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| Product NDC Code | 59088-365 | ||||
|---|---|---|---|---|---|
| Drug Name | Xrylix |
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| Type | Brand | ||||
| Dosage Form | KIT | ||||
| RxCUI drug identifier | 857700 | ||||
| Labeler Name | PureTek Corporation | ||||
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| Check if available Online | Get Medication Prices online with Discount |
Overdosage of Xrylix
Information about signs, symptoms, and laboratory findings of acute ovedosage and the general principles of overdose treatment.10. OVERDOSAGE There have been no known experiences of overdose with diclofenac sodium topical solution. Symptoms following acute NSAID overdose are usually limited to lethargy, drowsiness, nausea, vomiting, and epigastric pain, which are generally reversible with supportive care. Gastrointestinal bleeding can occur. Hypertension, acute renal failure, respiratory depression and coma may occur, but are rare. Anaphylactoid reactions have been reported with therapeutic ingestion of NSAIDs, and may occur following an overdose. Manage patients using symptomatic and supportive care following an NSAID overdose. 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 topical solution. Activated charcoal (60 to 100 g in adults, 1 to 2 g/kg in children) and/or osmotic cathartic may be indicated in patients seen within 4 hours of ingestion with symptoms or following a large overdose (5 to 10 times the usual dose). Forced diureses, alkalinization of urine, hemodialysis, or hemoperfusion may not be useful due to high protein binding. For additional information about overdose treatment, call a poison control center (1-800-222-1222).
Adverse reactions
Information about undesirable effects, reasonably associated with use of the drug, that may occur as part of the pharmacological action of the drug or may be unpredictable in its occurrence. Adverse reactions include those that occur with the drug, and if applicable, with drugs in the same pharmacologically active and chemically related class. There is considerable variation in the listing of adverse reactions. They may be categorized by organ system, by severity of reaction, by frequency, by toxicological mechanism, or by a combination of these.6. ADVERSE REACTIONS The most common adverse events with diclofenac sodium topical solution are application site reactions. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact IGI Laboratories, Inc. at 1-856-697-1441, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Studies Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of another drug cannot be directly compared to rates in the clinical trial of another drug and may not reflect the rates observed in practice. The data described below reflect exposure to diclofenac sodium topical solution of 911 patients treated between 4 and 12 weeks (mean duration of 49 days) in seven Phase 3 controlled trials, as well as exposure of 793 patients treated in an open-label study, including 463 patients treated for at least 6 months, and 144 patients treated for at least 12 months. The population mean age was approximately 60 years, 89% of patients were Caucasians, 64% were females, and all patients had primary osteoarthritis. The most common adverse events with diclofenac sodium topical solution were application site skin reactions. These events were the most common reason for withdrawing from the studies. Application site reactions: In controlled trials, the most common treatment related adverse events in patients receiving diclofenac sodium topical solution were application site skin reactions. Application site reactions were characterized by one or more of the following: dryness, erythema, induration, vesicles, paresthesia, pruritus, vasodilation, acne, and urticaria. The most frequent of these reactions were dry skin (32%), contact dermatitis characterized by skin erythema and induration (9%), contact dermatitis with vescicles (2%) and pruritus (4%). In one controlled trial, a higher rate of contact dermatitis with vesicles (4%) was observed after treatment of 152 subjects with the combination of diclofenac sodium topical solution and oral diclofenac. In the open label uncontrolled long-term safety study, contact dermatitis occurred in 13% and contact dermatitis with vesicles in 10% of patients, generally within the first 6 months of exposure, leading to a withdrawal rate for an application site event of 14%. Adverse events common to the NSAID class: In controlled trials, subjects treated with diclofenac sodium topical solution experienced some adverse events associated with the NSAID class more frequently than subjects using placebo (constipation, diarrhea, dyspepsia, nausea, flatulence, abdominal pain, edema; see Table 1 ). The combination of diclofenac sodium topical solution and oral diclofenac, compared to oral diclofenac alone, resulted in a higher rate of rectal hemorrhage (3% vs. less than 1%), and more frequent abnormal creatinine (12% vs. 7%), urea (20% vs. 12%), and hemoglobin (13% vs. 9%), but no difference in elevation of liver transaminases. Table 1: lists all adverse reactions occurring in ≥1% of patients receiving diclofenac sodium topical solution, where the rate in the diclofenac sodium topical solution group exceeded placebo, from seven controlled studies conducted in patients with osteoarthritis. Since these trials were of different durations, these percentages do not capture cumulative rates of occurrence. Table 1: Adverse Reactions occurring in ≥1% of patients treated with Diclofenac Sodium Topical Solution in placebo and oral diclofenac-controlled trials. Treatment Group: Diclofenac Sodium Topical Solution N=911 Topical Placebo N=332 Adverse Reaction Preferred Term according to COSTART N(%) N(%) Dry Skin (Application Site) 292 (32) 17 (5) Contact Dermatitis (Application Site) 83 (9) 6 (2) Dyspepsia 72 (8) 13 (4) Abdominal Pain 54 (6) 10 (3) Flatulence 35 (4) 1 (<1) Pruritus (Application Site) 34 (4) 7 (2) Diarrhea 33 (4) 7 (2) Nausea 33 (4) 3 (1) Pharyngitis 40 (4) 13 (4) Constipation 29 (3) 1 (<1) Edema 26 (3) 0 Rash (Non-Application Site) 25 (3) 5 (2) Infection 25 (3) 8 (2) Ecchymosis 19 (2) 1 (<1) Dry Skin (Non-Application Site) 19 (2) 1 (<1) Contact Dermatitis, vesicles (Application Site) 18 (2) 0 Paresthesia (Non-Application Site) 14 (2) 3 (<1) Accidental Injury 22 (2) 7 (2) Pruritus (Non-Application Site) 15 (2) 2 (<1) Sinusitis 10 (1) 2 (<1) Halitosis 11 (1) 1 (<1) Application Site Reaction (not otherwise specified) 11 (1) 3 (<1) 6.2 Postmarketing Experience In non – U.S. postmarketing surveillance, the following adverse reactions have been reported during post-approval use of diclofenac sodium topical solution. 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 reaction, asthenia, back pain, body odor, chest pain, edema, face edema, halitosis, headache, lack of drug effect, neck rigidity, pain Cardiovascular: palpitation, cardiovascular disorder Digestive: diarrhea, dry mouth, dyspepsia, gastroenteritis, decreased appetite, mouth ulceration, nausea, rectal hemorrhage, ulcerative stomatitis Metabolic and Nutritional: creatinine increased Musculoskeletal: leg cramps, myalgia Nervous: depression, dizziness, drowsiness, lethargy, paresthesia, paresthesia at application site Respiratory: asthma, dyspnea, laryngismus, laryngitis, pharyngitis Skin and Appendages: At the Application Site: contact dermatitis, contact dermatitis with vesicles, dry skin, pruritus, rash; Other Skin and Appendages Adverse Reactions: eczema, rash, pruritus, skin discoloration, urticaria Special senses: abnormal vision, blurred vision, cataract, ear pain, eye disorder, eye pain, taste perversion
| Treatment Group: | Diclofenac Sodium Topical Solution N=911 | Topical Placebo N=332 |
|---|---|---|
| Adverse Reaction | N(%) | N(%) |
| Dry Skin (Application Site) | 292 (32) | 17 (5) |
| Contact Dermatitis (Application Site) | 83 (9) | 6 (2) |
| Dyspepsia | 72 (8) | 13 (4) |
| Abdominal Pain | 54 (6) | 10 (3) |
| Flatulence | 35 (4) | 1 (<1) |
| Pruritus (Application Site) | 34 (4) | 7 (2) |
| Diarrhea | 33 (4) | 7 (2) |
| Nausea | 33 (4) | 3 (1) |
| Pharyngitis | 40 (4) | 13 (4) |
| Constipation | 29 (3) | 1 (<1) |
| Edema | 26 (3) | 0 |
| Rash (Non-Application Site) | 25 (3) | 5 (2) |
| Infection | 25 (3) | 8 (2) |
| Ecchymosis | 19 (2) | 1 (<1) |
