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Diclofenac Potassium

Class: Other Nonsteroidal Anti-inflammatory Agents
Note: This monograph also contains information on diclofenac epolamine, Diclofenac Sodium
Chemical Name: 2-[(2,6-dichlorophenyl)amino] benzeneacetic acid, monopotassium salt
Molecular Formula: C14H11C12NO2•KC14H11C12NO2.NaC20H24Cl2N2O3
CAS Number: 15307-81-0
Brands: Flector, Voltaren

Medically reviewed on November 21, 2016

Warning

    Cardiovascular Risk
  • Increased risk of serious (sometimes fatal) cardiovascular thrombotic events (e.g., MI, stroke).1 302 303 317 318 500 502 508 Risk may occur early in treatment and may increase with duration of use.500 502 505 506 508 (See Cardiovascular Thrombotic Effects under Cautions.)

  • Contraindicated in the setting of CABG surgery.508

    GI Risk
  • Increased risk of serious (sometimes fatal) GI events (e.g., bleeding, ulceration, perforation of the stomach or intestine).1 302 303 317 318 Serious GI events can occur at any time and may not be preceded by warning signs and symptoms.1 302 303 317 318 Geriatric individuals are at greater risk for serious GI events.1 302 303 317 318 (See GI Effects under Cautions.)

Introduction

See also: Orencia

Prototypical NSAIA;1 2 3 4 5 6 7 8 9 189 302 303 317 318 phenylacetic acid derivative;1 2 3 4 5 6 7 8 9 189 262 structurally related to meclofenamate sodium and mefenamic acid.203

Uses for Diclofenac Potassium

Inflammatory Diseases

Orally for symptomatic treatment of osteoarthritis,1 81 82 83 84 85 86 89 90 107 108 109 110 111 112 113 114 121 125 126 133 274 302 303 rheumatoid arthritis,1 74 75 76 77 78 79 80 87 88 107 115 116 117 118 119 121 125 126 129 254 302 303 and ankylosing spondylitis.1 91 120 121 125 127 274

Orally in fixed combination with misoprostol for the symptomatic treatment of osteoarthritis and rheumatoid arthritis in patients at high risk for developing NSAIA-induced gastric or duodenal ulcers and in patients at high risk for developing complications from these ulcers.284

Topically (as gel) for the symptomatic treatment of osteoarthritis-related joint pain.318 321 Used for joints amenable to topical therapy (e.g., hands, knees); has not been evaluated on joints of the spine, hip, or shoulder.318

Orally for management of juvenile rheumatoid arthritis.3 128 210

Orally for symptomatic relief of acute gouty arthritis.121 130 131 132

Orally or topically for symptomatic treatment of infusion-related superficial thrombophlebitis.310 311

Pain

Orally for relief of pain, including postoperative (e.g., orthopedic, gynecologic, oral) pain, in adults.276 277 278 279 303

Transdermally for relief of acute pain due to minor strains, sprains, and contusions.317 319

Dysmenorrhea

Orally for symptomatic management of primary dysmenorrhea.303

Diclofenac Potassium Dosage and Administration

General

  • Consider potential benefits and risks of diclofenac therapy as well as alternative therapies before initiating therapy with the drug.1 302 303 317

Administration

Oral Administration

Diclofenac sodium delayed-release (enteric-coated) and extended-release tablets are not recommended for relief of acute pain3 248 or primary dysmenorrhea1 because of slow onset of action.53 54 56 57 60 61

Topical Administration

Diclofenac Sodium 1% Gel

Apply gel 4 times daily to the affected joint.318 Use the dosing card from the manufacturer to measure the appropriate dose.318 Apply the gel within the oblong area of the dosing card up to the appropriate (2- or 4-g of gel) line; then use the dosing card to apply the gel.318 Gently massage the gel into the skin; ensure gel is applied to the entire affected joint (e.g., foot [including sole, top of foot, and toes], knee, ankle, hand [including palm, back of hand, and fingers], elbow, wrist).318

Allow application site to dry for 10 minutes before covering treated area with clothing; wait at least 60 minutes before bathing or showering.318 Wash hands after application unless the treated joint is in the hand.318

Do not apply to open wounds, infected or inflamed areas of skin, or areas affected with exfoliative dermatitis; avoid contact with eyes and mucous membranes.318

Do not expose treated joint to external heat or to natural or artificial sunlight; do not use occlusive dressings.318

