These Highlights Do Not Include All The Information Needed To Use Diclofenac Sodium Topical Solution Safely And Effectively. See Full Prescribing Information For Diclofenac Sodium Topical Solution.

Cardiovascular Thrombotic Events

• Nonsteroidal anti-inflammatory drugs (NSAIDs) cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction, and stroke, which can be fatal. This risk may occur early in treatment and may increase with duration of use [ see Warnings and Precautions (5.1) ].
• Diclofenac sodium is contraindicated in the setting of coronary artery bypass graft (CABG) surgery [ see Contraindications (4)and Warnings and Precautions (5.1) ].

Storage

Store at 20° to 25°C (68° to 77°F)[see USP Controlled Room Temperature].

Symptoms following acute NSAID overdosages have been typically limited to lethargy, drowsiness, nausea, vomiting, and epigastric pain, which have been generally reversible with supportive care. Gastrointestinal bleeding has occurred. Hypertension, acute renal failure, respiratory depression, and coma have occurred but were rare [ see Warnings and Precautions (5.1, 5.2, 5.4, 5.6) ].

Manage patients with symptomatic and supportive care following an NSAID overdosage. There are no specific antidotes. Emesis is not recommended due to a possibility of aspiration and subsequent respiratory irritation by DMSO contained in diclofenac sodium. Consider activated charcoal (60 to 100 grams in adults, 1 to 2 grams per kg of body weight in pediatric patients) and/or osmotic cathartic in symptomatic patients seen within four hours of ingestion or in patients with a large overdosage (5 to 10 times the recommended dosage). Forced diuresis, alkalinization of urine, hemodialysis, or hemoperfusion may not be useful due to high protein binding.

For additional information about overdosage treatment, contact a poison control center (1-800-222-1222).

Diclofenac sodium topical solution USP, 2% contains diclofenac sodium, a benzeneacetic acid derivative that is a nonsteroidal anti-inflammatory drug, and is available as a clear, colorless to slightly pink or orange solution for topical application. The chemical name is 2[(2,6-dichlorophenyl)amino]-benzeneacetic acid, monosodium salt. The molecular weight is 318.14. Its molecular formula is C ₁₄H ₁₀Cl ₂NNaO ₂, and it has the following chemical structure:

Each 1 gram of solution contains 20 mg of diclofenac sodium. The inactive ingredients: dimethyl sulfoxide USP (DMSO, 45.5% w/w), ethanol (31.46% v/v), hydroxypropyl cellulose, propylene glycol and purified water.

NSAIDs, including diclofenac, can lead to new onset of hypertension or worsening of preexisting hypertension, either of which may contribute to the increased incidence of CV events. Patients taking angiotensin converting enzyme (ACE) inhibitors, thiazide diuretics, or loop diuretics may have impaired response to these therapies when taking NSAIDs [ see Drug Interactions (7) ] .

Monitor blood pressure (BP) during the initiation of NSAID treatment and throughout the course of therapy.

Instruct patients to avoid exposure to natural or artificial sunlight on treated knee(s) because studies in animals indicated topical diclofenac treatment resulted in an earlier onset of ultraviolet light-induced skin tumors. The potential effects of diclofenac sodium on skin response to ultraviolet damage in humans are not known.

Avoid contact of diclofenac sodium with eyes and mucosa. Advise patients that if eye contact occurs, immediately wash out the eye with water or saline and consult a physician if irritation persists for more than an hour.

Safety and effectiveness in pediatric patients have not been established.

Elderly patients, compared to younger patients, are at greater risk for NSAID-associated serious cardiovascular, gastrointestinal, and/or renal adverse reactions. If the anticipated benefit for the elderly patient outweighs these potential risks, start dosing at the low end of the dosing range, and monitor patients for adverse effects [ see Warnings and Precautions (5.1, 5.2, 5.3, 5.6, 5.14) ].

Of the 911 patients treated with diclofenac sodium 1.5% in seven controlled, Phase 3 clinical trials, 444 subjects were 65 years of age and over. There was no age-related difference in the incidence of adverse events. Of the 793 patients treated with diclofenac sodium topical solution 1.5% in one open-labeled safety trial, 334 subjects were 65 years of age and over including 107 subjects 75 and over. There was no difference in the incidence of adverse events with long-term exposure to diclofenac sodium topical solution 1.5% for this elderly population.

In clinical trials of oral diclofenac containing products, meaningful elevations (i.e., more than 3 times the ULN) of AST (SGOT) occurred in about 2% of approximately 5,700 patients at some time during diclofenac treatment (ALT was not measured in all studies).

In a large, open-label, controlled trial of 3,700 patients treated with oral diclofenac for 2 to 6 months, patients were monitored first at 8 weeks and 1,200 patients were monitored again at 24 weeks. Meaningful elevations of ALT and/or AST occurred in about 4% of 3,700 patients and included marked elevations (greater than 8 times the ULN) in about 1% of the 3,700 patients. In that open-label study, a higher incidence of borderline (less than 3 times the ULN), moderate (3 to 8 times the ULN), and marked (greater than 8 times the ULN) elevations of ALT or AST was observed in patients receiving diclofenac when compared to other NSAIDs. Elevations in transaminases were seen more frequently in patients with osteoarthritis than in those with rheumatoid arthritis.

Almost all meaningful elevations in transaminases were detected before patients became symptomatic.

Abnormal tests occurred during the first 2 months of therapy with oral diclofenac in 42 of the 51 patients in all trials who developed marked transaminase elevations.

In postmarketing reports, cases of drug-induced hepatotoxicity have been reported in the first month, and in some cases, the first 2 months of NSAID therapy, but can occur at any time during treatment with diclofenac.

Postmarketing surveillance has reported cases of severe hepatic reactions, including liver necrosis, jaundice, fulminant hepatitis with and without jaundice, and liver failure. Some of these reported cases resulted in fatalities or liver transplantation.

In a European retrospective population-based, case-controlled study, 10 cases of oral diclofenac associated drug-induced liver injury with current use compared with non-use of diclofenac were associated with a statistically significant 4-fold adjusted odds ratio of liver injury. In this particular study, based on an overall number of 10 cases of liver injury associated with diclofenac, the adjusted odds ratio increased further with female gender, doses of 150 mg or more, and duration of use for more than 90 days.

Physicians should measure transaminases at baseline and periodically in patients receiving long-term therapy with diclofenac, because severe hepatotoxicity may develop without a prodrome of distinguishing symptoms. The optimum times for making the first and subsequent transaminase measurements are not known. Based on clinical trial data and postmarketing experiences, transaminases should be monitored within 4 to 8 weeks after initiating treatment with diclofenac. However, severe hepatic reactions can occur at any time during treatment with diclofenac.

