BONDLIDO

1 INDICATIONS AND USAGE BONDLIDO (lidocaine topical system 10%) is indicated in adults for relief of pain associated with post-herpetic neuralgia (PHN). BONDLIDO contains lidocaine, an amide local anesthetic, and is indicated in adults for relief of pain associated with post-herpetic neuralgia (PHN) ( 1 ).

2 DOSAGE AND ADMINISTRATION Due to differences in bioavailability, the efficacy of a lidocaine topical system does not necessarily correlate with dosage strength. Refer to the dosing instructions for the specific product being used ( 2 ). Apply BONDLIDO to intact skin to cover the most painful area. Apply the prescribed number of topical systems (maximum of two) only once for up to 12 hours in a 24-hour period (2) . Apply firm pressure for 20 seconds to ensure adequate adherence. 2.1 Important Dosage and Administration Information Due to differences in bioavailability, the efficacy of a lidocaine topical system does not necessarily correlate with dosage strength (i.e., concentration). Comparing different products on a nominal percentage-for-percentage basis may be misleading and the appropriate strength for a given indication may vary by product. Refer to the dosing instructions for the specific product being used. [see Clinical Pharmacology (12.3) ] . When BONDLIDO is used concomitantly with other products containing local anesthetic agents, the total amount of drug absorbed from all formulations must be considered. 2.2 Application Instructions Clearly instruct and advise patients: to apply BONDLIDO to intact skin to cover the most painful area. Apply the prescribed number of topical systems (maximum of 2), only once for up to 12 hours within a 24-hour period. Safety has not been established for application of more than 2 BONDLIDO topical systems per day. to apply firm pressure for 20 seconds to ensure an adequate adherence. that clothing may be worn over the area of application. to remove BONDLIDO if irritation or a burning sensation occurs during application. Advise patients not to reapply until the irritation subsides. to wash hands immediately after handling BONDLIDO and to avoid contact with eyes [see Warnings and Precautions (5.5) , Patient Counseling Information (17) ]. to not store BONDLIDO outside of the sealed pouch. to apply immediately after removal from the protective pouch. to fold used BONDLIDO so that the adhesive side sticks to itself. to safely discard used BONDLIDO where children and pets cannot get to them. to never apply external heat sources, such as heating pads or electric blankets, directly to BONDLIDO because plasma lidocaine levels may be increased [see Warnings and Precautions (5.2) , Patient Counseling Information (17) ]. that BONDLIDO may not stick if it gets wet and to avoid contact with water, such as bathing, swimming, or showering, while a BONDLIDO topical system is applied. If the BONDLIDO topical system comes off completely and will not stick to the skin, advise patients that they may apply a replacement BONDLIDO topical system and take the replacement BONDLIDO topical system off at the usual removal time. Advise patients not to wear BONDLIDO for more than 12 hours within a 24-hour period.

4 CONTRAINDICATIONS BONDLIDO is contraindicated in patients with a known history of sensitivity to local anesthetics of the amide type, or to any other component of the product. BONDLIDO is contraindicated in patients with a known history of sensitivity to local anesthetics of the amide type, or to any other component of the product ( 4 ).