Avoid application of sunscreens, cosmetics, lotions, moisturizers, insect repellents, or other topical agents to the same site; concomitant use with other topical agents not studied.318

Diclofenac Epolamine Transdermal System

Apply transdermal system to the most painful area twice daily.317 Apply to intact skin; do not apply to damaged skin (e.g., wounds, burns, infected areas of skin, areas affected with eczema or exudative dermatitis).317

Wash hands after handling the system.317

Avoid contact with eyes and mucous membranes.317

Do not wear the transdermal system while bathing or showering.317

If a system should begin to peel off during the period of use, the edges of the system may be taped to the skin.317

Dosage

Available as diclofenac potassium, diclofenac sodium, or diclofenac epolamine; dosage expressed in terms of the salt.1 302 303 317 318

To minimize the potential risk of adverse cardiovascular and/or GI events, use lowest effective dosage and shortest duration of therapy consistent with the patient’s treatment goals.1 302 303 317 Adjust dosage based on individual requirements and response; attempt to titrate to the lowest effective dosage.1 302 303 317

Based on safety reviews conducted to evaluate cardiovascular risk of diclofenac, some authorities (e.g., Health Canada) now recommend that systemic diclofenac dosage not exceed 100 mg daily (except on first day of treatment for dysmenorrhea when total dose of 200 mg may be administered).520 (See Cardiovascular Thrombotic Effects under Cautions.)

Commercially available diclofenac sodium enteric-coated tablets (e.g., Voltaren), diclofenac sodium extended-release tablets (e.g., Voltaren-XR), and diclofenac potassium immediate-release tablets are not necessarily bioequivalent on a mg-per-mg basis.1 302 303

Adults

Inflammatory Diseases
Oral

Some authorities (e.g., Health Canada) recommend that systemic diclofenac dosage for inflammatory diseases not exceed 100 mg daily.520 (See Cardiovascular Thrombotic Effects under Cautions.)

Osteoarthritis
Oral

May change dosage to 50 or 75 mg twice daily in patients who do not tolerate usual dosage; however, these dosages may be less effective in preventing NSAIA-induced ulcers.284

Preparation

Dosage

Diclofenac potassium conventional tablets

100–150 mg daily, given as 50 mg 2 or 3 times daily303

Diclofenac sodium delayed-release tablets

100–150 mg daily, given as 50 mg 2 or 3 times daily or 75 mg twice daily1

Diclofenac sodium extended-release tablets

100 mg once daily302

Diclofenac sodium (in fixed combination with misoprostol)

50 mg 3 times daily284

Topical (gel)

For lower extremity (i.e., knees, ankles, feet) joint pain, massage 4 g of diclofenac sodium 1% gel into the affected joint 4 times daily.318

For upper extremity (i.e., elbows, wrists, hands) joint pain, massage 2 g of diclofenac sodium 1% gel into the affected joint 4 times daily.318

If multiple joints are treated, total daily dose applied to all joints should be ≤32 g of gel daily.318

Rheumatoid Arthritis
Oral

May change dosage to 50 or 75 mg twice daily in patients who do not tolerate usual dosage; however, these dosages may be less effective in preventing NSAIA-induced ulcers.284

Preparation

Dosage

Diclofenac potassium conventional tablets

150–200 mg daily, given as 50 mg 3 or 4 times daily303

Diclofenac sodium delayed-release tablets

150–200 mg daily, given as 50 mg 3 or 4 times daily or 75 mg twice daily1

Diclofenac sodium extended-release tablets

100 mg once daily; may increase to 100 mg twice daily 302

Diclofenac sodium (in fixed combination with misoprostol)

50 mg 3 or 4 times daily284

Ankylosing Spondylitis
Oral

100–125 mg daily (as diclofenac sodium delayed-release tablets); administer as 25 mg 4 times daily, with 5th dose at bedtime as needed.1 91 125

Pain
Oral

50 mg 3 times daily (as diclofenac potassium conventional tablets).303 Some patients may benefit from initial dose of 100 mg (followed by 50-mg doses).303

Some authorities (e.g., Health Canada) recommend that dosage not exceed 100 mg daily.520 (See Cardiovascular Thrombotic Effects under Cautions.)

