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Diclofenac (Systemic)

Class: Other Nonsteroidal Anti-inflammatory Agents
Chemical Name: 2-[(2,6-dichlorophenyl)amino] benzeneacetic acid, monopotassium salt
Molecular Formula: C14H11C12NO2•KC14H11C12NO2.NaC20H24Cl2N2O3
CAS Number: 15307-81-0
Brands: Flector, Licart, Voltaren

Medically reviewed by Drugs.com. Last updated on Nov 9, 2020.

Warning

Special Alerts:

[Posted 10/15/2020]

AUDIENCE: Consumer, Patient, Health Professional, Pharmacy

ISSUE: FDA is warning that use of NSAIDs around 20 weeks or later in pregnancy may cause rare but serious kidney problems in an unborn baby. This can lead to low levels of amniotic fluid surrounding the baby and possible complications.

For prescription NSAIDs, FDA is requiring changes to the prescribing information to describe the risk of kidney problems in unborn babies that result in low amniotic fluid.

For over-the-counter (OTC) NSAIDs intended for use in adults, FDA will also update the Drug Facts labels, available at: [Web]. These labels already warn to avoid using NSAIDs during the last 3 months of pregnancy because the medicines may cause problems in the unborn child or complications during delivery. The Drug Facts labels already advise pregnant and breastfeeding women to ask a health care professional before using these medicines.

BACKGROUND:

NSAIDs

  • are a class of medicines available by prescription and OTC. They are some of the most commonly used medicines for pain and fever.

  • are used to treat medical conditions such as arthritis, menstrual cramps, headaches, colds, and the flu.

  • work by blocking the production of certain chemicals in the body that cause inflammation.

  • are available alone and combined with other medicines. Examples of NSAIDs include aspirin, ibuprofen, naproxen, diclofenac, and celecoxib.

Common side effects of NSAIDs include: stomach pain, constipation, diarrhea, gas, heartburn, nausea, vomiting, and dizziness.

RECOMMENDATION:

Consumers/Patients

  • If you are pregnant, do not use NSAIDs at 20 weeks or later in pregnancy unless specifically advised to do so by your health care professional because these medicines may cause problems in your unborn baby.

  • Many OTC medicines contain NSAIDs, including those used for pain, colds, flu, and insomnia, so it is important to read the Drug Facts labels, available at: [Web], to find out if the medicines contain NSAIDs.

  • Talk to your health care professional or pharmacist if you have questions or concerns about NSAIDs or which medicines contain them.

  • Other medicines, such as acetaminophen, are available to treat pain and fever during pregnancy. Talk to your pharmacist or health care professional for help deciding which might be best.

Health Care Professionals

  • FDA recommends that health care professionals should limit prescribing NSAIDs between 20 to 30 weeks of pregnancy and avoid prescribing them after 30 weeks of pregnancy. If NSAID treatment is determined necessary, limit use to the lowest effective dose and shortest duration possible. Consider ultrasound monitoring of amniotic fluid if NSAID treatment extends beyond 48 hours and discontinue the NSAID if oligohydramnios is found. FDA is warning that use of NSAIDs around 20 weeks gestation or later in pregnancy may cause fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment.

  • These adverse outcomes are seen, on average, after days to weeks of treatment, although oligohydramnios has been infrequently reported as soon as 48 hours after NSAID initiation.

  • Oligohydramnios is often, but not always, reversible with treatment discontinuation.

  • Complications of prolonged oligohydramnios may include limb contractures and delayed lung maturation. In some postmarketing cases of impaired neonatal renal function, invasive procedures such as exchange transfusion or dialysis were required.

  • If NSAID treatment is deemed necessary between 20 to 30 weeks of pregnancy, limit use to the lowest effective dose and shortest duration possible. As currently described in the NSAID labels, avoid prescribing NSAIDs at 30 weeks and later in pregnancy because of the additional risk of premature closure of the fetal ductus arteriosus.

  • The above recommendations do not apply to low-dose 81 mg aspirin prescribed for certain conditions in pregnancy.

  • Consider ultrasound monitoring of amniotic fluid if NSAID treatment extends beyond 48 hours. Discontinue the NSAID if oligohydramnios occurs and follow up according to clinical practice.

For more information visit the FDA website at: [Web] and [Web].

Warning

    Cardiovascular Risk
  • Increased risk of serious (sometimes fatal) cardiovascular thrombotic events (e.g., MI, stroke). Risk may occur early in treatment and may increase with duration of use. (See Cardiovascular Thrombotic Effects under Cautions.)

  • Contraindicated in the setting of CABG surgery.

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

Introduction

Prototypical NSAIA; phenylacetic acid derivative; structurally related to meclofenamate sodium and mefenamic acid.

