Diclofenac (Topical)

Pharmacologic Category

Nonsteroidal Anti-inflammatory Drug (NSAID); Nonsteroidal Anti-inflammatory Drug (NSAID), Topical

Dosing: Adult

Note: Solaraze gel has been discontinued in the United States for more than 1 year.

Note: Use the lowest effective dose for the shortest duration of time, consistent with individual patient treatment goals.

Actinic keratosis (AK): Topical: Apply 3% gel to lesion area twice daily for 60 to 90 days.

Acute pain (strains, sprains, contusions): Topical:

Patch: Apply 1 patch twice daily to most painful area.

Gel (Voltaren Emulgel [Canadian products]):

1.16%: Apply 2 g to 4 g to the skin over affected area(s) 3 or 4 times daily for up to 7 days.

2.32%: Apply 2 g to the skin over affected area(s) twice daily for up to 7 days (maximum: 4 g/24 hours).

Arthritis pain: Topical:

Gel 1% (OTC): Note: Do not use for >21 days or on >2 body parts at the same time.

Lower extremities: Apply 4 g of 1% gel to affected area 4 times daily.

Upper extremities: Apply 2 g of 1% gel to affected area 4 times daily.

Osteoarthritis: Topical:

Gel 1% (Rx): Note: Maximum total body dose of 1% gel should not exceed 32 g per day.

Lower extremities: Apply 4 g of 1% gel to affected area 4 times daily (maximum: 16 g per joint per day).

Upper extremities: Apply 2 g of 1% gel to affected area 4 times daily (maximum: 8 g per joint per day).

Solution: Knee:

1.5% solution: Apply 40 drops to each affected knee 4 times daily.

2% solution: Apply 2 pump actuations to each affected knee twice daily.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

* See Dosage and Administration in AHFS Essentials for additional information.

Dosing: Geriatric

Start at lower end of dosing range. Refer to adult dosing.

Dosing: Renal Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling; avoid use in patients with advanced renal disease.

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling; use with caution.

Dosing: Pediatric

Note: Solaraze gel has been discontinued in the US for >1 year.

Pain, acute (strains, sprains, contusions): Topical: Note: Use the lowest effective dose for the shortest duration of time, consistent with individual patient treatment goals.

Patch (Flector): Children ≥6 years and Adolescents: Apply 1 patch 2 times daily to most painful area for up to 14 days; Note: Coadministration with oral NSAIDs is not recommended.

Gel (Voltaren Emulgel 1.16% [Canadian product]): Adolescents ≥16 years: Apply to skin of affected area(s) 3 or 4 times daily for up to 7 days; Note: 2 to 4 g should be adequate to treat an area 400 to 800 cm2 (1 g is ~2 cm long strip of gel).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Renal Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling; avoid use in patients with advanced renal disease.

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling; use with caution.

Use: Labeled Indications

Gel 1%:

Rx: Relief of osteoarthritis pain in joints amenable to topical therapy (eg, ankle, elbow, foot, hand, knee, wrist).

OTC: Temporary relief of arthritis pain in the hand, wrist, elbow, foot, ankle, or knee.

Gel 3%: Treatment of actinic keratosis in conjunction with sun avoidance.

Gel 1.16% (Voltaren Emulgel), 2.32% (Voltaren Emulgel Extra Strength) [Canadian products]: Relief of pain associated with acute, localized joint/muscle injuries (eg, sports injuries, strains) in patients ≥16 years of age (1.16% gel) or ≥18 years of age (2.32% gel).

Patch: Treatment of acute pain due to minor strains, sprains, and contusions in adults and children ≥6 years of age.

Solution: Treatment of osteoarthritis pain of the knee.

* See Uses in AHFS Essentials for additional information.

Class and Related Monographs

Nonsteroidal Anti-Inflammatory Agents

Clinical Practice Guidelines

Osteoarthritis:

ACR/AF, “Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee,” February 2020

Administration: Topical

Gel: Apply to clean, dry, intact skin; do not apply to open wounds, eyes, or mucous membranes. Do not cover with occlusive dressings or apply heat, sunscreens, cosmetics, lotions, moisturizers, insect repellents, or other topical medications to affected area. Showering/bathing should be avoided for ≥1 hour following application. Wash hands immediately after application (unless hands are treated joint, then wait ≥1 hour to wash hands). Avoid sunlight to exposure areas. Avoid wearing clothes or gloves for ≥10 minutes after application.

1% formulation (Rx and OTC): Use dosing card to measure dose. Apply to affected area or joint and rub into skin gently, making sure to apply to entire affected area or joint.

3% formulation: Apply to lesion and smooth into skin gently.

Voltaren Emulgel [Canadian products]:

1.16% formulation: Apply to affected area and rub gently into skin; 1 g equals a strip ~2 cm long

2.32% formulation: Use dosing card to measure dose. Apply to affected area or joint and rub into skin gently, making sure to apply to entire affected area or joint.

