LidoSite™ Topical System
comprised of the
LidoSite™ Patch
(Lidocaine HCl / Epinephrine topical iontophoretic patch) 10%/0.1%
and the
LidoSite™ Controller

Local Anesthetic for Topical Use

Rx only

CAUTION: Contains sodium metabisulfite (See WARNINGS Section)

The LidoSite™ Topical System (LidoSite™ System) consists of a LidoSite™ Patch and a LidoSite™ Controller, a portable microprocessor-controlled battery-powered DC current source. The LidoSite™ System delivers lidocaine and epinephrine simultaneously by topical iontophoresis to achieve dermal analgesia on intact skin.

Iontophoresis is based on the principle that a soluble salt or drug can be transported across the skin barrier as a part of an electric current induced in the skin. The quantity and distribution of delivered drug(s) is dependent on the ion charge, molecular weight, intensity of the electric current, concentration of the drug(s), contact surface area of the delivery electrode, and duration of current. In most iontophoretic systems, iontophoresis is measured as total charge delivered in milliampere-minutes (mA-min) units. At the patch electrode pH (4.5), lidocaine HCl and epinephrine are both positively charged.

The LidoSite™ Controller is designed with a non-replaceable battery that provides up to 99 drug applications at 1.77 mA for 10 minutes (17.7 mA-min). Refer to the “LidoSite™ Topical System Instructions” for proper system operation.

The LidoSite™ Patch is for single use only and is disposable. The patch contains a 5-cm² circular drug reservoir that delivers lidocaine and epinephrine to the skin and an elongated return reservoir containing electrolytes to complete the electrical circuit.

The drug reservoir contains 100-mg lidocaine HCl, 1.05 mg of epinephrine (equivalent to 1.91 mg of epinephrine bitartrate) and excipients consisting of sodium chloride, glycerin, preservatives (2-phenoxyethanol, methyl-, ethyl-, propyl-, butyl-, and isobutyl-p-hydroxybenzoate), citric acid as a buffer and chelator, edetate disodium as a chelator, and sodium metabisulfite as an antioxidant, in a non-sterile hydrogel. The elongated return reservoir contains glycerin, sodium chloride, preservatives (2-phenoxyethanol, methyl-, ethyl-, propyl-, butyl-, and isobutyl-p-hydroxybenzoate), and monobasic sodium phosphate as an acidulating agent. The drug and return reservoirs are made from a polyvinylpyrrolidone (PVP) hydrogel.

Lidocaine is a local anesthetic of the amide type. Lidocaine hydrochloride is chemically designated as:

•  2-(Diethylamino)-2′, 6′-acetoxylidide mono-hydrochloride, monohydrate, is a white crystalline powder freely soluble in water, with a molecular weight of 288.81. Its molecular formula is C₁₄H₂₂N₂O•HCl and its structural formula is:

Epinephrine is a sympathomimetic (adrenergic) agent. Epinephrine bitartrate is designated chemically as:

•  1,2 Benzenediol, 4-[1-hydroxy-2-(methylamino)ethyl]-,(R)-, [R-(R*,R*)]-2,3-dihydroxybutanedioate (1:1) (salt) is a white, crystalline powder with a molecular weight of 333.29. Its molecular formula is C₉H₁₃NO₃•C₄H₆O₆ and its structural formula is:

In one randomized, double-blind, placebo-controlled, parallel-group, single-center study, 48 adult subjects were evaluated for the degree of dermal analgesia upon venipuncture or IV cannulation, typically within 10 minutes following treatment with LidoSite™ System or placebo (LidoSite™ Patch, no current) treatment. Less pain was reported following LidoSite™ System treatment compared to placebo at both sites, the antecubital fossa and the dorsum of the hand, as measured by a 10-cm visual analog scale (VAS). All subjects received treatment on each of their antecubital fossae prior to venipuncture, and on the dorsum of each hand prior to cannulation. Three of the treatments were with LidoSite™ System and one was with placebo. VAS scores for active and placebo treatments were 0.7 and 3.2, respectively, at the antecubital fossa, and 1.6 and 4.0, respectively, on the dorsum of the hand.

