naproxen (Naprosyn, Aleve Anaprox)
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Introduction
Tradename: Naprosyn, Aleve. Naproxen sodium. Tradename Anaprox. Delayed release naproxen. Tradename EC-Naprosyn.
Indications
- temporary relief of minor aches & pains
- fever
- inflammation
Contraindications
Dosage
250-500 mg PO BID 275-550 mg PO BID {Anaprox} 375-500 mg PO BID {EC-Naprosyn} Tabs 200, 250, 375, 500 mg. 275, 550 mg {Anaprox} 375, 550 mg {EC-Naprosyn}
Suspension: 125 mg/5 mL.
Pharmacokinetics
- rapid absorption from GI tract
- onset of action: 1 hour
- duration of action: up to 6-12 hours
- > 90% of drug is protein-bound
- metabolized in the liver by cyt P450 2C9
- < 1% of drug is excreted unchanged in the urine
elimination via liver
1/2life = 10-20 hours
protein binding = >99 %
elimination by hemodialysis = -
elimination by peritoneal dialysis = -
Monitor
- liver function tests periodically
Adverse effects
- common (> 10%)
- less common (1-10%)
- uncommon (< 1%)
- congestive heart failure*, hypertension, arrhythmias, epistaxis, confusion, hallucinations, aseptic meningitis, depression, peripheral neuropathy, urticaria, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, gastritis, GI ulceration, cystitis, agranulocytosis, anemia, hemolytic anemia, bone marrow depression, leukopenia, thrombocytopenia, hepatitis, angioedema, allergic rhinitis, toxic amblyopia, blurred vision, conjunctivitis, dry eyes, decreased hearing, polyuria, shortness of breath, polydypsia, tachycardia, hot flashes, drowsiness, insomnia, acute renal failure
- other
- gastritis
- upper GI bleed
- nephrotoxicity especially in patients with pre-existing renal disease
- interstitial nephritis* & minimal change glomerulonephropathy[13]
- triple whammy of NSAID, ACE inhibitor & diuretic with volume depletion decreases glomerular perfusion
- drowsiness
- increased incidence of cardiovascular & cerebrovascular events in the elderly (see ADAPT study)
- hazzard ratio for MI or sudden death 1.14[7]
- naproxen is NSAID with allegedly lowest cardiovascular risk[9][12]
- cardiovascular risk is increased in women (RR=1.22)[11]
- naproxen alone among NSAIDs not associated with increased risk of myocardial infarction[12]
* NSAIDS may increase salt & water retention
- in the setting of compensated heart failure, NSAIDs can lead to decompensated heart failure[14]
* 10 days of NSAID therapy prior to interstitial nephritis[15]
Drug interactions
- corticosteroids in combination
- increase clearance of salicylates
- increase nephrotoxicity
- increase GI toxicity
- NSAIDs decrease anti-hypertensive effects of ACE inhibitors
- triple whammy of NSAID, ACE inhibitor & diuretic with volume depletion decreases glomerular perfusion
- coumadin in combination: prolonged bleeding time
- probenecid may increase naproxen concentration
- magnesium & aluminum hydroxide decrease absorption
- naproxen may increase plasma levels of:
- any drug which inhibits cyt P450 2C9 can increase naproxen levels
- any drug which induces cyt P450 2C9 can diminish naproxen levels
- naproxen interferes with antiplatelet effect of aspirin[10]
- drug interaction(s) of cholinesterase inhibitors with NSAIDs
- drug interaction(s) of lithium carbonate with NSAIDs
- drug interaction(s) of NSAIDs with oral contraceptive
- drug interaction(s) of NSAIDs with SSRIs
- drug interaction(s) of NSAIDs with antidepressants
- drug interaction(s) of aspirin with NSAIDs
- drug interaction(s) of apixaban with NSAIDs
- drug interaction(s) of warfarin with NSAIDs
- drug interaction(s) of NSAIDs with beta blockers
