DICLOFENAC SODIUM- diclofenac sodium_gel

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 vivo effects. 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. The pharmacokinetics of diclofenac sodium were assessed in healthy volunteers following repeated applications during 7 days of diclofenac sodium topical gel to 1 knee (4 x 4 g per day) or to 2 knees and 2 hands (4 x 12 g per day) versus the recommended oral dose of diclofenac sodium for the treatment of osteoarthritis (3 x 50 mg per day). A summary of the pharmacokinetic parameters is presented in Table 2. Pharmacokinetic Parameters and Comparison of Diclofenac Sodium Topical Gel to Oral Diclofenac Sodium Tablets After Repeated Administration C max max max AUC 0-24 SD=standard deviation. CI=confidence interval. Treatment C max T max AUC 0-24 (ngh/mL) Mean +/- SD Median Mean +/- SD % of Oral (CI) Range % of Oral (CI) Diclofenac sodium topical gel 233 +/- 128 4 x 4 g per day 15 +/- 7. 3 14 (0-24) 5. 8% (=160 mg diclofenac sodium per day) 0. 7) Diclofenac sodium topical gel 53. 8 +/- 32 10 (0-24) 807 +/- 478 4 x 12 g per day 2. 7% (=480 mg diclofenac sodium per day) (1. 8) Diclofenac sodium tablets, orally 3 x 50 mg per day 2270 +/- 778 6. 5 (1-14) 3890 +/- 1710 (=150 mg diclofenac sodium per day) 100% 100% Systemic exposure (area under the concentration-time curve) and maximum plasma concentrations of diclofenac are significantly lower with diclofenac sodium topical gel than with comparable oral treatment of diclofenac sodium. Systemic exposure with recommended use of diclofenac sodium topical gel (4 x 4 g per day applied to 1 knee) is on average 17 times lower than with oral treatment. (Basis: treatment with diclofenac sodium topical gel of 1 knee, 4 times a day versus 50 mg, 3 times a day of oral diclofenac tablets. ) The amount of diclofenac sodium that is systemically absorbed from diclofenac sodium topical gel is on average 6% of the systemic exposure from an oral form of diclofenac sodium. The average peak plasma concentration with recommended use of diclofenac sodium topical gel (4 x 4 g per day applied to 1 knee) is 158 times lower than with the oral treatment. The pharmacokinetics of diclofenac sodium topical gel has been tested under conditions of moderate heat (application of a heat patch for 15 minutes prior to gel application) and of moderate exercise (first gel application followed by a 20-minute treadmill exercise). No clinically relevant differences of systemic absorption and of tolerability were found between applications of diclofenac sodium topical gel (4 x 4 g per day on 1 knee) with and under the conditions tested. However, the pharmacokinetics of diclofenac sodium topical gel was not tested under the condition of heat application following gel application. Therefore, concurrent use of diclofenac sodium topical gel and heat is not recommended. Drug Interaction Studies Aspirin see Drug Interactions ( 7.

Diclofenac sodium is a non-steroidal anti-inflammatory drug indicated for the relief of the pain of osteoarthritis of joints amenable to topical treatment, such as the knees and those of the hands. ( 1 Diclofenac sodium topical gel was not evaluated for use on joints of the spine, hip, or shoulder. 1 Diclofenac sodium topical gel is indicated for the relief of the pain of osteoarthritis of joints amenable to topical treatment, such as the knees and those of the hands. Diclofenac sodium topical gel has not been evaluated for use on the spine, hip, or shoulder.