Solution: Apply to clean, dry, intact skin; do not apply to eyes, mucous membranes, or open wounds. Wash hands before and after use. Do not shower or bathe for ≥30 minutes after applying. Allow knee to dry before applying clothing. Do not apply heat or occlusive dressing to treated knee; protect treated knee from sunlight. Cosmetics, insect repellant, lotion, moisturizer, sunscreens, or other topical medication may be applied to treated knee once solution has dried.

1.5% formulation: Apply 10 drops at a time either directly onto knee or into hand then onto knee (helps avoid spillage). Spread evenly around knee (front, back, sides). Repeat procedure until total dose applied and the knee is completely covered with solution.

2% formulation: The pump must be primed before first use. To prime, fully depress the pump 4 times while holding the bottle in an upright position. This portion should be discarded to ensure proper priming of the pump. No further priming of the bottle is required. Press the pump 2 times to deliver the solution onto the palm of the hand, and apply evenly around the front, back, and sides of the affected knee.

Patch: Apply to intact, nondamaged skin. Avoid contact with eye and mucosa. Remove transparent liner prior to applying to skin. Wash hands after applying, handling, or removing the patch. May tape down edges of patch, if peeling occurs; if problems with adhesion persist, may overlay the patch with a mesh netting sleeve. Should not be worn while bathing or showering. Fold used patches so the adhesive side sticks to itself; dispose of used patches out of reach of children and pets.

Administration: Pediatric

Topical:

Patch: Flector: Remove transparent liner prior to applying to skin. Apply to intact, nondamaged skin. Wash hands after applying, handling, or removing the patch. May tape down edges of patch if peeling occurs; if problems with adhesion persist, may overlay the patch with a mesh netting sleeve (must allow air to flow through and not be occlusive). Should not be worn while bathing or showering. Fold used patches so the adhesive side sticks to itself and dispose of out of reach of children and pets.

Gel: Voltaren Emulgel 1.16% gel formulation [Canadian products]: For topical use only; do not apply to open wounds, eyes, or mucous membranes. Do not cover with occlusive dressings. Wash hands immediately after application unless hands are site being treated.

Storage/Stability

Gel: Store between 20°C to 25°C (68°F to 77°F); do not freeze. Protect from heat. Avoid freezing.

Voltaren Emulgel [Canadian product]: Store at 15°C to 30°C (59°F to 86°F).

Solution: Store between 20°C to 25°C (68°F to 77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F).

Patch: Store between 20°C to 25°C (68°F to 77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F). Keep envelope sealed when not being used.

Medication Patient Education with HCAHPS Considerations

What is this drug used for?

• It is used to treat a precancerous skin problem called actinic keratosis.

• It is used to ease pain.

• It is used to treat arthritis.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Abdominal ulcers like severe abdominal or back pain; black, tarry, or bloody stools; vomiting blood or vomit that looks like coffee grounds; or weight gain or abnormal swelling

• Bleeding like vomiting blood or vomit that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; menstruation; bruises without a reason or that get bigger; or any severe or persistent bleeding

• Weakness on 1 side of the body, trouble speaking or thinking, change in balance, drooping on one side of the face, or blurred eyesight

• Kidney problems like unable to pass urine, blood in the urine, change in amount of urine passed, or weight gain

• Liver problems like dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes

• High potassium like abnormal heartbeat, confusion, dizziness, passing out, weakness, shortness of breath, numbness or tingling feeling

• Stevens-Johnson syndrome/toxic epidermal necrolysis like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in mouth, throat, nose, or eyes.

• Burning or numbness feeling

• Skin irritation

• Chest pain

• Shortness of breath

• Fast heartbeat

• Severe abdominal pain

• Severe back pain

• Excessive weight gain

• Swelling of arms or legs

• Severe dizziness

• Passing out

• Severe headache

• Vision changes

• Flu-like symptoms

• Severe loss of strength and energy

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Medication Safety Issues

​Sound-alike/look-alike issues:

​Other safety concerns:

​International issues:

Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:

Flector: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/206976s002lbl.pdf#page=20

NSAID: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/206976s000lbl.pdf#page=22

Pennsaid: https://www.fda.gov/media/77973/download

Solaraze: https://www.fda.gov/media/98021/download

Voltaren: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/022122s011lbl.pdf#page=22

Contraindications

Hypersensitivity to diclofenac (eg, anaphylactic reaction, serious skin reactions) or any component of the formulation; history of asthma, urticaria, or other allergic-type reactions after taking aspirin or other nonsteroidal anti-inflammatory drugs; use in the setting of coronary artery bypass graft surgery; use on nonintact or damaged skin, including exudative dermatitis, eczema, infected lesions, burns, or wounds.

OTC labeling: When used for self-medication, do not use if previous allergic reaction to any other pain reliever/fever reducer or for strains, sprains, bruises, or sport injuries; prior to or following cardiac surgery; >2 body areas at the same time; in the eyes, nose, or mouth.

