dye-KLOE-fen-ak

diclofenac potassium (oral)

• Cambia

• Cataflam

• Zipsor

diclofenac sodium (oral)

• Apo-Diclo [Canada]

• Voltaren

• Voltaren XR

diclofenac sodium (topical gel)

• Solaraze

• Voltaren Gel

diclofenac sodium (topical solution)

• Pennsaid

diclofenac epolamine (transdermal patch)

• Flector

Pregnancy Category
Category B (3% gel)
Category C (oral and topical solution [<30 wk gestation], 1% gel, patch)
Category D (oral and topical solution [≥30 wk gestation)

Ther. class.
nonopioid analgesics
nonsteroidal anti inflammatory agents

†For ophthalmic use see Ophthalmic Medications

• 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.

Inhibits prostaglandin synthesis.

Therapeutic Effect(s):

• Suppression of pain and inflammation.

• Relief of acute migraine attacks.

• Topical (Solaraze): Clearance of actinic keratosis lesions.

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

Contraindicated in:

• Hypersensitivity to diclofenac or other components of formulation;

• Cross-sensitivity may occur with other NSAIDs including aspirin;

• Active GI bleeding/ulcer disease;

• Patients undergoing coronary artery bypass graft surgery;

• Exudative dermatitis, eczema, infectious lesions, burns, or wounds.

Use Cautiously in:

• Severe renal/hepatic disease;

• Cardiovascular disease or risk factors for cardiovascular disease (may ↑ risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, especially with prolonged use);

• Heart failure or edema;

• History of porphyria;

• History of peptic ulcer disease and/or GI bleeding;

• Geri: Dose ↓ recommended; more susceptible to adverse reactions, including GI bleeding;

• Bleeding tendency or concurrent anticoagulant therapy;

• OB: Lactation: Not recommended for use during second half of pregnancy;

• Pedi: Safety not established.

CNS: dizziness, headache.

CV: hypertension.

EENT: tinnitus.

GI: GI BLEEDING, HEPATOTOXICITY, abdominal pain, constipation, diarrhea, dyspepsia, flatulence, heartburn, ↑ liver enzymes, nausea, vomiting.

GU: acute renal failure, hematuria.

Derm: EXFOLIATIVE DERMATITIS, STEVENS-JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS, pruritis, rashes, eczema, photosensitivity.

F and E: edema.

Hemat: anemia, prolonged bleeding time.

Local: Topical only—contact dermatitis, dry skin, exfoliation.

Misc: ALLERGIC REACTIONS INCLUDING ANAPHYLAXIS .

*CAPITALS indicates life-threatening.
*italic indicates most frequent.

Primarily noted for oral administration

Drug-Drug

• ↑ adverse GI effects with aspirin , other NSAIDs , or corticosteroids .

• May ↓ effectiveness of diuretics or antihypertensives .

• May ↑ levels/risk of toxicity from cyclosporine , lithium , or methotrexate .

• ↑ risk of bleeding with some cephalosporins , thrombolytic agents , antiplatelet agents , or warfarin .

• CYP2C9 inhibitors , including voriconazole may ↑ levels/risk of toxicity.

• CYP2C9 inducers , including rifampin may ↓ levels/effectivness.

• Concurrent use of oral NSAIDs during topical diclofenac therapy should be minimized.

Drug-Natural Products
↑ bleeding risk with arnica , chamomile , clove , dong quai , feverfew , garlic , ginger , ginkgo , Panax ginseng , and others.

• Different formulations of oral diclofenac (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 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 (Cambria)—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 be ↑ to 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..

Diclofenac Epolamine

• Topical (Adults): Flector—Apply 1 patch to most painful area twice daily..

• Diclofenac potassium immediate-release tablets (Cataflam): 50 mg

• Diclofenac potassium liquid-filled capsules (Zipsor): 50 mg

• Diclofenac potassium powder for oral solution (Cambria): 50 mg/packet

• Diclofenac sodium delayed-release (enteric-coated) tablets (Voltaren): 25 mg[canada], 50 mg, 75 mg

• Diclofenac sodium extended-release tablets (Voltaren XR): 75 mg[canada], 100 mg

• Diclofenac sodium gel: 1% (Voltaren gel), 3% (Solaraze)

• Diclofenac sodium topical solution: 1.5%

• Diclofenac epolamine transdermal patch: 180 mg/patch

• In combination with: misoprostol (Arthrotec). See combination drugs.

• Patients who have asthma, aspirin-induced allergy, and nasal polyps are at ↑ risk for developing hypersensitivity reactions.

• Monitor BP closely during initiation of treatment and periodically during therapy in patients with hypertension.

• Assess patient for skin rash frequently during therapy. Discontinue at first sign of rash; may be life-threatening. Stevens-Johnson syndrome may develop. Treat symptomatically; may recur once treatment is stopped.

Pain

• Assess pain and limitation of movement; note type, location, and intensity before and 30–60 min after administration.