DOSAGE AND ADMINISTRATION
Use the lowest effective dosage for shortest duration consistent with individual patient treatment goals ( 2. 1 Lower extremities: Apply the gel (4 g) to the affected area 4 times daily. Do not apply more than 16 g daily to any one affected joint of the lower extremities. 2 Upper extremities: Apply the gel (2 g) to the affected area 4 times daily. Do not apply more than 8 g daily to any one affected joint of the upper extremities. 3 Total dose should not exceed 32 g per day, over all affected joints. 3 2 Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals [ see Warnings and Precautions ( 5 The dosing card can be found attached to the inside of the carton. The proper amount of diclofenac sodium topical gel should be measured using the dosing card supplied in the drug product carton. The dosing card is made of clear polypropylene. The dosing card should be used for each application of drug product. The gel should be applied within the rectangular area of the dosing card up to the 2 gram or 4 gram line (2 g for each elbow, wrist, or hand, and 4g for each knee, ankle, or foot). The 2 g line is 2. 25 inches long. The 4 g line is 4. 5 inches long. The dosing card containing diclofenac sodium topical gel can be used to apply the gel. The hands should then be used to gently rub the gel into the skin. After using the dosing card, hold with fingertips, rinse, and dry. If treatment site is the hands, patients should wait at least one (1) hour to wash their hands. Apply the gel (4 g) to the affected foot, ankle, or knee 4 times daily. Diclofenac sodium topical gel should be gently massaged into the skin ensuring application to the entire affected foot, or knee or ankle. The entire foot includes the sole, top of the foot and the toes. Do not apply more than 16 g daily to any single joint of the lower extremities. Apply the gel (2 g) to the affected hand, wrist, or elbow 4 times daily. Diclofenac sodium topical gel should be gently massaged into the skin ensuring application to the entire affected hand, wrist, or elbow. The entire hand includes the palm, back of the hands, and the fingers. Do not apply more than 8 g daily to any single joint of the upper extremities. Total dose should not exceed 32 g per day, over all affected joints. Avoid showering/bathing for at least 1 hour after the application. Inform patient to wash his/her hands after use, unless the hands are the treated joint. If diclofenac sodium topical gel is applied to the hand(s) for treatment; inform patient not to wash the treated hand(s) for at least 1 hour after the application. Do not apply diclofenac sodium topical gel to open wounds. Avoid contact of diclofenac sodium topical gel with eyes and mucous membranes. Do not apply external heat and/or occlusive dressings to treated joints. Avoid exposure of the treated joint(s) to natural or artificial sunlight. Avoid concomitant use of diclofenac sodium topical gel on the treated skin site with other topical products, including sunscreens, cosmetics, lotions, moisturizers, insect repellants, or other topical medications. Concomitant use of diclofenac sodium topical gel with oral non-steroidal anti-inflammatory drugs (NSAIDs) has not been evaluated, and may increase adverse NSAIDs effects. Do not use combination therapy with diclofenac sodium topical gel and an oral NSAID unless the benefit outweighs the risk and conduct periodic laboratory evaluations. Avoid wearing of clothing or gloves for at least 10 minutes after applying diclofenac sodium topical gel.
Instructions for Use
