Flector® Patch (10 cm x 14 cm) is comprised of an adhesive material containing 1.3% diclofenac epolamine which is applied to a non-woven polyester felt backing and covered with a polypropylene film release liner. The release liner is removed prior to topical application to the skin.

Diclofenac epolamine is a non-opioid analgesic chemically designated as 2-[(2,6-dichlorophenyl) amino]benzeneacetic acid, (2-(pyrrolidin-1-yl) ethanol salt, with a molecular formula of C₂₀H₂₄Cl₂N₂O₃ (molecular weight 411.3), an n-octanol/water partition coefficient of 8 at pH 8.5, and the following structure:

Each adhesive patch contains 180 mg of diclofenac epolamine (13 mg per gram adhesive) in an aqueous base. It also contains the following inactive ingredients: 1,3-butylene glycol, dihydroxyaluminum aminoacetate, disodium edetate, D-sorbitol, fragrance (Dalin PH), gelatin, kaolin, methylparaben, polysorbate 80, povidone, propylene glycol, propylparaben, sodium carboxymethylcellulose, sodium polyacrylate, tartaric acid, titanium dioxide, and purified water.

Carefully consider the potential benefits and risks of Flector® Patch and other treatment options before deciding to use Flector® Patch. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS).

Flector® Patch is indicated for the topical treatment of acute pain due to minor strains, sprains, and contusions.

Carefully consider the potential benefits and risks of Flector® Patch and other treatment options before deciding to use Flector® Patch. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS).

The recommended dose of Flector® Patch is one (1) patch to the most painful area twice a day.

Flector® patch should not be applied to damaged or non-intact skin.

Flector® patch should not be worn when bathing or showering.

HANDLING AND DISPOSAL

Patients and caregivers should wash their hands after applying, handling or removing the patch. Eye contact should be avoided.

Flector® Patch is supplied in resealable envelopes, each containing 5 patches (10 cm x 14 cm), with one or two envelopes per box (NDC 64032-xxx-xx). Each individual patch is embossed with “Diclofenac Epolamine Patch 1.3%”.

• Each patch contains 180 mg of diclofenac epolamine in an aqueous base (13 mg of active per gram of adhesive or 1.3%).
• The product is intended for topical use only
• Keep out of reach of children and pets.
• The ENVELOPES SHOULD BE SEALED AT ALL TIMES WHEN NOT IN USE.
• Store at 25°C (77°F); excursions permitted to 15°-30°C (59°-86°F). [See USP Controlled Room Temperature].

Manufacturer: Teikoku Seiyaku Co., Ltd., Sanbonmatsu, Kagawa 769-2695, Japan Distributor:
FDA rev date: 1/31/2007

In controlled trials during the premarketing development of Flector® Patch, approximately 600 patients with minor sprains, strains, and contusions have been treated with Flector® Patch for up to two weeks.

Adverse Events Leading to Discontinuation of Treatment

In the controlled trials, 3% of patients in both the Flector® Patch and placebo patch groups discontinued treatment due to an adverse event. The most common adverse events leading to discontinuation were application site reactions, occurring in 2% of both the Flector® Patch and placebo patch groups. Application site reactions leading to dropout included pruritus, dermatitis, and burning.

Common Adverse Events

Localized Reactions

Overall, the most common adverse events associated with Flector® Patch treatment were skin reactions at the site of treatment.

Table 1 lists all adverse events, regardless of causality, occurring in 1% of patients in controlled trials of Flector® Patch. A majority of patients treated with Flector® Patch had adverse events with a maximum intensity of “mild” or “moderate.”

Foreign labeling describes that dermal allergic reactions may occur with Flector® Patch treatment. Additionally, the treated area may become irritated or develop itching, erythema, edema, vesicles, or abnormal sensation.

DRUG ABUSE AND DEPENDENCE

Controlled Substance Class

Flector® Patch is not a controlled substance.

Physical and Psychological Dependence

Diclofenac, the active ingredient in Flector® Patch, is an NSAID that does not lead to physical or psychological dependence.

ACE-inhibitors

Reports suggest that NSAIDs may diminish the antihypertensive effect of ACE-inhibitors. This interaction should be given consideration in patients taking NSAIDs concomitantly with ACE-inhibitors.