If abnormal liver tests persist or worsen, if clinical signs and/or symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g., eosinophilia, rash, abdominal pain, diarrhea, dark urine, etc.), diclofenac sodium should be discontinued immediately.

Inform patients of the warning signs and symptoms of hepatotoxicity (e.g., nausea, fatigue, lethargy, diarrhea, pruritus, jaundice, right upper quadrant tenderness, and "flu-like" symptoms). If clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g., eosinophilia, rash, etc.), discontinue diclofenac sodium immediately, and perform a clinical evaluation of the patient.

To minimize the potential risk for an adverse liver-related event in patients treated with diclofenac sodium, use the lowest effective dose for the shortest duration possible. Exercise caution when prescribing diclofenac sodium with concomitant drugs that are known to be potentially hepatotoxic (e.g., acetaminophen, antibiotics, antiepileptics).

Diclofenac sodium is contraindicated in the following patients:

• Known hypersensitivity (e.g., anaphylactic reactions and serious skin reactions) to diclofenac or any components of the drug product [ see Warnings and Precautions (5.7, 5.9) ]
• History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs. Severe, sometimes fatal, anaphylactic reactions to NSAIDs have been reported in such patients [ see Warnings and Precautions (5.7, 5.8) ]
• In the setting of coronary artery bypass graft (CABG) surgery [ see Warnings and Precautions (5.1) ]

The following adverse reactions are discussed in greater detail in other sections of the labeling:

• Cardiovascular Thrombotic Events [ see Warnings and Precautions (5.1) ]
• GI Bleeding, Ulceration and Perforation [ see Warnings and Precautions (5.2) ]
• Hepatotoxicity [ see Warnings and Precautions (5.3) ]
• Hypertension [ see Warnings and Precautions (5.4) ]
• Heart Failure and Edema [ see Warnings and Precautions (5.5) ]
• Renal Toxicity and Hyperkalemia [ see Warnings and Precautions (5.6) ]
• Anaphylactic Reactions [ see Warnings and Precautions (5.7) ]
• Serious Skin Reactions [ see Warnings and Precautions (5.9) ]
• Hematologic Toxicity [ see Warnings and Precautions (5.12) ]

See Table 3for clinically significant drug interactions with diclofenac.

Diclofenac Sodium (dye kloe' fen ak soe' dee um) Topical Solution USP, 2% w/w

Read the Medication Guide that comes with diclofenac sodium topical solution first. Be sure that you read, understand and follow these Instructions for Use before you use diclofenac sodium topical solution for the first time.

Important: For use on the skin only (topical). Do not get diclofenac sodium topical solution in your eyes, nose or mouth.

Before you use diclofenac sodium topical solution:

• Apply diclofenac sodium topical solution exactly as your health care provider tells you. Talk with your health care provider or pharmacist if you are not sure.
• Only use diclofenac sodium topical solution to treat pain from osteoarthritis in your knee or knees.
• Apply diclofenac sodium topical solution on clean, dry skin that does not have any cuts, infections or rashes.
• Use diclofenac sodium topical solution two times a day on your knee or knees as prescribed.
• If you get diclofenac sodium topical solution in your eyes, rinse your eyes right away with water or saline. Call your health care provider if your eyes are irritated for more than one hour.

Diclofenac sodium topical solution comes in a pump bottle.

If you are using a diclofenac sodium topical solution pump bottle follow the steps below:

Before you use diclofenac sodium topical solution pump bottle for the first time, you will need to prime the pump.To prime the pump, remove the cap (see Figure A ) and fully press the top of the pump all the way down 4 times while holding the bottle in an upright position (see Figure B ). Dispense this portion of the medicine into a tissue or paper towel and throw it away in a trash can. The pump is now ready to use. You should not need to prime the pump again.

Figure A.

Figure B.

Steps for using diclofenac sodium topical solution pump bottle:

Figure C.

Step 3: Apply diclofenac sodium topical solution evenly around the front, back, and sides of your knee. Diclofenac sodium topical solution should be applied without massaging the knee (see Figures D and E ).

After you use diclofenac sodium topical solution:

Do not:

• cover your knee with clothing until your knee is completely dry.
• put sunscreen, insect repellant, lotion, moisturizer, cosmetics, or other topical medicines on your knee until it is completely dry.
• take a shower or a bath for at least 30 minutes after you put diclofenac sodium topical solution on your knee(s).
• use heating pads or cover the treated area with bandages where you have applied diclofenac sodium topical solution.
• exercise following application of diclofenac sodium topical solution.
• use sunlamp and tanning beds. Protect your treated knee from sunlight. Wear clothes that cover your skin if you have to be in the sunlight.

How should I store diclofenac sodium topical solution?

• Store diclofenac sodium topical solution at room temperature between 68°F to 77°F (20°C to 25°C).

Keep diclofenac sodium topical solution and all medicines out of the reach of children.

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

Manufactured by: Taro Pharmaceuticals Inc., Brampton, Ontario, Canada L6T 1C1

Distributed by: Sun Pharmaceuticals U.S.A., Inc.,Cranbury, NJ 08512

Revised: April 2024

5259428 23

Diclofenac sodium topical solution is indicated for the treatment of the pain of osteoarthritis of the knee(s).

• Avoid showering/bathing for at least 30 minutes after the application of diclofenac sodium topical solution to the treated knee.
• Wash and dry hands after use.
• Do not apply diclofenac sodium topical solution to open wounds.
• Avoid contact of diclofenac sodium topical solution with eyes and mucous membranes.
• Do not apply external heat and/or occlusive dressings to treated knees.
• Avoid wearing clothing over the diclofenac sodium topical solution-treated knee(s) until the treated knee is dry.
• Protect the treated knee(s) from natural and artificial sunlight.
• Wait until the treated area is dry before applying sunscreen, insect repellant, lotion, moisturizer, cosmetics, or other topical medication to the same knee you have just treated with diclofenac sodium topical solution.
• Until the treated knee(s) is completely dry, avoid skin-to-skin contact between other people and the treated knee(s).
• Do not use combination therapy with diclofenac sodium and an oral NSAID unless the benefit outweighs the risk and conduct periodic laboratory evaluations.

Diclofenac has analgesic, anti-inflammatory, and antipyretic properties.

The mechanism of action of diclofenac sodium, like that of other NSAIDs, is not completely understood but involves inhibition of cyclooxygenase (COX-1 and COX-2).

Diclofenac is a potent inhibitor of prostaglandin synthesis in vitro. Diclofenac concentrations reached during therapy have produced in vivoeffects. Prostaglandins sensitize afferent nerves and potentiate the action of bradykinin in inducing pain in animal models. Prostaglandins are mediators of inflammation. Because diclofenac is an inhibitor of prostaglandin synthesis, its mode of action may be due to a decrease of prostaglandins in peripheral tissues.

