Diclona Lidocaine 4.5%, Diclofenac 1% .01 g/g; .045 g/g Gel, 99 g — NDC 68788-4013-9 (Billing 68788-4013-09)

WARNINGS Medicines intended to be applied to the skin should not be swallowed. Diclona™ is flammable . Keep away from open flame.

You should never heat, microwave, or add the medicine to hot water. Risk of Methemoglobinemia Cases of methemoglobinemia have been reported in association with lidocaine use. Although all patients are at risk for methemoglobinemia, patients with glucose-6-phosphate dehydrogenase deficiency, congenital or idiopathic methemoglobinemia, cardiac or pulmonary compromise, infants under 6 months of age, and concurrent exposure to oxidizing agents or their metabolites are more susceptible to developing the condition.

If lidocaine must be used in these patients, close monitoring for symptoms and signs of methemoglobinemia is recommended. Signs of methemoglobinemia may occur immediately or may be delayed some hours after exposure and are characterized by a cyanotic skin discoloration and/or abnormal coloration of the blood. Methemoglobin levels may continue to rise; therefore, immediate treatment is required to avert more serious central nervous system and cardiovascular adverse effects, including seizures, coma, arrhythmias, and death.

Risk of Serious Cardiovascular Events Cardiovascular Thrombotic Events Nonsteroidal anti-inflammatory drugs (NSAIDs) cause an increased risk of serious cardiovascular 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. Fetal Toxicity Avoid use of NSAIDs in pregnant women at about 30 weeks gestation and later.

NSAIDs increase the risk of premature closure of the fetal ductus arteriosus at approximately this gestational age. Use of NSAIDs at about 20 weeks gestation or later in pregnancy may cause fetal renal dysfunction leading to oligohydramnios and, in some case, neonatal renal impairment. If NSAID treatment is necessary between about 20 weeks and 30 weeks gestation, limit Diclona Gel use to the lowest effective dose and shortest duration possible.

Serious Skin Reactions Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) has been reported in patients taking NSAIDs such as Diclona Gel. DRESS typically, although not exclusively, presents with fever, rash, lymphadenopathy, and/or facial swelling. Heart Failure and Edema The Coxib and traditional NSAID Trialists’ Collaboration meta-analysis of randomized controlled trials demonstrated an approximately two-fold increase in hospitalizations for heart failure in COX-2 selective-treated patients and nonselective NSAID-treated patients compared to placebo-treated patients.

Avoid the use of Diclona Gel in patients with severe heart failure unless benefits are expected to outweigh the risk of worsening heart failure. If Diclona Gel is used in patients with severe heart failure, monitor patients for signs of worsening heart failure.

ADVERSE REACTIONS Application Site Reactions During or immediately after treatment with Diclona™, the skin at the site of application may develop blisters, bruising, burning sensation, depigmentation, dermatitis, discoloration, edema, erythema, exfoliation, irritation, papules, petechia, pruritus, vesicles, or may be the locus of abnormal sensation. These reactions are generally mild and transient, resolving spontaneously within a few minutes to hours. Other Adverse Events Due to the nature and limitation of spontaneous reports in post marketing surveillance, causality has not been established for additional reported adverse events including: Asthenia, confusion, disorientation, dizziness, headache, hyperesthesia, hypoesthesia, lightheadedness, metallic taste, nausea, nervousness, pain exacerbated, paresthesia, somnolence, taste alteration, vomiting, visual disturbances such as blurred vision, flushing, tinnitus, and tremor.

Systemic (Dose-Related) Reactions Systemic adverse reactions following appropriate use of Diclona™ are unlikely, due to the small dose absorbed (see CLINICAL PHARMACOLOGY, Pharmacokinetics). Systemic adverse effects of lidocaine is similar in nature to those observed with other amide local anesthetic agents, including CNS excitation and/or depression (light headedness, nervousness, apprehension, euphoria, confusion, dizziness, drowsiness, tinnitus, blurred or double vision, vomiting, sensations of heat, cold or numbness, twitching, tremors, convulsions, unconsciousness, respiratory depression and arrest).

