ZTLIDO

ZTLIDO (lidocaine topical system) 1.8% is a single-layer, drug-in-adhesive topical delivery system comprised of an adhesive material containing 36 mg lidocaine, which is applied to a pliable nonwoven cloth backing and covered with a polyethylene terephthalate film release liner. The release liner is removed prior to application to the skin. The size of ZTLIDO is 10 cm × 14 cm × 0.08 cm. Lidocaine, an amide local anesthetic, is chemically designated as acetamide, 2-(diethylamino)- N -(2,6-dimethylphenyl), has an octanol:water partition ratio of 43 at pH 7.4, and has the following structure: Each ZTLIDO contains 36 mg of lidocaine (18 mg per gram adhesive) in a non-aqueous base and also contains the following inactive ingredients: butylated hydroxytoluene, dipropylene glycol, isostearic acid, mineral oil, polyisobutylene, silicone dioxide, styrene/isoprene/styrene block copolymer, and terpene resin. Chemical Structure

ZTLIDO is indicated for relief of pain associated with post-herpetic neuralgia (PHN) in adults. ZTLIDO contains lidocaine, an amide local anesthetic, and is indicated for relief of pain associated with post-herpetic neuralgia (PHN) in adults ( 1 ).

Because of the difference in bioavailability of ZTLIDO compared to Lidoderm®, a different dosage strength is required to be administered to the patient. One ZTLIDO (lidocaine topical system) 1.8% provides equivalent lidocaine exposure to one Lidoderm (lidocaine patch 5%). ( 2.1 ) Apply ZTLIDO to intact skin to cover the most painful area. Apply the prescribed number of topical systems (maximum of 3) only once for up to 12 hours in a 24-hour period. ( 2.2 ) ZTLIDO may be cut into smaller sizes prior to removal of the release liner. ( 2.2 ) In patients who are debilitated or have impaired elimination, smaller areas of treatment are recommended. Achieve this by cutting ZTLIDO with scissors into a smaller size prior to removing the release liner. ( 2.2 ) 2.1 Important Dosage and Administration Instructions Because of the difference in bioavailability of ZTLIDO compared to Lidoderm (lidocaine patch 5%), a different dosage strength is required to be administered to the patient. One ZTLIDO (lidocaine topical system) 1.8% provides equivalent lidocaine exposure to one Lidoderm (lidocaine patch 5%) [see Clinical Pharmacology (12.3) ]. When ZTLIDO is used concomitantly with other products containing local anesthetic agents, the total amount of drug absorbed from all formulations must be considered. Clearly instruct and advise patients: to wash hands immediately after handling ZTLIDO and to avoid contact with eyes [see Warnings and Precautions (5.6) ] . to store ZTLIDO inside the sealed envelope out of the reach of children, pets, and others and to apply immediately after removal from the envelope. to fold used ZTLIDO so that the adhesive side sticks to itself and to safely discard used ZTLIDO or pieces of cut ZTLIDO where children and pets cannot get to them [see Warnings and Precautions (5.1) ] . to never apply external heat sources, such as heating pads or electric blankets, directly to ZTLIDO, because plasma lidocaine levels are increased. ZTLIDO can be applied, however, to the administration site after moderate heat exposure, such as 15 minutes of heating pad exposure on a medium setting [see Warnings and Precautions (5.2) , Clinical Pharmacology (12.3) ] . that clothing may be worn over the area of application. that ZTLIDO may be used during moderate exercise, such as biking for 30 minutes. that ZTLIDO may be exposed to water, such as showering for 10 minutes or immersion for 15 minutes. to dry the topical system, after water exposure, by gently patting the skin, not by rubbing the skin or topical system. that ZTLIDO topical systems that have lifted at the edges may be reattached by pressing firmly on the edges and that fully detached topical systems may be reapplied as originally directed. that if a ZTLIDO topical system comes off completely and will not stick to patient's skin, to remove and properly dispose of the used ZTLIDO and to apply a new ZTLIDO topical system for a total duration of 12 hours of used and new topical system together. that if irritation or a burning sensation occurs during application, to remove ZTLIDO and to not reapply until the irritation subsides [see Warnings and Precautions (5.4) ] . 2.2 Treatment of Post-Herpetic Neuralgia Advise patients to apply ZTLIDO to intact skin to cover the most painful area and to apply the prescribed number of topical systems (maximum of 3), only once for up to 12 hours within a 24-hour period (12 hours on and 12 hours off) [see Warnings and Precautions (5.2) ] . In patients who are debilitated or have impaired elimination, smaller areas of treatment are recommended. Achieve this by cutting ZTLIDO with scissors into a smaller size prior to removing the release liner.

ZTLIDO 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. ZTLIDO 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 )

The following serious adverse reactions are described elsewhere in the labeling: 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 from voluntary reports or clinical studies have been reported with 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 Scilex Pharmaceuticals Inc. at 1-866-SCILEX3 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Class I Antiarrhythmic Drugs: When ZTLIDO is used in patients receiving Class I antiarrhythmic drugs (such as tocainide and mexiletine) the toxic effects are additive and potentially synergistic. Consider risk/benefit before concomitant use. ( 7.2 ) Local Anesthetic Agents: When ZTLIDO is used concomitantly with other products containing local anesthetic agents, the effects are additive. Consider the amount of drug absorbed from all formulations when local anesthetics are administered concomitantly. ( 7.3 ) 7.1 Drugs That May Cause Methemoglobinemia When Used with ZTLIDO Patients who are administered local anesthetics may be 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-aminosalicyclic acid, sulfonamides Antimalarials chloroquine, primaquine Anticonvulsants phenobarbital, phenytoin, sodium valproate Other drugs acetaminophen, metoclopramide, quinine, sulfasalazine 7.2 Antiarrhythmic Drugs When ZTLIDO is used in patients receiving Class I antiarrhythmic drugs (such as tocainide and mexiletine), the toxic effects are additive and potentially synergistic. Consider risk/benefit during concomitant use. 7.3 Local Anesthetics When ZTLIDO is used concomitantly with other products containing local anesthetic agents, the effects are additive. Consider the amount of drug absorbed from all formulations when local anesthetic agents are administered concomitantly.

Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Wash hands thoroughly immediately after handling the topical system. Upon removal, fold the topical system in half so that the adhesive side sticks to itself. Discard used ZTLIDO and pieces of cut ZTLIDO in a manner that prevents accidental contact or ingestion by children, pets or others [see Dosage and Administration (2.2) , Warnings and Precautions (5.1) ] .