Anemia has occurred in NSAID-treated patients. This may be due to occult or gross blood loss, fluid retention, or an incompletely described effect on erythropoiesis. If a patient treated with diclofenac sodium has any signs or symptoms of anemia, monitor hemoglobin or hematocrit.

NSAIDs, including diclofenac sodium, may increase the risk of bleeding events. Co-morbid conditions such as coagulation disorders or concomitant use of warfarin, other anticoagulants, antiplatelet agents (e.g., aspirin), serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) may increase this risk. Monitor these patients for signs of bleeding [ see Drug Interactions (7) ].

• Hepatotoxicity: Inform patients of warning signs and symptoms of hepatotoxicity. Discontinue if abnormal liver tests persist or worsen or if clinical signs and symptoms of liver disease develop ( 5.3)
• Hypertension: Patients taking some antihypertensive medications may have impaired response to these therapies when taking NSAIDs. Monitor blood pressure ( 5.4, 7)
• Heart Failure and Edema: Avoid use of diclofenac sodium in patients with severe heart failure unless benefits are expected to outweigh risk of worsening heart failure ( 5.5)
• Renal Toxicity: Monitor renal function in patients with renal or hepatic impairment, heart failure, dehydration, or hypovolemia. Avoid use of diclofenac sodium in patients with advanced renal disease unless benefits are expected to outweigh risk of worsening renal function ( 5.6)
• Anaphylactic Reactions: Seek emergency help if an anaphylactic reaction occurs ( 5.7)
• Exacerbation of Asthma Related to Aspirin Sensitivity: Diclofenac sodium topical solution is contraindicated in patients with aspirin-sensitive asthma. Monitor patients with preexisting asthma (without aspirin sensitivity) ( 5.8)
• Serious Skin Reactions: Discontinue diclofenac sodium at first appearance of skin rash or other signs of hypersensitivity. ( 5.9, 5.15)
• Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): Discontinue and evaluate clinically ( 5.10)
• Fetal Toxicity: Limit use of NSAIDs, including diclofenac sodium topical solution, between about 20 to 30 weeks in pregnancy due to the risk of oligohydramnios/fetal renal dysfunction. Avoid use of NSAIDs in women at about 30 weeks gestation and later in pregnancy due to the risks of oligohydramnios/fetal renal dysfunction and premature closure of the fetal ductus arteriosus ( 5.11, 8.1).
• Hematologic Toxicity: Monitor hemoglobin or hematocrit in patients with any signs or symptoms of anemia ( 5.12, 7).
• Exposure to light: Avoid exposure of treated knee(s) to natural or artificial sunlight. ( 5.15)
• Eye Contact: Avoid contact of diclofenac sodium with eyes and mucosa. ( 5.16)
• Oral Nonsteroidal Anti-inflammatory Drugs: Avoid concurrent use with oral NSAIDs. ( 5.17)

Because serious GI bleeding, hepatotoxicity, and renal injury can occur without warning symptoms or signs, consider monitoring patients on long-term NSAID treatment with a CBC and a chemistry profile periodically [ see Warnings and Precautions (5.2, 5.3, 5.6) ].

Diclofenac has been associated with anaphylactic reactions in patients with and without known hypersensitivity to diclofenac and in patients with aspirin-sensitive asthma [ see Contraindications (4)and Warnings and Precautions (5.8) ].

Seek emergency help if an anaphylactic reaction occurs.

NSAIDs, including diclofenac, can cause serious skin adverse reactions such as exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. NSAIDs can also cause fixed drug eruption (FDE). FDE may present as a more severe variant known as generalized bullous fixed drug eruption (GBFDE), which can be lifethreatening.These serious events may occur without warning. Inform patients about the signs and symptoms of serious skin reactions, and to discontinue the use of diclofenac sodium topical solution at the first appearance of skin rash or any other sign of hypersensitivity. Diclofenac sodium topical solution is contraindicated in patients with previous serious skin reactions to NSAIDs [ see Contraindications (4) ]. Do not apply diclofenac sodium topical solution to open skin wounds, infections, inflammations, or exfoliative dermatitis, as it may affect absorption and tolerability of the drug.

Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals.

The recommended dose is 2 pump actuations on each painful knee, 2 times a day. ( 2)

• Apply diclofenac sodium topical solution to clean, dry skin. ( 2.1)
• Dispense 40 mg (2 pump actuations) directly onto the knee or first into the hand and then onto the knee. Spread evenly around front, back and sides of the knee. ( 2.1)
• Wash hands completely after administering the product. ( 2.2)
• Wait until the area is completely dry before covering with clothing or applying sunscreen, insect repellent, cosmetics, topical medications, or other substances. ( 2.2)
• Until the treated knee(s) is completely dry, avoid skin-to-skin contact between other people and the treated knee(s). ( 2.2)
• Do not get diclofenac sodium topical solution in your eyes, nose, or mouth ( 2.2).

The Coxib and traditional NSAID Trialists' Collaboration meta-analysis of randomized controlled trials demonstrated an approximately two-fold increase in hospitalizations for heart failure in COX-2 selective treated patients and nonselective NSAID-treated patients compared to placebo-treated patients. In a Danish National Registry study of patients with heart failure, NSAID use increased the risk of MI, hospitalization for heart failure, and death.

Additionally, fluid retention and edema have been observed in some patients treated with NSAIDs. Use of diclofenac may blunt the CV effects of several therapeutic agents used to treat these medical conditions (e.g., diuretics, ACE inhibitors, or angiotensin receptor blockers [ARBs]) [ see Drug Interactions (7) ].

Avoid the use of diclofenac sodium in patients with severe heart failure unless the benefits are expected to outweigh the risk of worsening heart failure. If diclofenac sodium is used in patients with severe heart failure, monitor patients for signs of worsening heart failure.

Diclofenac sodium topical solution USP, 2% w/w

In postmarketing surveillance, the following adverse reactions have been reported during post-approval use of diclofenac sodium topical solution 1.5%. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Body as a Whole:abdominal pain, accidental injury, allergic reactions, asthenia, back pain, body odor, chest pain, edema, face edema, halitosis, headache, neck rigidity, pain

Cardiovascular:palpitation, cardiovascular disorder

Gastrointestinal:diarrhea, dry mouth, dyspepsia, gastroenteritis, decreased appetite, lip swelling, mouth ulceration, nausea, rectal hemorrhage, ulcerative stomatitis, swollen tongue

Metabolic and Nutritional:creatinine increased

Musculoskeletal:leg cramps, myalgia

Nervous:depression, dizziness, drowsiness, lethargy, paresthesia at application site

Respiratory:asthma, dyspnea, laryngismus, laryngitis, pharyngitis, throat swelling

Skin and Appendages: At the Application Site:rash, skin burning sensation;

Other Skin and Appendages Adverse Reactions:eczema, skin discoloration, urticaria, exfoliative dermatitis, Stevens-Johnson

Syndrome (SJS), toxic epidermal necrolysis (TEN), and fixed drug eruption (FDE).

