Professional Information

Diclofenac

Pronouncation: (dye-KLOE-fen-ak)
Class: NSAID

Trade Names:
Cataflam
- Tablets 50 mg (as potassium)

Trade Names:
Diclofenac
- Tablets, delayed-release 25 mg (as sodium)
- Tablets, delayed-release 50 mg (as sodium)

Trade Names:
Flector
- Patch, transdermal 180 mg (as epolamine)

Trade Names:
Solaraze
- Gel 3%

Trade Names:
Voltaren
- Gel 1%
- Tablets, delayed-release 75 mg (as sodium)
- Solution, ophthalmic 0.1% (as sodium)

Trade Names:
Voltaren-XR
- Tablets, extended-release 100 mg (as sodium)

Apo-Diclo (Canada)
Apo-Diclo Rapide (Canada)
Apo-Diclo SR (Canada)
Novo-Difenac (Canada)
Novo-Difenac K (Canada)
Novo-Difenac SR (Canada)
Nu-Diclo (Canada)
Nu-Diclo-SR (Canada)
PMS-Diclofenac (Canada)
PMS-Diclofenac SR (Canada)
Voltaren Ophtha (Canada)
Voltaren Rapide (Canada)

Pharmacology

Decreases inflammation, pain, and fever, probably through inhibition of cyclooxygenase activity and prostaglandin synthesis.

Pharmacokinetics

Absorption

Bioavailability is approximately 50% because of first-pass metabolism (oral doseforms). Food decreases T _max and C _max .

Immediate-release tablets

T _max is approximately 1 h.

Extended-release (ER) tablets

T _max is approximately 5.3 h.

Delayed-release tablets (50 mg dose)

T _max is approximately 2.3 h.

Solaraze topical gel

Following application of 2 g 3 times daily for 6 days, mean AUC is 9 ng•h/mL, mean C _max is 4 ng/mL, and mean T _max is 4.5 h.

Topical patch

Following a single application of the patch on the upper inner arm, C _max of 0.7 to 6 ng/mL was noted between 10 and 20 h of application. With twice-daily application of patch, plasma concentrations ranged from 1.3 to 8.8 ng/mL after 5 days.

Voltaren gel

C _max with application of 160 mg/day is 15 ng/mL and 54 ng/mL with application of 480 mg/day. T _max is 14 h with the application of 160 mg/day and 10 h with the application of 480 mg/day. The amount reaching the systemic circulation is 158 times lower with 160 mg/day compared with oral treatment.

Distribution

More than 99% protein bound (albumin). Vd is approximately 1.4 L/kg (oral).

Metabolism

Undergoes hepatic metabolism; metabolized to 5 metabolites.

Elimination

Approximately 65% is excreted in urine and 35% in the bile. The t _½ is 1 to 2 h. Plasma elimination t _½ after application of topical patch is approximately 12 h.

Special Populations

Renal Function Impairment

No differences in pharmacokinetics have been detected in studies with patients with renal function impairment.

Hepatic Function Impairment

Since hepatic metabolism accounts for 100% of diclofenac elimination, patients with hepatic disease may require reduced doses.

Indications and Usage

Oral Immediate-release tablets

Treatment of primary dysmenorrhea; relief of mild to moderate pain.

Immediate-release, ER, and delayed-release tablets

Relief of signs and symptoms of osteoarthritis and rheumatoid arthritis.

Delayed-release tablets

Acute and long-term use in the relief of signs and symptoms of ankylosing spondylitis.

Ophthalmic

Treatment of postoperative inflammation after cataract removal; temporary relief of pain and photophobia following corneal refractive surgery.

Solaraze topical gel

Treatment of actinic keratosis.

Patch

Treatment of acute pain because of minor strains, sprains, and contusions.

Voltaren topical gel

Treatment of pain of osteoarthritis or joint pain amenable to topical treatment (eg, knees, hands).