Diclofenac Sodium Topical Gel, 1% Important: Use the dosing card that is inside the diclofenac sodium topical gel carton to correctly measure each dose. The dosing card is re-usable. Do not throw the dosing card away. Before you use diclofenac sodium topical gel for the first time, your healthcare provider or pharmacist should show you how to correctly measure your dose using the dosing card. Read this Instructions for Use Your healthcare provider has prescribed diclofenac sodium topical gel to help relieve arthritis pain in some of your joints. Diclofenac sodium topical gel may be used to treat arthritis pain in the arms (hands, wrists, and elbows) and in the legs (feet, ankles, and knees). It is not known if diclofenac sodium topical gel is safe and effective if used on your spine, hips, or shoulders. Use diclofenac sodium topical gel exactly how your healthcare provider prescribes it for you. Do not apply diclofenac sodium topical gel anywhere other than where your healthcare provider tells you to. Do not use more than a total of 32 grams of diclofenac sodium topical gel each day. If you add up the amount of diclofenac sodium topical gel as directed by your healthcare provider, it should not be more than 32 grams in one day. The dose for your hands, wrists, or elbows is 2 grams of diclofenac sodium topical gel each time you apply it. Apply diclofenac sodium topical gel 4 times a day (a total of 8 grams each day). Do not apply more than 8 grams each day to any one of your affected hands, wrists, or elbows. The dose for your feet, ankles, or knees is 4 grams of diclofenac sodium topical gel each time you apply it. Apply diclofenac sodium topical gel 4 times a day (a total of 16 grams each day). Do not apply more than 16 grams each day to any one of your affected feet, ankles, or knees. Some examples of diclofenac sodium topical gel application include: If you use 2 grams of diclofenac sodium topical gel on one hand, 4 times a day, your total dose for one day is 8 grams. If you use 4 grams of diclofenac sodium topical gel on one knee, 4 times a day, your total dose for one day is 16 grams. Your total dose for one day, treating one hand and one knee, is 8 grams plus 16 grams, which equals 24 grams of diclofenac sodium topical gel. Figure A Before you use a new tube of diclofenac sodium topical gel for the first time, open the foil seal that covers the tube opening by using the spiked top of the cap. Remember to remove the dosing card from the carton to measure your dose (see Figure A). Apply diclofenac sodium topical gel to clean, dry skin that does not have any cuts, open wounds, infections, or rashes. Do not use heating pads or apply bandages to where you have applied diclofenac sodium topical gel. Avoid exposing skin where you apply diclofenac sodium topical gel to sunlight and artificial light, such as tanning booths. Do not use sunscreens, cosmetics, lotions, moisturizers, insect repellants, or other topical medicines on the same skin areas where you have applied diclofenac sodium topical gel. Do not get diclofenac sodium topical gel in your eyes, nose, or mouth. Diclofenac sodium topical gel is only to be used on your skin (topical use). If you get diclofenac sodium topical gel in your eyes, rinse your eyes right away with water or saline. Talk with your healthcare provider if eye irritation lasts for more than one hour. What if I miss a dose? If you miss a dose of diclofenac sodium topical gel, continue with your next scheduled dose using the prescribed amount of diclofenac sodium topical gel. Do not double the dose. Applying 2 grams (2 g) of diclofenac sodium topical gel to hands, wrists, or elbows: Step 1 Step 2. Store the dosing card until next use. Applying 4 grams (4 g) of diclofenac sodium topical gel to feet, ankles, or knees: Step 1 Step 1 Step 2. Step 3 Refer to Steps 4 and 5 above. What are the ingredients in diclofenac sodium topical gel 1%? Active ingredient: Inactive ingredients: How should I store diclofenac sodium topical gel? Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F). Do not Store the dosing card with your diclofenac sodium topical gel. Keep diclofenac sodium topical gel, the dosing card, and all medicines out of the reach of children. This Medication Guide and Instructions for Use have been approved by the U. Food and Drug Administration. Manufactured by: DPT Laboratories, Ltd. 307 E Josephine Street San Antonio, TX 78215 Manufactured for: Exelan Pharmaceuticals, Inc. Boca Raton, FL 33432 Rev. 2/2020 fig-a fig-b-c-d fig-e-f-g.

