Biifenac 1000 Diclofenac Sodium and MENTHOL, UNSPECIFIED FORM Diclofenac Sodium Diclofenac Sodium Diclofenac Sodium Diclofenac Dimethyl Sulfoxide Propylene Glycol Alcohol Glycerin Water Tuvivex10 MENTHOL, UNSPECIFIED FORM MENTHOL, UNSPECIFIED FORM MENTHOL, UNSPECIFIED FORM WATER Emu Oil Alcohol Stearic Acid Glycerin GLYCERYL MONOSTEARATE MEDIUM-CHAIN TRIGLYCERIDES Cetyl Alcohol Caprylyl Glycol Phenoxyethanol Hexylene Glycol Squalane Stearyl Alcohol Cannabidiol Sodium Hydroxide ALOE VERA LEAF INDIAN FRANKINCENSE Arnica Montana Flower

Diclofenac Sodium Topical Solution, 1.5% w/w is a nonsteroidal anti-inflammatory drug, available as a clear, colorless to faintly pink orange solution for topical application. Diclofenac Sodium Topical Solution contains 1.5% w/w diclofenac sodium, a benzeneacetic acidderivative that is a nonsteroidal anti-inflammatory drug (NSAID), designated chemically as 2-[(2,6-dichlorophenyl) amino]-benzeneacetic acid, monosodium salt. It is a white to off-white crystalline powder, hygroscopic that is freely soluble in methanol, soluble in ethanol (96 %), sparingly soluble in water, practically insoluble in chloroform and in ether. The molecular weight is 318.14. Its molecular formula is CHClNNaO and it has the following structural formula: Each 1 mL of solution contains 16.05 mg of diclofenac sodium. The inactive ingredients in diclofenac sodium topical solution include: alcohol, dimethyl sulfoxide (DMSO, 45.5% w/w), glycerin, propylene glycol and purified water. Chemical Structure

Diclofenac sodium is indicated for the treatment of signs and symptoms of osteoarthritis of the knee(s) ( 1 ). Diclofenac sodium topical solution is a nonsteroidal anti-inflammatory drug indicated for the treatment of signs and symptoms of osteoarthritis of the knee(s). ( 1 ) Uses Aid for temporary local relief of minor pains of muscles and joints.

Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals. 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. Until the treated knee(s) is completely dry, avoid skin-to-skin contact between other people and the treated knee(s). ( 2.2 ) Do not get diclofenac sodium topical solution in your eyes, nose or mouth ( 2.2 ). 2.1 General Dosing Instructions Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals [see WARNING AND PRECAUTIONS (5.2) ] 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 natural or artificial sunlight Wait until the treated area is dry before applying sunscreen, insect repellant, lotion, moisturizer, cosmetics, or other topical medication to the same knee you have just treated with diclofenac sodium topical solution Until the treated knee(s) is completely dry, avoid skin-to-skin contact between other people and the treated knee(s). Do not use combination therapy with diclofenac sodium topical solution and an oral NSAID unless the benefit outweighs the risk and conduct periodic laboratory evaluations. Directions Adult and children two years of age or older. Apply to affected area not more than 3-4 times daily. Before using on children under 18 years of age, consult a physician.

Diclofenac sodium is contraindicated in the following patients: Known hypersensitivity (e.g., anaphylactic reactions and serious skin reactions) to diclofenac or any components of the drug product. [see WARNINGS AND PRECAUTIONS (5.7 , 5.9) ]. History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs. Severe, sometimes fatal, anaphylactic reactions to NSAIDs have been reported in such patients [see WARNINGS AND PRECAUTIONS (5.7 , 5.8) ]. In the setting of coronary artery bypass graft (CABG) surgery [see WARNINGS AND PRECAUTIONS (5.1) ]. Known hypersensitivity to diclofenac or any components of the drug product. ( 4 ) History of asthma, urticaria, or 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 ( ) with diclofenac sodium topical solution are application site reactions. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Lupin Pharmaceuticals Inc. at 1-800-399-2561 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 to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The data described below reflect exposure to diclofenac sodium 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 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 vesicles (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 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, 1.5% w/w in placebo and oral diclofenac-controlled trials. Treatment Group: Diclofenac Sodium Topical Solution, 1.5% w/w Topical Placebo Adverse Reaction Preferred Term according to COSTART N=911 N (%) N=332 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. 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

