FDA label fd0bc0ec-8a2e-4a4c-86fd-5d4f0a022c6d

WARNINGS DANGER-EXPLOSIVE HAZARD: This product could serve as an ignition source and should not be used in the presence of flammable anesthetics. Accidental Exposure in Children: Even a used LidoSite™ Patch contains a large amount of lidocaine (up to 100 mg). The potential exists for a small child to suffer serious adverse effects from chewing or ingesting a new or used LidoSite™ Patch. Children should be closely observed when treated with the LidoSite™ System, and LidoSite™ Patches should be stored and disposed of in the proper manner. Skin Reactions: Iontophoresis can cause skin irritation, burning sensation and/or burns. Patients should be warned of the possibilities and alerted to early signs such as itching or warmth. Patients should be instructed to notify appropriate personnel as soon as symptoms are detected. Longer than recommended durations of application, repeat applications or continued application after the occurrence of symptoms may increase the risk of local skin irritation or injury. Iontophoresis with the LidoSite™ Patch may cause transient, local blanching or erythema in the dermis under the patch. The redness under the elongated reservoir is normally uniform in color, while under the circular reservoir the color may be mottled. Sulfite Allergy: LidoSite™ Patch contains sodium metabisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms, and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown. Sulfite sensitivity is seen more frequently in asthmatic than in non-asthmatic people. Vasoconstriction Related to Epinephrine: Since the LidoSite™ Patch contains a vasoconstrictor, it should not be used on areas of the body supplied by end arteries or having otherwise compromised blood supply. Repeated applications should not be made to the same site. Patients with peripheral vascular disease and those with hypertensive vascular disease may exhibit an exaggerated vasoconstrictor response. LidoSite™ System should be used with caution in patients with severe coronary artery disease, hypertension or cardiac disrhythmias or in patients who are currently taking monoamine oxidase (MAO) inhibitors or tricyclic antidepressants.

ADVERSE REACTIONS Systemic (Dose Related) Reactions: Systemic adverse reactions following the iontophoresis of lidocaine and epinephrine using the LidoSite™ System according to the directions for use are unlikely due to the absorbed dose (See PHARMACOKINETICS section). Systemic adverse effects of lidocaine are similar in nature to those observed with other amide-type local anesthetics including either excitatory and/or depressant (lightheadedness, 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) CNS manifestations. Excitatory CNS reactions may be brief or may not occur at all, in which case the first manifestation may be drowsiness leading to unconsciousness. Cardiovascular manifestations are usually depressant and are characterized by bradycardia, hypotension, conduction abnormalities, dysrhythmias and/or cardiovascular collapse which may lead to cardiac arrest. Systemic adverse effects of epinephrine may include palpitations, tachycardia, hypertension, sweating, nausea and vomiting, respiratory difficulty, pallor, dizziness, weakness, tremor, headache, apprehension, nervousness and anxiety. Cardiac arrhythmias may follow the administration of epinephrine. Allergic: Allergic reactions, including anaphylactoid and anaphylactic, may occur as a result of sensitivity either to the local anesthetic agents or to the preservatives such as sodium metabisulfite. They may be characterized by cutaneous lesions, urticaria, angioedema, bronchospasm, tachycardia, hypotension or shock. Allergic reactions as a result of sensitivity to lidocaine are extremely rare and, if they occur, should be managed by conventional means. The detection of sensitivity by skin testing is of doubtful value. Most Common Adverse Events In placebo-controlled studies with LidoSite™ System, 4.5% of patients on placebo (N=333) and 4.5% of patients on LidoSite™ System (N=330) reported an adverse event. Because the placebo groups were not "no treatment" groups, but instead generally utilized an unaltered LidoSite™ Patch or an epinephrine only-containing patch with application of current, comparing the incidence of adverse events between the placebo and LidoSite™ System groups may not fully elucidate the incidence of adverse events that are attributable to iontophoresis, epinephrine or local irritation from patch application. In these studies, adverse events that occurred at a higher incidence in LidoSite™ System treated subjects compared to placebo treated subjects included subcutaneous hematoma (0.9% vs. 0.3%) and vasoconstriction (0.9% vs. 0.3%). In one study, the incidence of application site papules was reported to be as high as 12% and in another study the incidence of burns was reported to be as high as 8%. There were no serious adverse events attributed to LidoSite™ System treatment. In the overall safety database (812 patients administered LidoSite™ System) 0.8% of patients discontinued due to an adverse event. The most common reasons for discontinuation were: application site pain, N=4 (0.5%), application site burning, N=3 (0.4%), and pruritus, N=1 (0.1%). The most frequently observed adverse events from all studies are presented below: Summary of most frequently observed adverse events from all studies involving LidoSite™ System Adverse Event LidoSite™ System (N s =827, N t =925) N s =Number of Subjects, N t =Number of Treatments; % computed based on the number of treatments (N t ); In three Pharmacokinetic studies each subject received three treatments during the study. n (%) Placebo LidoSite™ System without lidocaine (N s =308, N t =308) n(%) LidoSite™ Patch without application of current (N s =25, N t =25) n(%) Pain/burning sensation with iontophoresis 22 (2.4) 18 (5.8) 0 Rash (includes macular & papular) 45 (4.9) 0 0 Burns 13 (1.4) 1 (0.3) 0 Subcutaneous hematoma 3 (0.3) 1 (0.3) 0 Marked vasoconstriction 3 (0.3) 2 (0.6) 0 Erythema 1 (0.1) 0 0 Urticaria 1 (0.1) 0 0

