DS Prep Pak

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.

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 oblong 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.

Lower extremities, including the knees, ankles, and feet

Apply the gel (4 g) to the affected foot or knee or ankle, 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.

Upper extremities including the elbows, wrists and hands

Apply the gel (2 g) to the affected hand or elbow or wrist, 4 times daily. VOLTAREN® GEL should be gently massaged into the skin ensuring application to the entire affected hand or elbow or wrist. 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.

Special Precautions

• Showering/bathing should be avoided for at least 1 hour after the application. Patient should wash his/her hands after use, unless the hands are the treated joint. If VOLTAREN® GEL is applied to the hand(s) for treatment; patient should not wash the treated hand(s) for at least 1 hour after the application.
• VOLTAREN® GEL should not be applied to open wounds.
• Contact of VOLTAREN® GEL with eyes and mucous membranes should be avoided.
• External heat and/or occlusive dressings should not be applied to treated joints.
• Exposure of the treated joint(s) to sunlight should be avoided.
• Avoid concomitant use of VOLTAREN® GEL on the treated skin with other topical products including sunscreens, cosmetics, lotions, moisturizers, insect repellants, or other topical medications [see Drug Interactions (7.9)].
• Concomitant use of VOLTAREN® GEL with oral non-steroidal anti-inflammatory drugs (NSAIDs) has not been evaluated, and may increase adverse NSAIDs effects.

Wearing of clothing or gloves should be avoided for at least 10 minutes after applying VOLTAREN® GEL.

The use of VOLTAREN ® GEL is contraindicated in patients with a known hypersensitivity to diclofenac.

VOLTAREN ® GEL should not be administered in patients who have experienced asthma, urticaria, or other 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 (5.1)].

VOLTAREN ® GEL is contraindicated in the setting of coronary artery bypass graft (CABG) surgery [see Warnings and Precautions (5.1)].

Cardiovascular Thrombotic Events

Clinical trials of several COX-2 selective and nonselective NSAIDs of up to three years duration have shown an increased risk of serious cardiovascular (CV) thrombotic events, myocardial infarction, and stroke, which can be fatal. All NSAIDs, both COX-2 selective and nonselective, may have a similar risk. Patients with known CV disease or risk factors for CV disease may be at greater risk. To minimize the potential risk for an adverse CV event in patients treated with NSAIDs, the lowest effective dose should be used for the shortest duration possible. Physicians and patients should remain alert for the development of such events, even in the absence of previous CV symptoms. Patients should be informed about the signs and/or symptoms of serious CV toxicity and the steps to take if they occur.

There is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious CV thrombotic events associated with NSAIDs use. The concurrent use of aspirin and NSAIDs such as diclofenac, does increase the risk of serious GI events [see Warnings and Precautions (5.2)].

Two large, controlled, clinical trials of a COX-2 selective NSAID for the treatment of pain in the first 10-14 days following CABG surgery found an increased incidence of myocardial infarction and stroke [see Contraindications (4)].

Gastrointestinal Effects – Risk of GI Ulceration, Bleeding, and Perforation

NSAIDs, including diclofenac, can cause serious gastrointestinal (GI) events including bleeding, ulceration, and perforation of the stomach, small intestine or large intestine, which can be fatal. These serious adverse events can occur at any time, with or without warning symptoms, in patients treated with NSAIDs. Only one in five patients who develop a serious upper GI adverse event on NSAID therapy is symptomatic. Upper GI ulcers, gross bleeding, or perforation caused by NSAIDs occur in approximately 1% of patients treated for 3-6 months, and in about 2-4% of patients treated for one year. These trends continue with longer duration of use, increasing the likelihood of developing a serious GI event at some time during the course of therapy. However, even short-term therapy is not without risk.