In a randomized, double-blind, placebo-controlled, single-center study, 48 pediatric patients were stratified by age group (5 to 7 years, 8 to 11 years, and 12 to 18 years) to compare the efficacy of LidoSite™ System with placebo (LidoSite™ Patch, no current) in the reduction of pain associated with venipuncture in the antecubital fossa.

Venipuncture occurred within 10 minutes of patch removal. Based on the Nine Face Integrated Scale (NFIS) scores (“A through I” scale, with an “A” face indicating a laughing child and an “I” face indicating a child crying vigorously), patients treated with LidoSite™ System experienced less pain during venipuncture than subjects treated with the placebo patch. The mean NFIS scores, calculated by equating “A” through “I” with “1” through “9,” respectively, for all age groups were 2.8 and 4.3 for LidoSite™ System and placebo, respectively.

Two prospective, randomized, double-blind, placebo-controlled (a patch with only epinephrine and with current applied) trials were conducted to assess the analgesia provided within 10 minutes following treatment during venipuncture or intravenous cannulation. The first trial used a 10-cm Visual Analog Scale (VAS) score to assess pain experienced by 270 subjects ≥ 18 years of age. The mean (SD) VAS score was significantly lower in the LidoSite™ System group, 0.8 (1.5) compared to the placebo group, 2.5 (2.3). The second trial utilized the NFIS to evaluate the pain experienced by 256 pediatric subjects ages 5 to 17 years. The median NFIS scores for all subjects in the LidoSite™ System and placebo treatment groups were C and E, respectively.

Pain reported during laser removal of superficial skin lesions such as port wine stain, telangiectasia, lipoma, keloid scar, or tattoo was evaluated in one controlled study with the LidoSite™ System. Sixty-six subjects (ages 9 to 79 years) were randomized to LidoSite™ System or placebo, (LidoSite™ System, a patch with only epinephrine and with current applied) prior to laser treatment. The dermatological procedures were performed within 20 minutes following treatment. At the end of the procedure, subjects rated their pain using the Ordered Category Anesthesia Scale (OCAS) (with 0 indicating no sensation and 6 indicating intolerable pain). In the LidoSite™ System group, 91% of subjects reported no pain or mild discomfort (OCAS scores of 0 to 3) compared to 53% of subjects in the placebo group. Among LidoSite™ System subjects, 4% of adults and 14% of children required supplemental anesthetic during the procedure compared to 21% of adults and 33% of children who received placebo treatments.

LidoSite™ System is a topical local anesthetic delivery system indicated for use on normal intact skin to provide local analgesia for superficial dermatological procedures such as venipuncture, intravenous cannulation, and laser ablation of superficial skin lesions.

LidoSite™ System is indicated for use on patients 5 years of age and older.

LidoSite™ System is contraindicated in patients with a known history of hypersensitivity to local anesthetics of the amide type, sulfites, or to any other component of the product (See also WARNINGS and PRECAUTIONS sections).

LidoSite™ System is contraindicated for use in patients with electrically-sensitive devices (e.g., pacemakers).

Rx Only

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:

Acute emergencies from local anesthetics are generally related to high plasma levels encountered during therapeutic use. (See ADVERSE REACTIONS, WARNINGS and PRECAUTIONS.) High lidocaine plasma levels are unlikely to occur from administration of LidoSite™ System when used as directed.

Repeated applications, multiple simultaneous applications, application in smaller patients, or in patients with impaired elimination may all contribute to increased blood concentrations of lidocaine. In addition, if other local anesthetics are administered at the same time, e.g. topically or by injection, the toxic effects are thought to be additive and could result in an overdose with systemic toxic reactions. There is generally an increase in severity of symptoms with increasing plasma concentrations of lidocaine. Systemic central nervous system (CNS) toxicity may occur over a range of plasma concentrations of local anesthetics. CNS toxicity may typically be found around 5000 ng/mL of lidocaine, however a small number of patients reportedly may show signs of toxicity at approximately 1000 ng/mL. CNS symptoms usually precede cardiovascular manifestations.

