DailyMed Label: Flector

DailyMed Label: Flector

2010

DailyMed Prescription

Flector

Diclofenac Epolamine

Physicians Total Care, Inc.

NDC: 54868-5962

NDC: 54868-5962

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 C 20 H 24 C l2 N 2 O 3 (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. image of chemical structure

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.

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.

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. 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 ). 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 ). 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. Patients should be instructed to promptly report signs or symptoms of unexplained weight gain or edema to their physicians (see WARNINGS, Cardiovascular Effects ). 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. 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 ). In late pregnancy, as with other NSAIDs, Flector® Patch should be avoided because it may cause premature closure of the ductus arteriosus. Patients should be advised not to use Flector® Patch if they have a 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. Patients should be informed that Flector® Patch should be used only on intact skin. 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. Patients and caregivers should be instructed to wash their hands after applying, handling or removing the patch. Patients should be informed that, if Flector® Patch begins to peel off, the edges of the patch may be taped down. 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 ). 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. Drug Interactions 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. Diuretics 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. Lithium 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. Methotrexate 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. Warfarin 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. 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 vial 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.

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.

The Flector® Patch is supplied in resealable envelopes, each containing 5 patches (10 cm x 14 cm), with 6 envelopes per box ( NDC 54868-5962-0 ).  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 25ºC (77ºF); excursions permitted to 15º-30ºC (59º-86ºF).  [See USP Controlled Room Temperature]. Manufacturer :  Teikoku Seiyaku Co., Ltd., Sanbonmatsu, Kagawa 769-2695, Japan Distributor : Alpharma Pharmaceuticals LLC, One New England Avenue, Piscataway, NJ 08854 (Telephone: 1-877-452-3426) Version June 2008 8283 Ed II/06.08 Relabeling of "Additional Barcode" by Physicians Total Care, Inc. Tulsa, OK      74146

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 (less than 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/m while resting, and 2.7 – 7.2 ng/mL during exercise. Distribution Diclofenac has a very high affinity (greater than 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.

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. image of figure 1 image of figure 2 image of figure 3 image of figure 4

Flector® Patch (diclofenac epolamine topical patch) 1.3% image of package label