Most common adverse reactions (incidence >2% of patients treated with diclofenac sodium and greater than placebo) are application site reactions, including dermatitis. 1 To report SUSPECTED ADVERSE REACTIONS, contact Cipla Limited at 1-866-604-3268 or FDA at 1-800-FDA-1088 or www. gov/medwatch 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. 11 Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice. During clinical development, 913 patients were exposed to diclofenac sodium topical gel in randomized, double-blind, multicenter, vehicle-controlled, parallel-group studies in osteoarthritis of the superficial joints of the extremities. Of these, 513 patients received diclofenac sodium topical gel for osteoarthritis of the knee and 400 were treated for osteoarthritis of the hand. Additionally, 583 patients were exposed to diclofenac sodium topical gel in an uncontrolled, open-label, long-term safety trial in osteoarthritis of the knee. Of these, 355 patients were treated for osteoarthritis of 1 knee and 228 were treated for osteoarthritis of both knees. Duration of exposure ranged from 8 to 12 weeks for the placebo-controlled studies, and up to 12 months for the open-label safety trial. Short-Term Placebo-Controlled Trials: Adverse reactions observed in at least 1% of patients treated with diclofenac sodium topical gel: Table 1 lists the types of application site reactions reported. Application site dermatitis was the most frequent type of application site reaction and was reported by 4% of patients treated with diclofenac sodium topical gel, compared to 1% of placebo patients. Non-serious Application Site Adverse Reactions (>=1% Diclofenac Sodium Patients) en dashShort-term Controlled Trials dagger Diclofenac sodium topical gel Placebo (vehicle) N=913 N=876 Adverse Reaction dagger N (%) N (%) Any application site reaction 62 (7) 19 (2) Application site dermatitis 32 (4) 6 (<1) Application site pruritus 7 (<1) 1 (<1) Application site erythema 6 (<1) 3 (<1) Application site paresthesia 5 (<1) 3 (<1) Application site dryness 4 (<1) 3 (<1) Application site vesicles 3 (<1) 0 Application site irritation 2 (<1) 0 Application site papules 1 (<1) 0 In the placebo-controlled trials, the discontinuation rate due to adverse reactions was 5% for patients treated with diclofenac sodium topical gel, and 3% for patients in the placebo group. Application site reactions, including application site dermatitis, were the most frequent reason for treatment discontinuation. Long-Term Open-Label Safety Trial: In the open-label, long-term safety study, distribution of adverse reactions was similar to that in the placebo-controlled studies. In this study, where patients were treated for up to 1 year with diclofenac sodium topical gel up to 32 g per day, application site dermatitis was observed in 11% of patients. Adverse reactions that led to the discontinuation of the study drug were experienced in 12% of patients. The most common adverse reaction that led to discontinuation of the study was application site dermatitis, which was experienced by 6% of patients.

Known hypersensitivity to diclofenac or any components of the drug product. ( 4 History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs. ( 4 In the setting of CABG surgery. ( 4 Diclofenac sodium is contraindicated in the following patients: Known hypersensitivity (e. , anaphylactic reactions and serious skin reactions) to diclofenac or any components of the drug product [ see Warnings and Precautions ( 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. 8 In the setting of coronary artery bypass graft (CABG) surgery [see Warnings and Precautions ( 5.

Pregnancy 5. 1 Infertility 8. 3 Pregnancy Category C prior to 30 weeks gestation; Category D starting 30 weeks gestation Risk Summary Use of NSAIDs, including diclofenac sodium, during the third trimester of pregnancy increases the risk of premature closure of the fetal ductus arteriosus. Avoid use of NSAIDs, including diclofenac sodium, in pregnant women starting at 30 weeks of gestation (third trimester). There are no adequate and well-controlled studies of diclofenac sodium in pregnant women. Human and animal studies indicate that diclofenac crosses the placenta. Data from observational studies regarding potential embryofetal risks of NSAID use in women in the first or second trimesters of pregnancy are inconclusive. In the general U. population, all clinically recognized pregnancies, regardless of drug exposure, have a background rate of 2-4% for major malformations, and 15-20% for pregnancy loss. In animal reproduction studies, no evidence of teratogenicity was observed in mice, rats, or rabbits given diclofenac during the period of organogenesis at doses up to approximately 5, 5, and 10 times, respectively, the maximum recommended topical dose of diclofenac sodium, despite the presence of maternal and fetal toxicity at these doses [see Data] Clinical Considerations Labor or Delivery There are no studies on the effects of diclofenac sodium during labor or delivery. In animal studies, NSAIDS, including diclofenac, inhibit prostaglandin synthesis, cause