Documentation of allergenic cross-reactivity for NSAIDs is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

Canadian labeling: Additional contraindications (not in US labeling):

Pennsaid: Concomitant use with other diclofenac containing products or other NSAIDS; active peptic ulcer; history of recurrent GI ulceration; active GI inflammatory disease; significant hepatic impairment or active hepatic disease; severely impaired or deteriorating renal function (CrCl <30 mL/minute); use in children; pregnancy; breastfeeding; prolonged treatment (>3 months)

Voltaren Emulgel: Concomitant use with other diclofenac-containing products or oral NSAIDS; pregnancy (last trimester)

Warnings/Precautions

Concerns related to adverse effects:

• Anaphylactoid reactions: Even in patients without prior exposure, anaphylactoid reactions may occur; patients with "aspirin triad" (bronchial asthma, aspirin intolerance, rhinitis) may be at increased risk. Contraindicated in patients who experience bronchospasm, asthma, rhinitis, or urticaria with NSAID or aspirin therapy (excluding 3% gel).

• Cardiovascular events: [US Boxed Warning]: NSAIDs cause an increased risk of serious (and potentially fatal) adverse cardiovascular thrombotic events, including MI and stroke. Risk may occur early during treatment and may increase with duration of use. Relative risk appears to be similar in those with and without known cardiovascular disease or risk factors for cardiovascular disease; however, absolute incidence of serious cardiovascular thrombotic events (which may occur early during treatment) was higher in patients with known cardiovascular disease or risk factors. New-onset hypertension or exacerbation of hypertension may occur (NSAIDs may also impair response to ACE inhibitors, thiazide diuretics, or loop diuretics); may contribute to cardiovascular events; monitor blood pressure; use with caution in patients with hypertension. May cause sodium and fluid retention, use with caution in patients with edema. Avoid use in patients with heart failure (ACCF/AHA [Yancy, 2013]). Avoid use in patients with recent MI unless benefits outweigh risk of cardiovascular thrombotic events. Use the lowest effective dose for the shortest duration of time, consistent with individual patient goals, to reduce risk of cardiovascular events; alternate therapies should be considered for patients at high risk.

• Gastrointestinal events: [US Boxed Warning]: NSAIDs cause an increased risk of serious gastrointestinal inflammation, ulceration, bleeding, and perforation (may be fatal); elderly patients and patients with history of peptic ulcer disease and/or GI bleeding are at greater risk for serious GI events. These events may occur at any time during therapy and without warning. Avoid use in patients with active GI bleeding. Use caution with a history of GI ulcers, concurrent therapy known to increase the risk of GI bleeding (eg, aspirin, anticoagulants and/or corticosteroids, selective serotonin reuptake inhibitors), advanced hepatic disease, coagulopathy, smoking, use of alcohol, or in elderly or debilitated patients. Use the lowest effective dose for the shortest duration of time, consistent with individual patient goals, to reduce risk of GI adverse events; alternate therapies should be considered for patients at high risk. When used concomitantly with aspirin, a substantial increase in the risk of gastrointestinal complications (eg, ulcer) occurs; concomitant gastroprotective therapy (eg, proton pump inhibitors) is recommended (Bhatt 2008).

• Hematologic effects: Platelet adhesion and aggregation may be decreased; may prolong bleeding time; patients with coagulation disorders or who are receiving anticoagulants should be monitored closely. Anemia may occur; patients on long-term NSAID therapy should be monitored for anemia. Rarely, NSAID use has been associated with potentially severe blood dyscrasias (eg, agranulocytosis, thrombocytopenia, aplastic anemia).

• Hepatic effects: Transaminase elevations have been observed with oral chronic use; closely monitor patients with any abnormal LFT. Rare (sometimes fatal) severe hepatic reactions (eg, fulminant hepatitis, hepatic necrosis, hepatic failure) have occurred with NSAID use; discontinue immediately if signs or symptoms of hepatic disease develop or if systemic manifestations occur.

• Hyperkalemia: NSAID use may increase the risk of hyperkalemia, particularly in the elderly, diabetics, renal disease, and with concomitant use of other agents capable of inducing hyperkalemia (eg, ACE inhibitors). Monitor potassium closely.

• Renal effects: NSAID use may compromise existing renal function; dose-dependent decreases in prostaglandin synthesis may result from NSAID use, reducing renal blood flow, which may cause renal decompensation (usually reversible). Patients with impaired renal function, dehydration, hypovolemia, heart failure, hepatic impairment, those taking diuretics and ACE inhibitors, and the elderly are at greater risk of renal toxicity. Long-term NSAID use may result in renal papillary necrosis and other renal injury/toxicity.

• Skin reactions: May cause potentially fatal serious skin adverse events, including exfoliative dermatitis, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN); may occur without warning; discontinue use at first sign of skin rash (or any other hypersensitivity). Do not apply topical products to open skin wounds, infected areas, inflammations, or exfoliative dermatitis.

Disease-related concerns:

• Asthma: Contraindicated in patients with aspirin-sensitive asthma (excluding 3% gel); severe and potentially fatal bronchospasm may occur. Use caution in patients with other forms of asthma.

• Coronary artery bypass graft surgery: [US Boxed Warning]: Use is contraindicated in the setting of coronary artery bypass graft (CABG) surgery. Risk of MI and stroke may be increased with use following CABG surgery.

