Naproxen

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Contents 1 Introduction 2 Indications 3 Dosage 4 Pharmacokinetics 5 Monitor 6 Adverse-effects 7 Drug-interactions 8 Laboratory 9 Mechanism-of-action 10 More General Terms 11 Additional Terms 12 Internet Database 13 References

Introduction

• Tradename: Naprosyn, Aleve. Naproxen sodium. Tradename Anaprox. Delayed release naproxen. Tradename EC-Naprosyn.

Indications

• temporary relief of minor aches & pains
• fever
• inflammation

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
  
• monitor with non steroidal anti-inflammatory agents (NSIADs)

Adverse-effects

• common (> 10%)

• rash, dizziness, abdominal cramps, heartburn, indigestion, nausea

• less common (1-10%)

• itching, tinnitus, fluid retention, headache, nervousness, vomiting

• 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
• 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 [9,37]
  
• drug adverse effects of NSAIDs

Drug-interactions

• corticosteroids in combination

• increase clearance of salicylates
• increase nephrotoxicity
• increase GI toxicity

• NSAIDs decrease anti-hypertensive effects of ACE inhibitors
• coumadin in combination: prolonged bleeding time
• probenecid may increase naproxen concentration
• magnesium & aluminum hydroxide decrease absorption
• naproxen may increase plasma levels of:

• digoxin
• Li+
• methotrexate

• 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 lithium carbonate with NSAIDs
• drug interaction(s) of NSAIDs with SSRIs
• drug interaction(s) of aspirin with NSAIDs
• drug interaction(s) of NSAIDs with beta blockers
• drug interaction(s) of NSAIDs with ARBs
• drug interaction(s) of NSAIDs with ACE inhibitors
• drug interaction(s) of NSAIDs, diuretics & angiotensin II receptor antagonists
• drug interaction(s) of NSAIDs, diuretics & ACE inhibitors
• drug interaction(s) of NSAIDs & loop diuretics
• drug interaction(s) of NSAIDs & aspirin

Laboratory

• specimen:

• serum, plasma ( heparin), urine
• stable for at least 14 days at -20 degrees C

• methods:

• serum/ plasma: HPLC, GC, fluorometry
• urine: HPLC

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

• non-steroidal anti-inflammatory agent (NSAID)

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)

Internet Database

PubChem: 1302
PubChem: 33340
PubChem: 156391
PubChem: 657352

References

1. The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
2. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
3. Kaiser Permanente Northern California Regional Drug Formulary, 1998
4. Clinical Guide to Laboratory Tests, 3rd ed. Teitz ed., W.B. Saunders, 1995
5. Prescriber's Letter 13(3): 2006 Cytochrome P450 drug interactions Detail-Document#: [1] (subscription needed) [2]
6. Journal Watch 21(18):143-44, 2001
7. 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: [3]
8. Prescriber's Letter 17(7): 2010 Recommended Lab Monitoring for Common Medications Liver Function Test Scheduling Detail-Document#: [4] (subscription needed) [5]
9. Prescriber's Letter 17(8): 2010 Managing NSAID Risks Detail-Document#: [6] (subscription needed) [7]
10. 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: [8]

naproxen (Naprosyn, Aleve Anaprox)