Aspirin

When Flector® Patch is administered with aspirin, the binding of diclofenac to protein is reduced, although the clearance of free diclofenac is not altered. The clinical significance of this interaction is not known; however, as with other NSAIDs, concomitant administration of diclofenac and aspirin is not generally recommended because of the potential of increased adverse effects.

Clinical studies, as well as post marketing observations, have shown that Flector® Patch may reduce the natriuretic effect-of furosemide and thiazides in some patients. This response has been attributed to inhibition of renal prostaglandin synthesis. During concomitant therapy with NSAIDs, the patient should be observed closely for signs of renal failure (see WARNINGS, Renal Effects), as well as to assure diuretic efficacy.

NSAIDs have produced an elevation of plasma lithium levels and a reduction in renal lithium clearance. The mean minimum lithium concentration increased 15% and the renal clearance was decreased by approximately 20%. These effects have been attributed to inhibition of renal prostaglandin synthesis by the NSAID. Thus, when NSAIDs and lithium are administered concurrently, subjects should be observed carefully for signs of lithium toxicity.

NSAIDs have been reported to competitively inhibit methotrexate accumulation in rabbit kidney slices. This may indicate that they could enhance the toxicity of methotrexate. Caution should be used when NSAIDs are administered concomitantly with methotrexate.

The effects of warfarin and NSAIDs on GI bleeding are synergistic, such that users of both drugs together have a risk of serious GI bleeding higher than users of either drug alone.

Cardiovascular Effects

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 an NSAID, 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 events 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 NSAID use. The concurrent use of aspirin and an NSAID does increase the risk of serious GI events (see GI WARNINGS).

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).

Hypertension

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

Congestive Heart Failure and Edema

Fluid retention and edema have been observed in some patients taking NSAIDs. Flector® Patch should be used with caution in patients with fluid retention or heart failure.

Gastrointestinal Effects- Risk of Ulceration, Bleeding, and Perforation

NSAIDs, including Flector® Patch, can cause serious gastrointestinal (GI) adverse events including inflammation, 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 those 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 for GI bleeding in patients treated with NSAIDs include concomitant use of oral corticosteroids or anticoagulants, longer duration of NSAID 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 in patients treated with an NSAID, the lowest effective dose should be used for the shortest possible duration. Patients and physicians should remain alert for signs and symptoms of GI ulceration and bleeding during NSAID therapy and promptly initiate additional evaluation and treatment if a serious GI adverse event is suspected. This should include discontinuation of the NSAID until a serious GI adverse event is ruled out. For high risk patients, alternate therapies that do not involve NSAIDs should be considered.

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 a nonsteroidal antiinflammatory drug 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.

Advanced Renal Disease

No information is available from controlled clinical studies regarding the use of Flector® Patch in patients with advanced renal disease. Therefore, treatment with Flector® Patch is not recommended in these patients with advanced renal disease. If Flector® Patch 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 known prior exposure to Flector® Patch. Flector® Patch 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 and PRECAUTIONS - Preexisting Asthma). Emergency help should be sought in cases where an anaphylactoid reaction occurs.

Skin Reactions

NSAIDs, including Flector® Patch, 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 use of the drug should be discontinued at the first appearance of skin rash or any other sign of hypersensitivity.

Pregnancy

In late pregnancy, as with other NSAIDs, Flector® Patch should be avoided because it may cause premature closure of the ductus arteriosus.

General

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

The pharmacological activity of Flector® Patch in reducing inflammation may diminish the utility of these diagnostic signs in detecting complications of presumed noninfectious, painful conditions.

Hepatic Effects

Borderline elevations of one or more liver tests may occur in up to 15% of patients taking NSAIDs including Flector® Patch. These laboratory abnormalities may progress, may remain unchanged, or may be transient with continuing therapy. Notable elevations of ALT or AST (approximately three or more times the upper limit of normal) have been reported in approximately 1% of patients in clinical trials with NSAIDs. In addition, rare cases of severe hepatic reactions, including jaundice and fatal fulminant hepatitis, liver necrosis and hepatic failure, some of them with fatal outcomes have been reported.

A patient with symptoms and/or signs suggesting liver dysfunction, or in whom an abnormal liver test has occurred, should be evaluated for evidence of the development of a more severe hepatic reaction while on therapy with Flector® Patch. If clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g., eosinophilia, rash, etc.), Flector® Patch should be discontinued.

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 erythropoiesis. Patients on long-term treatment with NSAIDs, including Flector® Patch, should have their hemoglobin or hematocrit checked if they exhibit any signs or symptoms of anemia.