| Dry Skin (Non-Application Site) | 19 (2) | 1 (<1) |
| Contact Dermatitis, vesicles (Application Site) | 18 (2) | 0 |
| Paresthesia (Non-Application Site) | 14 (2) | 3 (<1) |
| Accidental Injury | 22 (2) | 7 (2) |
| Pruritus (Non-Application Site) | 15 (2) | 2 (<1) |
| Sinusitis | 10 (1) | 2 (<1) |
| Halitosis | 11 (1) | 1 (<1) |
| Application Site Reaction (not otherwise specified) | 11 (1) | 3 (<1) |
Xrylix Drug Interactions
Information about and practical guidance on preventing clinically significant drug/drug and drug/food interactions that may occur in people taking the drug.7. DRUG INTERACTIONS Drug interactions with the use of diclofenac sodium topical solution have not been studied. The following drug interactions [sections 7.1 to 7.7] are noted for oral diclofenac sodium. Concomitant administration of diclofenac and aspirin is not generally recommended because of the potential of increased adverse effects including increased GAI bleeding. ( 7.1 ) Concomitant use of anticoagulants and diclofenac have a risk of serious GI bleeding higher than users of either drug alone. ( 7.2 ) 7.1 Aspirin When diclofenac is administered with aspirin, the binding of diclofenac to protein is reduced, although the clearance of free diclofenac is not altered. The clinical significance of this interaction is not known; however, as with other NSAIDs, concomitant administration of diclofenac and aspirin is not generally recommended because of the potential of increased adverse effects. 7.2 Anticoagulants The effects of anticoagulants such as warfarin and NSAIDs on GI bleeding are synergistic, such that users of both drugs together have a risk of serious GI bleeding higher than users of either drug alone. 7.3 ACE-Inhibitors NSAIDs may diminish the antihypertensive effect of angiotensin converting enzyme (ACE) inhibitors. Consider this interaction in patients taking NSAIDs concomitantly with ACE-inhibitors. 7.4 Diuretics Clinical studies, as well as postmarketing observations, have shown that NSAIDs can reduce the natriuretic effect of furosemide and thiazides in some patients. The response has been attributed to inhibition of renal prostaglandin synthesis. During concomitant therapy with NSAIDs, observe the patient closely for signs of renal failure [ see Warnings and Precautions (5.6) ] , as well as to assure diuretic efficacy. 7.5 Lithium NSAIDs have produced an elevation of plasma lithium levels and a reduction in renal lithium clearance. The mean minimum lithium concentration increased 15% and the renal clearance was decreased by approximately 20%. These effects have been attributed to inhibition of renal prostaglandin synthesis by the NSAID. Thus, when NSAIDs, including diclofenac, and lithium are administered concurrently, observe patients carefully for signs of lithium toxicity. 7.6 Methotrexate NSAIDs have been reported to competitively inhibit methotrexate accumulation in rabbit kidney slices. This may indicate that they could enhance the toxicity of methotrexate. Use caution when NSAIDs, including diclofenac, are administered concomitantly with methotrexate. 7.7 Cyclosporine Diclofenac, like other NSAIDs, may affect renal prostaglandins and increase the toxicity of certain drugs. Therefore, concomitant therapy with diclofenac may increase cyclosporine's nephrotoxicity. Use caution when diclofenac is administered concomitantly with cyclosporine. 7.8 Oral Nonsteroidal Anti-Inflammatory Drugs Concomitant use of oral NSAIDs with diclofenac sodium topical solution has been evaluated in one Phase 3 controlled trial and in combination with oral diclofenac, compared to oral diclofenac alone, resulted in a higher rate of rectal hemorrhage (3% vs. less than 1%), and more frequent abnormal creatinine (12% vs. 7%), urea (20% vs. 12) and hemoglobin (13% vs. 9%). Therefore, do not use combination therapy with diclofenac sodium topical solution and an oral NSAID unless the benefit outweighs the risk and conduct periodic laboratory evaluations. 7.9 Topical Treatments Instruct patients that before applying sunscreen, insect repellant, lotion, moisturizer, cosmetics, or other topical medication to the same skin surface of the knee treated with diclofenac sodium topical solution, they must wait until the treated area is completely dry.
Clinical pharmacology
Information about the clinical pharmacology and actions of the drug in humans.12. CLINICAL PHARMACOLOGY 12.1 Mechanism of Action The mechanism of action of diclofenac is similar to that of other nonsteroidal anti-inflammatory drugs. Diclofenac inhibits the enzyme, cyclooxygenase (COX), an early component of the arachidonic acid cascade, resulting in the reduced formation of prostaglandins, thromboxanes and prostacylin. It is not completely understood how reduced synthesis of these compounds results in therapeutic efficacy. 12.2 Pharmacodynamics Diclofenac, the active component of diclofenac sodium topical solution has anti-inflammatory, anti-nociception, and antipyretic effects. 12.3 Pharmacokinetics After topical administration to healthy human volunteers of single and multiple maximum doses of diclofenac sodium topical solution, 40 drops (approximately 1.2 mL) to each knee (80 drops total dose), the following diclofenac pharmacokinetic parameters were obtained: (see Table 2 ). Table 2: Single-Dose (80 drops) and Multiple Dose (80 drops four times daily for 7 days) Diclofenac Sodium Topical Solution Pharmacokinetic Parameters Pharmacokinetic Parameters Diclofenac sodium Normal Adults [N=18] (Age: 18-55 years) Normal Adults [N=19] (Age: 18-55 years) Single Dose Multiple Dose Four times daily for 7 days AUC 0-t 177.5 ± 72.6 ng.h/mL 695.4 ± 348.9 ng.h/mL AUC 0-inf 196.3 ± 68.5 ng.h/mL 745.2 ± 374.7 ng.h/mL Plasma C max 8.1 ± 5.9 ng/mL 19.4 ± 9.3 ng/mL Plasma T max (h) 11.0 ± 6.4 4.0 ± 6.5 Plasma t 1/2 (h) 36.7 ± 20.8 79.0 ± 38.1 Kel (h -1 ) 0.024 ± 0.010 0.011 ± 0.004 CL/F (L/h) 244.7 ± 84.7 Apparent total body clearance - Absorption Diclofenac systemic exposure from diclofenac sodium topical solution application (4 times daily for 1 week) was approximately 1/3 of the diclofenac systemic exposure from the Solaraze (diclofenac topical gel) application (twice daily for 4 weeks). Distribution Diclofenac is more than 99% bound to human serum proteins, primarily to albumin. Diclofenac diffuses into and out of the synovial fluid. Diffusion into the joint occurs when plasma levels are higher than those in the synovial fluid, after which the process reverses and synovial fluid levels are higher than plasma levels. It is not known whether diffusion into the joint plays a role in the effectiveness of diclofenac. Metabolism Five diclofenac metabolites have been identified in human plasma and urine. The metabolites include 4'-hydroxy-, 5-hydroxy-, 3'-hydroxy-, 4',5-dihydroxy- and 3'-hydroxy-4'-methoxy diclofenac. The major diclofenac metabolite, 4'-hydroxy-diclofenac, has very weak pharmacologic activity. The formation of 4'-hydroxy diclofenac is primarily mediated by CPY2C9. Both diclofenac and its oxidative metabolites undergo glucuronidation or sulfation followed by bilIary excretion. Acylglucuronidation mediated by UGT2B7 and oxidation mediated by CPY2C8 may also play a role in diclofenac metabolism. CYP3A4 is responsible for the formation of minor metabolites, 5-hydroxy and 3'-hydroxy-diclofenac. Excretion Diclofenac is eliminated through metabolism and subsequent urinary and biliary excretion of the glucuronide and the sulfate conjugates of the metabolites. Little or no free unchanged diclofenac is excreted in the urine. Special Populations Pediatric: The pharmacokinetics of diclofenac sodium topical solution has not been investigated in pediatric patients. Race: Pharmacokinetic differences due to race have not been studied. 12.4 Platelets The effect of diclofenac sodium topical solution on platelet function was evaluated in 10 healthy human volunteers as a sub-study of a multiple-dose pharmacokinetic study [see Pharmacokinetics (12.3) ]. Average (range) platelet aggregation time following stimulation with adenosine diphosphate, collagen, epinephrine and arachidonic acid was 101.3% (73.3 to 128.1), 99.8% (69.6 to 112.9), 109.9% (66.2 to 178.1) and 99.0% (15.5 to 126.6) of baseline value, respectively. These results indicate that there was no effect on platelet aggregation after application of the maximum clinical dose for 7 days [see Pharmacokinetics (12.3) ].