Contraindications

Treatment of perioperative pain in the setting of coronary artery bypass graft surgery; patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs; hypersensitivity to any component of the product; sensitivity to benzyl alcohol, diclofenac, polyethylene glycol monomethyl ether 350, or hyaluronate sodium (topical). Do not apply topical patch to nonintact or damaged skin regardless of the cause (eg, burns or wounds, eczema, exudative dermatitis, infected lesion).

Dosage and Administration

Different tablet formulations of diclofenac are not necessarily bioequivalent.

Actinic Keratosis
Adult

Topical gel Apply gel to lesions twice daily. The recommended duration of treatment is 60 to 90 days.

Analgesia and Primary Dysmenorrhea

PO 50ߙmg 3 times daily; may give initial dose of 100ߙmg if needed.

Ankylosing Spondylitis

PO Delayed-release 100 to 125ߙmg/day in divided doses; may give additional 25 mg at bedtime.

Minor Strains, Sprains, and Contusions
Adults

Topical patch Apply 1 patch to most painful area twice daily.

Osteoarthritis
Adults

ER tablets

100 mg daily.

Immediate-release, delayed-release tablets

100 to 150 mg/day in divided doses.

Topical gel

Using the dosing card supplied in the product carton, apply up to the 2 or 4 g line (2 g for elbows, wrist, or hand; 4 g for each knee, ankle, or foot). Apply 4 times daily by gently massaging gel into the skin, ensuring application to the entire affected area. Do not apply more than 8 g/day to any single joint of the upper extremities or more than 16 g/day to any single joint of the lower extremities.

Rheumatoid Arthritis
Adults

ER tablets

100 mg daily. If response is unsatisfactory, the dosage may be increased to 100 mg twice daily.

Delayed-release tablets

100 to 200 mg/day in divided doses.

Immediate-release tablets

150 to 200 mg/day in divided doses.

Ophthalmic
Cataract Surgery

1 drop in affected eye 4 times daily beginning 24 h after cataract surgery and continuing during the first 2 wk of postoperative period.

Corneal Refractive Surgery

1 or 2 drops within 1 h prior to corneal refractive surgery; then, within 15 min after surgery, apply 1 or 2 drops to the operative eye and continue 4 times daily for up to 3 days.

General Advice

ER and delayed-release tablets
Advise patient to swallow whole. Do not break, cut, crush, or chew tablet.

Ophthalmic solution
For ophthalmic use only.
If using other topical ophthalmic drugs, separate each medication by at least 5 min. Instill ophthalmic ointment last.

Solaraze topical gel
For dermatological use only.
Using gloves, gently smooth onto affected skin. Apply gel to adequately cover each lesion.
Avoid contact with the eyes, mouth, and other mucous membranes.

Topical patch
Do not apply to damaged or nonintact skin.
Do not wear when bathing or showering.

Voltaren topical gel
Do not apply to open wounds.
Avoid contact with eyes and mucous membranes.
Do not apply heat or occlusive dressing to treated joint.
Avoid exposure of treated joint to sunlight.
Do not use sunscreens, cosmetics, lotions, moisturizers, insect repellants, or other topical medications on the same site.
Avoid wearing clothing or gloves for at least 10 min after application.
Avoid showering for at least 1 h after application.
If used on the hand(s) for treatment, do not wash the treated hand(s) for at least 1 h after the application.

Storage/Stability

Tablets

Do not store immediate-release and ER tablets at temperatures higher than 86°F. Protect from moisture.

Ophthalmic solution

Store at 59° to 77°F. Protect from light.

Topical gel and patch

Store at 59° to 86°F. Do not freeze. Protect from heat.

Drug Interactions

ACE inhibitors

Antihypertensive effect of ACE inhibitors may be diminished.

Aminoglycosides (eg, gentamicin)

Aminoglycoside concentrations may be elevated, increasing the risk of adverse reactions.

Aspirin

Protein binding of diclofenac may be reduced; in addition, the risk of gastric erosion and bleeding may be increased.