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 receiving Flector® Patch who may be adversely affected by alterations 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 nonsteroidal anti-inflammatory drugs has been reported in such aspirin-sensitive patients, Flector® Patch should not be administered to patients with this form of aspirin sensitivity and should be used with caution in patients with preexisting asthma.

Eye Exposure

Contact of Flector® Patch with eyes and mucosa, although not studied, should be avoided. If eye contact occurs, immediately wash out the eye with water or saline. Consult a physician if irritation persists for more than an hour.

Accidental Exposure in Children

Even a used Flector® Patch contains a large amount of diclofenac epolamine (as much as 170 mg). The potential therefore exists for a small child or pet to suffer serious adverse effects from chewing or ingesting a new or used Flector® Patch. It is important for patients to store and dispose of Flector® Patch out of the reach of children and pets.

Information for Patients

Patients should be informed of the following information before initiating therapy with an NSAID and periodically during the course of ongoing therapy. Patients should also be encouraged to read the NSAID Medication Guide that accompanies each prescription dispensed.

1. Flector® Patch, like other NSAIDs, may cause serious CV side effects, such as MI or stroke, which may result in hospitalization and even death. Although serious CV events can occur without warning symptoms, patients should be alert for the signs and symptoms of chest pain, shortness of breath, weakness, slurring of speech, and should ask for medical advice when observing any indicative sign or symptoms. Patients should be apprised of the importance of this follow-up (see WARNINGS, Cardiovascular Effects).
2. Flector® Patch, like other NSAIDs, may cause GI discomfort and, rarely, serious GI side effects, such as ulcers and bleeding, which may result in hospitalization and even death. Although serious GI tract ulcerations and bleeding can occur without warning symptoms, patients should be alert for the signs and symptoms of ulcerations and bleeding, and should ask for medical advice when observing any indicative sign or symptoms including epigastric pain, dyspepsia, melena, and hematemesis. Patients should be apprised of the importance of this follow-up (see WARNINGS, Gastrointestinal Effects: Risk of Ulceration, Bleeding, and Perforation).
3. Flector® Patch, like other NSAIDs, may cause serious skin side effects such as exfoliative dermatitis, SJS, and TEN, which may result in hospitalizations and even death. Although serious skin reactions may occur without warning, patients should be alert for the signs and symptoms of skin rash and blisters, fever, or other signs of hypersensitivity such as itching, and should ask for medical advice when observing any indicative signs or symptoms. Patients should be advised to stop the drug immediately if they develop any type of rash and contact their physicians as soon as possible.
4. Patients should be instructed to promptly report signs or symptoms of unexplained weight gain or edema to their physicians (see WARNINGS, Cardiovascular Effects).
5. Patients should be informed of the warning signs and symptoms of hepatotoxicity (e.g., nausea, fatigue, lethargy, pruritus, jaundice, right upper quadrant tenderness, and "flu-like" symptoms). If these occur, patients should be instructed to stop therapy and seek immediate medical therapy.
6. Patients should be informed of the signs of an anaphylactoid reaction (e.g. difficulty breathing, swelling of the face or throat). If these occur, patients should be instructed to seek immediate emergency help (see WARNINGS).
7. In late pregnancy, as with other NSAIDs, Flector® Patch should be avoided because it may cause premature closure of the ductus arteriosus.
8. Patients should be advised not to use Flector® Patch if they have an aspirin-sensitive asthma. Flector® Patch, like other NSAIDs, could cause severe and even fatal bronchospasm in these patients (see PRECAUTIONS, Preexisting asthma). Patients should discontinue use of Flector® Patch and should immediately seek emergency help if they experience wheezing or shortness of breath.
9. Patients should be informed that Flector® Patch should be used only on intact skin.
10. Patients should be advised to avoid contact of Flector® Patch with eyes and mucosa. Patients should be instructed 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.
11. Patients and caregivers should be instructed to wash their hands after applying, handling or removing the patch.
12. Patients should be informed that, if Flector® Patch begins to peel off, the edges of the patch may be taped down.
13. Patients should be instructed not to wear Flector® Patch during bathing or showering. Bathing should take place in between scheduled patch removal and application (see DOSAGE AND ADMINISTRATION).
14. Patients should be advised to store Flector® Patch and to discard used patches out of the reach of children and pets. If a child or pet accidentally ingests Flector® Patch, medical help should be sought immediately (see PRECAUTIONS, Accidental Exposure in Children).