| Pharmacokinetic Parameters | Diclofenac sodium | |
|---|---|---|
| Normal Adults [N=18] (Age: 18-55 years) | Normal Adults [N=19] (Age: 18-55 years) | |
| Single Dose | Multiple Dose Four times daily for 7 days | |
| AUC 0-t | 177.5 ± 72.6 ng.h/mL | 695.4 ± 348.9 ng.h/mL |
| AUC 0-inf | 196.3 ± 68.5 ng.h/mL | 745.2 ± 374.7 ng.h/mL |
| Plasma C max | 8.1 ± 5.9 ng/mL | 19.4 ± 9.3 ng/mL |
| Plasma T max (h) | 11.0 ± 6.4 | 4.0 ± 6.5 |
| Plasma t 1/2 (h) | 36.7 ± 20.8 | 79.0 ± 38.1 |
| Kel (h -1) | 0.024 ± 0.010 | 0.011 ± 0.004 |
| CL/F (L/h) | 244.7 ± 84.7 | - |
Mechanism of action
Information about the established mechanism(s) of the drugÕs action in humans at various levels (for example receptor, membrane, tissue, organ, whole body). If the mechanism of action is not known, this field contains a statement about the lack of information.12.1 Mechanism of Action The mechanism of action of diclofenac is similar to that of other nonsteroidal anti-inflammatory drugs. Diclofenac inhibits the enzyme, cyclooxygenase (COX), an early component of the arachidonic acid cascade, resulting in the reduced formation of prostaglandins, thromboxanes and prostacylin. It is not completely understood how reduced synthesis of these compounds results in therapeutic efficacy.
Pharmacodynamics
Information about any biochemical or physiologic pharmacologic effects of the drug or active metabolites related to the drugÕs clinical effect in preventing, diagnosing, mitigating, curing, or treating disease, or those related to adverse effects or toxicity.12.2 Pharmacodynamics Diclofenac, the active component of diclofenac sodium topical solution has anti-inflammatory, anti-nociception, and antipyretic effects.
Pharmacokinetics
Information about the clinically significant pharmacokinetics of a drug or active metabolites, for instance pertinent absorption, distribution, metabolism, and excretion parameters.12.3 Pharmacokinetics After topical administration to healthy human volunteers of single and multiple maximum doses of diclofenac sodium topical solution, 40 drops (approximately 1.2 mL) to each knee (80 drops total dose), the following diclofenac pharmacokinetic parameters were obtained: (see Table 2 ). Table 2: Single-Dose (80 drops) and Multiple Dose (80 drops four times daily for 7 days) Diclofenac Sodium Topical Solution Pharmacokinetic Parameters Pharmacokinetic Parameters Diclofenac sodium Normal Adults [N=18] (Age: 18-55 years) Normal Adults [N=19] (Age: 18-55 years) Single Dose Multiple Dose Four times daily for 7 days AUC 0-t 177.5 ± 72.6 ng.h/mL 695.4 ± 348.9 ng.h/mL AUC 0-inf 196.3 ± 68.5 ng.h/mL 745.2 ± 374.7 ng.h/mL Plasma C max 8.1 ± 5.9 ng/mL 19.4 ± 9.3 ng/mL Plasma T max (h) 11.0 ± 6.4 4.0 ± 6.5 Plasma t 1/2 (h) 36.7 ± 20.8 79.0 ± 38.1 Kel (h -1 ) 0.024 ± 0.010 0.011 ± 0.004 CL/F (L/h) 244.7 ± 84.7 Apparent total body clearance - Absorption Diclofenac systemic exposure from diclofenac sodium topical solution application (4 times daily for 1 week) was approximately 1/3 of the diclofenac systemic exposure from the Solaraze (diclofenac topical gel) application (twice daily for 4 weeks). Distribution Diclofenac is more than 99% bound to human serum proteins, primarily to albumin. Diclofenac diffuses into and out of the synovial fluid. Diffusion into the joint occurs when plasma levels are higher than those in the synovial fluid, after which the process reverses and synovial fluid levels are higher than plasma levels. It is not known whether diffusion into the joint plays a role in the effectiveness of diclofenac. Metabolism Five diclofenac metabolites have been identified in human plasma and urine. The metabolites include 4'-hydroxy-, 5-hydroxy-, 3'-hydroxy-, 4',5-dihydroxy- and 3'-hydroxy-4'-methoxy diclofenac. The major diclofenac metabolite, 4'-hydroxy-diclofenac, has very weak pharmacologic activity. The formation of 4'-hydroxy diclofenac is primarily mediated by CPY2C9. Both diclofenac and its oxidative metabolites undergo glucuronidation or sulfation followed by bilIary excretion. Acylglucuronidation mediated by UGT2B7 and oxidation mediated by CPY2C8 may also play a role in diclofenac metabolism. CYP3A4 is responsible for the formation of minor metabolites, 5-hydroxy and 3'-hydroxy-diclofenac. Excretion Diclofenac is eliminated through metabolism and subsequent urinary and biliary excretion of the glucuronide and the sulfate conjugates of the metabolites. Little or no free unchanged diclofenac is excreted in the urine. Special Populations Pediatric: The pharmacokinetics of diclofenac sodium topical solution has not been investigated in pediatric patients. Race: Pharmacokinetic differences due to race have not been studied.