Special Senses:abnormal vision, blurred vision, cataract, ear pain, eye disorder, eye pain, taste perversion

Vascular:blood pressure increased, hypertension

• Infertility:NSAIDs are associated with reversible infertility. Consider withdrawal of diclofenac sodium in women who have difficulties conceiving. ( 8.3)

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals [ see Warnings and Precautions (5.2) ].

For relief of the pain of osteoarthritis (OA) of the knee(s), the recommended dose is 40 mg of diclofenac sodium (2 pump actuations) on each painful knee, 2 times a day.

Apply diclofenac sodium topical solution to clean, dry skin.

The pump must be primed before first use. Instruct patients to fully depress the pump mechanism (actuation) 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 should be required.

After the priming procedure, diclofenac sodium topical solution is properly dispensed by completely depressing the pump 2 times to achieve the prescribed dosage for one knee. Deliver the product directly into the palm of the hand and then apply evenly around front, back, and sides of the knee.

Application of diclofenac sodium topical solution in an amount exceeding or less than the recommended dose has not been studied and is therefore not recommended.

Advise the patient to read the FDA-approved patient labeling (Medication Guide) that accompanies each prescription dispensed. Inform patients, families, or their caregivers of the following information before initiating therapy with diclofenac sodium topical solution and periodically during the course of ongoing therapy.

Diclofenac sodium topical solution USP, 2% w/w is supplied as a clear, colorless to slightly pink-orange solution containing 20 mg of diclofenac sodium per gram of solution, in a white polypropylene-dose pump bottle with a clear cap. Each pump actuation delivers 20 mg of diclofenac sodium in 1 gram of solution.

Relabeled by:

PHOENIX RX LLC,

Hatboro, PA 19040 USA

Clinical trials of several COX-2 selective and nonselective NSAIDs of up to three years duration have shown an increased risk of serious cardiovascular (CV) thrombotic events, including myocardial infarction (MI), and stroke, which can be fatal. Based on available data, it is unclear that the risk for CV thrombotic events is similar for all NSAIDs. The relative increase in serious CV thrombotic events over baseline conferred by NSAID use appears to be similar in those with and without known CV disease or risk factors for CV disease. However, patients with known CV disease or risk factors had a higher absolute incidence of excess serious CV thrombotic events, due to their increased baseline rate. Some observational studies found that this increased risk of serious CV thrombotic events began as early as the first weeks of treatment. The increase in CV thrombotic risk has been observed most consistently at higher doses.

To minimize the potential risk for an adverse CV event in NSAID-treated patients, use the lowest effective dose for the shortest duration possible. Physicians and patients should remain alert for the development of such events, throughout the entire treatment course, even in the absence of previous CV symptoms. Patients should be informed about the symptoms of serious CV events and the steps to take if they occur.

There is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious CV thrombotic events associated with NSAID use. The concurrent use of aspirin and an NSAID, such as diclofenac, increases the risk of serious gastrointestinal (GI) events [ see Warnings and Precautions (5.2) ] .

The pharmacological activity of diclofenac sodium in reducing inflammation, and possibly fever, may diminish the utility of diagnostic signs in detecting infections.

Concomitant use of oral NSAIDs with diclofenac sodium 1.5% resulted in a higher rate of rectal hemorrhage, more frequent abnormal creatinine, urea and hemoglobin. Therefore, do not use combination therapy with diclofenac sodium and an oral NSAID unless the benefit outweighs the risk and conduct periodic laboratory evaluations.

3.8 FL.OZ.

(112 grams)

NDC 85509-1369-1

Dispense Enclosed

Medication Guide to Each Patient.

Diclofenac

Sodium

Topical Solution

USP, 2% w/w

FOR EXTERNAL

USE ONLY

Usual dosage:

Apply two pump actuations

to affected knee(s) two times

a day.

Keep this and all

medications out of the

reach of children.

Rx only

A subpopulation of patients with asthma may have aspirin-sensitive asthma which may include chronic rhinosinusitis complicated by nasal polyps; severe, potentially fatal bronchospasm; and/or intolerance to aspirin and other NSAIDs. Because cross-reactivity between aspirin and other NSAIDs has been reported in such aspirin-sensitive patients, diclofenac sodium is contraindicated in patients with this form of aspirin sensitivity [ see Contraindications (4) ]. When diclofenac sodium is used in patients with preexisting asthma (without known aspirin sensitivity), monitor patients for changes in the signs and symptoms of asthma.

NSAIDs, including diclofenac, cause serious gastrointestinal (GI) adverse events including inflammation, bleeding, ulceration, and perforation of the esophagus, stomach, small intestine, or large intestine, which can be fatal. These serious adverse events can occur at any time, with or without warning symptoms, in patients treated with NSAIDs. Only one in five patients who develop a serious upper GI adverse event on NSAID therapy is symptomatic. Upper GI ulcers, gross bleeding, or perforation caused by NSAIDs occurred in approximately 1% of patients treated for 3 to 6 months, and in about 2% to 4% of patients treated for one year. However, even short-term NSAID therapy is not without risk.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) has been reported in patients taking NSAIDs such as diclofenac sodium. Some of these events have been fatal or life-threatening. DRESS typically, although not exclusively, presents with fever, rash, lymphadenopathy, and/or facial swelling. Other clinical manifestations may include hepatitis, nephritis, hematological abnormalities, myocarditis, or myositis. Sometimes symptoms of DRESS may resemble an acute viral infection. Eosinophilia is often present. Because this disorder is variable in its presentation, other organ systems not noted here may be involved. It is important to note that early manifestations of hypersensitivity, such as fever or lymphadenopathy, may be present even though rash is not evident. If such signs or symptoms are present, discontinue diclofenac sodium and evaluate the patient immediately.

WARNING: RISK OF SERIOUS CARDIOVASCULAR AND GASTROINTESTINAL EVENTS

See full prescribing information for complete boxed warning.

