Indications
PO: Management of inflammatory disorders including:
Rheumatoid arthritis, Osteoarthritis, Ankylosing spondylitis.
Primary dysmenorrhea. Relief of mild to moderate
pain. Acute treatment of migraines (powder for oral
solution). Topical: Management of: Actinic keratoses
(Solaraze), Osteoarthritis (Voltaren Gel, Pennsaid [for
knees]). Transdermal: Acute pain due to minor
strains, sprains, and contusions.
Action
Inhibits prostaglandin synthesis. Therapeutic Effects:
Suppression of pain and inflammation. Relief of
acute migraine attacks. Topical (Solaraze): Clearance
of actinic keratosis lesions.
Pharmacokinetics
Absorption: Undergoes first-pass metabolism by
liver which results in 50% bioavailability. Oral diclofenac
sodium is a delayed-release dose form. Diclofenac
potassium is an immediate-release dose form. 6–
10% of topical gel is systemically absorbed.
Distribution: Crosses the placenta.
Protein Binding: 99%.
Metabolism and Excretion: Metabolized by the
liver (primarily by CYP2C9) to several metabolites; 65%
excreted in urine, 35% in bile.
Half-life: 2 hr.
TIME/ACTION PROFILE
ROUTE ONSET PEAK DURATION
PO (inflammation)
few days–1 wk 2 wk unknown
PO (pain) 30 min unknown up to 8 hr
Top (gel and
patch)
unknown 10–20 hr unknown
Top (solution)
unknown unknown unknown
Contraindications/Precautions
Contraindicated in: Hypersensitivity to diclofenac
or other components of formulation; Cross-sensitivity
may occur with other NSAIDs including aspirin; Active
GI bleeding/ulcer disease; Coronary artery bypass graft
(CABG) surgery; Exudative dermatitis, eczema, infectious
lesions, burns, or wounds.
Use Cautiously in: Severe renal/hepatic disease; Cardiovascular
disease or risk factors for cardiovascular disease
(mayqrisk of serious cardiovascular thrombotic
events, myocardial infarction, and stroke, especially with
prolonged use or use of higher doses); avoid use in patients
with recent MI or HF; Heart failure or edema; History
of porphyria; History of peptic ulcer disease and/or
GI bleeding; Geri: Doseprecommended; more susceptible
to adverse effects, including GI bleeding; Bleeding
tendency or concurrent anticoagulant therapy; OB, Lactation:
Not recommended for use during second half of
pregnancy; Pedi: Safety not established.
Adverse Reactions/Side Effects
CNS: dizziness, headache. CV: HF, MYOCARDIAL INFARCTION,
STROKE, edema, hypertension. EENT: tinnitus. GI:
GI BLEEDING, HEPATOTOXICITY, abdominal pain, constipation,
diarrhea, dyspepsia, flatulence, heartburn,qliver
enzymes, nausea, vomiting. GU: acute renal failure, hematuria.
Derm: EXFOLIATIVE DERMATITIS, STEVENS-JOHNSON
SYNDROME, TOXIC EPIDERMAL NECROLYSIS, pruritis,
rashes, eczema, photosensitivity. F and E: hyperkalemia.
Hemat: anemia, prolonged bleeding time. Local:
Topical only—contact dermatitis, dry skin, exfoliation.
Misc: allergic reactions including ANAPHYLAXIS.
Interactions
Primarily noted for oral administration.
Drug-Drug:qadverse GI effects with aspirin, other
NSAIDs, or corticosteroids. Maypeffectiveness of
diuretics or antihypertensives. Mayqlevels/risk of
toxicity from cyclosporine, lithium, or methotrexate.
qrisk of bleeding with anticoagulants, aspirin,
clopidogrel, ticagrelor, prasugrel, corticosteroids,
fibrinolytics, SNRIs, or SSRIs. CYP2C9 inhibitors,
including voriconazole mayqlevels/risk of
toxicity. CYP2C9 inducers, including rifampin may
plevels/effectivness. Concurrent use of oral NSAIDs
during topical diclofenac therapy should be minimized.