NSAIDs should be prescribed with extreme caution in patients with a prior history of ulcer disease or gastrointestinal bleeding. Patients with a prior history of peptic ulcer disease and/or gastrointestinal bleeding who use NSAIDs have a greater than 10-fold increased risk for developing a GI bleed compared to patients with neither of these risk factors. Other factors that increase the risk of GI bleeding in patients treated with NSAIDs include concomitant use of oral corticosteroids or anticoagulants, longer duration of NSAIDs therapy, smoking, use of alcohol, older age, and poor general health status. Most spontaneous reports of fatal GI events are in elderly or debilitated patients and therefore special care should be taken in treating this population.

To minimize the potential risk for an adverse GI event, the lowest effective dose should be used for the shortest possible duration. Physicians and patients should remain alert for signs and symptoms of GI ulceration and bleeding during diclofenac therapy and promptly initiate additional evaluation and treatment if a serious GI adverse event is suspected. For high-risk patients, alternate therapies that do not involve NSAIDs should be considered.

Hepatic Effects

Elevations of one or more liver tests may occur during therapy with diclofenac sodium. These laboratory abnormalities may progress, may remain unchanged, or may be transient with continued therapy. Borderline elevations (i.e. less than 3 times the ULN [ULN = the upper limit of normal range]) or greater elevations of transaminases occurred in about 15% of diclofenac-treated patients. Of the markers of hepatic function, ALT (SGPT) is recommended for the monitoring of liver injury.

In clinical trials, meaningful elevations (i.e., more than 3 times the ULN) of AST (GOT) (ALT was not measured in all studies) occurred in about 2% of approximately 5,700 patients at some time during diclofenac treatment. In a large, open-label, controlled trial of 3,700 patients treated for 2-6 months, patients were monitored first at 8 weeks and 1,200 patients were monitored again at 24 weeks. Meaningful elevations of ALT and/or AST occurred in about 4% of patients and included marked elevations (i.e., more than 8 times the ULN) in about 1% of the 3,700 patients. In that open-label study, a higher incidence of borderline (less than 3 times the ULN), moderate (3-8 times the ULN), and marked (>8 times the ULN) elevations of ALT or AST was observed in patients receiving diclofenac when compared to other NSAIDs. Elevations in transaminases were seen more frequently in patients with osteoarthritis than in those with rheumatoid arthritis.

Almost all meaningful elevations in transaminases were detected before patients became symptomatic. Abnormal tests occurred during the first 2 months of therapy with diclofenac in 42 of the 51 patients in all trials who developed marked transaminase elevations.

In postmarketing reports, cases of drug-induced hepatotoxicity have been reported in the first month, and in some cases, the first 2 months of therapy, but can occur at any time during treatment with diclofenac. Postmarketing surveillance has reported cases of severe hepatic reactions, including liver necrosis, jaundice, fulminant hepatitis with and without jaundice, and liver failure. Some of these reported cases resulted in fatalities or liver transplantation.

Physicians should measure transaminases periodically in patients receiving long-term therapy with diclofenac, because severe hepatotoxicity may develop without a prodrome of distinguishing symptoms. The optimum times for making the first and subsequent transaminase measurements are not known. Based on clinical trial data and postmarketing experiences, transaminases should be monitored within 4 to 8 weeks after initiating treatment with diclofenac. However, severe hepatic reactions can occur at any time during treatment with diclofenac.

If abnormal liver tests persist or worsen, if clinical signs and/or symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g., eosinophilia, rash, abdominal pain, diarrhea, dark urine, etc.), diclofenac sodium should be discontinued immediately. To minimize the possibility that hepatic injury will become severe between transaminase measurements, physicians should inform patients of the warning signs and symptoms of hepatotoxicity (e.g., nausea, fatigue, lethargy, diarrhea, pruritus, jaundice, right upper quadrant tenderness, and “flu-like” symptoms), and the appropriate action patients should take if these signs and symptoms appear.

To minimize the potential risk for an adverse liver related event in patients treated with diclofenac sodium, the lowest effective dose should be used for the shortest duration possible. Caution should be exercised in prescribing diclofenac sodium with concomitant drugs that are known to be potentially hepatotoxic (e.g., antibiotics, anti-epileptics).

