Diclo Gel 1% Pak diclofenac sodium, isopropyl alcohol Voltaren diclofenac sodium DICLOFENAC SODIUM DICLOFENAC AMMONIA CARBOMER HOMOPOLYMER TYPE C (ALLYL PENTAERYTHRITOL CROSSLINKED) COCO-CAPRYLATE/CAPRATE ISOPROPYL ALCOHOL MINERAL OIL POLYOXYL 20 CETOSTEARYL ETHER PROPYLENE GLYCOL WATER Alcohol Prep isopropyl alcohol ISOPROPYL ALCOHOL ISOPROPYL ALCOHOL WATER

VOLTAREN ® GEL (diclofenac sodium topical gel) is a nonsteroidal anti-inflammatory drug (NSAID) for topical use only. The chemical name is 2-[(2,6-dichlorophenyl)amino]benzene acetic 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 chemical structure: It contains the active ingredient, diclofenac sodium, in an opaque, white gel base. Diclofenac sodium is a white to slightly yellow crystalline powder. Diclofenac sodium is a benzeneacetic acid derivative. The inactive ingredients in VOLTAREN ® GEL include: carbomer homopolymer Type C, cocoyl caprylocaprate, fragrance, isopropyl alcohol, mineral oil, polyoxyl 20 cetostearyl ether, propylene glycol, purified water, and strong ammonia solution. image description

VOLTAREN ® 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. • VOLTAREN ® GEL has not been evaluated for use on the spine, hip, or shoulder. VOLTAREN ® 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. (1) • VOLTAREN ® GEL was not evaluated for use on joints of the spine, hip, or shoulder. (14.1) Uses Antiseptic cleanser Kills harmful bacteria and germs First aid to help prevent infection

Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals [ see Warnings and Precautions ( 5 ) ]. • Use the lowest effective dosage for the 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. ( 2.2 ) • 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. ( 2.3 ) • Total dose should not exceed 32 g per day, over all affected joints. ( 2.3 ) VOLTAREN ® GEL should be measured onto the enclosed dosing card to the appropriate 2 g or 4 g designation. ( 2 ) 2.1 Dosing Card [See the Patient Instructions for Use] The dosing card can be found attached to the inside of the carton. The proper amount of VOLTAREN® 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 4 g 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 VOLTAREN® 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. 2.2 Lower extremities, including the feet, ankles, or knees Apply the gel (4 g) to the affected foot, ankle, or knee 4 times daily. VOLTAREN® 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. 2.3 Upper extremities including the hands, wrists, or elbows Apply the gel (2 g) to the affected hand, wrist, or elbow 4 times daily. VOLTAREN® 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. 2.4 Special Precautions • 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 VOLTAREN® 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 VOLTAREN® GEL to open wounds. • Avoid contact of VOLTAREN® 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 VOLTAREN® GEL on the treated skin site with other topical products, including sunscreens, cosmetics, lotions, moisturizers, insect repellants, or other topical medications. • Concomitant use of VOLTAREN ® 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 VOLTAREN ® 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 VOLTAREN® GEL. Directions Use as part of your daily cleansing routine May be covered with a sterile bandage

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

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 VOLTAREN ® GEL and greater than placebo) are application site reactions, including dermatitis. (6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Sandoz Inc. at 1-800-525-8747 or FDA at 1-800-FDA-1088 or 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 VOLTAREN ® 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 VOLTAREN ® GEL for osteoarthritis of the knee and 400 were treated for osteoarthritis of the hand. Additionally, 583 patients were exposed to VOLTAREN ® 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 VOLTAREN ® GEL: Non-serious adverse reactions that were reported during the short-term placebo-controlled studies comparing VOLTAREN ® 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 VOLTAREN ® 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 VOLTAREN ® GEL, compared to 1% of placebo patients. Table 1: Non-serious Application Site Adverse Reactions (≥1% VOLTAREN ® GEL Patients) – Short-term Controlled Trials Adverse Reaction † VOLTAREN ® GEL 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 VOLTAREN ® 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 VOLTAREN ® 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.