• Nonsteroidal anti-inflammatory drugs (NSAIDs) cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction, and stroke, which can be fatal. This risk may occur early in treatment and may increase with duration of use ( 5.1)
• Diclofenac sodium is contraindicated in the setting of coronary artery bypass graft (CABG) surgery ( 4, 5.1)
• NSAIDs cause an increased risk of serious gastrointestinal (GI) adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients and patients with a prior history of peptic ulcer disease and/or GI bleeding are at greater risk for serious GI events ( 5.2)

Cardiovascular Thrombotic Events

• Nonsteroidal anti-inflammatory drugs (NSAIDs) cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction, and stroke, which can be fatal. This risk may occur early in treatment and may increase with duration of use [ see Warnings and Precautions (5.1) ].
• Diclofenac sodium is contraindicated in the setting of coronary artery bypass graft (CABG) surgery [ see Contraindications (4)and Warnings and Precautions (5.1) ].

Storage

Store at 20° to 25°C (68° to 77°F)[see USP Controlled Room Temperature].

Symptoms following acute NSAID overdosages have been typically limited to lethargy, drowsiness, nausea, vomiting, and epigastric pain, which have been generally reversible with supportive care. Gastrointestinal bleeding has occurred. Hypertension, acute renal failure, respiratory depression, and coma have occurred but were rare [ see Warnings and Precautions (5.1, 5.2, 5.4, 5.6) ].

Manage patients with symptomatic and supportive care following an NSAID overdosage. There are no specific antidotes. Emesis is not recommended due to a possibility of aspiration and subsequent respiratory irritation by DMSO contained in diclofenac sodium. Consider activated charcoal (60 to 100 grams in adults, 1 to 2 grams per kg of body weight in pediatric patients) and/or osmotic cathartic in symptomatic patients seen within four hours of ingestion or in patients with a large overdosage (5 to 10 times the recommended dosage). Forced diuresis, alkalinization of urine, hemodialysis, or hemoperfusion may not be useful due to high protein binding.

For additional information about overdosage treatment, contact a poison control center (1-800-222-1222).

Diclofenac sodium topical solution USP, 2% contains diclofenac sodium, a benzeneacetic acid derivative that is a nonsteroidal anti-inflammatory drug, and is available as a clear, colorless to slightly pink or orange solution for topical application. The chemical name is 2[(2,6-dichlorophenyl)amino]-benzeneacetic acid, monosodium salt. The molecular weight is 318.14. Its molecular formula is C ₁₄H ₁₀Cl ₂NNaO ₂, and it has the following chemical structure:

Each 1 gram of solution contains 20 mg of diclofenac sodium. The inactive ingredients: dimethyl sulfoxide USP (DMSO, 45.5% w/w), ethanol (31.46% v/v), hydroxypropyl cellulose, propylene glycol and purified water.

NSAIDs, including diclofenac, can lead to new onset of hypertension or worsening of preexisting hypertension, either of which may contribute to the increased incidence of CV events. Patients taking angiotensin converting enzyme (ACE) inhibitors, thiazide diuretics, or loop diuretics may have impaired response to these therapies when taking NSAIDs [ see Drug Interactions (7) ] .

Monitor blood pressure (BP) during the initiation of NSAID treatment and throughout the course of therapy.

Instruct patients to avoid exposure to natural or artificial sunlight on treated knee(s) because studies in animals indicated topical diclofenac treatment resulted in an earlier onset of ultraviolet light-induced skin tumors. The potential effects of diclofenac sodium on skin response to ultraviolet damage in humans are not known.

Avoid contact of diclofenac sodium with eyes and mucosa. Advise patients that if eye contact occurs, immediately wash out the eye with water or saline and consult a physician if irritation persists for more than an hour.

Safety and effectiveness in pediatric patients have not been established.

Elderly patients, compared to younger patients, are at greater risk for NSAID-associated serious cardiovascular, gastrointestinal, and/or renal adverse reactions. If the anticipated benefit for the elderly patient outweighs these potential risks, start dosing at the low end of the dosing range, and monitor patients for adverse effects [ see Warnings and Precautions (5.1, 5.2, 5.3, 5.6, 5.14) ].

Of the 911 patients treated with diclofenac sodium 1.5% in seven controlled, Phase 3 clinical trials, 444 subjects were 65 years of age and over. There was no age-related difference in the incidence of adverse events. Of the 793 patients treated with diclofenac sodium topical solution 1.5% in one open-labeled safety trial, 334 subjects were 65 years of age and over including 107 subjects 75 and over. There was no difference in the incidence of adverse events with long-term exposure to diclofenac sodium topical solution 1.5% for this elderly population.

In clinical trials of oral diclofenac containing products, meaningful elevations (i.e., more than 3 times the ULN) of AST (SGOT) occurred in about 2% of approximately 5,700 patients at some time during diclofenac treatment (ALT was not measured in all studies).

In a large, open-label, controlled trial of 3,700 patients treated with oral diclofenac for 2 to 6 months, patients were monitored first at 8 weeks and 1,200 patients were monitored again at 24 weeks. Meaningful elevations of ALT and/or AST occurred in about 4% of 3,700 patients and included marked elevations (greater than 8 times the ULN) in about 1% of the 3,700 patients. In that open-label study, a higher incidence of borderline (less than 3 times the ULN), moderate (3 to 8 times the ULN), and marked (greater than 8 times the ULN) elevations of ALT or AST was observed in patients receiving diclofenac when compared to other NSAIDs. Elevations in transaminases were seen more frequently in patients with osteoarthritis than in those with rheumatoid arthritis.

Almost all meaningful elevations in transaminases were detected before patients became symptomatic.

Abnormal tests occurred during the first 2 months of therapy with oral diclofenac in 42 of the 51 patients in all trials who developed marked transaminase elevations.

In postmarketing reports, cases of drug-induced hepatotoxicity have been reported in the first month, and in some cases, the first 2 months of NSAID therapy, but can occur at any time during treatment with diclofenac.

Postmarketing surveillance has reported cases of severe hepatic reactions, including liver necrosis, jaundice, fulminant hepatitis with and without jaundice, and liver failure. Some of these reported cases resulted in fatalities or liver transplantation.

In a European retrospective population-based, case-controlled study, 10 cases of oral diclofenac associated drug-induced liver injury with current use compared with non-use of diclofenac were associated with a statistically significant 4-fold adjusted odds ratio of liver injury. In this particular study, based on an overall number of 10 cases of liver injury associated with diclofenac, the adjusted odds ratio increased further with female gender, doses of 150 mg or more, and duration of use for more than 90 days.

Physicians should measure transaminases at baseline and periodically in patients receiving long-term therapy with diclofenac, because severe hepatotoxicity may develop without a prodrome of distinguishing symptoms. The optimum times for making the first and subsequent transaminase measurements are not known. Based on clinical trial data and postmarketing experiences, transaminases should be monitored within 4 to 8 weeks after initiating treatment with diclofenac. However, severe hepatic reactions can occur at any time during treatment with diclofenac.