Excitatory CNS reactions may be brief or not occur at all, in which case the first manifestation may be drowsiness merging into unconsciousness. Cardiovascular manifestations may include bradycardia, hypotension and cardiovascular collapse leading to arrest.

PRECAUTIONS General Diclona™ should be used with caution in patients with active gastrointestinal ulceration or bleeding and severe renal or hepatic impairments. Diclona Gel should not be applied to open skin wounds, infections, or exfoliative dermatitis. Hepatic Disease Patients with severe hepatic disease are at greater risk of developing toxic blood concentrations of lidocaine, because of their inability to metabolize lidocaine normally.

Allergic Reactions Patients allergic to para-aminobenzoic acid derivatives (procaine, tetracaine, benzocaine, etc.) have not shown cross sensitivity to lidocaine. However, Diclona Gel should be used with caution in patients with a history of drug sensitivities, especially if the etiologic agent is uncertain. Non-intact Skin Application to broken or inflamed skin, although not tested, may result in higher blood concentrations of lidocaine from increased absorption.

Diclona Gel is only recommended for use on intact skin. External Heat Sources Placement of external heat sources, such as heating pads or electric blankets, over Diclona Gel is not recommended as this has not been evaluated and may increase plasma lidocaine levels. Eye Exposure The contact of Diclona Gel with eyes, although not studied, should be avoided based on the findings of severe eye irritation with the use of similar products in animals.

If eye contact occurs, immediately wash out the eye with water or saline and protect the eye until sensation returns. Information for Patients Methemoglobinemia Inform patients that use of local anesthetics may cause methemoglobinemia, a serious condition that must be treated promptly. Advise patients or caregivers to stop use and seek immediate medical attention if they or someone in their care experience the following signs or symptoms: pale, gray, or blue colored skin (cyanosis); headache; rapid heart rate; shortness of breath; lightheadedness; or fatigue.

Drug Interactions Specific interaction studies between Diclona Gel and other topical or oral agents were not performed. Oral Nonsteroidal Anti-Inflammatory Drugs Although low, there is systemic exposure to diclofenac sodium following labeled use of Diclona Gel. Therefore, concomitant administration of Diclona Gel with oral NSAIDs or aspirin may result in increased NSAID adverse effects.

Antiarrhythmic Drugs Diclona Gel should be used with caution in patients receiving Class I antiarrhythmic drugs (such as tocainide and mexiletine) since the toxic effects are additive and potentially synergistic. Local Anesthetics When Diclona Gel is used concomitantly with other products containing local anesthetic agents, the amount absorbed from all formulations must be considered. Drugs That May Cause Methemoglobinemia When Used with Diclona Gel Patients who are administered local anesthetics are at increased risk of developing methemoglobinemia when concurrently exposed to the following drugs, which could include other local anesthetics: Examples of Drugs Associated with Methemoglobinemia: Class Examples Nitrates/Nitrites nitric oxide, nitroglycerin, nitroprusside, nitrous oxide Local anesthetics articaine, benzocaine, bupivacaine, lidocaine, mepivacaine, prilocaine, procaine, ropivacaine, tetracaine Antineoplastic agents cyclophosphamide, flutamide, hydroxyurea, ifosfamide, rasburicase, antibiotics dapsone, nitrofurantoin, para-aminosalicylic acid, sulfonamides, antimalarials chloroquine, primaquine anticonvulsants, phenobarbital, phenytoin, sodium valproate, opher drugs acetaminophen, metoclopramide, quinine, sulfasalazine carcinogenesis, mutagenesis.

Impairment of Fertility The effect of Diclona Gel on fertility has not been studied. Pregnancy Teratogenic Effects Pregnancy Category B. Diclona Gel has not been studied in pregnancy.

Labor and Delivery Diclona Gel has not been studied in labor and delivery. Nursing Mothers Diclona Gel has not been studied in nursing mothers. Pediatric Use Safety and effectiveness in pediatric patients have not been… [Excerpted — this section continues on DailyMed.]