| Pharmacokinetic Parameters | Diclofenac sodium | |
|---|---|---|
| Normal Adults [N=18] (Age: 18-55 years) | Normal Adults [N=19] (Age: 18-55 years) | |
| Single Dose | Multiple Dose Four times daily for 7 days | |
| AUC 0-t | 177.5 ± 72.6 ng.h/mL | 695.4 ± 348.9 ng.h/mL |
| AUC 0-inf | 196.3 ± 68.5 ng.h/mL | 745.2 ± 374.7 ng.h/mL |
| Plasma C max | 8.1 ± 5.9 ng/mL | 19.4 ± 9.3 ng/mL |
| Plasma T max (h) | 11.0 ± 6.4 | 4.0 ± 6.5 |
| Plasma t 1/2 (h) | 36.7 ± 20.8 | 79.0 ± 38.1 |
| Kel (h -1) | 0.024 ± 0.010 | 0.011 ± 0.004 |
| CL/F (L/h) | 244.7 ± 84.7 | - |
Contraindications
Information about situations in which the drug product is contraindicated or should not be used because the risk of use clearly outweighs any possible benefit, including the type and nature of reactions that have been reported.4. CONTRAINDICATIONS Diclofenac sodium topical solution is contraindicated in patients with a known hypersensitivity to diclofenac sodium or any other component of diclofenac sodium topical solution. Diclofenac sodium topical solution is contraindicated in patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. Severe, rarely fatal, anaphylactic-like reactions to NSAIDs have been reported in such patients [see Warnings and Precautions (5.7 , 5.10) ]. Diclofenac sodium topical solution is contraindicated in the setting of coronary artery bypass graft (CABG) surgery [see Warnings and Precautions (5.1) ]. Known hypersensitivity to diclofenac sodium. ( 4 ) History of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. ( 4 ) Use in the perioperative period of coronary artery bypass graft (CABG) surgery. ( 4 )
Description
General information about the drug product, including the proprietary and established name of the drug, the type of dosage form and route of administration to which the label applies, qualitative and quantitative ingredient information, the pharmacologic or therapeutic class of the drug, and the chemical name and structural formula of the drug.11. DESCRIPTION Diclofenac sodium topical solution is a clear, colorless to faintly pink-orange solution for topical application. Diclofenac sodium topical solution contains 1.5% w/w diclofenac sodium, a benzeneacetic acid derivative that is a nonsteroidal anti-inflammatory drug (NSAID), designated chemically as 2-[(2,6-dichlorophenyl)amino]-benzeneacetic acid, monosodium salt. The molecular weight is 318.14. Its molecular formula is C 14 H 10 Cl 2 NNaO 2 and it has the following structural formula: Each 1 mL of solution contains 16.05 mg of diclofenac sodium. In addition diclofenac sodium topical solution contains the following inactive ingredients: dimethyl sulfoxide USP (DMSO, 45.5% w/w), propylene glycol, alcohol, glycerin and purified water. image description
Dosage and administration
Information about the drug product’s dosage and administration recommendations, including starting dose, dose range, titration regimens, and any other clinically sigificant information that affects dosing recommendations.2. DOSAGE AND ADMINISTRATION For the relief of the signs and symptoms of osteoarthritis of the knee(s), the recommended dose is 40 drops on each painful knee, 4 times a day. ( 2 ) Apply diclofenac sodium topical solution to clean, dry skin. ( 2.1 ) Dispense diclofenac sodium topical solution 10 drops at a time either directly onto the knee or first into the hand and then onto the knee. Spread diclofenac sodium topical solution evenly around front, back and sides of the knee. Repeat this procedure until 40 drops have been applied and the knee is completely covered with solution. ( 2.1 ) Wash hands completely after administering the product. Wait until the area is completely dry before covering with clothing or applying sunscreen, insect repellent, cosmetics, topical medications, or other substances. Do not get diclofenac sodium topical solution in your eyes, nose or mouth. 2.1 General Instructions For the relief of the signs and symptoms of osteoarthritis of the knee(s), the recommended dose is 40 drops per knee, 4 times a day. Apply diclofenac sodium topical solution to clean, dry skin. To avoid spillage, dispense diclofenac sodium topical solution 10 drops at a time either directly onto the knee or first into the hand and then onto the knee. Spread diclofenac sodium topical solution evenly around front, back and sides of the knee. Repeat this procedure until 40 drops have been applied and the knee is completely covered with solution. To treat the other knee, if symptomatic, repeat the procedure. 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. 2.2 Special Precautions 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 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).
Dosage forms and strengths
Information about all available dosage forms and strengths for the drug product to which the labeling applies. This field may contain descriptions of product appearance.3. DOSAGE FORMS AND STRENGTHS 1.5% w/w topical solution 1.5% w/w topical solution ( 3 )
Indications and usage
A statement of each of the drug products indications for use, such as for the treatment, prevention, mitigation, cure, or diagnosis of a disease or condition, or of a manifestation of a recognized disease or condition, or for the relief of symptoms associated with a recognized disease or condition. This field may also describe any relevant limitations of use.1. INDICATIONS AND USAGE Diclofenac sodium topical solution is a nonsteroidal anti-inflammatory drug (NSAID) indicated for the treatment of signs and symptoms of osteoarthritis of the knee(s). Diclofenac sodium topical solution is a nonsteroidal anti-inflammatory drug (NSAID) indicated for the treatment of signs and symptoms of osteoarthritis of the knee(s). ( 1 )
Spl product data elements
Usually a list of ingredients in a drug product.Xrylix Diclofenac Sodium Diclofenac Sodium Diclofenac Sodium DIMETHYL SULFOXIDE PROPYLENE GLYCOL ALCOHOL GLYCERIN WATER DICLOFENAC SODIUM DICLOFENAC
Animal pharmacology and or toxicology
Information from studies of the drug in animals, if the data were not relevant to nor included in other parts of the labeling. Most labels do not contain this field.13.2 Animal Toxicology and/or Pharmacology Ocular Effects No adverse effects were observed using indirect ophthalmoscopy after multiple-daily dermal application to rats for 26 weeks and minipigs for 52 weeks of DMSO at twice the concentration found in diclofenac sodium topical solution. Published studies of dermal or oral administration of DMSO to rabbits, dogs and pigs described refractive changes of lens curvature and cortical fibers indicative of myopic changes and/or incidences of lens opacity or discoloration when evaluated using slit-lamp biomicroscopy examination, although no ocular abnormalities were observed in rhesus monkeys during daily oral or dermal treatment with DMSO for 9 to 18 months.
Carcinogenesis and mutagenesis and impairment of fertility
Information about carcinogenic, mutagenic, or fertility impairment potential revealed by studies in animals. Information from human data about such potential is part of the warnings field.13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenicity studies in mice and rats administered diclofenac sodium, as a dietary constituent for 2 years resulted in no significant increases in tumor incidence at doses up to 2 mg/kg/day corresponding to approximately 0.35-and 0.7-fold (mouse and rat, respectively) of the maximum recommended human topical dose (MRHD) of diclofenac sodium topical solution (based on apparent bioavailability and body surface area comparison). In a dermal carcinogenicity study conducted in albino mice, daily topical applications of diclofenac sodium for two years at concentrations up to 0.035% diclofenac sodium (a 43-fold lower diclofenac sodium concentration than present in diclofenac sodium topical solution) did not increase neoplasm incidence. In a photococarcinogenicity study conducted in hairless mice, topical application of diclofenac sodium at doses up to 0.035% diclofenac sodium (a 43-fold lower diclofenac sodium concentration than present in diclofenac sodium topical solution) resulted in an earlier median time of onset of tumors. Mutagenesis: Diclofenac was not mutagenic or clastogenic in a battery of genotoxicity tests that included the bacterial reverse mutation assay, in vitro mouse lymphoma point mutation assay, chromosomal aberration studies in Chinese hamster ovarian cells in vitro , and in vivo rat chromosomal aberration assay of bone marrow cells. Impairment of Fertility: Fertility studies have not been conducted with diclofenac sodium topical solution. Diclofenac sodium administered to male and female rats at doses up to 4 mg/kg/day (1.4-fold of the MRHD of diclofenac sodium topical solution based on apparent bioavailability and body surface area comparison) did not affect fertility. Studies have not been conducted to determine the safety of DMSO on fertility.
