Xiclo

1. ​INDICATIONS & USAGE Xiclo™ Transdermal Patch is indicated in adults over the age of 12 years old for the treatment of signs and symptoms of osteoarthritis of the joints, and of acute and chronic pain in muscles and joints associated with muscle soreness, strains, sprains, arthritis, simple backache, muscle stiffness, and more.

2. DOSAGE & ADMINISTRATION 2.1 General Dosing Instructions Use Xiclo™ Transdermal Patch only on dry, intact (unbroken) skin. Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals. Avoid contact with eyes and mucous membranes. Avoid concomitant use of Xiclo™ Transdermal Patch on the treated skin site with other external products, including sunscreens, cosmetics, lotions, moisturizers, insect repellants, or other external medications. Do not use combination therapy with diclofenac and an oral NSAID unless the benefit outweighs the risk and conduct periodic assessments. 2.2 Dosing and Instructions for Use Tear open pouch bag and remove one patch. Place remaining patches back in pouch bag and seal pouch bag closed. Peel the clear plastic film away and apply Xiclo™ Transdermal Patch to intact skin to cover most painful area. Apply one patch per day for up to 12 hours within a 24-hout period (12 on, 12 off). One single Xiclo™ Transdermal Patch may be used twice per day. To re-use after the first application, place the clear plastic film back onto the medicated hydrogel pad.

5. WARNINGS, PRECAUTIONS & ADVERSE REACTIONS 5.1 Risk of Serious Cardiovascular and Gastrointestinal Events Nonsteroidal anti-inflammatory drugs (NSAIDs) can cause an increased risk of serious cardiovascular (CV) thrombotic events, including myocardial infarction and stroke, which can be fatal. This risk may occur early in treatment and may increase with duration of use. NSAIDs, including diclofenac, can lead to new onset of hypertension, or worsening of preexisting hypertension, either of which may contribute to the increased incidence of CV events. To minimize the potential risk for an adverse CV event in NSAID-treated patients, use the lowest effective dose for the shortest duration possible. Avoid the use of diclofenac external in patients with a recent MI unless the benefits are expected to outweigh the risk of recurrent CV thrombotic events. If diclofenac external is used in patients with a recent MI, monitor patients for signs of cardiac ischemia. Avoid using NSAIDs within 14 days following coronary artery bypass graft (CABG) surgery. 5.2 Gastrointestinal Bleeding, Ulceration, and Perforation Nonsteroidal anti-inflammatory drugs (NSAIDs) can cause an increased risk of serious gastrointestinal (GI) adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Other factors that increase the risk of GI bleeding in patients treated with NSAIDs include concomitant use of oral corticosteroids, aspirin, anticoagulants, or selective serotonin reuptake inhibitors (SSRIs). Elderly patients and patients with a prior history of peptic ulcer disease and/or GI bleeding are at greater risk for serious GI events. Additionally, patients with advanced liver disease and/or coagulopathy are at increased risk for GI bleeding. 5.3 Hepatotoxicity 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. Monitor for 4 to 8 weeks after initiating treatment with diclofenac. However, severe hepatic reactions can occur at any time during treatment with diclofenac. 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). To minimize potential risk for an adverse liver-related event in patients treated with diclofenac external, exercise caution when prescribing diclofenac external with concomitant drugs that are known to be potentially hepatotoxic (e.g., acetaminophen, antibiotics, antiepileptics). 5.4 Renal Toxicity and Hyperkalemia Renal Toxicity 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, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors or ARBs, and the elderly. Discontinuation of NSAID therapy was usually followed by recovery to the pretreatment state. Avoid the use of diclofenac external in patients with advanced renal disease unless the benefits are expected to outweigh the risk of worsening renal function. If diclofenac is used in patients with advanced renal dise…

4. CONTRAINDICATIONS Xiclo™ Transdermal Patch is contraindicated in patients with a known history of hypersensitivity to non-steroidal anti-inflammatory medications such as diclofenac. Diclofenac is contraindicated in the setting of coronary artery bypass graft (CABG) surgery. History of asthma, uticaria, or allergic-type reactions after absorbing non-steroidal anti-inflammatory drugs (NSAIDs) should also be considered.

6. DRUG INTERACTIONS Drugs That Interfere with Hemostasis Monitor patients with concomitant use of diclofenac external with anticoagulants (e.g., warfarin), antiplatelet agents (e.g., aspirin), selective serotonin reuptake inhibitors (SSRIs), and serotonin norepinephrine reuptake inhibitors (SNRIs) for signs of bleeding. Aspirin Concomitant use of diclofenac external and analgesic doses of aspirin is not generally recommended because of the increased risk of bleeding. ACE Inhibitors, Angiotensin Receptor Blockers, and Beta-Blockers When these drugs are administered concomitantly, patients should be adequately hydrated. Assess renal function at the beginning of the concomitant treatment. Diuretics During concomitant use of diclofenac external with diuretics, observe patients for signs of worsening renal function, in addition to assuring diuretic efficacy including antihypertensive effects. Digoxin During concomitant use of diclofenac external and digoxin, monitor serum digoxin levels. Lithium During concomitant use of diclofenac external and lithium, monitor patients for signs of lithium toxicity. Methotrexate During concomitant use of diclofenac external and methotrexate, monitor patients for methotrexate toxicity. Cyclosporine During concomitant use of diclofenac external and cyclosporine, monitor patients for signs of worsening renal function. Pemetrexed Concomitant use of diclofenac external and pemetrexed may increase the risk of pemetrexed-associated myelosuppression, renal, and GI toxicity.