Azole antifungal agents (eg, fluconazole)

Diclofenac plasma concentrations may be elevated, increasing the risk of adverse reactions.

Bisphosphonates (eg, alendronate)

Coadministration may increase the risk of gastric ulceration.

Cyclosporine

May increase nephrotoxicity.

Digoxin

May increase digoxin serum concentrations.

Furosemide and thiazide diuretics

May inhibit diuretic and antihypertensive effects.

Heparin

Risk of hemorrhagic adverse reactions may be increased.

Lithium

May decrease lithium Cl.

Methotrexate

May increase methotrexate levels.

SSRIs (eg, fluoxetine)

Risk of upper GI bleeding may be increased.

Warfarin

May increase risk of gastric erosion and bleeding.

Laboratory Test Interactions

May prolong bleeding time.

Adverse Reactions

Cardiovascular

Topical gel ( Solaraze )

Hypertension (2%).

CNS

Ophthalmic

Dizziness, headache, insomnia (3% or less).

Oral

Dizziness, headache (1% to 10%).

Topical gel ( Solaraze )

Headache (7%); asthenia, hypokinesia (2%); migraine (1%).

Topical patch

Dizziness, headache, hyperkinesia, hypoesthesia, paresthesia, somnolence (1%).

Dermatologic

Oral

Pruritus, rash (1% to 10%).

Topical gel ( Solaraze )

Pruritus (52%); rash (46%); dry skin (27%); contact dermatitis (33%); exfoliation (24%); vesiculobullous rash (4%); hyperesthesia, photosensitivity (3%); alopecia, skin carcinoma, skin ulcer (2%); acne (1%).

Topical gel ( Voltaren )

Application-site dermatitis (4%).

Topical patch

Pruritus (5%); application-site dryness, atrophy, discoloration, erythema, hyperhidrosis, irritation, vesicles (4%); dermatitis (2%).

EENT

Ophthalmic

Lacrimation complaints (30%); keratitis (28%); elevated IOP, transient ocular burning and stinging (15%); abnormal vision, acute elevated IOP, blurred vision, conjunctivitis, corneal deposits, corneal edema, corneal lesions, corneal opacity, discharge, eyelid swelling, injection, iritis, irritation, itching, lacrimation disorder, ocular allergy, redness (5% or less); rhinitis (3% or less); corneal erosion, corneal infiltrates, corneal perforation, corneal thinning, corneal ulceration, epithelial breakdown, superficial punctuate keratitis (postmarketing).

Oral

Tinnitus (1% to 10%).

Topical gel ( Solaraze )

Conjunctivitis (4%); eye pain (2%).

GI

Ophthalmic

Abdominal pain, nausea, vomiting (3% or less).

Oral

Abdominal pain, constipation, diarrhea, dyspepsia, flatulence, GI ulcers (gastric/duodenal), gross bleeding/perforation, heartburn, nausea, vomiting (1% to 10%).

Topical gel ( Solaraze )

Dyspepsia (3%); abdominal pain, diarrhea (2%).

Topical patch

Nausea, constipation, diarrhea, dry mouth, gastritis, upper abdominal pain, and vomiting (3%); dysgeusia (2%); dyspepsia (1%).

Genitourinary

Topical gel ( Solaraze )

Hematuria (2%).

Hematologic-Lymphatic

Oral

Anemia, increased bleeding time (1% to 10%).

Hepatic

Oral

Elevated liver enzymes (1% to 10%).

Local

Topical gel ( Solaraze )

Application-site reaction (84%); pain (26%); paresthesia (20%); edema (4%).

Metabolic-Nutritional

Oral

Edema (1% to 10%).

Topical gel ( Solaraze )

Increased CPK (4%); increased AST (3%); increased ALT, increased creatinine (2%); hypercholesterolemia, hyperglycemia (1%).

Musculoskeletal

Topical gel ( Solaraze )

Back pain (4%); myalgia (3%); arthralgia, arthrosis, neck pain (2%).