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 their CBC and a chemistry profile checked periodically. If clinical signs and symptoms consistent with liver or renal disease develop, systemic manifestations occur (e.g., eosinophilia, rash, etc.) or if abnormal liver tests persist or worsen, Flector® Patch should be discontinued.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

Long-term studies in animals have not been performed to evaluate the carcinogenic potential of either diclofenac epolamine or Flector® Patch.

Mutagenesis

Diclofenac epolamine is not mutagenic in Salmonella Typhimurium strains, nor does it induce an increase in metabolic aberrations in cultured human lymphocytes, or the frequency of micronucleated cells in the bone marrow micronucleus test performed in rats.

Impairment of Fertility

Male and female Sprague Dawley rats were administered 1, 3, or 6 mg/kg/day diclofenac epolamine via oral gavage (males treated for 60 days prior to conception and during mating period, females treated for 14 days prior to mating through day 19 of gestation). Diclofenac epolamine treatment with 6 mg/kg/day resulted in increased early resorptions and postimplantation losses; however, no effects on the mating and fertility indices were found. The 6 mg/kg/day dose corresponds to 3-times the maximum recommended daily exposure in humans based on a body surface area comparison.

Pregnancy

Teratogenic Effects. Pregnancy Category C.

Pregnant Sprague Dawley rats were administered 1, 3, or 6 mg/kg diclofenac epolamine via oral gavage daily from gestation days 6-15. Maternal toxicity, embryotoxicity, and increased incidence of skeletal anomalies were noted with 6 mg/kg/day diclofenac epolamine, which corresponds to 3-times the maximum recommended daily exposure in humans based on a body surface area comparison. Pregnant New Zealand White rabbits were administered 1, 3, or 6 mg/kg diclofenac epolamine via oral gavage daily from gestation days 6-18. No maternal toxicity was noted; however, embryotoxicity was evident at 6 mg/kg/day group which corresponds to 6.5-times the maximum recommended daily exposure in humans based on a body surface area comparison.

There are no adequate and well-controlled studies in pregnant women. Flector® Patch should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nonteratogenic Effects

Because of the known effects of nonsteroidal anti-inflammatory drugs on the fetal cardiovascular system (closure of ductus arteriosus), use during pregnancy (particularly late pregnancy) should be avoided.

Male rats were orally administered diclofenac epolamine (1, 3, 6 mg/kg) for 60 days prior to mating and throughout the mating period, and females were given the same doses 14 days prior to mating and through mating, gestation, and lactation. Embryotoxicity was observed at 6 mg/kg diclofenac epolamine (3-times the maximum recommended daily exposure in humans based on a body surface area comparison), and was manifested as an increase in early resorptions, post-implantation losses, and a decrease in live fetuses. The number of live born and total born were also reduced as was F1 postnatal survival, but the physical and behavioral development of surviving F1 pups in all groups was the same as the deionized water control, nor was reproductive performance adversely affected despite a slight treatment-related reduction in body weight.

Labor and Delivery

In rat studies with NSAIDs, as with other drugs known to inhibit prostaglandin synthesis, an increased incidence of dystocia, delayed parturition, and decreased pup survival occurred. The effects of Flector® Patch on labor and delivery in pregnant women are unknown.

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human-milk and because of the potential for serious adverse reactions in nursing infants from Flector® Patch, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

Clinical studies of Flector® Patch did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.

Diclofenac, as with any NSAID, is known to be substantially excreted by the kidney, and the risk of toxic reactions to Flector® Patch 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 Flector® Patch in the elderly, and it may be useful to monitor renal function.

There is limited experience with overdose of Flector® Patch. In clinical studies, the maximum single dose administered was one Flector® Patch containing 180 mg of diclofenac epolamine. There were no serious adverse events.

Should systemic side effects occur due to incorrect use or accidental overdose of this product, the general measures recommended for intoxication with non-steroidal anti-inflammatory drugs should be taken.

Flector® Patch is contraindicated in patients with known hypersensitivity to diclofenac.

Flector® Patch should not be given to patients who have experienced asthma, urticaria, or 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 - Anaphylactoid Reactions, and PRECAUTIONS - Preexisting Asthma).

Flector® Patch is contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery (see WARNINGS).