Hypertension

NSAIDs, including VOLTAREN ® GEL, can lead to the onset of new hypertension or worsening of preexisting hypertension, either of which may contribute to the increased incidence of cardiovascular events. Patients taking thiazides or loop diuretics may have impaired response to these therapies when taking NSAIDs. NSAIDs, including VOLTAREN ® GEL should be used with caution in patients with hypertension. Blood pressure should be monitored closely during the initiation of therapy with VOLTAREN ® GEL and throughout the course of therapy.

Congestive Heart Failure and Edema

Fluid retention and edema have been observed in some patients treated with NSAIDs, including VOLTAREN ® GEL. VOLTAREN ® GEL should be used with caution in patients with fluid retention or heart failure.

Renal Effects

Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury. Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. In these patients, administration of an NSAID may cause a dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation. Patients at greatest risk of this reaction are those with impaired renal function, heart failure, liver dysfunction, those taking diuretics and ACE-inhibitors, and the elderly. Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment state.

No information is available from controlled clinical studies regarding the use of VOLTAREN ® GEL in patients with advanced renal disease. Therefore, treatment with VOLTAREN ® GEL is not recommended in patients with advanced renal disease. If VOLTAREN ® GEL therapy is initiated, close monitoring of the patient's renal function is advisable.

Anaphylactoid Reactions

As with other NSAIDs, anaphylactoid reactions may occur in patients without prior exposure to VOLTAREN ® GEL. VOLTAREN ® GEL should not be given to patients with the aspirin triad. This symptom complex typically occurs in asthmatic patients who experience rhinitis with or without nasal polyps, or who exhibit severe, potentially fatal bronchospasm after taking aspirin or other NSAIDs [see Contraindications (4), Warnings and Precautions (5.7)]. Emergency help should be sought in cases where an anaphylactoid reaction occurs.

Skin Reactions

NSAIDs, including VOLTAREN ® GEL, can cause serious skin adverse events such as exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. These serious events may occur without warning. Patients should be informed about the signs and symptoms of serious skin manifestations, and the use of the drug should be discontinued at the first appearance of skin rash or any other signs of hypersensitivity.

VOLTAREN ® GEL should not be applied to open skin wounds, infections, inflammations, or exfoliative dermatitis, as it may affect absorption and tolerability of the drug. VOLTAREN ® GEL should not be allowed to come into contact with the eyes or with mucous membranes.

The effect of VOLTAREN ® GEL under occlusive dressings has not been evaluated, and should be avoided.

Pregnancy

As with other NSAIDs, VOLTAREN ® GEL should be avoided in late pregnancy, because it may cause premature closure of the ductus arteriosus.

Corticosteroid treatment

VOLTAREN ® GEL cannot be expected to substitute for corticosteroids or to treat corticosteroid insufficiency. Abrupt discontinuation of corticosteroids may lead to exacerbation of corticosteroid-responsive illness. Patients on prolonged corticosteroid therapy should have their therapy tapered slowly if a decision is made to discontinue corticosteroids.

Inflammation

The pharmacological activity of diclofenac in reducing inflammation, and possibly fever, may diminish the utility of these diagnostic signs in detecting infectious complications of presumed noninfectious, painful conditions.

Hematological Effects

Anemia is sometimes seen in patients receiving NSAIDs. This may be due to fluid retention, occult or gross GI blood loss, or an incompletely described effect upon erythropoeisis. Patients on long-term treatment with NSAIDs, including VOLTAREN ® GEL, should have their hemoglobin or hematocrit checked if they exhibit any signs or symptoms of anemia or blood loss.

NSAIDs inhibit platelet aggregation and have been shown to prolong bleeding time in some patients. Unlike aspirin, their effect on platelet function is quantitatively less, of shorter duration, and reversible. Patients treated with VOLTAREN ® GEL who may be adversely affected by alteration in platelet function, such as those with coagulation disorders or patients receiving anticoagulants should be carefully monitored.