Uses for Diclofenac (Systemic)

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Inflammatory Diseases

Orally for symptomatic treatment of osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis.

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.

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

Orally for management of juvenile rheumatoid arthritis.

Orally for symptomatic relief of acute gouty arthritis.

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

Pain

Orally for relief of pain, including postoperative (e.g., orthopedic, gynecologic, oral) pain, in adults.

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

Dysmenorrhea

Orally for symptomatic management of primary dysmenorrhea.

Diclofenac (Systemic) Dosage and Administration

General

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

Administration

Oral Administration

Diclofenac sodium delayed-release (enteric-coated) and extended-release tablets are not recommended for relief of acute pain or primary dysmenorrhea because of slow onset of action.

Topical Administration

Diclofenac Sodium 1% Gel

Apply gel 4 times daily to the affected joint. Use the dosing card from the manufacturer to measure the appropriate dose. 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. 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).

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

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.

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

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.

Diclofenac Epolamine Transdermal System

Apply transdermal system to the most painful area twice daily. 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).

Wash hands after handling the system.

Avoid contact with eyes and mucous membranes.

Do not wear the transdermal system while bathing or showering.

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

Dosage

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Available as diclofenac potassium, diclofenac sodium, or diclofenac epolamine; dosage expressed in terms of the salt.

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. Adjust dosage based on individual requirements and response; attempt to titrate to the lowest effective dosage.

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). (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.

Adults

Inflammatory Diseases
Oral

Some authorities (e.g., Health Canada) recommend that systemic diclofenac dosage for inflammatory diseases not exceed 100 mg daily. (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.

Preparation

Dosage

Diclofenac potassium conventional tablets

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

Diclofenac sodium delayed-release tablets

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

Diclofenac sodium extended-release tablets

100 mg once daily

Diclofenac sodium (in fixed combination with misoprostol)

50 mg 3 times daily

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.

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.

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

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.

Preparation

Dosage

Diclofenac potassium conventional tablets

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

Diclofenac sodium delayed-release tablets

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

Diclofenac sodium extended-release tablets

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

Diclofenac sodium (in fixed combination with misoprostol)

50 mg 3 or 4 times daily

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.

Pain
Oral

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

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

Topical (transdermal system)

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

Dysmenorrhea
Oral

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

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. (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). (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. Maximum 16 g of gel applied daily to any single lower extremity joint and 8 g applied daily to any single upper extremity joint.

Special Populations

Renal Impairment

Dosage adjustment not required.

Hepatic Impairment

Reduction of oral dosage may be necessary.

Cautions for Diclofenac (Systemic)

Contraindications

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

  • Known hypersensitivity to diclofenac or any ingredient in the formulation.

  • History of asthma, urticaria, or other sensitivity reaction precipitated by aspirin or other NSAIAs.

  • In the setting of CABG surgery.

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

Warnings/Precautions

Warnings

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

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.

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

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.

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

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.

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

Increased 1-year mortality rate observed in patients receiving NSAIAs following MI; 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.

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. FDA states that limitations of these studies and indirect comparisons preclude definitive conclusions regarding relative risks of NSAIAs.

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. 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). (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.

Some clinicians suggest that it may be prudent to avoid NSAIA use, whenever possible, in patients with cardiovascular disease. 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. Contraindicated in the setting of CABG surgery.

No consistent evidence that concomitant use of low-dose aspirin mitigates the increased risk of serious adverse cardiovascular events associated with NSAIAs. (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.

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

Hypertension

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

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

Heart Failure and Edema

Fluid retention and edema reported.

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

NSAIAs may diminish cardiovascular effects of diuretics, ACE inhibitors, or angiotensin II receptor antagonists used to treat heart failure or edema. (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.

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

Renal Effects

Direct renal injury, including renal papillary necrosis, reported in patients receiving long-term NSAIA therapy.

Potential for overt renal decompensation. 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. (See Renal Impairment under Cautions.)

Sensitivity Reactions

Hypersensitivity Reactions

Anaphylactoid reactions (e.g., anaphylaxis, angioedema) reported.

Immediate medical intervention and discontinuance for anaphylaxis.

Avoid in patients with aspirin triad (aspirin sensitivity, asthma, nasal polyps); caution in patients with asthma.

Dermatologic Reactions

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

General Precautions

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

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

Hepatic Effects

Severe, sometimes fatal, reactions including jaundice, fulminant hepatitis, liver necrosis, and hepatic failure reported rarely with diclofenac.

Elevations of serum ALT or AST reported.

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

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).

Hematologic Effects

Anemia reported rarely. Determine hemoglobin concentration or hematocrit in patients receiving long-term therapy if signs or symptoms of anemia occur.

May inhibit platelet aggregation and prolong bleeding time.