Nonclinical toxicology
Information about toxicology in non-human subjects.13. NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenicity studies in mice and rats administered diclofenac sodium, as a dietary constituent for 2 years resulted in no significant increases in tumor incidence at doses up to 2 mg/kg/day corresponding to approximately 0.35-and 0.7-fold (mouse and rat, respectively) of the maximum recommended human topical dose (MRHD) of diclofenac sodium topical solution (based on apparent bioavailability and body surface area comparison). In a dermal carcinogenicity study conducted in albino mice, daily topical applications of diclofenac sodium for two years at concentrations up to 0.035% diclofenac sodium (a 43-fold lower diclofenac sodium concentration than present in diclofenac sodium topical solution) did not increase neoplasm incidence. In a photococarcinogenicity study conducted in hairless mice, topical application of diclofenac sodium at doses up to 0.035% diclofenac sodium (a 43-fold lower diclofenac sodium concentration than present in diclofenac sodium topical solution) resulted in an earlier median time of onset of tumors. Mutagenesis: Diclofenac was not mutagenic or clastogenic in a battery of genotoxicity tests that included the bacterial reverse mutation assay, in vitro mouse lymphoma point mutation assay, chromosomal aberration studies in Chinese hamster ovarian cells in vitro , and in vivo rat chromosomal aberration assay of bone marrow cells. Impairment of Fertility: Fertility studies have not been conducted with diclofenac sodium topical solution. Diclofenac sodium administered to male and female rats at doses up to 4 mg/kg/day (1.4-fold of the MRHD of diclofenac sodium topical solution based on apparent bioavailability and body surface area comparison) did not affect fertility. Studies have not been conducted to determine the safety of DMSO on fertility. 13.2 Animal Toxicology and/or Pharmacology Ocular Effects No adverse effects were observed using indirect ophthalmoscopy after multiple-daily dermal application to rats for 26 weeks and minipigs for 52 weeks of DMSO at twice the concentration found in diclofenac sodium topical solution. Published studies of dermal or oral administration of DMSO to rabbits, dogs and pigs described refractive changes of lens curvature and cortical fibers indicative of myopic changes and/or incidences of lens opacity or discoloration when evaluated using slit-lamp biomicroscopy examination, although no ocular abnormalities were observed in rhesus monkeys during daily oral or dermal treatment with DMSO for 9 to 18 months.
Package label principal display panel
The content of the principal display panel of the product package, usually including the product’s name, dosage forms, and other key information about the drug product.PRINCIPAL DISPLAY PANEL - Xrylix™ Xrylix™ contains Diclofenac Sodium Topical Solution (1.5% w/w, 5 fl oz / 150 mL) and Xrylix Sheets (Kinesiology Tape / Cross Tape, 30 Sheets). Rx Only For External Use Only Packaged in the USA by: PureTek Corporation San Fernando, CA 91340 For questions or information call toll free: 877-921-7873 List No. 36500 GLV Rev. 36717 image description
Recent major changes
A list of the section(s) that contain substantive changes that have been approved by FDA in the product labeling. The headings and subheadings, if appropriate, affected by the change are listed together with each section’s identifying number and the month and year on which the change was incorporated in the labeling.Dosage and Administration ( 2 ). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . 10/2013
Spl unclassified section
Information not classified as belonging to one of the other fields. Approximately 40% of labeling with effective_time between June 2009 and August 2014 have information in this field.Xrylix™ Sheets (Kinesiology Tape / Cross Tape) Xrylix™ Sheets is a taping therapy based on acupuncture principles to improve circulation through the skin and control tension and relief of the muscles and the ligaments. The tape is non-medicated, hypoallergenic, and adheres well to the skin. Directions for use: Use only as prescribed by your physician. Apply to clean, dry skin only. Apply tape to affected area as directed, then rub the tape to activate the adhesive properties. Remove the tape in the same direction as the growth of hair. Apply baby oil or other oily lotion for easier removal. Removing with warm water will cause removal to become more difficult. General taping for most body parts Apply tape where you have strain, sprains, muscle stiffness, inflammation or pain. Taping for the knee and feet Knee(s): Apply tape to the knee as directed. Ankle(s): Apply tape to the ankle as directed. Feet: Apply tape on the center of the dorsum of the foot. Precautions • Use only as directed by your physician. • Remove tape and discontinue use if tape causes itching or rash. • Do not use on the wounds, skin infections or other parts where there is a skin problem. It will cause a blister and peel off the skin. • If you experience any unpleasant side effects, take tape off immediately and notify your doctor. • Keep Xrylix™ Sheets in a dry and cool place away from the sunlight. • Speak with your doctor or pharmacist if there is no change or worsening of your condition. Keep out of direct sunlight and Under 40ºC (104ºF). Storage time above these conditions should not exceed 18 hours. Manufactured for: PureTek Corporation San Fernando, CA 91340 For questions or information call toll-free: 877-921-7873 List No. 90054 JPM Rev. 29364
Xrylix: Information for patients
Information necessary for patients to use the drug safely and effectively, such as precautions concerning driving or the concomitant use of other substances that may have harmful additive effects.17. PATIENT COUNSELING INFORMATION See FDA-Approved Patient Labeling ( Medication Guide and Instructions for Use ). 17.1 Patient/Caregiver Instructions Inform patients of the following information before initiating therapy with an NSAID and periodically during the course of ongoing therapy. Encourage patients to read the NSAID Medication Guide that accompanies each prescription dispensed prior to using diclofenac sodium topical solution [see Medication Guide and Instructions for Use ]. 17.2 Cardiovascular Effects Diclofenac sodium topical solution, like other NSAIDs, may cause serious DV side effects, such as MI or stroke, which may result in hospitalization and even death. Although serious CV events can occur without warning symptoms, instruct patients to be alert for the signs and symptoms of chest pain, shortness of breath weakness, slurring of speech, and to ask for medical advice when observing any indicative sign or symptoms. Inform patients of the importance of this follow-up [see Warnings and Precautions (5.1) ]. 17.3 Gastrointestinal Effects Diclofenac sodium topical solution, like other NSAIDs, may cause GI discomfort and, rarely, serious GI side effects, such as ulcers and bleeding, which may result in hospitalization and even death. Although serious GI tract ulcerations and bleeding can occur without warning symptoms, inform patients to be alert for the signs and symptoms of ulceration and bleeding, and to ask for medical advice when observing any indicative sign or symptoms including epigastric pain, dyspepsia, melena, and hematemesis. Instruct patients of the importance of this follow-up [see Warnings and Precautions (5.2) ]. 17.4 Hepatotoxicity Inform patients of the warning signs and symptoms of hepatotoxicity (e.g., nausea, fatigue, lethargy, pruritus, jaundice, right upper quadrant tenderness, and "flu-like" symptoms). If these occur, instruct patients to stop therapy with diclofenac sodium topical solution and seek immediate medical therapy [see Warnings and Precautions (5.3) ]. 17.5 Adverse Skin Reactions Diclofenac sodium topical solution, like other NSAIDs, can cause serious systemic skin side effects such as exfoliative dermatitis, SJS, and TEN, which may result in hospitalizations and even death. Although serious systemic skin reactions may occur without warning, instruct patients to be alert for the signs and symptoms of skin rash and blisters, fever, or other signs of hypersensitivity such as itching, and to ask for medical advice when observing any indicative signs or symptoms [see Warnings and Precautions (5.8) ]. Advise patients to stop diclofenac sodium topical solution immediately if they develop any type of generalized rash and contact their physicians as soon as possible. Diclofenac sodium topical solution can cause a localized skin reaction at the application site. Advise patients to contact their physicians as soon as possible of they develop any type of localized application site rash. Instruct patients not to apply diclofenac sodium topical solution to open skin wounds, infections, inflammations, or exfoliative dermatitis, as it may affect absorption and reduce tolerability of the drug. Instruct patients to wait until the area treated with diclofenac sodium topical solution is completely dry before applying sunscreen, insect repellant, lotion, moisturizer, cosmetics, or other topical medication. Instruct patients to minimize or avoid exposure of treated knee(s) to natural or artificial sunlight. 17.6 Weight Gain and Edema Instruct patients to promptly report to their physician signs or symptoms of unexplained weight gain or edema following treatment with diclofenac sodium topical solution [see Warnings and Precautions (5.5) ]. 17.7 Anaphylactoid Reactions Inform patients of the signs of an anaphylactoid reaction (e.g. difficulty breathing, swelling of the face or throat). If these occur, instruct patients to seek immediate emergency help [see Warnings and Precautions (5.7) ]. 17.8 Effects During Pregnancy Instruct patients who are pregnant or intending to become pregnant not to use diclofenac sodium topical solution [see Use in Specific Populations (8.1) and Impairment of Fertility (13.1) ]. 17.9 Eye Exposure Instruct patients to avoid contact of diclofenac sodium topical solution with the 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. 17.10 Prevention of Secondary Exposure Instruct patients to avoid skin-to-skin contact between other people and the knee(s) to which diclofenac sodium topical solution was applied until the knee(s) is completely dry.