delayed parturition, and increase the incidence of stillbirth. Data Animal data Reproductive and developmental studies in animals demonstrated that diclofenac sodium administration during organogenesis did not produce teratogenicity despite the induction of maternal toxicity and fetal toxicity in mice at oral doses up to 20 mg/kg/day (approximately 5 times the maximum recommended human dose (MRHD) of diclofenac sodium based on bioavailability and body surface area (BSA) comparison), and in rats and rabbits at oral doses up to 10 mg/kg/day (approximately 5 and 10 times the MRHD based on bioavailability and BSA comparison). In a study in which pregnant rats were orally administered 2 or 4 mg/kg diclofenac (approximately 1 and 2 times the MRHD based on bioavailability and BSA comparison) from Gestation Day 15 through Lactation Day 21, significant maternal toxicity (peritonitis, mortality) was noted. These maternally toxic doses were associated with dystocia, prolonged gestation, reduced fetal weights and growth, and reduced fetal survival. Risk Summary Based on available data, diclofenac may be present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for CATAFLAM and any potential adverse effects on the breastfed infant from the CATAFLAM or from the underlying maternal condition. Data One woman treated orally with a diclofenac salt, 150 mg/day, had a milk diclofenac level of 100 mcg/L, equivalent to an infant dose of about 0. 03 mg/kg/day. Diclofenac was not detectable in breast milk in 12 women using diclofenac (after either 100 mg/day orally for 7 days or a single 50 mg intramuscular dose administered in the immediate postpartum period). Infertility Females Based on the mechanism of action, the use of prostaglandin-mediated NSAIDs, including diclofenac sodium, may delay or prevent rupture of ovarian follicles, which has been associated with reversible infertility in some women. Published animal studies have shown that administration of prostaglandin synthesis inhibitors has the potential to disrupt prostaglandin-mediated follicular rupture required for ovulation. Small studies in women treated with NSAIDs have also shown a reversible delay in ovulation. Consider withdrawal of NSAIDs, including diclofenac sodium, in women who have difficulties conceiving or who are undergoing investigation of infertility. 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. Of the total number of subjects treated with diclofenac sodium topical gel in clinical studies, 498 were 65 years of age and over. No overall differences in effectiveness or safety were observed between these subjects and younger subjects, but greater sensitivity to the effect of NSAIDs in some older individuals cannot be ruled out. Diclofenac, as with any NSAID, is known to be substantially excreted by the kidney, and the risk of toxic reactions to diclofenac sodium may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken when using diclofenac sodium topical gel in the elderly, and it may be useful to monitor renal function.

Drugs that Interfere with Hemostasis (e. warfarin, aspirin, SSRIs/SNRIs) 7 ACE Inhibitors, Angiotensin Receptor Blockers (ARB), or Beta-Blockers 7 ACE Inhibitors and ARBs 7 Diuretics 7 Digoxin 7 See Table 2 for clinically significant drug interactions with diclofenac. Table 2: Clinically Significant Drug Interactions with Diclofenac Drugs That Interfere with Hemostasis Clinical Impact: Diclofenac and anticoagulants such as warfarin have a synergistic Intervention: Monitor patients with concomitant use of diclofenac sodium see Warnings and Precautions ( 5. Aspirin Clinical Impact: Controlled clinical studies showed that the concomitant use see Warnings and Precautions ( 5. Intervention: Concomitant use of diclofenac sodium and analgesic doses see Warnings and Precautions ( 5. ACE Inhibitors, Angiotensin Receptor Blockers, and Beta-Blockers Clinical Impact: NSAIDs may diminish the antihypertensive effect of angiotensin Intervention: During concomitant use of diclofenac sodium and ACE-inhibitors, Warnings and Precautions ( 5. Diuretics Clinical Impact: Clinical studies, as well as post-marketing observations, Intervention: During concomitant use of diclofenac sodium with diuretics, see Warnings and Precautions ( 5. Digoxin Clinical Impact: The concomitant use of diclofenac with digoxin has been Intervention: During concomitant use of diclofenac sodium and Lithium Clinical Impact: NSAIDs have produced elevations in plasma lithium Intervention: During concomitant use of diclofenac sodium and Methotrexate Clinical Impact: Concomitant use of NSAIDs and methotrexate may Intervention: During concomitant use of diclofenac sodium and Cyclosporine Clinical Impact: Concomitant use of diclofenac sodium and Intervention: During concomitant use of diclofenac sodium and NSAIDs and Salicylates Clinical Impact: Concomitant use of diclofenac with other NSAIDs or see Warnings and Precautions ( 5. Intervention: The concomitant use of diclofenac with other NSAIDs Pemetrexed Clinical Impact: Concomitant use of diclofenac sodium and Intervention: During concomitant use of diclofenac sodium and.