Precautions Specific to Diclofenac Sodium 1% Gel

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

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

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

Precautions Specific to Diclofenac Epolamine Transdermal System

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

Do not apply to nonintact or damaged skin.

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.

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

Other Precautions

Not a substitute for corticosteroid therapy; not effective in the management of adrenal insufficiency.

May mask certain signs of infection.

Obtain CBC and chemistry profile periodically during long-term use.

Specific Populations

Pregnancy

Category C. Avoid use in third trimester because of possible premature closure of the ductus arteriosus.

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

Lactation

Distributed into milk; discontinue nursing or the drug.

Pediatric Use

Safety and efficacy not established in children.

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

Geriatric Use

Oral diclofenac: Caution advised. Fatal adverse GI effects reported more frequently in geriatric patients than younger adults.

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.

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

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

Hepatic Impairment

Reduction of oral dosage may be necessary.

Renal Impairment

Metabolites eliminated principally via the kidney.

Use with caution in patients with renal disease. Use not recommended in patients with advanced renal disease; close monitoring of renal function advised if used.

Common Adverse Effects

Oral diclofenac: Abdominal pain or cramps, constipation, diarrhea, flatulence, GI bleeding, GI perforation, peptic ulcer, vomiting, dyspepsia, nausea, dizziness, headache, liver function test abnormalities, renal function abnormalities, anemia, prolonged bleeding time, pruritus, rash, tinnitus, edema.

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

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

Interactions for Diclofenac (Systemic)

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.

Specific Drugs

Drug

Interaction

Comments

ACE inhibitors

Reduced BP response to ACE inhibitor

Possible deterioration of renal function in individuals with renal impairment

Monitor BP

Angiotensin II receptor antagonists

Reduced BP response to angiotensin II receptor antagonist

Possible deterioration of renal function in individuals with renal impairment

Antacids (magnesium- or aluminum-containing)

Delayed diclofenac absorption

Anticoagulants (warfarin)

Possible bleeding complications

Caution advised

Aspirin

Decreased peak plasma concentration and AUC of diclofenac; limited data indicate that diclofenac does not inhibit antiplatelet effect of aspirin

Increased risk of GI ulceration and other complications

No consistent evidence that low-dose aspirin mitigates the increased risk of serious cardiovascular events associated with NSAIAs

Manufacturer states that concomitant use not recommended

Cyclosporine

Possible increase in nephrotoxic effects of cyclosporine

Caution advised

Diuretics (furosemide, thiazides)

Reduced natriuretic effects

Monitor for diuretic efficacy and renal failure

Lithium

Increased plasma lithium concentrations

Monitor for lithium toxicity

Methotrexate

Severe, sometimes fatal toxicity associated with increased plasma methotrexate concentrations

Caution advised

Quinolones (ciprofloxacin)

Possible increased risk of seizures

Diclofenac (Systemic) Pharmacokinetics

Absorption

Bioavailability

Well absorbed following oral administration. Undergoes first-pass metabolism; only 50–60% of a dose reaches systemic circulation as unchanged drug.

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).

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

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

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

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

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

Onset

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

Duration

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

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.

Distribution

Extent

Widely distributed in animals.

Following oral administration, concentrations in synovial fluid may exceed those in plasma.

Plasma Protein Binding

>99%.

Elimination

Metabolism

Metabolized in the liver via hydroxylation and conjugation. Some metabolites may exhibit anti-inflammatory activity.

Elimination Route

Excreted in urine (65%) and in feces via biliary elimination (35%) as metabolites.

Half-life

Oral preparations: 1–2 hours.

Diclofenac epolamine transdermal system: Approximately 12 hours.

Special Populations

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

In patients with renal impairment, plasma clearance not substantially altered, although clearance of metabolites may be decreased.

Stability

Storage

Oral

Tablets

Tight containers at ≤30°C.

Topical

Gel

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

Transdermal System

25°C (may be exposed to 15–30°C).

Actions

  • Inhibits cyclooxygenase-1 (COX-1) and COX-2.

  • Pharmacologic actions similar to those of other prototypical NSAIAs; exhibits anti-inflammatory, analgesic, and antipyretic activity.

Advice to Patients

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

  • Importance of reading the medication guide for NSAIAs that is provided each time the drug is dispensed.

  • Risk of serious cardiovascular events (e.g., MI, stroke).

  • Risk of GI bleeding and ulceration.

  • Risk of serious skin reactions. Risk of anaphylactoid and other sensitivity reactions.

  • Risk of hepatotoxicity.

  • Importance of seeking immediate medical attention if signs and symptoms of a cardiovascular event (chest pain, dyspnea, weakness, slurred speech) occur.

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

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

  • 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.

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

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

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

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

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

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.

  • Importance of informing patients of other important precautionary information. (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

Licart

Institut Biochemique

* 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 2021, Selected Revisions November 9, 2020. 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.

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