Topical (transdermal system)

Apply 1 transdermal system (diclofenac epolamine 1.3%) twice daily.317

Dysmenorrhea
Oral

50 mg 3 times daily (as diclofenac potassium conventional tablets).303 Some patients may benefit from initial dose of 100 mg (followed by 50-mg doses).303

Some authorities (e.g., Health Canada) state that a total dose of 200 mg may be administered on the first day of treatment for dysmenorrhea but subsequent dosage should not exceed 100 mg daily.520 (See Cardiovascular Thrombotic Effects under Cautions.)

Prescribing Limits

Adults

Based on safety reviews conducted to evaluate cardiovascular risk of diclofenac, some authorities (e.g., Health Canada) now recommend that systemic diclofenac dosage not exceed 100 mg daily (except on first day of treatment for dysmenorrhea when total dose of 200 mg may be administered).520 (See Cardiovascular Thrombotic Effects under Cautions.)

Inflammatory Diseases
Osteoarthritis
Topical (gel)

Maximum total daily dose applied to all affected joints: 32 g of diclofenac sodium 1% gel.318 Maximum 16 g of gel applied daily to any single lower extremity joint and 8 g applied daily to any single upper extremity joint.318

Special Populations

Renal Impairment

Dosage adjustment not required.1 3 72 247 248 302 303

Hepatic Impairment

Reduction of oral dosage may be necessary.1 302 303

Cautions for Diclofenac Potassium

Contraindications

  • Known hypersensitivity to diclofenac or any ingredient in the formulation.1 302 303 317 318

  • History of asthma, urticaria, or other sensitivity reaction precipitated by aspirin or other NSAIAs.1 141 144 145 146 147 168 225 302 303 317 318

  • In the setting of CABG surgery.508

  • Diclofenac sodium in fixed combination with misoprostol is contraindicated in pregnant women.284

Warnings/Precautions

Warnings

Consider potential benefits and risks of diclofenac therapy as well as alternative therapies before initiating therapy with the drug.1 302 303 317 Use lowest effective dosage and shortest duration of therapy consistent with the patient’s treatment goals.1 302 303 317 318

Cardiovascular Thrombotic Effects

NSAIAs (selective COX-2 inhibitors, prototypical NSAIAs) increase the risk of serious adverse cardiovascular thrombotic events (e.g., MI, stroke) in patients with or without cardiovascular disease or risk factors for cardiovascular disease.500 502 508

Findings of FDA review of observational studies, meta-analysis of randomized controlled trials, and other published information500 501 502 indicate that NSAIAs may increase the risk of such events by 10–50% or more, depending on the drugs and dosages studied.500

Relative increase in risk appears to be similar in patients with or without known underlying cardiovascular disease or risk factors for cardiovascular disease, but the absolute incidence of serious NSAIA-associated cardiovascular thrombotic events is higher in those with cardiovascular disease or risk factors for cardiovascular disease because of their elevated baseline risk.500 502 506 508

Increased risk may occur early (within the first weeks) following initiation of therapy and may increase with higher dosages and longer durations of use.500 502 505 506 508

In controlled studies, increased risk of MI and stroke observed in patients receiving a selective COX-2 inhibitor for analgesia in first 10–14 days following CABG surgery.508

In patients receiving NSAIAs following MI, increased risk of reinfarction and death observed beginning in the first week of treatment.505 508

Increased 1-year mortality rate observed in patients receiving NSAIAs following MI;500 508 511 absolute mortality rate declined somewhat after the first post-MI year, but the increased relative risk of death persisted over at least the next 4 years.508 511

Some systematic reviews of controlled observational studies and meta-analyses of randomized studies suggest naproxen may be associated with lower risk of cardiovascular thrombotic events compared with other NSAIAs.312 313 314 316 500 501 502 503 506 FDA states that limitations of these studies and indirect comparisons preclude definitive conclusions regarding relative risks of NSAIAs.500

Findings from some meta-analyses and systematic reviews also suggest that cardiovascular risk of diclofenac, particularly at higher dosages (e.g., ≥150 mg daily), is similar to that observed with selective COX-2 inhibitors.312 313 501 503 506 520 521 Some authorities (e.g., Health Canada) now recommend that systemic diclofenac dosage not exceed 100 mg daily (except for first day of treatment for dysmenorrhea).520 (See Dosage under Dosage and Administration.)