If abnormal liver tests persist or worsen, if clinical signs and/or symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g., eosinophilia, rash, abdominal pain, diarrhea, dark urine, etc.), diclofenac sodium should be discontinued immediately.

Inform patients of the warning signs and symptoms of hepatotoxicity (e.g., nausea, fatigue, lethargy, diarrhea, pruritus, jaundice, right upper quadrant tenderness, and "flu-like" symptoms). If clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g., eosinophilia, rash, etc.), discontinue diclofenac sodium immediately, and perform a clinical evaluation of the patient.

To minimize the potential risk for an adverse liver-related event in patients treated with diclofenac sodium, use the lowest effective dose for the shortest duration possible. Exercise caution when prescribing diclofenac sodium with concomitant drugs that are known to be potentially hepatotoxic (e.g., acetaminophen, antibiotics, antiepileptics).

Diclofenac sodium is contraindicated in the following patients:

• Known hypersensitivity (e.g., anaphylactic reactions and serious skin reactions) to diclofenac or any components of the drug product [ see Warnings and Precautions (5.7, 5.9) ]
• History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs. Severe, sometimes fatal, anaphylactic reactions to NSAIDs have been reported in such patients [ see Warnings and Precautions (5.7, 5.8) ]
• In the setting of coronary artery bypass graft (CABG) surgery [ see Warnings and Precautions (5.1) ]

The following adverse reactions are discussed in greater detail in other sections of the labeling:

• Cardiovascular Thrombotic Events [ see Warnings and Precautions (5.1) ]
• GI Bleeding, Ulceration and Perforation [ see Warnings and Precautions (5.2) ]
• Hepatotoxicity [ see Warnings and Precautions (5.3) ]
• Hypertension [ see Warnings and Precautions (5.4) ]
• Heart Failure and Edema [ see Warnings and Precautions (5.5) ]
• Renal Toxicity and Hyperkalemia [ see Warnings and Precautions (5.6) ]
• Anaphylactic Reactions [ see Warnings and Precautions (5.7) ]
• Serious Skin Reactions [ see Warnings and Precautions (5.9) ]
• Hematologic Toxicity [ see Warnings and Precautions (5.12) ]

See Table 3for clinically significant drug interactions with diclofenac.

Diclofenac Sodium (dye kloe' fen ak soe' dee um) Topical Solution USP, 2% w/w

Read the Medication Guide that comes with diclofenac sodium topical solution first. Be sure that you read, understand and follow these Instructions for Use before you use diclofenac sodium topical solution for the first time.

Important: For use on the skin only (topical). Do not get diclofenac sodium topical solution in your eyes, nose or mouth.

Before you use diclofenac sodium topical solution:

• Apply diclofenac sodium topical solution exactly as your health care provider tells you. Talk with your health care provider or pharmacist if you are not sure.
• Only use diclofenac sodium topical solution to treat pain from osteoarthritis in your knee or knees.
• Apply diclofenac sodium topical solution on clean, dry skin that does not have any cuts, infections or rashes.
• Use diclofenac sodium topical solution two times a day on your knee or knees as prescribed.
• If you get diclofenac sodium topical solution in your eyes, rinse your eyes right away with water or saline. Call your health care provider if your eyes are irritated for more than one hour.

Diclofenac sodium topical solution comes in a pump bottle.

If you are using a diclofenac sodium topical solution pump bottle follow the steps below:

Before you use diclofenac sodium topical solution pump bottle for the first time, you will need to prime the pump.To prime the pump, remove the cap (see Figure A ) and fully press the top of the pump all the way down 4 times while holding the bottle in an upright position (see Figure B ). Dispense this portion of the medicine into a tissue or paper towel and throw it away in a trash can. The pump is now ready to use. You should not need to prime the pump again.

Figure A.

Figure B.

Steps for using diclofenac sodium topical solution pump bottle:

Figure C.

Step 3: Apply diclofenac sodium topical solution evenly around the front, back, and sides of your knee. Diclofenac sodium topical solution should be applied without massaging the knee (see Figures D and E ).

After you use diclofenac sodium topical solution:

Do not:

• cover your knee with clothing until your knee is completely dry.
• put sunscreen, insect repellant, lotion, moisturizer, cosmetics, or other topical medicines on your knee until it is completely dry.
• take a shower or a bath for at least 30 minutes after you put diclofenac sodium topical solution on your knee(s).
• use heating pads or cover the treated area with bandages where you have applied diclofenac sodium topical solution.
• exercise following application of diclofenac sodium topical solution.
• use sunlamp and tanning beds. Protect your treated knee from sunlight. Wear clothes that cover your skin if you have to be in the sunlight.

How should I store diclofenac sodium topical solution?

• Store diclofenac sodium topical solution at room temperature between 68°F to 77°F (20°C to 25°C).

Keep diclofenac sodium topical solution and all medicines out of the reach of children.

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

Manufactured by: Taro Pharmaceuticals Inc., Brampton, Ontario, Canada L6T 1C1

Distributed by: Sun Pharmaceuticals U.S.A., Inc.,Cranbury, NJ 08512

Revised: April 2024

5259428 23

Diclofenac sodium topical solution is indicated for the treatment of the pain of osteoarthritis of the knee(s).

• Avoid showering/bathing for at least 30 minutes after the application of diclofenac sodium topical solution to the treated knee.
• Wash and dry hands after use.
• Do not apply diclofenac sodium topical solution to open wounds.
• Avoid contact of diclofenac sodium topical solution with eyes and mucous membranes.
• Do not apply external heat and/or occlusive dressings to treated knees.
• Avoid wearing clothing over the diclofenac sodium topical solution-treated knee(s) until the treated knee is dry.
• Protect the treated knee(s) from natural and artificial sunlight.
• Wait until the treated area is dry before applying sunscreen, insect repellant, lotion, moisturizer, cosmetics, or other topical medication to the same knee you have just treated with diclofenac sodium topical solution.
• Until the treated knee(s) is completely dry, avoid skin-to-skin contact between other people and the treated knee(s).
• Do not use combination therapy with diclofenac sodium and an oral NSAID unless the benefit outweighs the risk and conduct periodic laboratory evaluations.

Diclofenac has analgesic, anti-inflammatory, and antipyretic properties.

The mechanism of action of diclofenac sodium, like that of other NSAIDs, is not completely understood but involves inhibition of cyclooxygenase (COX-1 and COX-2).

Diclofenac is a potent inhibitor of prostaglandin synthesis in vitro. Diclofenac concentrations reached during therapy have produced in vivoeffects. Prostaglandins sensitize afferent nerves and potentiate the action of bradykinin in inducing pain in animal models. Prostaglandins are mediators of inflammation. Because diclofenac is an inhibitor of prostaglandin synthesis, its mode of action may be due to a decrease of prostaglandins in peripheral tissues.