Spl medguide
Information about the patient medication guide that accompanies the drug product. Certain drugs must be dispensed with an accompanying medication guide. This field may contain information about when to consult the medication guide and the contents of the medication guide.Medication Guide for Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) (See the end of this Medication Guide for a list of prescription NSAID medicines.) What is the most important information I should know about medicines called Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)? NSAID medicines may increase the chance of a heart attack or stroke that can lead to death. This chance increases: with longer use of NSAID medicines in people who have heart disease NSAID medicines should never be used right before or after a heart surgery called a "coronary artery bypass graft (CABG)." NSAID medicines can cause ulcers and bleeding in the stomach and intestines at any time during treatment. Ulcers and bleeding: can happen without warning symptoms may cause death The chance of a person getting an ulcer or bleeding increases with: taking medicines called "corticosteroids" and "anticoagulants" longer use smoking drinking alcohol older age having poor health NSAID medicines should only be used: exactly as prescribed at the lowest dose possible for your treatment for the shortest time needed What are Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)? NSAID medicines are used to treat pain and redness, swelling, and heat (inflammation) from medical conditions such as: different types of arthritis menstrual cramps and other types of short-term pain Who should not take a Non-Steroidal Anti-Inflammatory Drug (NSAID)? Do not take an NSAID medicine: if you had an asthma attack, hives, or other allergic reaction with aspirin or any other NSAID medicine for pain right before or after heart bypass surgery Tell your healthcare provider: about all of your medical conditions. about all of the medicines you take. NSAIDs and some other medicines can interact with each other and cause serious side effects. Keep a list of your medicines to show to your healthcare provider and pharmacist. if you are pregnant, NSAID medicines should not be used by pregnant women late in their pregnancy. if you are breastfeeding. Talk to your doctor. What are the possible side effects of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)? Serious side effects include: heart attack stroke highblood pressure heart failure from body swelling (fluid retention) kidney problems including kidney failure bleeding and ulcers in the stomach and intestine low red blood cells (anemia) life-threatening skin reactions life-threatening allergic reactions liver problems including liver failure asthma attacks in people who have asthma Other side effects include: stomach pain constipation diarrhea gas heartburn nausea vomiting dizziness Get emergency help right away if you have any of the following symptoms: shortness of breath or trouble breathing chest pain slurred speech weakness in one part or side of your body swelling of the face or throat Stop your NSAID medicine and call your healthcare provider right away if you have any of the following symptoms: nausea more tired or weaker than usual itching your skin or eyes look yellow stomach pain flu-like symptoms vomit blood there is blood in your bowel movement or it is black and sticky like tar unusual weight gain skin rash or blisters with fever swelling of the arms and legs, hands and feet These are not all the side effects with NSAID medicines. Talk to your healthcare provider or pharmacist for more information about NSAID medicines. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. Other information about Non-Steroidal Anti-Inflammatory Drugs (NSAIDs): Aspirin is an NSAID medicine but it does not increase the chance of a heart attack. Aspirin can cause bleeding in the brain, stomach, and intestines. Aspirin can also cause ulcers in the stomach and intestines. Some of these NSAID medicines are sold in lower doses without a prescription (over-the-counter). Talk to your healthcare provider before using over-the-counter NSAIDs for more than 10 days. NSAID medicines that need a prescription Generic Name Tradename Celecoxib Celebrex® Diclofenac Flector, Cataflam®, Voltaren®, Arthrotec™(combined with misoprostol), PENNSAID® (Diclofenac Sodium Topical Solution) Diflunisal Dolobid® Etodolac Lodine®, Lodine® XL Fenoprofen Nalfon®, Nalfon® 200 Flurbiprofen Ansaid® Ibuprofen Motrin®, Tab-Profen®, Vicoprofen® Vicoprofen contains the same dose of ibuprofen as over-the-counter (OTC) NSAID, and is usually used for less than 10 days to treat pain. The OTC NSAID label warns that long term continuous use may increase the risk of heart attack or stroke. (combined with hydrocodone), Cambunox™ (combined with oxycodone) Indomethacin Indocin®, Indocin® SR, Indo-Lemmon™, Indomethagan™ Ketoprofen Oruvail® Ketorolac Toradol® Mefenamic Acid Ponstel® Meloxicam Mobic® Nabumetone Relafen® Naproxen Naprosyn®, Anaprox®, Anaprox® DS, EC-Naproxyn®, Naprelan®, Naprapac® (copackaged with lansoprazole) Oxaprozin Daypro® Piroxicam Feldene® Sulindac Clinoril® Tolmetin Tolectin®, Tolectin® DS, Tolectin® 600 This Medication Guide has been approved by the U.S. Food and Drug Administration.