• Hepatic impairment: Use with caution in patients with hepatic impairment; patients with advanced hepatic disease are at an increased risk of GI bleeding with NSAIDs.

• Renal impairment: Avoid use in advanced renal disease.

Special populations:

• Elderly: Elderly patients are at greater risk for serious GI, cardiovascular and/or renal adverse events; use with caution.

Dosage form specific issues:

• Appropriate use: Avoid contact with eyes and mucous membranes.

• Benzoyl alcohol and derivatives: Some dosage forms may contain benzoyl alcohol; large amounts of benzoyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity ("gasping syndrome") in neonates; the "gasping syndrome" consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension and cardiovascular collapse (AAP ["Inactive" 1997]; CDC, 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzoyl alcohol with caution in neonates. See manufacturer's labeling.

• Gel: Avoid occlusive dressings and/or heat application to treated area.

• Patch: Contains conducting metal (eg, aluminum); remove patch prior to MRI.

• Gel, patch, solution: Combination use with oral NSAIDs is not recommended due to increased risk of adverse reactions (eg, rectal hemorrhage; more frequent abnormal creatinine, urea, hemoglobin); do not use concomitantly unless benefit outweighs risks, and monitor patient with periodic laboratory evaluations.

Other warnings/precautions:

• Self-medication (OTC use): Prior to self-medication, patients should contact health care provider if they have had recurring stomach pain; ulcers; bleeding problems; high blood pressure; asthma; heart, liver, or kidney disease; other serious medical problems; are currently taking a diuretic, aspirin, or anticoagulant; or are ≥60 years of age. Discontinue use and contact health care provider if pain gets worse or lasts >21 days; redness or swelling occurs in affected area; fever or skin irritation occurs; signs of GI bleeding, heart disease, or stroke occur. Onset of pain relief may take up to 7 days after starting therapy; discontinue use if no pain relief after 7 days.

* See Cautions in AHFS Essentials for additional information.

Geriatric Considerations

Instruct patient or caregiver on appropriate use of topical diclofenac products.

Warnings: Additional Pediatric Considerations

Children and adolescents may experience a higher frequency of certain adverse effects than adults, particularly headache (9% vs 1%) and dyspepsia (3% to 1%).

Reproductive Considerations

The chronic use of NSAIDs in females of reproductive potential may be associated with infertility that is reversible upon discontinuation of the medication. Consider discontinuing use in females having difficulty conceiving or those undergoing investigation of fertility.

Pregnancy Considerations

Diclofenac crosses the placenta following systemic administration. The amount of diclofenac available systemically following topical application is less in comparison to oral doses. Reversible constriction of the ductus arteriosus in utero has been observed following topical application of diclofenac (Torloni 2006). Because NSAIDs may cause premature closure of the ductus arteriosus, product labeling for diclofenac specifically states use should be avoided starting at 30 weeks' gestation.

Breast-Feeding Considerations

Diclofenac is present in breast milk following oral administration. It is not known if diclofenac can be detected in breast milk following topical application.

The amount of diclofenac available systemically following topical application is less in comparison to oral doses. According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.

Lexicomp Pregnancy & Lactation, In-Depth

• Diclofenac (Systemic)
• Diclofenac (Topical)

Briggs' Drugs in Pregnancy & Lactation

• Diclofenac

Adverse Reactions

Topical gel:

>10%:

Dermatologic: Application-site scaling (6% to 24%), contact dermatitis (2%; application site: 33%), xeroderma (3%; application site: 27%)

Local: Application site pain (15% to 26%), application site pruritus (31% to 52%; nonapplication site: 4%), application site rash (35% to 46%; nonapplication site: 4%)

1% to 10%:

Cardiovascular: Chest pain (1% to 2%), hypertension (1% to 2%)

Dermatologic: Acne vulgaris (application site: 1%), alopecia (application site: 2%), dermal ulcer (1% to 2%), skin photosensitivity (application site: 3%), vesiculobullous dermatitis (4%)

Endocrine & metabolic: Hypercholesterolemia (1%), hyperglycemia (1%)

Gastrointestinal: Abdominal pain (1% to 2%), diarrhea (2%), dyspepsia (2%)

Genitourinary: Hematuria (2%)

Hepatic: Increased serum alanine aminotransferase (2%), increased serum aspartate aminotransferase (3%)

Hypersensitivity: Hypersensitivity reaction (1%)

Local: Application site edema (3% to 4%)

Nervous system: Headache (7%), hyperesthesia (application site: 3%), migraine (1%), paresthesia (≤8%; including application site)

Neuromuscular and skeletal: Arthralgia (2%), arthropathy (2%), asthenia (2%), back pain (4%), hypokinesia (2%), increased creatine phosphokinase in blood specimen (4%), myalgia (2% to 3%), neck pain (2%)

Ophthalmic: Eye pain (2%)

Respiratory: Asthma (2%), dyspnea (2%), sinusitis (2%)

<1%:

Dermatologic: Papule of skin (application site), seborrhea, skin hypertrophy, urticaria