Flector® Patch should not be applied to non-intact or damaged skin resulting from any etiology e.g. exudative dermatitis, eczema, infected lesion, burns or wounds.

Pharmacodynamics

Flector® Patch applied to intact skin provides local analgesia by releasing diclofenac epolamine from the patch into the skin. Diclofenac is a nonsteroidal anti-inflammatory drug (NSAID). In pharmacologic studies, diclofenac has shown anti-inflammatory, analgesic, and antipyretic activity. As with other NSAIDs, its mode of action is not known; its ability to inhibit prostaglandin synthesis, however, may be involved in its anti-inflammatory activity, as well as contribute to its efficacy in relieving pain associated with inflammation.

Pharmacokinetics

Absorption

Following a single application of the Flector® Patch on the upper inner arm, peak plasma concentrations of diclofenac (range 0.7 - 6 ng/mL) were noted between 10 - 20 hours of application. Plasma concentrations of diclofenac in the range of 1.3 - 8.8 ng/mL were noted after five days with twice-a-day Flector® Patch application.

Systemic exposure (AUC) and maximum plasma concentrations of diclofenac, after repeated dosing for four days with Flector® Patch, were lower ( < 1%) than after a single oral 50-mg diclofenac sodium tablet.

The pharmacokinetics of Flector® Patch has been tested in healthy volunteers at rest or undergoing moderate exercise (cycling 20 min/h for 12 h at a mean HR of 100.3 bpm). No clinically relevant differences in systemic absorption were observed, with peak plasma concentrations in the range of 2.2 - 8.1 ng/mL while resting, and 2.7 - 7.2 ng/mL during exercise.

Distribution

Diclofenac has a very high affinity ( > 99%) for human serum albumin.

Metabolism and Excretion

The plasma elimination half-life of diclofenac after application of Flector® Patch is approximately 12 hours. Diclofenac is eliminated through metabolism and subsequent urinary and biliary excretion of the glucuronide and the sulfate conjugates of the metabolites.

Clinical Studies

Efficacy of Flector® Patch was demonstrated in two of four studies of patients with minor sprains, strains, and contusions. Patients were randomly assigned to treatment with the Flector® Patch, or a placebo patch identical to the Flector® Patch minus the active ingredient. In the first of these two studies, patients with ankle sprains were treated once daily for a week. In the second study, patients with sprains, strains and contusions were treated twice daily for up to two weeks. Pain was assessed over the period of treatment. Patients treated with the Flector® Patch experienced a greater reduction in pain as compared to patients randomized to placebo patch as evidenced by the responder curves presented below.

Figure 1: Patients Achieving Various Levels of Pain Relief at Day 3; 14-Day Study

Figure 2: Patients Achieving Various Levels of Pain Relief at End of Study; 14-Day Study

Figure 3: Patients Achieving Various Levels of Pain Relief at Day 3; 7-Day Study

Figure 4: Patients Achieving Various Levels of Pain Relief at End of Study; 7-Day Study

Medication Guide for Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)

(See the end of this Medication Guide for a list of prescription NSAID medicines.)

What is the most important information I should know about medicines called Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)? NSAID medicines may increase the chance of a heart attack or stroke that can lead to death.

This chance increases:

• with longer use of NSAID medicines
• in people who have heart disease

NSAID medicines should never be used right before or after a heart surgery called a “coronary artery bypass graft” (CABG).

NSAID medicines can cause ulcers and bleeding in the stomach and intestines at any time during treatment. Ulcers and bleeding:

• can happen without warning symptoms
• may cause death

The chance of a person getting an ulcer or bleeding increases with:

• taking medicines called “corticosteroids” and “anticoagulants”
• longer use
• smoking
• drinking alcohol
• older age
• having poor health

NSAID medicines should only be used:

• exactly as prescribed
• at the lowest dose possible for your treatment
• for the shortest time needed

What are Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)?

NSAID medicines are used to treat pain and redness, swelling, and heat (inflammation) from medical conditions such as:

• different types of arthritis
• menstrual cramps and other types of short-term pain

Who should not take a Non-Steroidal Anti-Inflammatory Drug (NSAID)?

Do not take an NSAID medicine:

• if you had an asthma attack, hives, or other allergic reaction with aspirin or any other NSAID medicine
• for pain right before or after heart bypass surgery

Tell your healthcare provider:

• about all of your medical conditions.
• about all of the medicines you take. NSAIDs and some other medicines can interact with each other and cause serious side effects. Keep a list of your medicines to show to your healthcare provider and pharmacist.
• if you are pregnant. NSAID medicines should not be used by pregnant women late in their pregnancy.
• if you are breastfeeding. Talk to your doctor.