Use NSAIAs with caution and careful monitoring (e.g., monitor for development of cardiovascular events throughout therapy, even in those without prior cardiovascular symptoms) and at the lowest effective dosage for the shortest duration necessary.1 302 303 317 318 500 508

Some clinicians suggest that it may be prudent to avoid NSAIA use, whenever possible, in patients with cardiovascular disease.505 511 512 516 Avoid use in patients with recent MI unless benefits of therapy are expected to outweigh risk of recurrent cardiovascular thrombotic events; if used, monitor for cardiac ischemia.508 Contraindicated in the setting of CABG surgery.508

No consistent evidence that concomitant use of low-dose aspirin mitigates the increased risk of serious adverse cardiovascular events associated with NSAIAs.1 302 303 317 318 502 508 (See Specific Drugs under Interactions.)

GI Effects

Serious GI toxicity (e.g., bleeding, ulceration, perforation) can occur with or without warning symptoms; increased risk in those with a history of GI bleeding or ulceration, geriatric patients, smokers, those with alcohol dependence, and those in poor general health.1 167 181 187 256 259 260 267 268 282 292 300 302 303 317 318

For patients at high risk for complications from NSAIA-induced GI ulceration (e.g., bleeding, perforation), consider concomitant use of misoprostol;249 254 284 292 293 alternatively, consider concomitant use of a proton-pump inhibitor (e.g., omeprazole)249 254 292 or use of an NSAIA that is a selective inhibitor of COX-2 (e.g., celecoxib).249

Hypertension

Hypertension and worsening of preexisting hypertension reported; either event may contribute to the increased incidence of cardiovascular events.1 302 303 317 318 Use with caution in patients with hypertension; monitor BP.1 302 303 317 318

Impaired response to ACE inhibitors, angiotensin II receptor antagonists, β-blockers, and certain diuretics may occur.1 302 303 317 318 508 (See Specific Drugs under Interactions.)

Heart Failure and Edema

Fluid retention and edema reported.1 302 303 317 318 508

NSAIAs (selective COX-2 inhibitors, prototypical NSAIAs) may increase morbidity and mortality in patients with heart failure.500 501 504 507 508

NSAIAs may diminish cardiovascular effects of diuretics, ACE inhibitors, or angiotensin II receptor antagonists used to treat heart failure or edema.508 (See Specific Drugs under Interactions.)

Manufacturer recommends avoiding use in patients with severe heart failure unless benefits of therapy are expected to outweigh risk of worsening heart failure; if used, monitor for worsening heart failure.508

Some experts recommend avoiding use, whenever possible, in patients with reduced left ventricular ejection fraction and current or prior symptoms of heart failure.507

Renal Effects

Direct renal injury, including renal papillary necrosis, reported in patients receiving long-term NSAIA therapy.1 302 303 317 318

Potential for overt renal decompensation.1 171 302 303 317 318 Increased risk of renal toxicity in patients with renal or hepatic impairment or heart failure, in geriatric patients, in patients with volume depletion, and in those receiving a diuretic, ACE inhibitor, or angiotensin II receptor antagonist.1 160 174 185 191 284 302 303 306 315 317 318 (See Renal Impairment under Cautions.)

Sensitivity Reactions

Hypersensitivity Reactions

Anaphylactoid reactions (e.g., anaphylaxis, angioedema) reported.1 302 303 317 318

Immediate medical intervention and discontinuance for anaphylaxis.1 302 303 317 318

Avoid in patients with aspirin triad (aspirin sensitivity, asthma, nasal polyps); caution in patients with asthma.1 302 303 317 318

Dermatologic Reactions

Serious skin reactions (e.g., exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis) reported; can occur without warning.1 302 303 317 318 Discontinue at first appearance of rash or any other sign of hypersensitivity (e.g., blisters, fever, pruritus).1 302 303 317 318

General Precautions

Do not use multiple diclofenac-containing preparations concomitantly.1 302 303 Concomitant use of diclofenac sodium 1% gel and oral NSAIAs may increase risk of adverse effects.318

Observe the usual cautions, precautions, and contraindications associated with misoprostol therapy when diclofenac is used in fixed combination with misoprostol.284

Hepatic Effects

Severe, sometimes fatal, reactions including jaundice, fulminant hepatitis, liver necrosis, and hepatic failure reported rarely with diclofenac.1 302 303 317 318 323

