1 INDICATIONS AND USAGE 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.

Diclofenac sodium topical gel 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.

Diclofenac sodium topical gel was not evaluated for use on joints of the spine, hip, or shoulder.

(14.1)

6 ADVERSE REACTIONS 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) ] Most common adverse reactions (incidence >2% of patients treated with diclofenac sodium topical gel and greater than placebo) are application site reactions, including dermatitis.

( 6.1) To report SUSPECTED ADVERSE REACTIONS, contact Encube Ethicals Private Limited at 1-833-285-4151 or FDA at 1-800-FDA-1088 o r www.fda.gov/medwatch .

6.1 Clinical Trials Experience 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: Non-serious adverse reactions that were reported during the short-term placebo-controlled studies comparing diclofenac sodium topical gel and placebo (vehicle gel) over study periods of 8 to 12 weeks (16 g per day), were application site reactions.

These were the only adverse reactions that occurred in >1% of treated patients with a greater frequency in the diclofenac sodium topical gel group (7%) than the placebo group (2%).

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.

Table 1.

Non-serious Application Site Adverse Reactions (≥1% diclofenac sodium topical gel Patients) – Short-term Controlled Trials Adverse Reaction † Diclofenac sodium topical gel, 1% N=913 Placebo (vehicle) N=876 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 † Preferred Term according to MedDRA 9.1.

In the placebo-controlled trials, the discontinuation rate due to adverse reactions was 5% for patients treated with diclofenac sodium topical gel 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.