What are the possible side effects of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)?

Get emergency help right away if you have any of the following symptoms:

• shortness of breath or trouble breathing
• chest pain
• weakness in one part or side of your body
• slurred speech
• swelling of the face or throat

Stop your NSAID medicine and call your healthcare provider right away if you have any of the following symptoms:

• nausea
• more tired or weaker than usual
• itching
• your skin or eyes look yellow
• stomach pain
• flu-like symptoms
• vomit blood
• there is blood in your bowel movement or it is black and sticky like tar
• unusual weight gain
• skin rash or blisters with fever
• swelling of the arms and legs, hands and feet

These are not all the side effects with NSAID medicines. Talk to your healthcare provider or pharmacist for more information about NSAID medicines.

Other information about Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)

• Aspirin is an NSAID medicine but it does not increase the chance of a heart attack. Aspirin can cause bleeding in the brain, stomach, and intestines. Aspirin can also cause ulcers in the stomach and intestines.
• Some of these NSAID medicines are sold in lower doses without a prescription (over-the-counter). Talk to your healthcare provider before using over-the-counter NSAIDs for more than 10 days.

NSAID medicines that need a prescription

This Medication Guide has been approved by the U.S. Food and Drug Administration.

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

DICLOFENAC PATCH - TOPICAL

(dye-KLO-fen-ack)

COMMON BRAND NAME(S): Flector

WARNING: This drug may infrequently cause serious (rarely fatal) bleeding from the stomach or intestines. This side effect can occur without warning at any time during treatment with diclofenac. The elderly are at increased risk for serious stomach/intestinal bleeding.

Drugs related to diclofenac have rarely caused blood clots that result in serious (possibly fatal) heart attacks and strokes. This medication might also rarely cause similar problems. The risk of these serious side effects may increase if you have heart disease or if you use this medication for a longer time. Talk to your doctor or pharmacist about the benefits and risks of treatment, as well as other possible medication choices.

Stop using diclofenac and seek immediate medical attention if you notice any of the following rare but very serious side effects: black/bloody stools, persistent stomach/abdominal pain, vomit that looks like coffee grounds, chest pain, shortness of breath, weakness on one side of the body, sudden vision changes, slurred speech.

This medication should not be used right before or after heart bypass surgery.

USES: Diclofenac patches are used to relieve pain from various conditions (e.g., sprained ankle). This medication is known as a nonsteroidal anti-inflammatory drug (NSAID).

HOW TO USE: Read the Medication Guide provided by your pharmacist before you start using diclofenac and each time you get a refill. If you have any questions, consult your doctor or pharmacist.

The patch comes in a resealable envelope. When opening the envelope for the first time, cut it open as instructed. Remove a patch from the envelope and reseal the envelope. It is important to reseal the envelope after each opening, or the remaining patches will not stick correctly.

Before applying the patch, remove the clear liner. Apply the patch to the skin to cover the most painful area. Do not apply the patch on burns, cuts, or irritated skin (e.g., eczema). Change the patch usually every 12 hours or as directed by your doctor. Fold the used patch in half with the sticky sides together, and discard out of reach of children and pets.

If the patch begins to peel off, you may tape the edges to the skin.

Do not wear the patch during bathing or showering. Take baths/showers at times that you normally change the patch.

To avoid getting the medication in your eyes, nose, mouth, or vaginal area, wash your hands after handling the patch. If the medication or patch does come in contact with those areas, flush with plenty of water. Contact your doctor immediately if irritation persists.

Dosage is based on your medical condition and response to treatment. To reduce side effect risks (e.g., stomach bleeding), use this medication at the lowest effective dose for the shortest possible length of time. Do not increase your dose or use it more often than prescribed. Discuss the risks and benefits with your doctor or pharmacist.

If you are using this drug "as needed" (not on a regular schedule), remember that pain medications work best if they are used as the first signs of pain occur. If you wait until the pain has worsened, the medicine may not work as well.

Tell your doctor if your pain persists or worsens.

SIDE EFFECTS: See also Warning section.