Elevations of serum ALT or AST reported.1 302 303 317 318 323

Monitor for symptoms and/or signs suggesting liver dysfunction.1 302 303 317 318 323 Obtain serum transaminase values 4–8 weeks after initiating therapy; monitor periodically during long-term therapy.317 318 323 ALT (SGPT) is the recommended hepatic function marker for monitoring liver injury.317 318 323

Discontinue if abnormal liver function test results persist or worsen, if clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g., eosinophilia, rash).1 164 255 302 303 317 318 323

Hematologic Effects

Anemia reported rarely.1 302 303 317 318 Determine hemoglobin concentration or hematocrit in patients receiving long-term therapy if signs or symptoms of anemia occur.1 248 302 303 317 318

May inhibit platelet aggregation and prolong bleeding time.3 40 41 42 43 165 166

Precautions Specific to Diclofenac Sodium 1% Gel

Minimize or avoid exposure of treated areas to natural or artificial sunlight.318 Topical application of diclofenac gel formulations has resulted in early onset of ultraviolet (UV) light-related skin tumors in animal studies.318 321 The potential effects of topical diclofenac gel on skin response to UV damage in humans are not known.318

Application to nonintact skin may alter absorption and tolerability; apply only to intact skin.318

Avoid contact with the eyes and mucous membranes.318 If contact with the eyes occurs, thoroughly rinse the eyes with water or saline.318 If ocular irritation persists for >1 hour, consult a clinician.318

Precautions Specific to Diclofenac Epolamine Transdermal System

Avoid contact with eyes and mucous membranes.317 If contact with the eyes occurs, thoroughly rinse the eyes with water or saline.317 If ocular irritation persists for >1 hour, consult a clinician.317

Do not apply to nonintact or damaged skin.317

Patient should bathe or shower after removing one transdermal system and before applying a new system; the transdermal system should not be worn during bathing or showering.317

Store and discard transdermal systems in a manner that avoids accidental exposure or ingestion by children or pets.317

Other Precautions

Not a substitute for corticosteroid therapy; not effective in the management of adrenal insufficiency.1 248 302 303 317 318

May mask certain signs of infection.1 302 303 317 318

Obtain CBC and chemistry profile periodically during long-term use.1 302 303 317 318

Specific Populations

Pregnancy

Category C.1 302 303 317 318 Avoid use in third trimester because of possible premature closure of the ductus arteriosus.1 302 303 317 318

Category X (in fixed combination with misoprostol).284 Misoprostol exhibits abortifacient activity and can cause serious fetal harm.284

Lactation

Distributed into milk; 3 discontinue nursing or the drug.1 302 303 317 318

Pediatric Use

Safety and efficacy not established in children.1 302 303 317 318

Good results with oral diclofenac obtained in a limited number of children 3–16 years of age for the management of juvenile rheumatoid arthritis.3 128 210

Geriatric Use

Oral diclofenac: Caution advised.1 302 303 Fatal adverse GI effects reported more frequently in geriatric patients than younger adults.1 302 303 317 318

Diclofenac sodium 1% gel: No substantial difference in safety and efficacy in individuals ≥65 years of age compared with younger individuals; possibility of greater sensitivity to the drug in some geriatric individuals.318

Diclofenac epolamine transdermal system: Insufficient experience in individuals ≥65 years of age to determine whether geriatric patients respond differently than younger individuals.317

Use diclofenac with caution because of age-related decreases in renal function.317 318 May be useful to monitor renal function.317 318

Hepatic Impairment

Reduction of oral dosage may be necessary.1 302 303

Renal Impairment

Metabolites eliminated principally via the kidney.1 302 303

Use with caution in patients with renal disease.1 302 303 317 318 Use not recommended in patients with advanced renal disease; close monitoring of renal function advised if used.1 248 302 303 304 317 318

Common Adverse Effects

Oral diclofenac: Abdominal pain or cramps,1 75 86 93 107 113 136 302 303 constipation,1 75 113 132 134 136 302 303 diarrhea,1 84 86 87 93 95 125 134 302 303 flatulence,1 302 303 GI bleeding,1 302 303 GI perforation, 1 302 303 peptic ulcer,1 302 303 vomiting, 1 302 303 dyspepsia,1 302 303 nausea,1 76 78 84 85 93 95 96 97 98 99 109 111 113 126 129 134 165 302 303 dizziness,1 102 107 113 125 129 165 302 303 headache,1 89 90 91 93 95 107 110 113 118 125 127 129 132 165 302 303 liver function test abnormalities,1 116 125 165 189 209 223 255 302 303 renal function abnormalities,1 302 303 anemia,1 302 303 prolonged bleeding time,1 302 303 pruritus,1 302 303 rash,1 302 303 tinnitus,1 302 303 edema.1 109 125 132 159 165 302 303