Plasma levels of lidocaine were below the minimum level of quantitation, 5 ng/ml, in healthy adult or pediatric subjects after three sequential LidoSite™ System applications on different sites over a 3.5-hour period. Toxic levels of lidocaine may cause seizures, decreases in cardiac output, total peripheral resistance and mean arterial pressure, as well as life-threatening dysrhythmias and cardiac arrest. The management of overdose includes close monitoring, supportive care, and symptomatic treatment. Dialysis is of negligible value in the treatment of acute overdose with lidocaine. In the absence of massive topical overdose or oral ingestion, evaluation should include assessment for other etiologies of these clinical effects and overdosage from other sources of lidocaine (consult package insert for parenteral lidocaine for further information on the management of overdose).

Epinephrine blood levels did not exceed the normal physiological range (<50 pg/ml), after a single LidoSite™ System application. Overdosage of epinephrine can cause hypertension, tachycardia, cardiac dysrhythmias, cerebral hemorrhage and pulmonary edema. It is unlikely that overdosage would be caused by use of LidoSite™ System as labeled and patients with symptoms or sign of overdose should be evaluated for other etiologies of these clinical effects or overdosage from other sources of epinephrine (consult package insert for epinephrine injection).

LidoSite™ Controller can only be used with the LidoSite™ Patch as the complete LidoSite™ System, and LidoSite™ Patches should only be used with a LidoSite™ Controller.

LidoSite™ System should be applied only by a health care practitioner in a health care setting.

One LidoSite™ Patch is to be used with one LidoSite™ Controller. Do not use a damaged or altered patch. To administer, see the “LidoSite™ Topical System Instructions” contained in this package insert. Following iontophoresis and patch removal, the treatment site should be cleansed according to standard practice prior to the medical procedure. Disinfecting agents containing heavy metal ions (mercury, zinc, copper, etc.) should not be used for skin disinfection prior to iontophoresis as they have been associated with swelling and edema.

LidoSite™ Controller should not be subjected to any sterilization procedure.

LidoSite™ Controller should be disposed of in a trash receptacle.

The LidoSite™ Topical System utilizes a solid-state electronic controller and a pre-filled patch to form an iontophoretic drug delivery system. The LidoSite™ Controller requires only an ON button actuation to start the treatment. Two light emitting diode (LED) indicators inform the user of the delivery status. The LidoSite™ Controller is designed with a non-replaceable battery that provides up to 99 drug applications at 1.77 mA for 10 minutes (17.7 mA-min).

The LidoSite™ Controller is not designed to be serviced or repaired. The unit is sealed, contains a non-replaceable battery, and requires no calibration.

No Flashing GREEN and YELLOW During Self Check

If the controller does not go through the alternating GREEN and YELLOW flashing indicators when the ON button is first pressed, discard the unit.

Constant YELLOW indicator

The battery is below operational limits and the unit should be discarded.

No Flashing GREEN indicator With Patch Connected

• The patch is improperly connected to the controller, or
• The patch was previously used, or
• The patch was improperly placed on the patient or no skin was detected.

B. Braun Clinical and Technical Support
824 Twelfth Avenue
Bethlehem, PA 18018
Phone: 800-854-6851

The LidoSite™ Topical System is protected by U.S. patents: 5,246,418; 5,873,850; 6,377,847; 6,385,488; 6,402,732; 6,522,919; 6,629,968; 6,635,045. Additional patents pending.

LidoSite™ Patches are supplied as individually pouched, single-use, iontophoretic patches containing 10% Lidocaine and 0.1% Epinephrine, and are to be used only in conjunction with the LidoSite™ Controller. LidoSite™ Patches and LidoSite™ Controllers are available as follows:

Rx only. Store LidoSite™ Patches at controlled room temperature (20°C-25°C; 68°F-77°F). Excursions permitted between 15°-30° C (see USP Controlled Room Temperature).