Drug-Natural Products:qbleeding risk with arnica,
chamomile, clove, dong quai, feverfew, garlic,
ginger, ginkgo, Panax ginseng, and others.
Route/Dosage
Different formulations of oral diclofenac (diclofenac capsules,
diclofenac sodium enteric-coated tablets, diclofenac
sodium extended-release tablets, and diclofenac
potassium immediate-release tablets) are not bioequivalent
and should not be substituted on a mg-to-mg basis.
Diclofenac
PO (Adults): Acute pain—18–35 mg 3 times daily;
Osteoarthritis—35 mg 3 times daily.
Hepatic Impairment
PO (Adults): Do not exceed dose of 18 mg 3 times daily.
Diclofenac Potassium
PO (Adults): Analgesic/antidysmenorrheal (Cataflam)—
100 mg initially, then 50 mg 3 times daily as
needed; Analgesic (Zipsor)—25 mg 4 times daily;
Rheumatoid arthritis (Cataflam)—50 mg 3–4 times
daily; Osteoarthritis (Cataflam)—50 mg 2–3 times
daily; Osteoarthritis (Cambia)—one packet (50 mg)
given as a single dose.
Diclofenac Sodium
PO (Adults): Rheumatoid arthritis (delayed-release
[enteric-coated] tablets)—50 mg 3–4 times daily or
75 mg twice daily (usual maintenance dose 25 mg 3
times daily). Rheumatoid arthritis (extended-release
tablets)—100 mg once daily; if unsatisfactory response,
dose may beqto 100 mg twice daily. Osteoarthritis
(delayed-release [enteric-coated] tablets)—
50 mg 2–3 times daily or 75 mg twice daily. Osteoarthritis
(extended-release tablets)—100 mg once
daily. Ankylosing spondylitis (delayed-release [enteric-
coated] tablets)—25 mg 4 times daily, with an
additional 25 mg given at bedtime, if necessary.
Topical (Adults): Solaraze—Apply to lesions twice
daily for 60–90 days; Voltaren gel—Lower extremities
(knees, ankles, feet): Apply 4 g to affected area 4 times
daily (maximum of 16 g per joint/day); Upper extremities
(elbows, wrists, hands): Apply 2 g to affected area 4
times daily (maximum of 8 g per joint/day); Maximum
total body dose should not exceed 32 g/day; Pennsaid—
Apply 40 drops to affected knee(s) 4 times daily.
Rect (Adults): Insert 50 mg or 100 mg rectally as single
dose to substitute for final oral daily dose (max
combined dose [rectal and oral]: 100 mg/day).
Diclofenac Epolamine
Topical (Adults): Flector—Apply 1 patch to most
painful area twice daily.
Availability (generic available)
Diclofenac capsules (Zorvolex): 18 mg, 35 mg. Diclofenac
potassium immediate-release tablets
(Cataflam): 50 mg. Cost: Generic—$156.55/100.
Diclofenac potassium liquid-filled capsules (Zipsor): 25 mg. Cost: $478.80/100. Diclofenac potassium
powder for oral solution (Cambia): 50 mg/
packet. Cost: $29.04/1 pkt. Diclofenac sodium delayed-
release (enteric-coated) tablets (Voltaren):
25 mg, 50 mg, 75 mg. Cost: Generic—25 mg
$142.18/100, 50 mg $147.23/100, 75 mg $177.39/
100. Diclofenac sodium extended-release tablets
(Voltaren XR): 75 mg, 100 mg. Cost: Generic—
100 mg $281.42/100. Diclofenac sodium gel: 1%
(Voltaren gel), 3% (Solaraze). Cost: 1% $46.48/100 g,
3% $931.92/100 g. Diclofenac sodium rectal suppository:
50 mg, 100 mg. Diclofenac sodium
topical solution: 1.5%. Cost: $289.67/150 mL. Diclofenac
epolamine transdermal patch: 180 mg/
patch. Cost: $239.70/30. In combination with:
misoprostol (Arthrotec). See Appendix B.
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