5 WARNINGS AND PRECAUTIONS Accidental Exposure : A used BONDLIDO topical system contains residual lidocaine after use. It is important for patients to store and dispose of BONDLIDO out of the reach of children, pets, and others (5.1). Excessive Dosing : Applying BONDLIDO to larger surface areas or for a longer duration than recommended could result in increased absorption and high blood concentrations of lidocaine, leading to serious adverse effects ( 5.2 ). Non-Intact Skin : May result in higher blood concentrations of lidocaine from increased absorption ( 5.2 ). External Heat Sources : External heat sources may increase drug exposure, leading to overexposure of lidocaine ( 5.2 ). Methemoglobinemia : Cases of methemoglobinemia have been reported in association with local anesthetic use ( 5.3 ). Application Site Reactions : Severe skin irritation may occur with BONDLIDO if applied for a longer period than instructed ( 5.4 ). Hypersensitivity Reactions : Patients with an allergy to PABA derivatives may have cross-sensitivity to BONDLIDO( 5.5 ). Eye Exposure : If eye contact occurs, immediately wash out the eye with water or saline and protect the eye using, for example, eyeglasses/eye wear, until sensation returns ( 5.6 ). 5.1 Accidental Exposure A used BONDLIDO topical system contains residual lidocaine after use. The potential exists for a small child or a pet to suffer serious adverse effects from chewing or ingesting new or used BONDLIDO. It is important for patients to store and dispose of BONDLIDO properly, and keep out of the reach of children, pets, and others [see Dosage and Administration (2) ] . 5.2 Excessive Dosing Lidocaine toxicity could be expected at lidocaine blood concentrations above 5 µg/mL. The blood concentration of lidocaine is determined by the rate of systemic absorption and elimination. Longer duration of application, application of more than the recommended number of BONDLIDO, smaller patients, or impaired elimination may all contribute to increasing the blood concentration of lidocaine. If lidocaine overdose is suspected, check drug blood concentration. Management of overdose includes close monitoring, supportive care, and symptomatic treatment [see Overdosage (10) ]. Improper Application and Duration of Use : Application of more than the recommended number of BONDLIDO or applying BONDLIDO for longer than the recommended wearing time (12 hours of every 24 hours) could result in increased absorption and high blood concentrations of lidocaine, leading to adverse effects. Advise patients on proper application and duration [see Patient Counseling Information (17) ] . Hepatic Disease : Impaired elimination may contribute to increasing blood concentrations of lidocaine. Patients with severe hepatic disease are at greater risk of developing toxic blood concentrations of lidocaine because of their inability to metabolize lidocaine normally. Non-Intact Skin : Application to broken or inflamed skin, although not tested, may result in higher blood concentrations of lidocaine from increased absorption. BONDLIDO is only recommended for use on intact skin. Advise patients not to apply BONDLIDO to non-intact skin [see Patient Counseling Information (17) ] . External Heat Sources : External heat sources may increase drug exposure, leading to overexposure to lidocaine. Advise patients not to apply external heat sources to BONDLIDO during administration [see Patient Counseling Information (17) ]. 5.3 Methemoglobinemia Cases of methemoglobinemia have been reported in association with local anesthetic 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 clinical manifestations of the condition. If local anesthetics 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. Discontinue BONDLIDO and any other oxidizing agents. Depending on the severity of the signs and symptoms, patients may respond to supportive care, i.e., oxygen therapy, hydration. A more severe clinical presentation may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. 5.4 Application Site Reactions During or immediately after treatment with BONDLIDO, 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. If application site reactions occur while the topical system is being worn, advise the patient to remove BONDLIDO and not to reapply until skin reactions subside. 5.5 Hypersensitivity Reactions Patients allergic to para-aminobenzoic acid (PABA) derivatives (procaine, tetracaine, benzocaine, etc.) have not shown cross-sensitivity to lidocaine. However, be aware of the potential for cross-sensitivity in patients allergic to PABA derivatives, especially if the etiologic agent is uncertain. Manage hypersensitivity reactions by conventional means. The detection of sensitivity by skin testing is of doubtful value. 5.6 Eye Exposure The contact of BONDLIDO with eyes, although not studied, should be avoided based on findings of severe eye irritation with the application of similar products in animals. If eye contact occurs, immediately wash out the eye with water or saline and protect the eye using, for example, eye glasses/eye wear, until sensation returns.

7 DRUG INTERACTIONS Antiarrhythmic Drugs: When BONDLIDO is used in patients receiving Class I antiarrhythmic drugs (such as tocainide or mexiletine), the toxic effects are additive and potentially synergistic. Consider risk/benefit during concomitant use ( 7.1 ). Local Anesthetics: When BONDLIDO is used concomitantly with other products containing local anesthetic agents, the effects are additive. The amount absorbed from all formulations must be considered for safe use ( 7.2 ). 7.1 Antiarrhythmic Drugs When BONDLIDO is used in patients receiving Class I antiarrhythmic drugs (such as tocainide or mexiletine), the toxic effects are additive and potentially synergistic. Consider risk/benefit during concomitant use. 7.2 Local Anesthetics When BONDLIDO is used concomitantly with other products containing local anesthetic agents, the effects are additive. The amount absorbed from all formulations must be considered for safe use. 7.3 Drugs That May Cause Methemoglobinemia When Used with BONDLIDO 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 Other drugs acetaminophen, metoclopramide, quinine, sulfasalazine