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 effect on bleeding. The concomitant use of diclofenac and anticoagulants have an increased risk of serious bleeding compared to the use of either drug alone. • S er otonin release by platelets plays an important role in hemostasis. Case-control and cohort epidemiological studies showed that concomitant use of drugs that interfere with serotonin reuptake and an NSAID may potentiate the risk of bleeding more than an NSAID alone. Intervention: Monitor patients with concomitant use of VOLTAREN ® GEL with anticoagulants (e.g., warfarin), antiplatelet agents (e.g., aspirin), selective serotonin reuptake inhibitors (SSRIs), and serotonin norepinephrine reuptake inhibitors (SNRIs) for signs of bleeding [see Warnings and Precautions ( 5.11 )]. Aspirin Clinical Impact: Controlled clinical studies showed that the concomitant use of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than the use of NSAIDs alone. In a clinical study, the concomitant use of an NSAID and aspirin was associated with a significantly increased incidence of GI adverse reactions as compared to use of the NSAID alone [see Warnings and Precautions ( 5.2 )]. Intervention: Concomitant use of VOLTAREN ® GEL and analgesic doses of aspirin is not generally recommended because of the increased risk of bleeding [see Warnings and Precautions ( 5.11 )]. VOLTAREN ® GEL is not a substitute for low dose aspirin for cardiovascular protection. ACE Inhibitors, Angiotensin Receptor Blockers, and Beta-Blockers Clinical Impact: • NSAIDs may diminish the antihypertensive effect of angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), or beta blockers (including propranolol). • In patients who are elderly, volume-depleted (including those on diuretic therapy), or have renal impairment, co-administration of an NSAID with ACE inhibitors or ARBs may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Intervention: • During concomitant use of VOLTAREN ® GEL and ACE-inhibitors, ARBs, or beta- blockers, monitor blood pressure to ensure that the desired blood pressure is obtained. • During concomitant use of VOLTAREN ® GEL and ACE-inhibitors or ARBs in patients who are elderly, volume-depleted, or have impaired renal function, monitor for signs of worsening renal function [see Warnings and Precautions ( 5.6 )]. •When these drugs are administered concomitantly, patients should be adequately hydrated. Assess renal function at the beginning of the concomitant treatment and periodically thereafter . Diuretics Clinical Impact: Clinical studies, as well as post-marketing observations, showed that NSAIDs reduced the natriuretic effect of loop diuretics (e.g., furosemide) and thiazide diuretics in some patients. This effect has been attributed to the NSAID inhibition of renal prostaglandin synthesis. Intervention: During concomitant use of VOLTAREN ® GEL with diuretics, observe patients for signs of worsening renal function, in addition to assuring diuretic efficacy including antihypertensive effects [ see Warnings and Precautions ( 5.6 )]. Digoxin Clinical Impact: The concomitant use of diclofenac with digoxin has been reported to increase the serum concentration and prolong the half-life of digoxin. Intervention: During concomitant use of VOLTAREN ® GEL and digoxin, monitor serum digoxin levels. Lithium Clinical Impact: NSAIDs have produced elevations in plasma lithium levels and reductions in renal lithium clearance. The mean minimum lithium concentration increased 15%, and the renal clearance decreased by approximately 20%. This effect has been attributed to NSAID inhibition of renal prostaglandin synthesis. Intervention: During concomitant use of VOLTAREN ® GEL and lithium, monitor patients for signs of lithium toxicity. Methotrexate Clinical Impact: Concomitant use of NSAIDs and methotrexate may increase the risk for methotrexate toxicity (e.g., neutropenia, thrombocytopenia, renal dysfunction). Intervention: During concomitant use of VOLTAREN ® GEL and methotrexate, monitor patients for methotrexate toxicity. Cyclosporine Clinical Impact: Concomitant use of VOLTAREN ® GEL and cyclosporine may increase cyclosporine's nephrotoxicity. Intervention: During concomitant use of VOLTAREN ® GEL and cyclosporine, monitor patients for signs of worsening renal function. NSAIDs and Salicylates Clinical Impact: Concomitant use of diclofenac with other NSAIDs or salicylates (e.g., diflunisal, salsalate) increases the risk of GI toxicity, with little or no increase in efficacy [see Warnings and Precautions ( 5.2 )]. Intervention: The concomitant use of diclofenac with other NSAIDs or salicylates is notrecommended. Pemetrexed Clinical Impact: Concomitant use of VOLTAREN ® GEL and pemetrexed may increase the risk of pemetrexed-associated myelosuppression, renal, and GI toxicity (see the pemetrexed prescribing information). Intervention: During concomitant use of VOLTAREN ® GEL and pemetrexed, in patients with renal impairment whose creatinine clearance ranges from 45 to 79 mL/min, monitor for myelosuppression, renal and Gl toxicity. NSAIDs with short elimination half-lives (e.g., diclofenac, indomethacin) should be avoided for a period of two days before, the day of, and two days following administration of pemetrexed. In the absence of data regarding potential interaction between pemetrexed and NSAIDs with longer half-lives (e.g., meloxicam, nabumetone), patients taking these NSAIDs should interrupt dosing for at least five days before, the day of, and two days following pemetrexed administration. • Drugs that Interfere with Hemostasis (e.g. warfarin, aspirin, SSRIs/SNRIs) : Monitor patients for bleeding who are concomitantly using VOLTAREN ® GEL with drugs that interfere with hemostasis. Concomitant use of VOLTAREN ® GEL and analgesic doses of aspirin is not generally recommended ( 7 ) • ACE Inhibitors, Angiotensin Receptor Blockers (ARB), or Beta-Blockers : Concomitant use with VOLTAREN ® GEL may diminish the antihypertensive effect of these drugs. Monitor blood pressure ( 7 ) • ACE Inhibitors and ARBs : Concomitant use with VOLTAREN ® GEL in elderly, volume depleted, or those with renal impairment may result in deterioration of renal function. In such high risk patients, monitor for signs of worsening renal function ( 7 ) • Diuretics: NSAIDs can reduce natriuretic effect of furosemide and thiazide diuretics. Monitor patients to assure diuretic efficacy including antihypertensive effects ( 7 ) • Digoxin: Concomitant use with VOLTAREN ® GEL can increase serum concentration and prolong half-life of digoxin. Monitor serum digoxin levels ( 7 )

Purpose Antiseptic

Do not use With electrocautery procedures In the eyes

Stop use and ask a doctor if Irritation and redness develops If condition persists for more than 72 hours, consult a physician

Keep out of reach of children If swallowed, get medical help or contact a Poison Control Center right away

Other Information Store at room temperature 15°-30°C (59°-86°F) Avoid excessive heat