Preexisting Asthma

Patients with asthma may have aspirin-sensitive asthma. The use of aspirin in patients with aspirin sensitive asthma has been associated with severe bronchospasm, which can be fatal. Since cross reactivity, including bronchospasm, between aspirin and other non-steroidal anti-inflammatory drugs has been reported in such aspirin-sensitive patients, VOLTAREN ® GEL should not be administered to patients with this form of aspirin sensitivity and should be used with caution in patients with preexisting asthma.

Sun Exposure

Patients should minimize or avoid exposure to natural or artificial sunlight on treated areas because studies in animals indicated topical diclofenac treatment resulted in an earlier onset of ultraviolet light induced skin tumors. The potential effects of VOLTAREN ® GEL on skin response to ultraviolet damage in humans are not known.

Eye Exposure

Contact of VOLTAREN ® GEL with eyes and mucosa, although not studied, should be avoided. Patients should be advised that if eye contact occurs, they should immediately wash out the eye with water or saline and consult a physician if irritation persists for more than an hour.

Laboratory Tests

Because serious GI tract ulcerations and bleeding can occur without warning symptoms, physicians should monitor for signs or symptoms of GI bleeding. Patients on long-term treatment with NSAIDs, should have a CBC and a chemistry profile checked periodically. If abnormal liver tests or renal tests persist or worsen, VOLTAREN ® GEL should be discontinued.

There has been no experience of overdose with VOLTAREN ® GEL.

No events of accidental ingestion have been reported with VOLTAREN ® GEL. Effects similar to those observed after an overdose of diclofenac tablets can be expected if substantial amounts of VOLTAREN ® GEL are ingested. Symptoms following acute oral NSAID overdoses 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. Anaphylactoid reactions have been reported with therapeutic ingestion of NSAIDs, and may occur after an overdose.

In the event of oral ingestion resulting in significant systemic side effects, it is recommended that the stomach be emptied by vomiting or lavage. Forced diuresis may theoretically be beneficial because the drug is excreted in the urine. The effect of dialysis or hemoperfusion in the elimination of diclofenac (99% protein-bound) remains unproven. In addition to supportive measures, the use of oral activated charcoal may help to reduce the absorption of diclofenac. Supportive and symptomatic treatment should be given for complications such as renal failure, convulsions, gastrointestinal irritation, and respiratory depression.

For additional information about overdose treatment, call a Poison Control Center (1-800-222-1222).

VOLTAREN ® GEL (diclofenac sodium)

Important: Use the dosing card that is inside the VOLTAREN ® GEL carton to correctly measure each dose. The dosing card is re-usable. Do not throw the dosing card away. Before you use VOLTAREN ® 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 before you start using VOLTAREN ® GEL and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment.

Your healthcare provider has prescribed VOLTAREN ® GEL to help relieve arthritis pain in some of your joints. VOLTAREN ® 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 VOLTAREN ® GEL is safe and effective if used on your spine, hips, or shoulders.

• Use VOLTAREN ® GEL exactly how your healthcare provider prescribes it for you. Do not apply VOLTAREN ® GEL anywhere other than where your doctor tells you to.
• Do not use more than a total of 32 grams of VOLTAREN ® GEL each day. If you add up the amount of VOLTAREN ® 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 VOLTAREN ® GEL each time you apply it.

• Apply VOLTAREN ® 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 VOLTAREN ® GEL each time you apply it.

• Apply VOLTAREN ® 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 knees, ankles, or feet.

Some examples of VOLTAREN ® GEL applications include:

• If you use 2 grams of VOLTAREN ® GEL on one hand, 4 times a day, your total dose for one day is 8 grams
• If you use 4 grams of VOLTAREN ® 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 VOLTAREN ® GEL.

Figure A

• Before you use a new tube of VOLTAREN ® 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 VOLTAREN ® GEL to clean, dry skin that does not have any cuts, infections or rashes.
• Do not use heating pads or apply bandages where you have applied VOLTAREN ® GEL.
• Avoid exposing skin where you apply VOLTAREN ® 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 VOLTAREN ® GEL.
• Do not get VOLTAREN ® GEL in your eyes, nose, or mouth. VOLTAREN ® GEL is only to be used on your skin (topical use). If you get VOLTAREN ® 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 VOLTAREN ® GEL, continue with your next scheduled dose using the prescribed amount of VOLTAREN ® GEL. Do not double the dose.