Renal

Oral

Abnormal renal function (1% to 10%).

Respiratory

Topical gel ( Solaraze )

Asthma, dyspnea, pharyngitis, pneumonia, rhinitis, sinusitis (2%).

Ophthalmic

Exacerbation of asthma, dyspnea.

Miscellaneous

Ophthalmic

Asthenia, chills, facial edema, fever, pain, viral infection (3% or less).

Topical gel ( Solaraze )

Flu syndrome (10%); accidental injury, infection (4%); chest pain, pain (2%); allergic reaction (1%).

Precautions

Warnings

NSAIDs may cause an increased risk of serious CV thrombotic events, MI, and stroke, which can be fatal. This risk may increase with length of therapy. Patients with CV disease or risk factors for CV disease may be at greater risk. NSAIDs cause an increased risk of serious GI adverse reactions, including bleeding, inflammation, perforation of the stomach or intestines, and ulceration, which can be fatal. These events can occur any time during use and without warning symptoms. Elderly patients are at greater risk of serious GI events.

Monitor

Monitor for signs and symptoms of GI bleeding. Closely monitor BP during the initiation of treatment and throughout the course of therapy. Carefully monitor patients who may be adversely affected by alterations in platelet function (eg, patients with coagulation disorders or those receiving anticoagulant therapy). Obtain baseline assessments of pain and ability to perform activities of daily living. Ensure CBC, serum electrolytes, and serum transaminases are evaluated periodically during prolonged therapy. Note dark, tarry stools; epigastric pain; indigestion; or unusual bleeding or bruising. If used in patients with advanced renal disease, monitor renal function. Monitor refractive stability for a year following corneal refractive procedures in patients treated with the ophthalmic solution.

Pregnancy

Category C (immediate-release tablets, ER tablets, ophthalmic solution, topical patch, delayed-release tablets, Voltaren topical gel). Category B ( Solaraze topical gel). Can cause premature closure of the ductus arteriosus; avoid in late pregnancy.

Lactation

Undetermined.

Children

Safety and efficacy not established.

Elderly

Use with caution.

Renal Function

Acute renal function impairment, hyperkalemia, hyponatremia, interstitial nephritis, and renal papillary necrosis may occur. Not recommended in patients with advanced renal disease.

Hepatic Function

Monitor patient for signs and symptoms of hepatic function impairment. If noted, discontinue therapy immediately.

Special Risk Patients

Use with caution in patients with fluid retention, heart failure, or hypertension.

Anaphylactoid reactions

Do not give diclofenac to patients with the aspirin triad, which typically occurs in patients with asthma who experience rhinitis with or without nasal polyps, or those who exhibit severe, potentially fatal bronchospasm after taking aspirin or other NSAIDs.

Asthma

Patients with asthma may have aspirin-sensitive asthma, which may be associated with severe and sometimes fatal bronchospasm. Do not administer diclofenac to patients with this type of aspirin-sensitivity because of possible cross-reactivity.

Bleeding

There have been reports that ocularly applied NSAIDs may cause increased bleeding of ocular tissue in conjunction with surgery.

Hepatic effects

Borderline elevations of 1 or more LFTs may occur in patients taking diclofenac.

Hypertension

New hypertension or worsening of preexisting hypertension, either of which may contribute to increased risk of CV events, may occur.

Long-term use

Renal papillary necrosis and other renal injury may occur.

Platelet effects

NSAIDs inhibit platelet aggregation and have been reported to prolong bleeding time.

Skin reactions

Serious and sometimes fatal skin adverse reactions, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, may occur.

Overdosage

Symptoms

Acute renal failure, coma, drowsiness, epigastric pain, GI bleeding, hypertension, lethargy, nausea, respiratory depression, vomiting.

