratory
- rash
- increased liver function tests
- decreased libido
- serum K+ increases of > 20% in 4% of patients[6]
- SciGen Pharmaceuticals has voluntary recalled ~1% of irbesartan, due presence of N-nitrosodiethylamine (NDEA), a probable human carcinogen Oct 2018[9]
- 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
Drug interactions
- any drug which inhibits cyt P450 2C9 can increase irbesartan levels: cimetidine
- any drug which induces cyt P450 2C9 can diminish irbesartan levels: phenobarbital, ketoconazole
- use caution with concurrent administration of K+ or K+-sparing diuretics
- drug interaction(s) of calcineurin inhibitors with ARBs
- drug interaction(s) of calcium channel blockers with ARBs
- drug interaction(s) of renin-angiotensin-aldosterone inhibitors with trimethoprim-sulfamethoxazole
- drug interaction(s) of ARB with trimethoprim
- 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 NSAIDs, diuretics & angiotensin II receptor antagonists
- drug interaction(s) of NSAIDs & antihypertensives
Mechanism of action
- angiotensin II receptor antagonist
- reduces progression of albuminuria in patients with diabetes mellitus type 2[4]
More general terms
Additional terms
Component of
References
- ↑ The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
- ↑ Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998 - not on National VA formulary
- ↑ Prescriber's Letter 13(3): 2006 Cytochrome P450 drug interactions Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=220233&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 4.0 4.1 Journal Watch 21(20):163, 2001 Parving H et al, NEJM 345:870, 2001
- ↑ 5.0 5.1 Prescriber's Letter 9(11):61 2002
- ↑ 6.0 6.1 6.2 Geriatric Dosage Handbook, 6th edition, Selma et al eds, Lexi-Comp, Cleveland, 2001
- ↑ The ACTIVE I Investigators. Irbesartan in patients with atrial fibrillation. N Engl J Med 2011 Mar 10; 364:928. PMID: https://www.ncbi.nlm.nih.gov/pubmed/21388310
- ↑ 8.0 8.1 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 9.3 Brooks M FDA Issues Alert on Irbesartan Due to Contamination. Medscape - Nov 01, 2018. https://www.medscape.com/viewarticle/904270
FDA Safety Alert. Jan 3, 2019 FDA updates on angiotensin II receptor blocker (ARB) recalls including valsartan, losartan and irbesartan. https://www.fda.gov/drugs/drugsafety/ucm613916.htm