Anemia has occurred in NSAID-treated patients. This may be due to occult or gross blood loss, fluid retention, or an incompletely described effect on erythropoiesis. If a patient treated with diclofenac sodium has any signs or symptoms of anemia, monitor hemoglobin or hematocrit.

NSAIDs, including diclofenac sodium, may increase the risk of bleeding events. Co-morbid conditions such as coagulation disorders or concomitant use of warfarin, other anticoagulants, antiplatelet agents (e.g., aspirin), serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) may increase this risk. Monitor these patients for signs of bleeding [ see Drug Interactions (7) ].

• Hepatotoxicity: Inform patients of warning signs and symptoms of hepatotoxicity. Discontinue if abnormal liver tests persist or worsen or if clinical signs and symptoms of liver disease develop ( 5.3)
• Hypertension: Patients taking some antihypertensive medications may have impaired response to these therapies when taking NSAIDs. Monitor blood pressure ( 5.4, 7)
• Heart Failure and Edema: Avoid use of diclofenac sodium in patients with severe heart failure unless benefits are expected to outweigh risk of worsening heart failure ( 5.5)
• Renal Toxicity: Monitor renal function in patients with renal or hepatic impairment, heart failure, dehydration, or hypovolemia. Avoid use of diclofenac sodium in patients with advanced renal disease unless benefits are expected to outweigh risk of worsening renal function ( 5.6)
• Anaphylactic Reactions: Seek emergency help if an anaphylactic reaction occurs ( 5.7)
• Exacerbation of Asthma Related to Aspirin Sensitivity: Diclofenac sodium topical solution is contraindicated in patients with aspirin-sensitive asthma. Monitor patients with preexisting asthma (without aspirin sensitivity) ( 5.8)
• Serious Skin Reactions: Discontinue diclofenac sodium at first appearance of skin rash or other signs of hypersensitivity. ( 5.9, 5.15)
• Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): Discontinue and evaluate clinically ( 5.10)
• Fetal Toxicity: Limit use of NSAIDs, including diclofenac sodium topical solution, between about 20 to 30 weeks in pregnancy due to the risk of oligohydramnios/fetal renal dysfunction. Avoid use of NSAIDs in women at about 30 weeks gestation and later in pregnancy due to the risks of oligohydramnios/fetal renal dysfunction and premature closure of the fetal ductus arteriosus ( 5.11, 8.1).
• Hematologic Toxicity: Monitor hemoglobin or hematocrit in patients with any signs or symptoms of anemia ( 5.12, 7).
• Exposure to light: Avoid exposure of treated knee(s) to natural or artificial sunlight. ( 5.15)
• Eye Contact: Avoid contact of diclofenac sodium with eyes and mucosa. ( 5.16)
• Oral Nonsteroidal Anti-inflammatory Drugs: Avoid concurrent use with oral NSAIDs. ( 5.17)

Because serious GI bleeding, hepatotoxicity, and renal injury can occur without warning symptoms or signs, consider monitoring patients on long-term NSAID treatment with a CBC and a chemistry profile periodically [ see Warnings and Precautions (5.2, 5.3, 5.6) ].

Diclofenac has been associated with anaphylactic reactions in patients with and without known hypersensitivity to diclofenac and in patients with aspirin-sensitive asthma [ see Contraindications (4)and Warnings and Precautions (5.8) ].

Seek emergency help if an anaphylactic reaction occurs.

NSAIDs, including diclofenac, can cause serious skin adverse reactions such as exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. NSAIDs can also cause fixed drug eruption (FDE). FDE may present as a more severe variant known as generalized bullous fixed drug eruption (GBFDE), which can be lifethreatening.These serious events may occur without warning. Inform patients about the signs and symptoms of serious skin reactions, and to discontinue the use of diclofenac sodium topical solution at the first appearance of skin rash or any other sign of hypersensitivity. Diclofenac sodium topical solution is contraindicated in patients with previous serious skin reactions to NSAIDs [ see Contraindications (4) ]. Do not apply diclofenac sodium topical solution to open skin wounds, infections, inflammations, or exfoliative dermatitis, as it may affect absorption and tolerability of the drug.

Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals.

The recommended dose is 2 pump actuations on each painful knee, 2 times a day. ( 2)

• Apply diclofenac sodium topical solution to clean, dry skin. ( 2.1)
• Dispense 40 mg (2 pump actuations) directly onto the knee or first into the hand and then onto the knee. Spread evenly around front, back and sides of the knee. ( 2.1)
• Wash hands completely after administering the product. ( 2.2)
• Wait until the area is completely dry before covering with clothing or applying sunscreen, insect repellent, cosmetics, topical medications, or other substances. ( 2.2)
• Until the treated knee(s) is completely dry, avoid skin-to-skin contact between other people and the treated knee(s). ( 2.2)
• Do not get diclofenac sodium topical solution in your eyes, nose, or mouth ( 2.2).

The Coxib and traditional NSAID Trialists' Collaboration meta-analysis of randomized controlled trials demonstrated an approximately two-fold increase in hospitalizations for heart failure in COX-2 selective treated patients and nonselective NSAID-treated patients compared to placebo-treated patients. In a Danish National Registry study of patients with heart failure, NSAID use increased the risk of MI, hospitalization for heart failure, and death.

Additionally, fluid retention and edema have been observed in some patients treated with NSAIDs. Use of diclofenac may blunt the CV effects of several therapeutic agents used to treat these medical conditions (e.g., diuretics, ACE inhibitors, or angiotensin receptor blockers [ARBs]) [ see Drug Interactions (7) ].

Avoid the use of diclofenac sodium in patients with severe heart failure unless the benefits are expected to outweigh the risk of worsening heart failure. If diclofenac sodium is used in patients with severe heart failure, monitor patients for signs of worsening heart failure.

Diclofenac sodium topical solution USP, 2% w/w

In postmarketing surveillance, the following adverse reactions have been reported during post-approval use of diclofenac sodium topical solution 1.5%. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Body as a Whole:abdominal pain, accidental injury, allergic reactions, asthenia, back pain, body odor, chest pain, edema, face edema, halitosis, headache, neck rigidity, pain

Cardiovascular:palpitation, cardiovascular disorder

Gastrointestinal:diarrhea, dry mouth, dyspepsia, gastroenteritis, decreased appetite, lip swelling, mouth ulceration, nausea, rectal hemorrhage, ulcerative stomatitis, swollen tongue

Metabolic and Nutritional:creatinine increased

Musculoskeletal:leg cramps, myalgia

Nervous:depression, dizziness, drowsiness, lethargy, paresthesia at application site

Respiratory:asthma, dyspnea, laryngismus, laryngitis, pharyngitis, throat swelling

Skin and Appendages: At the Application Site:rash, skin burning sensation;

Other Skin and Appendages Adverse Reactions:eczema, skin discoloration, urticaria, exfoliative dermatitis, Stevens-Johnson

Syndrome (SJS), toxic epidermal necrolysis (TEN), and fixed drug eruption (FDE).