Itching, burning, irritation, redness, or dry skin may occur at the application site. Nausea or change in taste may also occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these unlikely but serious side effects occur: stomach pain, swelling hands/feet, sudden/unexplained weight gain, vision changes, hearing changes (e.g., ringing in the ears), mental/mood changes (e.g., depression), fast/pounding heartbeat, persistent/severe headache, fainting.

Tell your doctor immediately if any of these rare but very serious side effects occur: change in the amount of urine, easy bruising/bleeding, signs of infection (e.g., fever, persistent sore throat), unexplained stiff neck, seizures.

This drug may rarely cause serious (possibly fatal) liver problems. Stop using diclofenac and tell your doctor immediately if you notice any of the following rare but serious side effects: yellowing eyes/skin, dark urine, unusual/extreme tiredness, severe stomach/abdomen pain, persistent nausea/vomiting.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before using diclofenac, tell your doctor or pharmacist if you are allergic to it; or to aspirin; or to other NSAIDs (e.g., ibuprofen, naproxen, celecoxib); or if you have any other allergies.

This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: aspirin-sensitive asthma (a history of worsening breathing with runny/stuffy nose after taking aspirin or other NSAIDs), recent heart bypass surgery (CABG).

Before using this medication, tell your doctor or pharmacist your medical history, especially of: stomach/intestine problems (e.g., bleeding, ulcers), kidney disease, liver disease, poorly controlled diabetes, heart disease (e.g., heart failure, history of heart attack), high blood pressure, stroke, swelling (edema, water retention), a severe loss of body water (dehydration), blood disorders (e.g., anemia, bleeding/clotting problems), asthma, growths in the nose (nasal polyps).

Before having surgery, tell your doctor or dentist that you are using this medication.

This medicine may cause stomach bleeding. Daily use of alcohol and tobacco may increase your risk for stomach bleeding, especially when combined with this medicine. Limit alcohol and stop smoking. Consult your doctor or pharmacist for more information.

This medication may make you more sensitive to the sun. Avoid prolonged sun exposure, tanning booths, and sunlamps. Use a sunscreen and wear protective clothing when outdoors.

Older adults may be more sensitive to the side effects of this drug, especially stomach/intestinal bleeding and kidney effects.

During the first 6 months of pregnancy, this medication should be used only when clearly needed. It is not recommended for use during the last 3 months of pregnancy due to possible harm to the unborn baby and interference with normal labor/delivery. Discuss the risks and benefits with your doctor.

Based on information from related drugs, this medication may pass into breast milk. While there have been no reports of harm to nursing infants, consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor or pharmacist first.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: anti-platelet drugs (e.g., clopidogrel), "blood thinners" (e.g., warfarin, heparin, enoxaparin), cidofovir, corticosteroids (e.g., prednisone), cyclosporine, desmopressin, digoxin, high blood pressure medications (e.g., ACE inhibitors such as lisinopril, beta blockers such as atenolol), lithium, methotrexate, pemetrexed, probenecid, SSRI antidepressants (e.g., fluoxetine, sertraline), tenofovir, "water pills" (diuretics such as hydrochlorothiazide, furosemide, triamterene).

Check all prescription and nonprescription medicine labels carefully for other pain/fever drugs (NSAIDs such as aspirin, celecoxib, ibuprofen). These drugs are similar to this medication, so taking one of these drugs while also taking this medication may increase your risk of side effects. However, if your doctor has prescribed low doses of aspirin to prevent heart attack or stroke (usually at dosages of 81-325 milligrams a day), you should continue to take the aspirin. Daily use of NSAIDs (e.g., ibuprofen) may decrease aspirin's ability to prevent heart attack/stroke. Consult your doctor or pharmacist for more details and to discuss other possible treatments (e.g., acetaminophen) for your pain/fever.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: This medication may be harmful if swallowed. If overdose or swallowing is suspected, contact your local poison control center or emergency room immediately. US residents can call the US National Poison Hotline at 1-800-222-1222.

NOTES: Do not share this medication with others.

Laboratory and/or medical tests (e.g., complete blood count, liver and kidney function tests) may be performed periodically to check for side effects. Consult your doctor for more details.

MISSED DOSE: If you are prescribed this drug on a regular schedule (not just "as needed") and you miss a dose, use it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store patches in the envelope at room temperature at 77 degrees F (25 degrees C). Brief storage between 59-86 degrees F (15-30 degrees C) is permitted. Always reseal envelope after opening. The patches expire 3 months after the envelope is first opened. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.