Arthritis

• Assess arthritic pain (note type, location, intensity) and limitation of movement before and periodically during therapy.

Actinic Keratosis

• Assess lesions prior to and periodically during therapy.

Lab Test Considerations

• Diclofenac has minimal effect on bleeding time and platelet aggregation.

» May cause ↓ in hemoglobin and hematocrit.

» Monitor CBC and liver function tests within 4–8 wk of initiating diclofenac and periodically during therapy. May cause ↑ serum alkaline phosphatase, LDH, AST, and ALT concentrations.

» Monitor BUN and serum creatinine periodically during therapy. May cause ↑ BUN and serum creatinine.

• Acute pain (Indications)

• Impaired physical mobility (Indications)

• Administration in higher than recommended doses does not provide increased effectiveness but may cause increased side effects. Use lowest effective dose for shortest period of time.

• PO: Take with food or milk to minimize gastric irritation. May take first 1–2 doses on an empty stomach for more rapid onset. Do not crush or chew enteric-coated or extended-release tablets.

• Dysmenorrhea: Administer as soon as possible after the onset of menses. Prophylactic treatment has not been shown to be effective.

• Topical: Gel should be applied to intact skin; do not use on open wounds. An adequate amount of gel should be applied to cover the entire lesion.

• Topical: Dispense solution 10 drops at a time either directly onto knee or first into the hand and then onto knee. Spread solution evenly around front, back and sides of the knee. Repeat until 40 drops have been applied and knee is completely covered with solution.

• Transdermal: Apply patch to the most painful area twice a day. Do not apply to non-intact or damaged skin resulting from any etiology (exudative dermatitis, eczema, infected lesion, burns, wounds). Avoid contact with eyes; wash hands after applying, handling, or removing patch.

• Caution patient to avoid concurrent use of alcohol, aspirin, acetaminophen, other NSAIDs, or other OTC medications without consulting health care professional.

• Instruct patient to notify health care professional of medication regimen before treatment or surgery.

• May cause serious side effects: CV (MI or stroke), GI (ulcers, bleeding), skin (exfoliative dermatitis, Stevens-Johnson Syndrome, toxic epidermal necrolysis) and hypersensitivity (anaphylaxis). May occur without warning symptoms. Advise patient to stop medication and notify health care professional immediately if symptoms of CV side effects (chest pain, shortness of breath, weakness, slurring of speech), GI side effects (epigastric pain, dyspepsia, melana, hematemesis), skin side effects (skin rash, blisters, fever, itching) or hypersensitivity reactions (difficulty breathing or swelling of face or throat) occur. Inform patient that risk for heart attack or stroke that can lead to death increases with longer use of NSAID medications and in people who have heart disease and that risk of ulcer increases with concurrent use of corticosteroids and anticoagulants, longer use, smoking, drinking alcohol, older age, and having poor health.

• Advise patient to notify health care professional promptly if unexplained weight gain, swelling of arms and legs or hands and feet, nausea, fatigue, lethargy, rash, pruritis, yellowing of skin or eyes, itching, stomach pain, vomiting blood, bloody or tarry stools, or flu-like symptoms occur.

• Instruct female patients to inform health care professional if they plan or suspect pregnancy. Caution female patient to avoid use of diclofenac in last trimester of pregnancy and to notify health care professional if breastfeeding.

• PO: Instruct patient to take diclofenac with a full glass of water and to remain in an upright position for 15–30 min after administration. Take missed doses as soon as possible within 1–2 hr if taking once or twice a day or unless almost time for next dose if taking more than twice a day. Do not double doses.

» May cause drowsiness or dizziness. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.

» Caution patient to wear sunscreen and protective clothing to prevent photosensitivity reactions.

• Topical: Advise patient to minimize use of concurrent NSAIDs during topical therapy. Instruct patient to read Medication Guide before starting therapy and with each Rx refill in case changes have been made.

» Instruct patient to avoid covering lesion with occlusive dressing and to avoid applying sunscreen or cosmetics to the affected area.

» Advise patient that it may take up to 1 mo for complete healing of the lesion to occur.

• Transdermal: Instruct patient on correct application procedure for patch. Apply patch to most painful area. Change patch every 12 hr. Remove patch if irritation occurs. Fold used patches so adhesive sticks to itself and discard where children and pets cannot get them. Encourage patient to read the NSAID Medication Guide that accompanies the prescription.

» Instruct patients if patch begins to peel off to tape the edges. Do not wear patch during bathing or showering. Bathing should take place between scheduled patch removal and application.

» Advise patient referred for MRI test to discuss patch with referring health care professional and MRI facility to determine if removal of patch is necessary prior to test and for directions for replacing patch.

• Decrease in severity of mild-to-moderate pain.

» Increased ease of joint movement. Patients who do not respond to one NSAID may respond to another. May require 2 wk or more for maximum effects.

• Decrease in or healing of lesions in actinic keratosis. Optimal effect may not be seen until 30 days after discontinuation of therapy. Lesions that do not heal should be re-evaluated.