Special Senses:abnormal vision, blurred vision, cataract, ear pain, eye disorder, eye pain, taste perversion

Vascular:blood pressure increased, hypertension

• Infertility:NSAIDs are associated with reversible infertility. Consider withdrawal of diclofenac sodium in women who have difficulties conceiving. ( 8.3)

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals [ see Warnings and Precautions (5.2) ].

For relief of the pain of osteoarthritis (OA) of the knee(s), the recommended dose is 40 mg of diclofenac sodium (2 pump actuations) on each painful knee, 2 times a day.

Apply diclofenac sodium topical solution to clean, dry skin.

The pump must be primed before first use. Instruct patients to fully depress the pump mechanism (actuation) 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 should be required.

After the priming procedure, diclofenac sodium topical solution is properly dispensed by completely depressing the pump 2 times to achieve the prescribed dosage for one knee. Deliver the product directly into the palm of the hand and then apply evenly around front, back, and sides of the knee.

Application of diclofenac sodium topical solution in an amount exceeding or less than the recommended dose has not been studied and is therefore not recommended.

Advise the patient to read the FDA-approved patient labeling (Medication Guide) that accompanies each prescription dispensed. Inform patients, families, or their caregivers of the following information before initiating therapy with diclofenac sodium topical solution and periodically during the course of ongoing therapy.

Diclofenac sodium topical solution USP, 2% w/w is supplied as a clear, colorless to slightly pink-orange solution containing 20 mg of diclofenac sodium per gram of solution, in a white polypropylene-dose pump bottle with a clear cap. Each pump actuation delivers 20 mg of diclofenac sodium in 1 gram of solution.

Relabeled by:

PHOENIX RX LLC,

Hatboro, PA 19040 USA

Clinical trials of several COX-2 selective and nonselective NSAIDs of up to three years duration have shown an increased risk of serious cardiovascular (CV) thrombotic events, including myocardial infarction (MI), and stroke, which can be fatal. Based on available data, it is unclear that the risk for CV thrombotic events is similar for all NSAIDs. The relative increase in serious CV thrombotic events over baseline conferred by NSAID use appears to be similar in those with and without known CV disease or risk factors for CV disease. However, patients with known CV disease or risk factors had a higher absolute incidence of excess serious CV thrombotic events, due to their increased baseline rate. Some observational studies found that this increased risk of serious CV thrombotic events began as early as the first weeks of treatment. The increase in CV thrombotic risk has been observed most consistently at higher doses.

To minimize the potential risk for an adverse CV event in NSAID-treated patients, use the lowest effective dose for the shortest duration possible. Physicians and patients should remain alert for the development of such events, throughout the entire treatment course, even in the absence of previous CV symptoms. Patients should be informed about the symptoms of serious CV events and the steps to take if they occur.

There is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious CV thrombotic events associated with NSAID use. The concurrent use of aspirin and an NSAID, such as diclofenac, increases the risk of serious gastrointestinal (GI) events [ see Warnings and Precautions (5.2) ] .

The pharmacological activity of diclofenac sodium in reducing inflammation, and possibly fever, may diminish the utility of diagnostic signs in detecting infections.

Concomitant use of oral NSAIDs with diclofenac sodium 1.5% resulted in a higher rate of rectal hemorrhage, more frequent abnormal creatinine, urea and hemoglobin. Therefore, do not use combination therapy with diclofenac sodium and an oral NSAID unless the benefit outweighs the risk and conduct periodic laboratory evaluations.

3.8 FL.OZ.

(112 grams)

NDC 85509-1369-1

Dispense Enclosed

Medication Guide to Each Patient.

Diclofenac

Sodium

Topical Solution

USP, 2% w/w

FOR EXTERNAL

USE ONLY

Usual dosage:

Apply two pump actuations

to affected knee(s) two times

a day.

Keep this and all

medications out of the

reach of children.

Rx only

A subpopulation of patients with asthma may have aspirin-sensitive asthma which may include chronic rhinosinusitis complicated by nasal polyps; severe, potentially fatal bronchospasm; and/or intolerance to aspirin and other NSAIDs. Because cross-reactivity between aspirin and other NSAIDs has been reported in such aspirin-sensitive patients, diclofenac sodium is contraindicated in patients with this form of aspirin sensitivity [ see Contraindications (4) ]. When diclofenac sodium is used in patients with preexisting asthma (without known aspirin sensitivity), monitor patients for changes in the signs and symptoms of asthma.

NSAIDs, including diclofenac, cause serious gastrointestinal (GI) adverse events including inflammation, bleeding, ulceration, and perforation of the esophagus, stomach, small intestine, or large intestine, which can be fatal. These serious adverse events can occur at any time, with or without warning symptoms, in patients treated with NSAIDs. Only one in five patients who develop a serious upper GI adverse event on NSAID therapy is symptomatic. Upper GI ulcers, gross bleeding, or perforation caused by NSAIDs occurred in approximately 1% of patients treated for 3 to 6 months, and in about 2% to 4% of patients treated for one year. However, even short-term NSAID therapy is not without risk.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) has been reported in patients taking NSAIDs such as diclofenac sodium. Some of these events have been fatal or life-threatening. DRESS typically, although not exclusively, presents with fever, rash, lymphadenopathy, and/or facial swelling. Other clinical manifestations may include hepatitis, nephritis, hematological abnormalities, myocarditis, or myositis. Sometimes symptoms of DRESS may resemble an acute viral infection. Eosinophilia is often present. Because this disorder is variable in its presentation, other organ systems not noted here may be involved. It is important to note that early manifestations of hypersensitivity, such as fever or lymphadenopathy, may be present even though rash is not evident. If such signs or symptoms are present, discontinue diclofenac sodium and evaluate the patient immediately.

WARNING: RISK OF SERIOUS CARDIOVASCULAR AND GASTROINTESTINAL EVENTS

See full prescribing information for complete boxed warning.

• Nonsteroidal anti-inflammatory drugs (NSAIDs) cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction, and stroke, which can be fatal. This risk may occur early in treatment and may increase with duration of use ( 5.1)
• Diclofenac sodium is contraindicated in the setting of coronary artery bypass graft (CABG) surgery ( 4, 5.1)
• NSAIDs cause an increased risk of serious gastrointestinal (GI) adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients and patients with a prior history of peptic ulcer disease and/or GI bleeding are at greater risk for serious GI events ( 5.2)