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|
| Generic Name | Tradename |
|---|---|
| Celecoxib | Celebrex® |
| Diclofenac | Flector, Cataflam®, Voltaren®, Arthrotec™(combined with misoprostol), PENNSAID® (Diclofenac Sodium Topical Solution) |
| Diflunisal | Dolobid® |
| Etodolac | Lodine®, Lodine® XL |
| Fenoprofen | Nalfon®, Nalfon® 200 |
| Flurbiprofen | Ansaid® |
| Ibuprofen | Motrin®, Tab-Profen®, Vicoprofen® |
| Indomethacin | Indocin®, Indocin® SR, Indo-Lemmon™, Indomethagan™ |
| Ketoprofen | Oruvail® |
| Ketorolac | Toradol® |
| Mefenamic Acid | Ponstel® |
| Meloxicam | Mobic® |
| Nabumetone | Relafen® |
| Naproxen | Naprosyn®, Anaprox®, Anaprox® DS, EC-Naproxyn®, Naprelan®, Naprapac® (copackaged with lansoprazole) |
| Oxaprozin | Daypro® |
| Piroxicam | Feldene® |
| Sulindac | Clinoril® |
| Tolmetin | Tolectin®, Tolectin® DS, Tolectin® 600 |
Spl patient package insert
Information necessary for patients to use the drug safely and effectively.Patient Instructions for Use Diclofenac Sodium Topical Solution 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 healthcare provider tells you. Talk with your healthcare 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 4 times each day on your knee or knees as prescribed. Your total dose for each knee is 40 drops of diclofenac topical solution, each time you use it. If you get diclofenac sodium topical solution in your eyes, rinse your eyes right away with water or saline. Call your healthcare provider if your eyes are irritated for more than one hour. Steps for using diclofenac sodium topical solution: Step 1. Wash your hands with soap and water before and after applying diclofenac sodium topical solution. Step 2. Put 10 drops of diclofenac sodium topical solution either on your hand or directly on your knee (See Figure A ). Step 3. Spread diclofenac sodium topical solution evenly on the front, back and sides of your knee (see Figures B and C ). Repeat steps 2 and 3, three times so that your knee is completely covered with a total of 40 drops of diclofenac sodium topical solution. Figure B Figure C Step 4. If your healthcare provider has prescribed diclofenac sodium topical solution for both knees, repeat steps 2 and 3 for the other knee. After you use diclofenac sodium topical solution: Wash your hands with soap and water right away after applying diclofenac sodium topical solution. Do not touch the treated knee or allow another person to touch the knee treated with diclofenac sodium topical solution until your knee is completely dry. 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 apply bandages to the skin where you have applied diclofenac sodium topical solution. use sunlamps and tanning beds. Protect your treated knee from sunlight. Wear clothes that cover your skin if you have to be in sunlight. How should I store diclofenac sodium topical solution? Store diclofenac sodium topical solution 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. Brands mentioned are trademarks of their respective owners. Manufactured by: IGI Laboratories, Inc. Buena, NJ 08310 Distributed by: PureTek Corporation San Fernando, CA 91340 image description image description image description
Clinical studies
This field may contain references to clinical studies in place of detailed discussion in other sections of the labeling.14. CLINICAL STUDIES 14.1 Pivotal Studies in Osteoarthritis of the Knee The use of diclofenac sodium topical solution for the treatment of the signs and symptoms of osteoarthritis of the knee was evaluated in two double-blind controlled trials conducted in the U.S. and Canada, involving patients treated with diclofenac sodium topical solution at a dose of 40 drops four times a day for 12 weeks. Diclofenac sodium topical solution was compared to topical placebo (2.3% DMSO with other excipients) and/or topical vehicle solution (45.5% w/w DMSO with other excipients), applied directly to the study knee. In both trials, diclofenac sodium topical solution treatment resulted in statistically significant clinical improvement compared to placebo and/or vehicle, in all three primary efficacy variables – pain, physical function (Western Ontario and McMaster Universities LK3.1 OA Index (WOMAC) pain and physical function dimensions) and Patient Overall Health Assessment (POHA)/Patient Global Assessment (PGA). Numerical results are summarized in Tables 3 and 4. Table 3: Change in treatment outcomes after 12 weeks of treatment in one study of efficacy of Diclofenac Sodium Topical Solution Efficacy Variable Study I Mean baseline score and mean change in efficacy variables after 12 weeks of treatment Mean Baseline score Diclofenac sodium N=154 Topical placebo placebo formulation included 2.3% DMSO N=155 Topical vehicle vehicle formulation included 45.5% DMSO N=161 WOMAC pain score (Likert 3.1, 0-20) 13 -6.0 -4.7 -4.7 WOMAC physical function (Likert 3.1, 0-68) 42 -15.7 -12.3 -12.1 POHA (0-4) 2.3 -1.0 -0.4 -0.6 Table 4: Change in treatment outcomes after 12 weeks of treatment in one study of efficacy of Diclofenac Sodium Topical Solution Efficacy Variable Study II Mean baseline score and mean change in efficacy variables after 12 weeks of treatment Mean Baseline score Diclofenac sodium N=164 Topical vehicle vehicle formulation included 45.5% DMSO N=162 WOMAC pain score (Likert 3.1, 0-20) 13 -5.9 -4.4 WOMAC physical function (Likert 3.1, 0-68) 42 -15.3 -10.3 PGA (0-4) 3.1 -1.3 -1.0
| Efficacy Variable | Study I Mean baseline score and mean change in efficacy variables after 12 weeks of treatment | |||
|---|---|---|---|---|
| Mean Baseline score | Diclofenac sodium N=154 | Topical placebo | Topical vehicle | |
| WOMAC pain score (Likert 3.1, 0-20) | 13 | -6.0 | -4.7 | -4.7 |
| WOMAC physical function (Likert 3.1, 0-68) | 42 | -15.7 | -12.3 | -12.1 |
| POHA (0-4) | 2.3 | -1.0 | -0.4 | -0.6 |
| Efficacy Variable | Study II Mean baseline score and mean change in efficacy variables after 12 weeks of treatment | |||
|---|---|---|---|---|
| Mean Baseline score | Diclofenac sodium N=164 | Topical vehicle | ||
| WOMAC pain score (Likert 3.1, 0-20) | 13 | -5.9 | -4.4 | |
| WOMAC physical function (Likert 3.1, 0-68) | 42 | -15.3 | -10.3 | |
| PGA (0-4) | 3.1 | -1.3 | -1.0 | |
Geriatric use
Information about any limitations on any geriatric indications, needs for specific monitoring, hazards associated with use of the drug in the geriatric population.8.5 Geriatric Use Of the 911 patients treated with diclofenac sodium topical solution 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 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 for this elderly population. As with any NSAID, use caution in treating the elderly (65 years and older) and it may be useful to monitor renal function since they are more likely to have decreased baseline renal function.
Labor and delivery
Information about the drug’s use during labor or delivery, whether or not the use is stated in the indications section of the labeling, including the effect of the drug on the mother and fetus, on the duration of labor or delivery, on the possibility of delivery-related interventions, and the effect of the drug on the later growth, development, and functional maturation of the child.8.2 Labor and Delivery The effects of diclofenac sodium topical solution on labor and delivery in pregnant women are unknown. In rat studies maternal exposure to diclofenac, as with other NSAID drugs, known to inhibit prostaglandin synthesis, increased the incidence of dystocia, delayed parturition, and decreased offspring survival.
Nursing mothers
Information about excretion of the drug in human milk and effects on the nursing infant, including pertinent adverse effects observed in animal offspring.8.3 Nursing Mothers It is not known whether this drug is excreted in human milk; however, there is a case report in the literature indicating that diclofenac can be detected at low levels in breast milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from diclofenac sodium topical solution, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Pediatric use
Information about any limitations on any pediatric indications, needs for specific monitoring, hazards associated with use of the drug in any subsets of the pediatric population (such as neonates, infants, children, or adolescents), differences between pediatric and adult responses to the drug, and other information related to the safe and effective pediatric use of the drug.8.4 Pediatric Use Safety and effectiveness in pediatric patients have not been established.
Pregnancy
Information about effects the drug may have on pregnant women or on a fetus. This field may be ommitted if the drug is not absorbed systemically and the drug is not known to have a potential for indirect harm to the fetus. It may contain information about the established pregnancy category classification for the drug. (That information is nominally listed in the teratogenic_effects field, but may be listed here instead.)8.1 Pregnancy Pregnancy Category C prior to 30 weeks gestation; Category D starting 30 weeks gestation. Teratogenic Effects: There are no adequate and well-controlled studies of diclofenac sodium topical solution in pregnant women. Diclofenac sodium topical solution should not be used by pregnant women as its safe use has not been adequately determined and starting at 30 weeks gestation, diclofenac and other NSAIDs should be avoided by pregnant women as premature closure of the ductus arteriosus in the fetus may occur. Developmental studies in animals demonstrated that diclofenac sodium administration did not produce teratogenicity despite the induction of maternal toxicity and fetal toxicity in mice at doses up to 20 mg/kg/day (0.6-fold the maximum recommended human dose [MRHD] of 154 mg/day based on body surface area comparison), and in rats and rabbits at doses up to 10 mg/kg/day (approximately 0.6-fold and 1.3-fold the MRHD, respectively). Published reproductive and developmental studies of dimethyl sulfoxide (DMSO, the solvent used in diclofenac sodium topical solution) are equivocal as to potential teratogenicity. Nonteratogenic Effects: In rats, maternally toxic doses of diclofenac were associated with dystocia, prolonged gestation, reduced fetal weights and growth, and reduced fetal survival.