Diclofenac sodium 1% gel: Application site reactions (e.g., dermatitis).318

Diclofenac epolamine transdermal system: Application site reactions (e.g., pruritus, dermatitis), nausea, altered taste.317

Interactions for Diclofenac Potassium

Protein-bound Drugs

Only minimally displaces other highly protein-bound drugs from binding sites; however, may be displaced from binding sites by other highly protein-bound drugs.51 52 59 61

Specific Drugs

Drug

Interaction

Comments

ACE inhibitors

Reduced BP response to ACE inhibitor1 248 302 303 317 318

Possible deterioration of renal function in individuals with renal impairment315

Monitor BP1 248 302 303 317 318

Angiotensin II receptor antagonists

Reduced BP response to angiotensin II receptor antagonist315

Possible deterioration of renal function in individuals with renal impairment315

Antacids (magnesium- or aluminum-containing)

Delayed diclofenac absorption3 189 238

Anticoagulants (warfarin)

Possible bleeding complications1 302 303 317 318

Caution advised1 302 303

Aspirin

Decreased peak plasma concentration and AUC of diclofenac;22 61 184 202 302 303 limited data indicate that diclofenac does not inhibit antiplatelet effect of aspirin262

Increased risk of GI ulceration and other complications1 302 303 317 318

No consistent evidence that low-dose aspirin mitigates the increased risk of serious cardiovascular events associated with NSAIAs305 317 318 502 508

Manufacturer states that concomitant use not recommended1 302 303 317 318

Cyclosporine

Possible increase in nephrotoxic effects of cyclosporine1 302 303 318

Caution advised1 302 303 318

Diuretics (furosemide, thiazides)

Reduced natriuretic effects1 22 179 302 303 317 318

Monitor for diuretic efficacy and renal failure1 302 303 317 318

Lithium

Increased plasma lithium concentrations1 176 188 265 302 303 317 318

Monitor for lithium toxicity1 302 303 317 318

Methotrexate

Severe, sometimes fatal toxicity associated with increased plasma methotrexate concentrations175 307

Caution advised1 302 303 317 318

Quinolones (ciprofloxacin)

Possible increased risk of seizures183 197 198

Diclofenac Potassium Pharmacokinetics

Absorption

Bioavailability

Well absorbed following oral administration.1 3 51 52 53 57 68 189 302 303 Undergoes first-pass metabolism; only 50–60% of a dose reaches systemic circulation as unchanged drug.1 52 53 73 284 302 303

Peak plasma concentration usually attained within about 1 hour (diclofenac potassium conventional tablets), 2 hours (diclofenac sodium delayed-release tablets), or 5.25 hours (diclofenac sodium extended-release tablets).1 3 51 52 302 303 307

Absorbed into systemic circulation following topical administration as gel or transdermal system; plasma concentrations generally very low compared with oral administration.3 227 317 318

Following application of a single diclofenac epolamine transdermal system to intact skin on the upper arm, peak plasma concentrations occur in 10–20 hours.317

Following topical application of diclofenac sodium 1% gel, peak plasma concentrations occur in about 10–14 hours.318

Moderate exercise does not alter systemic absorption of topically applied diclofenac (transdermal system or 1% gel).317 318

Application of a heat patch for 15 minutes before application of the 1% gel did not affect systemic absorption.318 Not established whether application of heat following gel application affects systemic absorption.318

Onset

Single 50- or 100-mg doses of diclofenac potassium provide pain relief within 30 minutes.307

Duration

Pain relief lasts up to 8 hours following administration of single 50- or 100-mg doses of diclofenac potassium.307

Food

Food delays time to reach peak plasma concentration but does not affect extent of absorption following administration as conventional, delayed-release, or extended-release tablets.1 302 303

Distribution

Extent

Widely distributed in animals.3 51 52

Following oral administration, concentrations in synovial fluid may exceed those in plasma.1 3 62 63 64 65 66 67 68 69 302 303

Plasma Protein Binding

>99%.1 3 51 52 58 59 66 302 303 317

Elimination

Metabolism

Metabolized in the liver via hydroxylation and conjugation.1 3 51 52 68 70 302 303 Some metabolites may exhibit anti-inflammatory activity.1 3 22 302 303