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. Serotonin 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 diclofenac sodium 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 NSAID alone [see WARNINGS AND PRECAUTIONS (5.2) ] Intervention Concomitant use of diclofenac sodium and analgesic doses of aspirin is not generally recommended because of the increased risk of bleeding [see WARNINGS AND PRECAUTIONS (5.11) ]. Diclofenac sodium 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 diclofenac sodium and ACE-inhibitors, ARBs, or beta-blockers, monitor blood pressure to ensure that the desired blood pressure is obtained During concomitant use of diclofenac sodium 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 diclofenac sodium 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 Intervention: concentration and prolong the half-life digoxin. During concomitant use of diclofenac sodium 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. 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 diclofenac sodium and lithium, monitor patients for signs of lithium toxicity. Methotrexate Clinical Impact; Concomitant use of NSAIDs and methotrexate may increase the risk of methotrexate toxicity (e.g., neutropenia, thrombocytopenia, renal dysfunction). Intervention : During concomitant use of diclofenac sodium and methotrexate, monitor patients for methotrexate toxicity. Cyclosporine Clinical Impact: Concomitant use of diclofenac sodium and cyclosporine may increase cyclosporine's nephrotoxicity. Intervention: During concomitant use of diclofenac sodium and cyclosporine, monitor patients for signs or 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) ]. Concomitant use of oral NSAIDs with diclofenac sodium has been evaluated in one Phase 3 controlled trial and in combination with oral diclofenac, compared to oral diclofenac alone, resulted in ahigher 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%). Intervention: The concomitant use of diclofenac with other NSAIDs or salicyclates is not recommended. Do not use combination therapy with diclofenac sodium and an oral NSAID unless the benefit outweighs the risk and conduct periodic laboratory evaluations Pemetrexed Clinical Impact: Concomitant use of diclofenac sodium and pemetrexed may increase the risk of pemetrexed-associated myelosuppression, renal, and GI toxicity (see the pemetrexed prescribing info). Intervention: During concomitant use of diclofenac sodium and pemetrexed, in patients with renal impairment whose creatinine clearance ranges from 45 to 79 mL/min, monitor for myelosuppression, renal and GI 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 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 ): M onitor patients for bleeding who are concomitantly using diclofenac sodium with drugs that interfere with hemostasis. Concomitant use of diclofenac sodium and analgesic doses of aspirin is not generally recommended ( 7 ) ACE Inhibitors, Angiotensin Receptor Blockers (ARB), or Beta- Blockers : C oncomitant use with diclofenac sodium may diminish the antihypertensive effect of these drugs. Monitor blood pressure ( 7 ) ACE Inhibitors and ARBs : Concomitant use with diclofenac sodium 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 diclofenac sodium can increase serum concentration and prolong half-life of digoxin. Monitor serum digoxin levels ( 7 )

Purpose Topical Analgesic

KEEP OUT OF REACH OF CHILDREN. IF SWALLOWED, GET MEDICAL HELP RIGHT AWAY. For reporting serious adverse event or obtain product information, contact 1-844-720-7251.

Storage Store at 25°C (77°F); excursions permitted to 15 to 30°C (59 to 86°F) [See USP Controlled Room Temperature]. Other information WARNING: FLAMMABLE PRODUCT Store in a cool, dry place at 20 - 25 C (68 to 77 F) with lid closed tightly. Storage Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [See USP Controlled Room Temperature]. KEEP THIS AND ALL MEDICATION OUT OF REACH OF CHILDREN

For Questions or Comments please call 1-844-720-7251