1. Preparation of the Application Site

a) Examine the treatment site, ensuring that the application area is free of scars, scratches, wounds, bruises and not covered with excessive hair that could affect patch adherence to the skin.
	b) Briskly rub the area with an isopropyl alcohol swab to remove dry skin, oils, and other surface matter.
	c) Allow the area to dry thoroughly.

2. Application of LidoSite™ Patch to Skin

	a) Open pouch from the V-shaped seal by peeling back the sealed sides approximately half way to expose the white tab of the patch.
	b) Grasp the white tab and remove the patch from the pouch. Visually inspect the patch for creases or other apparent damage. Do not use if damaged.
	c) Hold the patch by the white tab with the transparent, protective plastic cover side up. Remove the plastic cover. Check to ensure the white pads remain with the cover. If either pad or portion of the pad detaches from the cover, discard the patch.
	d) Using the handling tabs on opposite sides of the patch, position the center of the circular reservoir on the area to be treated and apply to the skin. If the patch folds upon itself or adhesive sections stick to each other, discard the patch and apply another.
e) Starting from the center of the circular reservoir, apply light pressure and move outwards to the edges of the patch to secure uniformly. Repeat for the oblong reservoir.

3. LidoSite™ Controller Operation

a) Prior to connecting the controller, an optional self-check car be performed to verify the treatments remaining. Depress the "ON" button, located in the middle of the controller, until the device beeps once and/or the LEDs starts blinking. The controller is ready to use after the GREEN and YELLOW indicators blink alternately for two (2) seconds and the unit beeps once again, The LCD will display "doses remain".
b) The LidoSite™ controller can be clipped to the patient's clothing or held in place using the supplied strap. Place the controller such that the interconnect can reach the patch with some slack remaining in the cable.
c) Connect the patch to the controller by inserting the tab into the interconnect.
d) Ensure the patch is in frill contact with the skin (step 2e).
e) During treatment advise the patient to minimize movement.
f) After the patch is connected to the controller, depress the "ON" button until the device beeps once and/or the LEDs starts blinking to initiate delivery. A self-check will be performed.
After the self-check, the GREEN indicator should begin flashing at a rate of once per second, indicating that delivery is in progress. The GREEN light will continue to flash slowly during the 10 minute treatment.
IF THE GREEN LIGHT DOES NOT START FLASHING, CHECK THAT (1) THE PATCH TAB IS FULLY INSERTED IN THE INTERCONNECT AND (2) THE PATCH IS COMPLETELY ADHERED TO THE PATIENT'S SKIN.
g) When the treatment is complete, the controller will beep three times and increase the flashing rate of the GREEN light to four times per second.
h) If the YELLOW light flashes at 4 times per second, the medication may not have been delivered to the application site. This may be caused by a higher than normal skin resistance of the patient and may not necessarily be a malfunction of the patch or controller. Be aware that sufficient medication may or may not be present to produce the desired effect. A tactile check of the skin site may be performed at the application site to help determine a subjective level of medication effect. A second application using a new LidoSite™ Patch may be applied after 30 minutes to a different skin site. LidoSite™ Patches should not be reapplied to a skin site that had previously been treated with a patch. Only one (1) patch should be used at a time.

4. Removal and Disposal

a) Grasp the interconnect tab and disconnect the patch from the controller. The lights will go OFF and the controller will automatically turn OFF. The patch tab is slit when removed from the interconnect preventing reuse of the patch.
b) LidoSite™ Patch should be disposed of as medical waste.
c) Remove the controller.

5. Preparation of the Treatment Site

B|BRAUN

* For use with LidoSite™ Patch and LidoSite™ Controller

(Lidocaine HCI/Epinephrine Topical lontophorebc Patch) 10%/0.1%