Local: Application site irritation, application site reaction (skin carcinoma, hypertonia, skin hypertrophy lacrimation disorder, maculopapular rash, purpuric rash, vasodilation), application site vesicles

Topical solution:

>10%: Dermatologic: Xeroderma (application site: 22% to 32%; nonapplication site: 2%)

1% to 10%:

Cardiovascular: Edema (3%)

Dermatologic: Contact dermatitis (application site: 2% to 9%), desquamation (application site: 7%), ecchymosis (2%), pruritus (application site: 2% to 4%; nonapplication site: 2%), skin rash (2% to 3%; including application site)

Gastrointestinal: Abdominal pain (6%), constipation (3%), diarrhea (4%), dyspepsia (8%), flatulence (4%), halitosis (1%), nausea (2% to 4%)

Genitourinary: Urinary tract infection (3%)

Hematologic & oncologic: Bruise (2%)

Infection: Infection (3%)

Local: Application site erythema (4%), application site induration (2%), application site pain (2%), application site vesicles (2%)

Nervous system: Paresthesia (2%, including application site)

Respiratory: Paranasal sinus congestion (2%), sinusitis (1%)

Transdermal patch:

1% to 10%:

Dermatologic: Dermatitis (2%), hyperhidrosis (application site: ≤4%), localized erythema (application site: ≤4%), localized vesiculation (application site: ≤4%), skin discoloration (application site: ≤4%), xeroderma (application site: ≤4%)

Gastrointestinal: Constipation (≤3%), diarrhea (≤3%), dysgeusia (2%), gastritis (≤3%), nausea (3%), upper abdominal pain (≤3%), vomiting (≤3%), xerostomia (≤3%)

Local: Application site atrophy (≤4%), local irritation (application site: ≤4%)

Nervous system: Dizziness (≤1%), hypoesthesia (≤1%)

Neuromuscular & skeletal: Hyperkinetic muscle activity (≤1%)

Frequency not defined (any formulation):

Cardiovascular: Acute myocardial infarction, cerebrovascular accident, hypertension, thrombosis, vasodilation (application site)

Dermatologic: Acne vulgaris (application site), dermatological reaction, exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria (application site)

Gastrointestinal: Esophageal perforation, gastrointestinal hemorrhage, gastrointestinal perforation, gastrointestinal ulcer

Hypersensitivity: Anaphylaxis

Postmarketing (any formulation):

Cardiovascular: Cardiac disorder, chest pain, facial edema, hypertension, increased blood pressure, lip edema, palpitations

Dermatologic: Burning sensation of skin, crusted skin, eczema, skin discoloration, urticaria

Gastrointestinal: Aphthous stomatitis, decreased appetite, dysgeusia, gastroenteritis, oral mucosa ulcer, xerostomia

Hematologic & oncologic: Rectal hemorrhage

Hepatic: Increased serum transaminases (Daniels 2018)

Hypersensitivity: Hypersensitivity reaction, tongue edema

Nervous system: Depression, dizziness, drowsiness, headache, lethargy

Neuromuscular & skeletal: Asthenia, back pain, lower limb cramp, myalgia, neck stiffness

Ophthalmic: Blurred vision, cataract, eye pain, visual disturbance

Otic: Otalgia

Renal: Increased serum creatinine

Respiratory: Asthma, dyspnea, laryngismus, laryngitis, pharyngeal edema, pharyngitis

* See Cautions in AHFS Essentials for additional information.

Allergy and Idiosyncratic Reactions

• Nonsteroidal Anti-inflammatory Drug (NSAID) Allergy

Metabolism/Transport Effects

Substrate of CYP1A2 (minor), CYP2B6 (minor), CYP2C19 (minor), CYP2C8 (minor), CYP2C9 (minor), CYP2D6 (minor), CYP3A4 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions Open Interactions

Alcohol (Ethyl): May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents (Topical). Specifically, the risk of GI bleeding may be increased with this combination. Risk C: Monitor therapy

Angiotensin II Receptor Blockers: Nonsteroidal Anti-Inflammatory Agents (Topical) may diminish the therapeutic effect of Angiotensin II Receptor Blockers. Risk C: Monitor therapy

Angiotensin-Converting Enzyme Inhibitors: Nonsteroidal Anti-Inflammatory Agents (Topical) may diminish the therapeutic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Anticoagulants: Nonsteroidal Anti-Inflammatory Agents (Topical) may enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Beta-Blockers: Nonsteroidal Anti-Inflammatory Agents (Topical) may diminish the therapeutic effect of Beta-Blockers. Risk C: Monitor therapy

Corticosteroids (Systemic): Nonsteroidal Anti-Inflammatory Agents (Topical) may enhance the adverse/toxic effect of Corticosteroids (Systemic). Specifically, the risk of gastrointestinal bleeding, ulceration, and perforation may be increased. Risk C: Monitor therapy

CycloSPORINE (Systemic): Nonsteroidal Anti-Inflammatory Agents (Topical) may enhance the adverse/toxic effect of CycloSPORINE (Systemic). Specifically, the nephrotoxicity of cyclosporine (systemic) may be increased. Risk C: Monitor therapy