OVERDOSAGE
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. 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).
NONCLINICAL TOXICOLOGY
Carcinogenesis Carcinogenicity studies in mice and rats administered diclofenac sodium as a dietary constituent for 2 years at doses up to 2 mg/kg/day (approximately 0.5 and 1 times, respectively, the maximum recommended human topical dose of diclofenac sodium based on bioavailability and body surface area (BSA) comparison) resulted in no significant increases in tumor incidence. In a dermal carcinogenicity study conducted in albino mice, daily topical applications of a diclofenac sodium gel product for two years at concentrations up to 0.035% diclofenac sodium (a 29-fold lower diclofenac sodium concentration than present in diclofenac sodium topical gel) did not increase neoplasm incidence. In a photococarcinogenicity study conducted in hairless mice, topical application of a diclofenac sodium gel product at doses up to 0.035% diclofenac sodium (a 29-fold lower diclofenac sodium concentration than present in diclofenac sodium topical gel) 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 in vitro in vivo Impairment of Fertility Diclofenac did not affect male or female fertility in rats at doses up to 4 mg/kg/day (approximately 2 times than the maximum human topical dose of diclofenac sodium based on bioavailability and BSA comparison).
CLINICAL STUDIES
Study 1 evaluated the efficacy of diclofenac sodium topical gel for the treatment of osteoarthritis of the knee in a 12-week, randomized, double-blind, multicenter, placebo-controlled, parallel-group trial. Diclofenac sodium topical gel was administered at a dose of 4 g, 4 times daily, on 1 knee (16 g per day). Pain as assessed by the patients at Week 12 using the WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) Pain Subindex was lower in the diclofenac sodium topical gel group than the placebo group. Study 2 evaluated the efficacy of diclofenac sodium topical gel for the treatment of osteoarthritis in subjects with osteoarthritis of the hand in an 8-week, randomized, double-blind, multicenter, placebo-controlled, parallel-group study. Diclofenac sodium topical gel was administered at a dose of 2 g per hand, 4 times daily, on both hands (16 g per day). Pain in the target hand as assessed by the patients at Weeks 4 and 6 on a visual analog scale from 0 to 100 was lower in the diclofenac sodium topical gel group than the placebo group. Table 4. Efficacy outcomes of Diclofenac sodium in Studies 1 and 2 * WOMAC = Western Ontario McMaster Osteoarthritis Index. # Scale from 0 (best) to 100 (worst). dagger Difference is adjusted using an analysis of covariance (ANCOVA) model with main effects of treatment and center and baseline covariate. double dagger Difference is adjusted using an analysis of covariance (ANCOVA) model with main effects of treatment, center, indicator of pain in the CMC-1joint, and baseline as a covariate, and the treatment-by-CMC-1 strata. Diclofenac sodium Placebo Adjusted Difference topical gel (Vehicle) (Placebo en dashDiclofenac sodium topical gel) Study 1 (Knee) Sample Size 127 119 WOMAC Pain Mean Outcome 28 37 Δ=7dagger *# at Week 12 95% Confidence Interval (1, 12) Study 2 (Hand) Sample Size 198 187 Pain Intensity# Mean Outcome 43 50 Δ=7double dagger at Week 4 95% Confidence Interval (2, 12) Study 2 (Hand) Sample Size 198 187 Pain Intensity# Mean Outcome 40 47 Δ=7double dagger at Week 6 95% Confidence Interval (1, 13)

EXELAN PHARMACEUTICALS INC.

DICLOFENAC SODIUM- diclofenac sodium_gel Product manual source documgent