Diclofenac

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Contents 1 Introduction 2 Indications 3 Contraindications 4 Dosage 5 Pharmacokinetics 6 Monitor 7 Adverse-effects 8 Drug-interactions 9 Laboratory 10 Mechanism-of-action 11 More General Terms 12 Additional Terms 13 Internet Database 14 References

Introduction

• Tradenames: Voltaren, Cataflam, Flector patch

Indications

• temporary relief of minor aches, pains, fever
• migraine
• inflammation: osteoarthritis
• ophthalmic

• treatment of post-operative inflammation after cataracts surgery

Contraindications

• Caution:

• patients on anticoagulation therapy
• surgical patients with known bleeding tendencies
  

• pregnancy category = b
• safety in lactation = -
• safety in lactation = ?

Dosage

• 50 mg PO BID/ TID
• 100 mg PO QD (extended release Voltaren XR)
  

• Tabs: 25, 50, 75 mg; 100 mg (Voltaren XR) Capusle: liquid-filled Zipsor
  
• Oral solution: Cambia for migraine
  
• Topical agent:

• in DMSO, Voltaren Gel, apply QID [7,8]
• Flector patch BID
• Pennsaid, topical solution for osteoarthritis of the knee (Diclofenac Sodium Topical Solution 1.5%)
  Ophthalmic agent:
• 1 drop QID beginning 24 hours after surgery & continuing for 2 weeks

• Solution: ophthalmic 0.1% (5 mL)

Pharmacokinetics

• food decreases rate, but not extent of absorption
• mean plasma levels after oral doses of 50 & 75 mg are 1.5 & 1.9 mg/L, respectively
• metabolized in the liver by cyt P450 2C9
  

• elimination via liver
• 1/2life = 1-2 hours
• protein binding = >99 %
• elimination by hemodialysis = -
• elimination by peritoneal dialysis = -

Monitor

• serum ALT & serum AST 4-8 weeks after starting ANY diclofenac product & then periodically [10]
• monitor blood pressure as hypertension can occur with NSAIDs
  
• monitor with non steroidal anti-inflammatory agents (NSIADs)

Adverse-effects

• ( ophthalmic)
• ocular irritation, transient (> 10%)
• keratitis (1-10%)
• elevated intraocular pressure (1-10%)
• uncommon (< 1%)

• blurred vision, change in vision, anterior chamber reaction, ocular allergy, nausea/vomiting, anaphylaxis, increased sweating

• patients with hdrogel soft contact lenses have experienced ocular irritation
• other

• dizziness, drowsiness, edema, rash, peptic ulceration, GI bleed [4]
• hepatotoxicity with 1% topical gel can occur at any time during treatment with diclofenac [9]

• cardiovascular risk

• greater than that of rofecoxib ( Vioxx) RR=1.91 vs 1.66
• dose-depenedent cardiovascular risk [11]
  

• drug adverse effects of NSAIDs

Drug-interactions

• aluminum & magnesium hydroxide may decrease diclofenac absorption
• diclofenac may decrease renal elimination of:

• Li+
• digoxin
• methotrexate

• diclofenac may decrease antihypertensive & diuretic effects of furosemide & HCTZ
• diclofenac may increase renal toxicity of cyclosporine
• any drug which inhibits cyt P450 2C9 can increase diclofenac levels
• any drug which induces cyt P450 2C9 can diminish diclofenac levels
  
• 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 ( EDTA), urine
• methods:

• serum/ plasma: HPLC, GC
• urine: GC

Mechanism-of-action

• non-specific inhibition of cyclo-oxygenase ( COX-1 & COX-2)
• weak anti- platelet activity (weaker than naproxen)

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)

Internet Database

PubChem: 3033
PubChem: 27194
PubChem: 66378

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, NW Tietz (ed) 3rd ed, WB Saunders, Philadelpha 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 24(23):177, 2004
   - Roth SH, Shainhouse JZ. Efficacy and safety of a topical diclofenac solution (pennsaid) in the treatment of primary osteoarthritis of the knee: a randomized, double-blind, vehicle-controlled clinical trial. Arch Intern Med. 2004 Oct 11;164(18):2017-23. PMID: [3]
   - Tugwell PS, Wells GA, Shainhouse JZ. Equivalence study of a topical diclofenac solution (pennsaid) compared with oral diclofenac in symptomatic treatment of osteoarthritis of the knee: a randomized controlled trial. J Rheumatol. 2004 Oct;31(10):2002-12. PMID: [4]
8. Prescriber's Letter 15(1): 2008 New Topical NSAIDs: Voltaren Gel and Flector Patch Detail-Document#: [5] (subscription needed) [6]
9. FDA MedWatch Voltaren Gel (diclofenac sodium topical gel) 1% - Hepatic Effects Labeling Changes [7]
10. Prescriber's Letter 17(4): 2010 New Drug: Pennsaid (Diclofenac Sodium Topical Solution 1.5%) COMMENTARY: New Drug: Pennsaid (Diclofenac Sodium Topical Solution 1.5%) GUIDELINES: Choosing Non-Opioid Analgesics for Osteoarthritis (AHRQ, 2009) Detail-Document#: [8] (subscription needed) [9]
11. Fosbol EL et al Cause-Specific Cardiovascular Risk Associated With Nonsteroidal Antiinflammatory Drugs Among Healthy Individuals. Circ Cardiovasc Qual Outcomes published online Jun 8, 2010; DOI:10.1161/CIRCOUTCOMES.109.861104 [10]
12. Prescriber's Letter 17(7): 2010 Recommended Lab Monitoring for Common Medications Detail-Document#: [11] (subscription needed) [12]

diclofenac (Voltaren, Cataflam, Flector patch, Cambia, Pennsaid, Zipsor)