Deferasirox: Nonsteroidal Anti-Inflammatory Agents (Topical) may enhance the adverse/toxic effect of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased. Risk C: Monitor therapy

Digoxin: Nonsteroidal Anti-Inflammatory Agents (Topical) may increase the serum concentration of Digoxin. Risk C: Monitor therapy

Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry): May enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents (Topical). Risk C: Monitor therapy

Lithium: Nonsteroidal Anti-Inflammatory Agents (Topical) may increase the serum concentration of Lithium. Risk C: Monitor therapy

Loop Diuretics: Nonsteroidal Anti-Inflammatory Agents (Topical) may diminish the therapeutic effect of Loop Diuretics. Risk C: Monitor therapy

Methotrexate: Nonsteroidal Anti-Inflammatory Agents (Topical) may increase the serum concentration of Methotrexate. Risk C: Monitor therapy

Nonsteroidal Anti-Inflammatory Agents: (Topical) may enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the risk of gastrointestinal (GI) toxicity is increased. Management: Coadministration of systemic nonsteroidal anti-inflammatory drugs (NSAIDs) and topical NSAIDs is not recommended. If systemic NSAIDs and topical NSAIDs, ensure the benefits outweigh the risks and monitor for increased NSAID toxicities. Risk D: Consider therapy modification

Salicylates: Nonsteroidal Anti-Inflammatory Agents (Topical) may enhance the adverse/toxic effect of Salicylates. Specifically, the risk of gastrointestinal (GI) toxicity is increased. Management: Coadministration of salicylates and topical NSAIDs is not recommended. If salicylates and topical NSAIDs are coadministered, ensure the benefits outweigh the risks and monitor for increased NSAID toxicities. Risk D: Consider therapy modification

Selective Serotonin Reuptake Inhibitors: Nonsteroidal Anti-Inflammatory Agents (Topical) may enhance the antiplatelet effect of Selective Serotonin Reuptake Inhibitors. Risk C: Monitor therapy

Serotonin/Norepinephrine Reuptake Inhibitors: May enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents (Topical). Risk C: Monitor therapy

Tacrolimus (Systemic): Nonsteroidal Anti-Inflammatory Agents (Topical) may enhance the nephrotoxic effect of Tacrolimus (Systemic). Risk C: Monitor therapy

Tenofovir Products: Nonsteroidal Anti-Inflammatory Agents (Topical) may enhance the nephrotoxic effect of Tenofovir Products. Risk C: Monitor therapy

Thiazide and Thiazide-Like Diuretics: Nonsteroidal Anti-Inflammatory Agents (Topical) may diminish the therapeutic effect of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy

Voriconazole: May increase the serum concentration of Diclofenac (Topical). Risk C: Monitor therapy

Monitoring Parameters

CBC, liver enzymes (periodically during chronic therapy starting 4 to 8 weeks after initiation), BUN/serum creatinine; potassium; monitor urine output; occult blood loss; blood pressure (baseline and during treatment)

Advanced Practitioners Physical Assessment/Monitoring

Instruct patient on proper application and observe for skin reactions.

Nursing Physical Assessment/Monitoring

Educate patient that this medication is not a cure but treats pain only during use. Instruct patient in proper application of medication and monitor skin for rash, blisters, peeling. Avoid use of occlusive dressings and applying heat to site of application.

Product Availability

Solaraze gel has been discontinued in the United States for >1 year.

Dosage Forms Considerations

Diclozor therapy pack contains diclofenac gel (2 x 100 g) and occlusive dressings (10s).

DSG Pak contains Voltaren gel (100 g) and occlusive dressings (20s).

DST Plus Pak kit contains diclofenac gel.

EnovaRX-Diclofenac Sodium is a compounding kit for the preparation of diclofenac cream. Refer to manufacturer's labeling for compounding instructions.

Lexixryl therapy pack contains diclofenac solution (150 mL) and Xrylix kinesiology/cross tape (30s).

Rexaphenac is a compounding kit for the preparation of diclofenac cream. Refer to manufacturer's labeling for compounding instructions.

Xrylix therapy pack contains diclofenac solution (150 mL) and Xrylix kinesiology/cross tape (30s).

Vopac MDS kit contains diclofenac solution.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Cream, Transdermal, as sodium:

EnovaRX-Diclofenac Sodium: 2.5% (120 g) [contains cetyl alcohol]

Rexaphenac: 1% (120 g) [contains isopropyl alcohol, propylene glycol]

Gel, Transdermal, as sodium:

Solaraze: 3% (100 g [DSC]) [contains benzyl alcohol, polyethylene glycol, sodium hyaluronate]

Voltaren: 1% (50 g, 100 g, 150 g, 350 g) [contains isopropyl alcohol, propylene glycol]

Generic: 1% (100 g); 3% (100 g)

Kit, Transdermal, as sodium:

Diclo Gel: 1% [DSC] [contains isopropyl alcohol, propylene glycol]

DST Plus Pak: 1% [DSC] [contains isopropyl alcohol, propylene glycol]

Vopac MDS: 1.5% [DSC] [contains propylene glycol]

