Flector Information
Flector (Diclofenac)
Flector (Diclofenac) Cardiovascular Risk
Flector (Diclofenac) Description
Flector (Diclofenac) ® 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 CHCNO (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.
Flector (Diclofenac) Clinical Pharmacology
Following a single application of the Flector (Diclofenac) 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 (Diclofenac) Patch application.
Systemic exposure (AUC) and maximum plasma concentrations of diclofenac, after repeated dosing for four days with Flector (Diclofenac) ® Patch, were lower (
The pharmacokinetics of Flector (Diclofenac) ® 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.
Diclofenac has a very high affinity (>99%) for human serum albumin.
The plasma elimination half-life of diclofenac after application of Flector (Diclofenac) 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.
Flector (Diclofenac) Indications And Usage
Carefully consider the potential benefits and risks of Flector (Diclofenac) ® Patch and other treatment options before deciding to use Flector (Diclofenac) ® Patch. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see).
Flector (Diclofenac) ® Patch is indicated for the topical treatment of acute pain due to minor strains, sprains, and contusions.
Flector (Diclofenac) Contraindications
Flector (Diclofenac) ® Patch is contraindicated in patients with known hypersensitivity to diclofenac.
Flector (Diclofenac) ® 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, and).
Flector (Diclofenac) ® Patch is contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery (see).
Flector (Diclofenac) ® 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.
Flector (Diclofenac) Warnings
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).
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).
NSAIDs, including Flector (Diclofenac) ® 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 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.
Flector (Diclofenac) Precautions
Flector (Diclofenac) ® 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 (Diclofenac) ® Patch in reducing inflammation may diminish the utility of these diagnostic signs in detecting complications of presumed noninfectious, painful conditions.
Borderline elevations of one or more liver tests may occur in up to 15% of patients taking NSAIDs including Flector (Diclofenac) ® 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 (Diclofenac) ® Patch. If clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g., eosinophilia, rash, etc.), Flector (Diclofenac) ® Patch should be discontinued.
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 (Diclofenac) ® 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 (Diclofenac) ® 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.
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.
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.
When Flector (Diclofenac) ® 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 (Diclofenac) ® 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), 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.
Long-term studies in animals have not been performed to evaluate the carcinogenic potential of either diclofenac epolamine or Flector (Diclofenac) Patch.
Diclofenac epolamine is not mutagenic in 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.
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.
Clinical studies of Flector (Diclofenac) ® 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 (Diclofenac) ® 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 (Diclofenac) ® Patch in the elderly, and it may be useful to monitor renal function.
Flector (Diclofenac) Adverse Reactions
In controlled trials during the premarketing development of Flector (Diclofenac) ® Patch, approximately 600 patients with minor sprains, strains, and contusions have been treated with Flector (Diclofenac) ® Patch for up to two weeks.
Localized Reactions
Overall, the most common adverse events associated with Flector (Diclofenac) ® 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 (Diclofenac) ® Patch. A majority of patients treated with Flector (Diclofenac) ® Patch had adverse events with a maximum intensity of “mild” or “moderate.”
Foreign labeling describes that dermal allergic reactions may occur with Flector (Diclofenac) ® Patch treatment. Additionally, the treated area may become irritated or develop itching, erythema, edema, vesicles, or abnormal sensation.
Flector (Diclofenac) Overdosage
There is limited experience with overdose of Flector (Diclofenac) ® Patch. In clinical studies, the maximum single dose administered was one Flector (Diclofenac) ® 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 (Diclofenac) Dosage And Administration
Carefully consider the potential benefits and risks of Flector (Diclofenac) ® Patch and other treatment options before deciding to use Flector (Diclofenac) ® Patch. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see).
The recommended dose of Flector (Diclofenac) ® Patch is one (1) patch to the most painful area twice a day.
Flector (Diclofenac) ® patch should not be applied to damaged or non-intact skin.
Flector (Diclofenac) ® patch should not be worn when bathing or showering.
Flector (Diclofenac) How Supplied
The Flector (Diclofenac) ® Patch is supplied in resealable envelopes, containing 1 patch (10 cm x 14 cm) (NDC 21695-707-01). It is also supplied in boxes of 30 patches (NDC 21695-707-30). Each individual patch is embossed with “Diclofenac Epolamine Patch 1.3%”.
Manufacturer: Teikoku Seiyaku Co., Ltd., Sanbonmatsu, Kagawa 769-2695, JapanDistributor: Alpharma Pharmaceuticals LLC, One New England Avenue, Piscataway, NJ 08854 (Telephone: 1-877-452-3426)
Repackaged by: Rebel Distributors Corp, Thousand Oaks, CA 91320
Flector (Diclofenac) Principal Display Panel