Teratogenic effects
Pregnancy category A: Adequate and well-controlled studies in pregnant women have failed to demonstrate a risk to the fetus in the first trimester of pregnancy, and there is no evidence of a risk in later trimesters. Pregnancy category B: Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women. Pregnancy category C: Animal reproduction studies have shown an adverse effect on the fetus, there are no adequate and well-controlled studies in humans, and the benefits from the use of the drug in pregnant women may be acceptable despite its potential risks. Pregnancy category D: There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but the potential benefits from the use of the drug in pregnant women may be acceptable despite its potential risks (for example, if the drug is needed in a life-threatening situation or serious disease for which safer drugs cannot be used or are ineffective). Pregnancy category X: Studies in animals or humans have demonstrated fetal abnormalities or there is positive evidence of fetal risk based on adverse reaction reports from investigational or marketing experience, or both, and the risk of the use of the drug in a pregnant woman clearly outweighs any possible benefit (for example, safer drugs or other forms of therapy are available).Teratogenic Effects: There are no adequate and well-controlled studies of diclofenac sodium topical solution in pregnant women. Diclofenac sodium topical solution should not be used by pregnant women as its safe use has not been adequately determined and starting at 30 weeks gestation, diclofenac and other NSAIDs should be avoided by pregnant women as premature closure of the ductus arteriosus in the fetus may occur. Developmental studies in animals demonstrated that diclofenac sodium administration did not produce teratogenicity despite the induction of maternal toxicity and fetal toxicity in mice at doses up to 20 mg/kg/day (0.6-fold the maximum recommended human dose [MRHD] of 154 mg/day based on body surface area comparison), and in rats and rabbits at doses up to 10 mg/kg/day (approximately 0.6-fold and 1.3-fold the MRHD, respectively). Published reproductive and developmental studies of dimethyl sulfoxide (DMSO, the solvent used in diclofenac sodium topical solution) are equivocal as to potential teratogenicity.
Use in specific populations
Information about use of the drug by patients in specific populations, including pregnant women and nursing mothers, pediatric patients, and geriatric patients.8. USE IN SPECIFIC POPULATIONS Pregnancy: Not recommended for use during pregnancy. ( 8.1 ) Nursing Mothers: Use with caution, as it is not known if diclofenac is excreted in human milk. ( 8.3 ) 8.1 Pregnancy Pregnancy Category C prior to 30 weeks gestation; Category D starting 30 weeks gestation. Teratogenic Effects: There are no adequate and well-controlled studies of diclofenac sodium topical solution in pregnant women. Diclofenac sodium topical solution should not be used by pregnant women as its safe use has not been adequately determined and starting at 30 weeks gestation, diclofenac and other NSAIDs should be avoided by pregnant women as premature closure of the ductus arteriosus in the fetus may occur. Developmental studies in animals demonstrated that diclofenac sodium administration did not produce teratogenicity despite the induction of maternal toxicity and fetal toxicity in mice at doses up to 20 mg/kg/day (0.6-fold the maximum recommended human dose [MRHD] of 154 mg/day based on body surface area comparison), and in rats and rabbits at doses up to 10 mg/kg/day (approximately 0.6-fold and 1.3-fold the MRHD, respectively). Published reproductive and developmental studies of dimethyl sulfoxide (DMSO, the solvent used in diclofenac sodium topical solution) are equivocal as to potential teratogenicity. Nonteratogenic Effects: In rats, maternally toxic doses of diclofenac were associated with dystocia, prolonged gestation, reduced fetal weights and growth, and reduced fetal survival. 8.2 Labor and Delivery The effects of diclofenac sodium topical solution on labor and delivery in pregnant women are unknown. In rat studies maternal exposure to diclofenac, as with other NSAID drugs, known to inhibit prostaglandin synthesis, increased the incidence of dystocia, delayed parturition, and decreased offspring survival. 8.3 Nursing Mothers It is not known whether this drug is excreted in human milk; however, there is a case report in the literature indicating that diclofenac can be detected at low levels in breast milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from diclofenac sodium topical solution, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. 8.4 Pediatric Use Safety and effectiveness in pediatric patients have not been established. 8.5 Geriatric Use Of the 911 patients treated with diclofenac sodium topical solution 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 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 for this elderly population. As with any NSAID, use caution in treating the elderly (65 years and older) and it may be useful to monitor renal function since they are more likely to have decreased baseline renal function.
How supplied
Information about the available dosage forms to which the labeling applies, and for which the manufacturer or distributor is responsible. This field ordinarily includes the strength of the dosage form (in metric units), the units in which the dosage form is available for prescribing, appropriate information to facilitate identification of the dosage forms (such as shape, color, coating, scoring, and National Drug Code), and special handling and storage condition information.16. HOW SUPPLIED/STORAGE AND HANDLING Diclofenac Sodium Topical Solution is supplied as a clear, colorless to faintly pink-orange solution containing 16.05 mg of diclofenac sodium per mL of solution, in a white high density polyethylene bottle with a white low-density dropper cap. NDC Number & Size 150 mL bottle NDC # 59088-372-10 Storage Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [See USP Controlled RoomTemperature].
Storage and handling
Information about safe storage and handling of the drug product.Storage Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [See USP Controlled RoomTemperature].
Boxed warning
Information about contraindications or serious warnings, particularly those that may lead to death or serious injury.WARNING: CARDIOVASCULAR AND GASTROINTESTINAL RISK Cardiovascular Risk Nonsteroidal anti-inflammatory drugs (NSAIDs) may cause an increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. This risk may increase with duration of use. Patients with cardiovascular disease or risk factors for cardiovascular disease may be at greater risk [see Warnings and Precautions (5.1) ]. Diclofenac sodium topical solution is contraindicated in the perioperative setting of coronary artery bypass graft (CABG) surgery [see Contraindications (4) ] . Gastrointestinal Risk NSAIDs cause an increased risk of serious gastrointestinal 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 are at greater risk for serious gastrointestinal events [see Warnings and Precautions (5.2) ]. WARNING: CARDIOVASCULAR AND GASTROINTESTINAL RISK See full prescribing information for complete boxed warning Cardiovascular Risk Nonsteroidal anti-inflammatory drugs (NSAIDS) may cause an increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. Patients with cardiovascular disease or risk factors for cardiovascular disease may be at greater risk. ( 5.1 ) Diclofenac sodium topical solution is contraindicated for the treatment of perioperative pain in the setting of coronary artery bypass graft (CABG) surgery. ( 4 ) Gastrointestinal Risk NSAIDs, including diclofenac sodium topical solution cause an increased risk of serious gastrointestinal 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 are at greater risk for serious gastrointestinal events. ( 5.2 )
Disclaimer: Do not rely on openFDA or Phanrmacy Near Me to make decisions regarding medical care. While we make every effort to ensure that data is accurate, you should assume all results are unvalidated. Source: OpenFDA, Healthporta Drugs API