- drug interaction(s) of NSAIDs with ARBs
- drug interaction(s) of NSAIDs with aldosterone antagonis
- drug interaction(s) of NSAIDs with glucocorticoid
- drug interaction(s) of NSAIDs, diuretics & angiotensin II receptor antagonists
- drug interaction(s) of NSAIDs, diuretics & ACE inhibitors
- drug interaction(s) of NSAIDs with ACE inhibitors
- drug interaction(s) of NSAIDs & antihypertensives
- drug interaction(s) of NSAIDs & loop diuretics
- drug interaction(s) of NSAIDs & aspirin
Laboratory
- specimen:
- methods:
Mechanism of action
- propionic acid class NSAID
- analgesic
- anti-pyretic
- anti-inflammatory
- may be most effective NSAID in inhibiting formation of PGE2
- anti-platelet activity greater than ibuprofen & diclofenac[6]
More general terms
Additional terms
- cytochrome P450 2C9; cytochrome P450 BP-1; cytochrome P450 MP-4; S-mephenytoin-4-hydroxylase; limonene 6-monooxygenase; limonene 7-monooxygenase (CYP2C9, CYP2C10)
- prostaglandin E2 (PGE2, dinoprostone, Prepidil, Cervidil)
Component of
- naproxen/pseudoephedrine
- lansoprazole/naproxen (Prevacid PAC)
- naproxen/sumatriptan (Treximet)
- esomeprazole/naproxen (Vimovo)
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
- ↑ Kaiser Permanente Northern California Regional Drug Formulary, 1998
- ↑ Clinical Guide to Laboratory Tests, 3rd ed. Teitz ed., W.B. Saunders, 1995
- ↑ 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
- ↑ 6.0 6.1 Journal Watch 21(18):143-44, 2001
- ↑ 7.0 7.1 Journal Watch 25(7):56, 2005
Graham DJ, Campen D, Hui R, Spence M, Cheetham C, Levy G, Shoor S, Ray WA. Risk of acute myocardial infarction and sudden cardiac death in patients treated with cyclo-oxygenase 2 selective and non-selective non-steroidal anti-inflammatory drugs: nested case-control study. Lancet. 2005 Feb 5;365(9458):475-81. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15705456 - ↑ Prescriber's Letter 17(7): 2010 Recommended Lab Monitoring for Common Medications Liver Function Test Scheduling Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=260704&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 9.0 9.1 Prescriber's Letter 17(8): 2010 Managing NSAID Risks Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=260810&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 10.0 10.1 Anzellotti P et al. Low-dose naproxen interferes with the antiplatelet effects of aspirin in healthy subjects: Recommendations to minimize the functional consequences. Arthritis Rheum 2011 Mar; 63:850. PMID: https://www.ncbi.nlm.nih.gov/pubmed/21360514
- ↑ 11.0 11.1 Bavry AA, Thomas F, Allison M, et al. Nonsteroidal anti-inflammatory drugs and cardiovascular outcomes in women: results from the Women's Health Initiative. Circ Cardiovasc Qual Outcomes. 2014;7:603-610 PMID: https://www.ncbi.nlm.nih.gov/pubmed/25006185
- ↑ 12.0 12.1 12.2 Dubreuil M, Louie-Gao Q, Peloquin CE, Choi HK, Zhang Y, Neogi T. Risk of myocardial infarction with use of selected non-steroidal anti-inflammatory drugs in patients with spondyloarthritis and osteoarthritis. Ann Rheum Dis 2018 Aug; 77:1137 PMID: https://www.ncbi.nlm.nih.gov/pubmed/29674321 https://ard.bmj.com/content/77/8/1137
- ↑ 13.0 13.1 Baccouche K, Alaya Z, Azzabi A et al Minimal-change disease and interstitial nephritis secondary to non-steroidal anti-inflammatory drugs (naproxen). Therapie. 2016 Oct;71(5):515-517. PMID: https://www.ncbi.nlm.nih.gov/pubmed/27203163
- ↑ 14.0 14.1 Geriatric Review Syllabus, 11th edition (GRS11) Harper GM, Lyons WL, Potter JF (eds) American Geriatrics Society, 2022
- ↑ 15.0 15.1 NEJM Knowledge+