Patch, Transdermal, as epolamine:

Flector: 1.3% (5 ea, 30 ea) [contains edetate disodium, methylparaben, polysorbate 80, propylene glycol, propylparaben]

Generic: 1.3% (5 ea, 30 ea)

Solution, Transdermal, as sodium:

Klofensaid II: 1.5% (150 mL [DSC]) [contains alcohol, usp, dimethyl sulfoxide, glycerin, propylene glycol]

Pennsaid: 2% (2 g, 112 g) [contains propylene glycol]

Generic: 1.5% (150 mL)

Therapy Pack, Transdermal, as sodium:

Diclo Gel with Xrylix Sheets: 1% (1 ea [DSC]) [contains isopropyl alcohol, propylene glycol]

Diclozor: 1% (1 ea) [contains isopropyl alcohol, propylene glycol]

Lexixryl: 1.5% (1 ea [DSC]) [contains propylene glycol]

Xrylix: 1.5% (1 ea) [contains propylene glycol]

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Transdermal, as sodium:

Pennsaid: 1.5% (15 mL, 30 mL, 60 mL) [contains propylene glycol]

Generic: 1.5% (15 mL, 30 mL, 60 mL, 120 mL, 150 mL)

Anatomic Therapeutic Chemical (ATC) Classification

• D11AX18
• M02AA15

Generic Available (US)

Yes

Pricing: US

Gel (Diclofenac Sodium Transdermal)

1% (per gram): $0.04 - $0.58

3% (per gram): $1.12 - $11.79

Gel (Voltaren Transdermal)

1% (per gram): $0.16

Patch (Diclofenac Epolamine Transdermal)

1.3% (per each): $13.43 - $14.17

Patch (Flector Transdermal)

1.3% (per each): $14.92

Solution (Diclofenac Sodium Transdermal)

1.5% (per mL): $1.74 - $9.73

Solution (Pennsaid Transdermal)

2% (per gram): $26.65

Therapy Pack (Xrylix Transdermal)

1.5% (per each): $4,961.96

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Mechanism of Action

Reversibly inhibits cyclooxygenase-1 and 2 (COX-1 and 2) enzymes, which results in decreased formation of prostaglandin precursors; has antipyretic, analgesic, and anti-inflammatory properties

Other proposed mechanisms not fully elucidated (and possibly contributing to the anti-inflammatory effect to varying degrees), include inhibiting chemotaxis, altering lymphocyte activity, inhibiting neutrophil aggregation/activation, and decreasing proinflammatory cytokine levels.

Pharmacodynamics/Kinetics

Absorption: Gel 3%: 6% to 10%.

Protein binding: >99%, primarily to albumin.

Metabolism: Hepatic; undergoes first-pass metabolism; forms several metabolites (1 with weak activity).

Half-life elimination: Patch: ~12 hours; Solution 1.5%: 36.7 ± 20.8 hours (single application).

Time to peak, serum: Patch: 10 to 20 hours; Solution 1.5%: 11 ± 6.4 hours (single application); Gel 3%: 4.5 ± 8 hours; Gel 1%: 10 to 14 hours.

Excretion: Urine (~65%); feces (~35%).

Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions

Effects on Dental Treatment

No significant effects or complications reported

Effects on Bleeding

No information available to require special precautions

Index Terms

Diclofenac Diethylamine [CAN]; Diclofenac Epolamine; Diclofenac Sodium; Voltaren Arthritis Pain OTC 1% Gel

FDA Approval Date

July 28, 1988

References

Ahlfors CE. Benzyl alcohol, kernicterus, and unbound bilirubin. J Pediatr. 2001;139(2):317-319.[PubMed 11487763]

Bhatt DL, Scheiman J, Abraham NS, et al; American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents. ACCF/ACG/AHA 2008 expert consensus document on reducing the gastrointestinal risks of antiplatelet therapy and NSAID use: a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents. J Am Coll Cardiol. 2008;52(18):1502-1517.[PubMed 19017521]

Centers for Disease Control (CDC). Neonatal deaths associated with use of benzyl alcohol--United States. MMWR Morb Mortal Wkly Rep. 1982;31(22):290-291.[PubMed 6810084]

Daniels AM, Gibbs LM, Herndon CM. Elevated transaminases with topical diclofenac: a case report. J Pain Palliat Care Pharmacother. 2018;32(2-3):161–164.[PubMed 30645151]10.1080/15360288.2018.1546257

Diclofenac sodium solution (topical) [prescribing information]. Orlando, FL: Ingenus Pharmaceuticals, LLC; August 2018.

Flector (diclofenac epolamine) [prescribing information]. Bristol, TN: King Pharmaceuticals; March 2019.

"Inactive" ingredients in pharmaceutical products: update (subject review). American Academy of Pediatrics Committee on Drugs. Pediatrics. 1997;99(2):268-278.[PubMed 9024461]

Klofensaid II (diclofenac) [prescribing information]. San Fernando, CA: PureTek Corporation; March 2016.