<table> <col/> <col/> <col/> <col/> <tbody> <tr> <td align="center" rowspan="2" styleCode=" Botrule Toprule Lrule Rrule "> <paragraph>Adverse Event</paragraph> </td> <td align="center" rowspan="2" styleCode=" Botrule Toprule Lrule Rrule "> <paragraph>LidoSite&#x2122; System (N_s=827, N_t=925)<footnote ID="FOOT_9984">N_s=Number of Subjects, N_t=Number of Treatments; % computed based on the number of treatments (N_t); In three Pharmacokinetic studies each subject received three treatments during the study.</footnote> n (%)</paragraph> </td> <td align="center" colspan="2" styleCode=" Botrule Toprule Lrule Rrule "> <paragraph>Placebo</paragraph> </td> </tr> <tr> <td align="center" styleCode=" Botrule Toprule Lrule Rrule ">LidoSite&#x2122; System without lidocaine (N_s =308, N_t=308)<footnoteRef IDREF="FOOT_9984"/> n(%)</td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule ">LidoSite&#x2122; Patch without application of current (N_s =25, N_t =25)<footnoteRef IDREF="FOOT_9984"/> n(%)</td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule ">Pain/burning sensation with iontophoresis</td> <td align="center" valign="top" styleCode=" Botrule Toprule Lrule Rrule ">22 (2.4)</td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> <paragraph>18 (5.8)</paragraph> </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule ">0</td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule ">Rash (includes macular &amp; papular)</td> <td align="center" valign="top" styleCode=" Botrule Toprule Lrule Rrule ">45 (4.9)</td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule ">0</td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule ">0</td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule ">Burns</td> <td align="center" valign="top" styleCode=" Botrule Toprule Lrule Rrule ">13 (1.4)</td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule "> <paragraph>1 (0.3)</paragraph> </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule ">0</td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule ">Subcutaneous hematoma</td> <td align="center" valign="top" styleCode=" Botrule Toprule Lrule Rrule "> <paragraph>3 (0.3) </paragraph> </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule ">1 (0.3)</td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule ">0</td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule ">Marked vasoconstriction</td> <td align="center" valign="top" styleCode=" Botrule Toprule Lrule Rrule "> <paragraph>3 (0.3)</paragraph> </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule ">2 (0.6)</td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule ">0</td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule ">Erythema</td> <td align="center" valign="top" styleCode=" Botrule Toprule Lrule Rrule "> <paragraph>1 (0.1) </paragraph> </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule ">0</td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule ">0</td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule ">Urticaria </td> <td align="center" valign="top" styleCode=" Botrule Toprule Lrule Rrule "> <paragraph>1 (0.1) </paragraph> </td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule ">0</td> <td align="center" styleCode=" Botrule Toprule Lrule Rrule ">0</td> </tr> </tbody> </table>