Elimination Route

Excreted in urine (65%) and in feces via biliary elimination (35%) as metabolites.1 3 51 55 56 70 71 302 303

Half-life

Oral preparations: 1–2 hours.2 53 57 60 302 303

Diclofenac epolamine transdermal system: Approximately 12 hours.317

Special Populations

In geriatric patients, pharmacokinetic profile similar to that in younger adults.307

In patients with renal impairment, plasma clearance not substantially altered,1 3 208 302 303 although clearance of metabolites may be decreased.3 72

Stability

Storage

Oral

Tablets

Tight containers at ≤30°C.1 302 303

Topical

Gel

25°C (may be exposed to 15–30°C).318 Do not freeze.318

Transdermal System

25°C (may be exposed to 15–30°C).317

Actions

Advice to Patients

  • Importance of reading the medication guide for NSAIAs that is provided each time the drug is dispensed.1 302 303 317 318

  • Risk of serious cardiovascular events (e.g., MI, stroke).1 302 303 317 318 500 508

  • Risk of GI bleeding and ulceration.1 167 181 302 303 317 318

  • Risk of serious skin reactions.1 302 303 317 318 Risk of anaphylactoid and other sensitivity reactions.1 302 303 317 318

  • Risk of hepatotoxicity.1 302 303 317 318

  • Importance of seeking immediate medical attention if signs and symptoms of a cardiovascular event (chest pain, dyspnea, weakness, slurred speech) occur.1 302 303 317 318 500 508

  • Importance of notifying clinician if signs and symptoms of GI ulceration or bleeding, unexplained weight gain, or edema develops.1 302 303 317 318

  • Importance of discontinuing diclofenac and contacting clinician if rash or other signs of hypersensitivity (blisters, fever, pruritus) develop.1 302 303 317 318 Importance of seeking immediate medical attention if an anaphylactic reaction occurs.1 302 303 317 318

  • Importance of discontinuing therapy and contacting clinician immediately if signs and symptoms of hepatotoxicity (nausea, anorexia, fatigue, lethargy, pruritus, jaundice, upper right quadrant tenderness, flu-like symptoms) occur.1 302 303 317 318

  • Risk of heart failure or edema; importance of reporting dyspnea, unexplained weight gain, or edema.508

  • Importance of warning patients to keep diclofenac transdermal system out of the reach of children and pets and to safely dispose of used units.317 Importance of properly disposing of dosing cards used to apply diclofenac gel.318

  • Importance of adhering to instructions for administration of topical gel or transdermal system.317 318

  • Importance of avoiding or limiting exposure of skin treated with diclofenac gel to natural or artificial sunlight.318

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 302 303 317 318 Importance of avoiding diclofenac in late pregnancy (third trimester).1 302 303 317 318

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.1 302 303 317 318

  • Importance of informing patients of other important precautionary information.1 302 303 317 318 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Diclofenac Epolamine

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Topical

Transdermal System

1.3%

Flector

King

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Diclofenac Potassium

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

50 mg*

Diclofenac Potassium Tablets

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Diclofenac Sodium

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, delayed-release (enteric-coated)

25 mg*

Diclofenac Sodium Delayed-release Tablets

50 mg*

Diclofenac Sodium Delayed-release Tablets

75 mg*

Diclofenac Sodium Delayed-release Tablets

Voltaren

Novartis

Tablets, extended-release

100 mg*

Diclofenac Sodium Extended Release Tablets

Voltaren-XR

Novartis

Topical

Gel

1%

Voltaren

Novartis

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Diclofenac Sodium Combinations

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, delayed-release (enteric-coated core), film-coated

50 mg diclofenac sodium enteric-coated core, with 200 mcg of misoprostol outer layer*

Arthrotec

Searle

Diclofenac Sodium and Misoprostol Delayed-release Tablets

75 mg diclofenac sodium enteric-coated core, with 200 mcg of misoprostol outer layer*

Arthrotec

Searle

Diclofenac Sodium and Misoprostol Delayed-release Tablets

AHFS DI Essentials. © Copyright 2018, Selected Revisions November 21, 2016. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Novartis. Voltaren (diclofenac sodium enteric-coated tablets) prescribing information. East Hanover, NJ; 2006 Jan.

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