Patient Information

Advise patient that dose is individualized based upon severity of symptoms and response to therapy.
Advise patient to take prescribed dose without regard to meals, but to take with food, milk, or antacids if stomach upset occurs.
Advise patient not to cut, crush, chew, or break tablets, and to swallow whole with a full glass of water.
Caution patient to avoid alcohol, aspirin-containing medications, and smoking while taking this drug.
Caution patient to avoid product late in pregnancy because it may cause premature closure of the ductus arteriosus.
Advise patient to seek emergency medical assistance if any of the following occur: chest pain, shortness of breath or trouble breathing, slurred speech, swelling of the face or throat, weakness in one part or on one side of body.
Advise patient if a dose is missed, to take it as soon as possible. If close to next dose, do not double the dose; instead, take next dose as scheduled.
Advise patient to discontinue drug and notify health care provider if any of the following occur: changes in urine patterns, fatigue, fever, GI upset, itching, joint pain, persistent nausea, persistent or recurrent black stools, skin rash, unusual bleeding or bruising, visual disturbances, weight gain or edema, yellowing of skin or eyes.
Advise patient to avoid unnecessary exposure to sunlight or tanning lamps and to use sunscreen and wear protective clothing to avoid photosensitivity reactions.

Ophthalmic solution
Remind patient that eye drops are for use in the eye only.
Teach patient proper technique for instilling eye drops: wash hands; do not allow dropper to touch eye. Tilt head back, look up and pull lower eyelid down, then instill prescribed number of drops. Close eye for 2 to 3 min and apply gentle pressure to bridge of nose for 1 to 2 min. Do not rub eye.
Advise patient not to touch top of dropper bottle to eye, fingers, or other surface.
Advise patient that if more than 1 topical ophthalmic drug is being used, administer the drugs at least 5 min apart. Administer ointment last.
Except for use of bandage hydrogel soft contact lens during first 3 days after refractive surgery, advise patients wearing soft contact lenses not to use the ophthalmic solution.
Inform patient that temporary stinging and burning are the most common adverse reactions and to contact health care provider if these occur and are bothersome.
Advise patient to contact eye doctor if eye or eyelid inflammation is noted, or if eye symptoms do not improve or they worsen.
Instruct patient wearing contact lenses to remove lenses when instilling eye drops.

Topical gel
Advise patient that gel will not work immediately, but to expect a slow improvement over several weeks. Inform patient that gel usually is applied daily for 60 to 90 days and that complete healing of the lesion(s) may not be evident for up to 30 days following cessation of therapy.
Advise patient to gently smooth gel onto skin lesions twice daily as directed by health care provider.
Teach patient or caregiver proper technique for applying gel: wash hands; gently smooth enough gel onto affected skin to adequately cover each lesion; wash hands after applying gel.
Caution patient not to apply gel to open skin wounds, infected skin, or skin that is scaling.
Caution patient to avoid contact with eyes. Advise patient that if gel does come into contact with eyes to wash them with large amounts of cool water and contact health care provider if eye irritation occurs.
Advise patient to talk with health care provider before using any other topical agents (eg, astringents, cosmetics, medicated soaps) on treated skin.
Caution patient that drug may cause drowsiness or dizziness and to use caution while driving or performing other tasks requiring mental alertness until tolerance is determined.
Advise patient that avoiding ultraviolet light is an important part of therapy and to avoid exposure to sunlight or tanning lamps, use sunscreen, and wear protective clothing during treatment.
Advise patient to notify health care provider if condition does not improve or it worsens, or if application-site reactions (eg, dry skin, irritation, rash, redness, scaling) develop and are bothersome.

Topical patch
Instruct patient to wash hands after applying, handling, or removing the patch.
Caution patients to use patch only on intact skin.
Advise patients to avoid contact with eyes or mucosa. If eye contact occurs, instruct patient to immediately wash out the eye with water or saline and contact their health care provider if irritation persists for more than 1 h.
Instruct patient that if patch begins to peel off, the edges may be taped down.
Instruct patient not to wear patch when bathing or showering.