diclofenac topical (Rx)

>10%

Dry skin (25-27%)

Rash (20-35%)

Contact dermatitis (19-33%)

Pain (15-26%)

Paresthesia (≤ 20%)

Pruritus (≤ 52%)

Exfoliation (6-24%)

1-10%

Hypertension

Chest pain

Skin ulcer

Diarrhea

Dyspepsia

Alepesia

Photosensitivity

Edema

Conjunctivitis

Hematuria

Asthma

Pneumonia

<1%

Application site pruritus

Other application site reactions

Postmarketing Reports

Dermal allergic reactions

Photoallergic reactions

Contraindications

Hypersensitivity to diclofenac, aspirin other NSAIDs or any ingredient

CABG perioperative period

History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs

Flector patch: Use on non-intact or damaged skin resulting from any etiology, including exudative dermatitis, eczema, infection lesions, burns or wounds

Cautions

Long-term administration of NSAIDs resulted in renal papillary necrosis and other renal injury; renal toxicity also seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion

Risks of: cardiovascular thrombotic events; GI bleeding & ulceration; hepatotoxicity (with Na-salt)

Anemia has occurred in NSAID-treated patients

Diclofenac associated with anaphylactic reactions in patients with and without known hypersensitivity to diclofenac and in patients with aspirin-sensitive asthma

May lead to new onset or worsening of preexisting hypertension, either of which may contribute to the increased incidence of CV events; coadministration with angiotensin converting enzyme (ACE) inhibitors, thiazide diuretics, or loop diuretics may have impaired response to these therapies when taking NSAIDs

Randomized controlled trials demonstrated an ~2-fold increase in hospitalizations for heart failure in COX-2 selective-treated patients and nonselective NSAID-treated patients compared to placebo-treated patients

Increases in serum potassium concentration reported with use of NSAIDs, even in some patients without renal impairment; patients with normal renal function, these effects have been attributed to a hyporeninemic-hypoaldosteronism state

NSAIDs can cause serious skin adverse reactions such as exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal and may occur without warning

Diclofenac may cause premature closure of the fetal ductus arteriosus; avoid use of NSAIDs in pregnant women starting at 30 weeks of gestation (third trimester) (see Pregnancy)

Pharmacological activity of diclofenac in reducing inflammation, and possibly fever, may diminish the utility of these diagnostic signs in detecting infections

Because serious GI bleeding, hepatotoxicity, and renal injury can occur without warning symptoms or signs, consider monitoring patients on long-term NSAID treatment with a CBC and a chemistry profile periodically

Even a used diclofenac contains a large amount of diclofenac epolamine (as much as 170 mg); potential therefore exists for a small child or pet to suffer serious adverse effects from chewing or ingesting a new or used drug; store and keep out of the reach of children and pets

Avoid contact of diclofenac with eyes and mucosa

Concomitant use of oral and topical NSAIDs may result in a higher rate of hemorrhage, more frequent abnormal creatinine, urea and hemoglobin

Pregnancy

Published literature reports that use of NSAIDs after 30 weeks’ gestation increases the risk of premature closure of the fetal ductus arteriosus

Data from observational studies regarding potential embryofetal risks of NSAID use, including diclofenac, in women in the first or second trimester of pregnancy are inconclusive

Clinical considerations

• Avoid use of NSAIDs in pregnant women after 30 weeks’ gestation because NSAIDs can cause premature closure of the fetal ductus arteriosus

Lactation

Data from published literature reports with oral preparations of diclofenac indicate the presence of small amounts of diclofenac in human milk

There are no data on the effects on the breastfed infant or the effects on milk production

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Decreases formation of prostaglandin by inhibiting cyclooxygenase enzymes 1 and 2; may have anti-inflammatory effects by inhibiting chemotaxis, inhibiting neutrophil aggregation/activation, and decreasing proinflammatory cytokine levels

Absorption

Absorption: 10% in epidermis (Solaraze gel); 6% systemic (Voltaren gel); 2-3% (topical solution)

Peak plasma time: 4.5 hr (Solaraze); 10-14 hr (Voltaren gel); 10-20 hr (Flector Patch); 6 hr (Licart)

Peak plasma concentration: 1.01 (Licart); 2.2-8.1 ng/mL (Flector Patch; while resting), and 2.7-7.2 ng/mL (Flector Patch; during exercise)

AUC: 18.58 ng·hr/mL (Licart)

Distribution

Protein bound: >99%

Metabolism

Metabolites: 4'- hydroxy- (very weak pharmacological activity), 5-hydroxy-, 3'-hydroxy-, 4',5-dihydroxy- and 3'-hydroxy-4'-methoxy diclofenac

Primarily mediated by CPY2C9 Both diclofenac and its oxidative metabolites undergo glucuronidation or sulfation followed by biliary excretion

Acylglucuronidation mediated by UGT2B7 and oxidation mediated by CPY2C8

CY3A4 is responsible for the formation of minor metabolites, 5-hydroxy and 3’-hydroxy- diclofenac.

Excretion

Half-Life: 12 hr (patch)

Excretion: Urine (~65%); bile (~35%, conjugates of unchanged diclofenac)

Topical Administration

Wash your hands after applying, handling, or removing

Do not apply external heat and/or occlusive dressings to treated joints

Do not apply to open wounds

Avoid contact with eyes and mucous membranes

Avoid exposure of the treated joint(s) to natural or artificial sunlight

Avoid use on treated skin site with other topical products, including sunscreens, cosmetics, lotions, moisturizers, insect repellants, or other topical medications

Concomitant use with oral NSAIDs not evaluated, and may increase adverse NSAIDs effects

Gel

• Avoid showering/bathing for at least 1 hr after application; wash hands after use, unless hands are the treated joint
• If applied to hand(s) for treatment; inform patient not to wash the treated hand(s) for at least 1 hr after the application
• Avoid wearing of clothing or gloves for at least 10 minutes after applying gel

Topical system or transdermal patch

• If patch begins to peel-off, tape down edges of the topical system
• If problems with adhesion persist, overlay topical system with a mesh netting sleeve, where appropriate (eg, to secure topical systems applied to ankles, knees, or elbows)
• Do not apply to non-intact or damaged skin resulting from any etiology (eg, exudative dermatitis, eczema, infected lesion, burns, wounds)
• Do not wear when bathing or showering

Storage

Gel: Store at 20-25°C (68-77°F)

Transdermal patch: Store at 20-25°C (68-77°F); excursions permitted between 15-30°C (59-86°F)

Topical system

• Store at 20-25°C (68-77°F); excursions permitted between 15-30°C (59-86°F)
• Once envelope is opened, stable up to 6 months, if stored at room temperature in the re-sealed envelope