Laine L, Goldkind L, Curtis SP, Connors LG, Yanqiong Z, Cannon CP. How common is diclofenac-associated liver injury? Analysis of 17,289 arthritis patients in a long-term prospective clinical trial. Am J Gastroenterol, 2009;104(2):356-362.[PubMed 19174782]

Licart (diclofenac epolamine) topical system [prescribing information]. Parsippany, NJ: IBSA Pharma Inc; May 2020.

Morales DR, Lipworth BJ, Guthrie B, et al. Safety risks for patients with aspirin-exacerbated respiratory disease after acute exposure to selective nonsteroidal anti-inflammatory drugs and COX-2 inhibitors: Meta-analysis of controlled clinical trials. J Allergy Clin Immunol. 2014;134(1):40-45.[PubMed 24388008]10.1016/j.jaci.2013.10.057

Pennsaid 1.5% (diclofenac sodium) [prescribing information]. Hazelwood, MO: Mallinckrodt Brand Pharmaceuticals; May 2016.

Pennsaid 2% (diclofenac sodium) [prescribing information]. Lake Forest, IL: Horizon Medicines LLC; March 2020.

Pennsaid 1.5% (diclofenac sodium) [product monograph]. Montreal, Quebec, Canada: Paladin Labs Inc; October 2010.

Shehab N, Lewis CL, Streetman DD, Donn SM. Exposure to the pharmaceutical excipients benzyl alcohol and propylene glycol among critically ill neonates. Pediatr Crit Care Med. 2009;10(2):256-259.[PubMed 19188870]

Solaraze (diclofenac sodium) [prescribing information]. Melville, NY: PharmaDerm; May 2016.

Torloni MR, Cordioli E, Zamith MM, et al. Reversible constriction of the fetal ductus arteriosus after maternal use of topical diclofenac and methyl salicylate. Ultrasound Obstet Gynecol. 2006;27(2):227-229.[PubMed 16355417]

Voltaren (diclofenac sodium) [prescribing information]. Malvern, PA: Endo Pharmaceuticals, Inc; February 2018.

Voltaren (diclofenac sodium) [prescribing information]. Malvern, PA: Endo Pharmaceuticals, Inc; February 2018.

Voltaren (diclofenac sodium) topical gel 1% [prescribing information]. Warren, NJ: GlaxoSmithKline Consumer Healthcare Inc; received February 2020.

Voltaren Emulgel Joint-Pain (diclofenac sodium) [product monograph]. Mississauga, Ontario, Canada: GlaxoSmithKline Consumer Healthcare Inc; September 2016.

Voltaren Emulgel (diclofenac sodium) [product monograph]. Mississauga, Ontario, Canada: GlaxoSmithKline Consumer Healthcare Inc; September 2016.

Yancy CW, Jessup M, Bozkurt B, et al; American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation. 2013;128(16):e240-e327.[PubMed 23741058]

Brand Names: International

Adiflam (ET); Algipatch (LK); Almiral Gel (MY, SG, TW); Arthosure (PK); Bi Su Fu (CN); Bufaflam Emulgel (ID); Canfol (TW); Cataflam (VE); Cataflam Emulgel (BR); Clofast (BH); Clofec Gel (HK); Clofen Creamagel (KW, SA); Curinflam (AR, HK); Diclac (EE); Dicloren (TW); Dosanac (SG, TH); Fastaid Gel (LK); Flexy Gel (TH); Flogosin D (UY); Galtaren (ID); Get-Go-Plus (PH); Jonac Gel (LK); Locagel (AE, QA); Lofenac (TH); Megatic Emulgel (ID); Myfenax (TH); N-Ke'ev Gel (IL); N-Zen Gel (TH); Nac Gel (IN); Novarin (BD); Novo-Difenac (HK); Olfen (TT); Olfen Gel (MY, SG, UA); Painelief Cool Gel (TH); Panaflex Extra (MY); Panaflex Extra Gel (SG); Panamax Gel (SG); Panamax Patch (SG); Physicare Gel (IL); Rapten Gel (UA); Relaxyl Gel (IN); Remethan Gel (SG, TW); Renvol Emulgel (ID); Rumafen (BH); Solaraze (DE, DK, FI, IE, NO, PT, SE); Solaraze Gel (AU); Swiss Relief (IL); Tondonac Gel (HK); Travmagel (MT); Uniren (SG); Vofenac (TR); Voldic (BH); Volfenac Gel (CR, DO, GT, HN, NI, PA, SV); Volini (LK); Voltadex Emulgel (ID); Voltareactigo (FR); Voltaren (HR, IS, RO, ZW); Voltaren Emulgel (AR, AU, BE, BH, CH, CL, CO, CY, CZ, DE, DK, EE, EG, FI, ID, JO, KW, LB, LT, LU, LV, MT, MY, NO, NZ, PE, PH, PL, QA, SA, SE, SI, SK, TH, TR, TW, UA, VN); Voltarene Emulgel (FR); Voltarol Emulgel (GB, IE); Voltex Kool (HK); Voltic Emulgel (KW, QA); Voren Gel (PH); Vottaren Emulgel (KR); Voveran Emulgel (IN)

Last Updated 10/9/20