Applying 2 grams (2 g) of VOLTAREN ® GEL to hands, wrists, or elbows:

Step 1. Remove the dosing card that is attached inside the VOLTAREN ® GEL carton. Use the dosing card to correctly measure each dose of VOLTAREN ® GEL. To measure the correct amount of VOLTAREN ® GEL, place the dosing card on a flat surface so that you can read the print. If the print is backwards, flip dosing card over (See Figure A). If you lose or misplace your dosing card, you can ask your pharmacist for a new one or call 1-800-398-5876. Ask your healthcare provider or pharmacist to show you how to correctly measure your dose of VOLTAREN ® GEL while you are waiting to receive your new dosing card.

Step 2. Squeeze VOLTAREN ® GEL onto the dosing card evenly, up to the 2 g line (a 2.25 inch length of gel). Make sure that the gel covers the entire 2 gram area of the dosing card (See Figure B). Put the cap back on the tube of VOLTAREN ® GEL. Ask your healthcare provider or pharmacist if you are not sure how to correctly measure your dose of VOLTAREN ® GEL.

Step 3. Apply the gel to your hand, wrist, or elbow. You can use the dosing card to apply the gel (See Figure C). Then, use your hands to gently rub the gel into the skin (See Figure D). Do not share your dosing card with another person. Make sure to cover the entire affected hand, wrist or elbow with the gel. Remember that the hand includes the palm of your hand, the top of your hand, and your fingers.

Step 4. After using the dosing card, hold end with fingertips, rinse and dry. Store the dosing card until next use. Do not shower or bathe for at least 1 hour after applying VOLTAREN ® GEL. Do not wash your treated hands for at least 1 hour after applying the VOLTAREN ® GEL.

Step 5. After applying VOLTAREN ® GEL, wait 10 minutes before covering the treated skin with gloves or clothing.

Applying 4 grams (4 g) of VOLTAREN ® GEL to feet, ankles, or knees:

• Step 1. Refer to Step 1 above.

Step 2.Squeeze VOLTAREN ® GEL onto the dosing card evenly up to the 4 g line (a 4.5 inch length of gel), making sure the gel covers the 4 g area of the dosing card (See Figure E). Put the cap back on the tube of VOLTAREN ® GEL. Ask your healthcare provider or pharmacist if you are not sure how to correctly measure your dose of VOLTAREN ® GEL.

Step 3. Apply VOLTAREN ® GEL to your foot, ankle, or knee. You can use the dosing card to apply the gel (See Figure F). Then, use your hands to gently rub the gel into the skin (See Figure G). Do not share your dosing card with another person. Make sure to cover your entire foot, ankle, or knee area with the gel. For example, cover the skin above, below, inside and outside the knee cap. Remember that the foot includes the sole of your foot, the top of your foot and your toes.

Refer to Steps 4 and 5 above. Wash your hands after applying VOLTAREN ® GEL to your foot, ankle, or knee.

What are the ingredients in VOLTAREN ® GEL?

Active ingredient: diclofenac sodium

Inactive ingredients: carbomer homopolymer Type C, cocoyl caprylocaprate, fragrance, isopropyl alcohol, mineral oil, polyoxyl 20 cetostearyl ether, propylene glycol, purified water, and strong ammonia solution.

How should I store VOLTAREN ® GEL? Store at 20°C to 25°C (68°F to 77°F). Do not freeze VOLTAREN ® GEL. Store the dosing card with your VOLTAREN ® GEL.

Keep VOLTAREN ® 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.S. Food and Drug Administration.

Marketed by:

Alvix Laboratories, LLC

6601 Sunplex Drive

Ocean Springs, MS 39564

Manufactured by:

Novartis Pharma Produktions GmbH,

Wehr, Germany for

Sandoz Inc., Princeton, NJ 08540

Revised: November 2014