6 ADVERSE REACTIONS The following serious adverse reactions are described elsewhere in the labeling: Accidental Exposure [see Warnings and Precautions (5.1) ] Excessive Dosing/Overexposure to Lidocaine [see Warnings and Precautions (5.2) ] Methemoglobinemia [see Warnings and Precautions (5.3) ] Application Site Reactions [see Warnings and Precautions (5.4) ] Hypersensitivity Reactions [see Warnings and Precautions (5.5) ] Eye Irritation [see Warnings and Precautions (5.6) ] The following adverse reactions associated with the use of lidocaine were identified in clinical trials or postmarketing reports for lidocaine. Because some of these reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Skin and subcutaneous tissues : blisters, bruising, burning sensation, depigmentation, dermatitis, discoloration, edema, erosions, erythema, exfoliation, flushing, irritation, papules, petechia, pruritus, vesicles, and abnormal sensation. Immune system : angioedema, bronchospasm, dermatitis, dyspnea, hypersensitivity, laryngospasm, pruritus, shock, and urticaria. Central Nervous System : lightheadedness, nervousness, apprehension, euphoria, confusion, dizziness, drowsiness, tinnitus, blurred or double vision, sensations of heat, cold or numbness, twitching, tremors, convulsions, unconsciousness, somnolence, respiratory depression and arrest. Cardiovascular : bradycardia, hypotension, and cardiovascular collapse leading to arrest. Other : asthenia, disorientation, headache, hyperesthesia, hypoesthesia, metallic taste, nausea, pain exacerbated, paresthesia, taste alteration, and vomiting. Common adverse reactions are application site reactions such as irritation, erythema, and pruritus ( 6 ). To report SUSPECTED ADVERSE REACTIONS, contact MEDRx USA, Inc. at TELEPHONE or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

8.1 Pregnancy Risk Summary The limited human data with lidocaine in pregnant woman are not sufficient to inform drug-associated risk for major birth defects and miscarriage. The use of lidocaine for labor neuraxial analgesia has not been associated with an increased incidence of adverse fetal effects either during delivery or during the neonatal period [see Data ]. Should BONDLIDO be used concomitantly with other products containing lidocaine, consider total drug doses contributed by all formulations. In a published animal reproduction study, pregnant rats administered lidocaine by continuous subcutaneous infusion at a dose approximately 12 times the maximum recommended daily dose (MRDD) of 400 mg in BONDLIDO during the period of organogenesis resulted in lower fetal body weights. In a published animal reproduction study, pregnant rats administered lidocaine, containing 1:100,000 epinephrine, injected into the masseter muscle of the jaw or into the gum of the lower jaw at approximately 0.14 times the MRDD on Gestation Day 11 resulted in developmental delays in neonates [see Data ]. The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies carry some risk of birth defects, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Human Data In 22 parturient women given 1.5% lidocaine epidural anesthesia, there were no effects on neonatal behavior, using the early neonatal neurobehavioral scale (ENNS). Neuraxial analgesia also did not affect fetal heart rate, beat-to-beat variability, or uterine activity. Animal Data Reproductive studies with lidocaine have been performed in rats at doses up to 30 mg/kg (0.73 times the maximum recommended daily dose [MRDD] of 400 mg from BONDLIDO on a mg/m 2 basis) subcutaneously and have revealed no evidence of harm to the fetus due to lidocaine. In a published study, lidocaine administered to pregnant rats by continuous subcutaneous infusion during the period of organogenesis at 100, 250, and 500 mg/kg/day, did not produce any structural abnormalities, but did result in lower fetal weights at 500 mg/kg/day dose (approximately 12 times the MRDD on a mg/m 2 basis) in the absence of maternal toxicity. In a published study, lidocaine containing 1:100,000 epinephrine at a dose of 6 mg/kg (approximately 0.14 times the MRDD on a mg/m 2 basis) injected into the masseter muscle of the jaw or into the gum of the lower jaw of pregnant Long-Evans hooded rats on Gestation Day 11 resulted in developmental delays in the neonates. Developmental delays were observed for negative geotaxis, static righting reflex, visual discrimination response, sensitivity and response to thermal and electrical shock stimuli, and water maze acquisition. The developmental delays of the neonatal animals were transient, with responses becoming comparable to untreated animals later in life. The clinical relevance of these animal data is uncertain.