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DESCRIPTION Lidocaine Ointment, USP 5% contains a local anesthetic agent and is administered topically. See INDICATIONS AND USAGE for specific uses. Lidocaine Ointment, USP 5% contains lidocaine USP, which is chemically designated as acetamide, 2-(diethylamino)-N-(2,6-dimethylphenyl)-, and has the following structural formula: Composition of Lidocaine Ointment, USP 5%: acetamide, 2-(diethylamino)-N-(2,6-dimethylphenyl)-, (lidocaine) 5% in a water miscible ointment vehicle containing polyethylene glycols. lidocaine-fig1

CLINICAL PHARMACOLOGY Mechanism of action: Lidocaine stabilizes the neuronal membrane by inhibiting the ionic fluxes required for the initiation and conduction of impulses, thereby effecting local anesthetic action. Onset of anesthesia: Lidocaine Ointment 5% effects local, topical anesthesia. The onset of action is 3-5 minutes. It is ineffective when applied to intact skin. Hemodynamics: Excessive blood levels may cause changes in cardiac output, total peripheral resistance, and mean arterial pressure. These changes may be attributable to a direct depressant effect of the local anesthetic agent on various components of the cardiovascular system. Pharmacokinetics and metabolism: Lidocaine may be absorbed following topical administration to mucous membranes, its rate and extent of absorption depending upon the specific site of application, duration of exposure, concentration, and total dosage. In general, the rate of absorption of local anesthetic agents following topical application occurs most rapidly after intratracheal administration. Lidocaine is also well-absorbed from the gastrointestinal tract, but little intact drug appears in the circulation because of biotransformation in the liver. Lidocaine is metabolized rapidly by the liver, and metabolites and unchanged drug are excreted by the kidneys. Biotransformation includes oxidative N-dealkylation, ring hydroxylation, cleavage of the amide linkage, and conjugation. N-dealkylation, a major pathway of biotransformation, yields the metabolites monoethylglycinexylidide and glycinexylidide. The pharmacological/toxicological actions of these metabolites are similar to, but less potent than, those of lidocaine. Approximately 90% of lidocaine administered is excreted in the form of various metabolites, and less than 10% is excreted unchanged. The primary metabolite in urine is a conjugate of 4-hydroxy-2,6-dimethylaniline. The plasma binding of lidocaine is dependent on drug concentration, and the fraction bound decreases with increasing concentration. At concentrations of 1 to 4 μg of free base per mL, 60 to 80 percent of lidocaine is protein bound. Binding is also dependent on the plasma concentration of the alpha-l-acid glycoprotein. Lidocaine crosses the blood-brain and placental barriers, presumably by passive diffusion. Studies of lidocaine metabolism following intravenous bolus injections have shown that the elimination half-life of this agent is typically 1.5 to 2.0 hours. Because of the rapid rate at which lidocaine is metabolized, any condition that affects liver function may alter lidocaine kinetics. The half-life may be prolonged two-fold or more in patients with liver dysfunction. Renal dysfunction does not affect lidocaine kinetics but may increase the accumulation of metabolites. Factors such as acidosis and the use of CNS stimulants and depressants affect the CNS levels of lidocaine required to produce overt systemic effects. Objective adverse manifestations become increasingly apparent with increasing venous plasma levels above 6.0 μg free base per mL. In the rhesus monkey arterial blood levels of 18-21 μg/mL have been shown to be threshold for convulsive activity.

INDICATIONS & USAGE Lidocaine Ointment 5% is indicated for production of anesthesia of accessible mucous membranes of the oropharynx. It is also useful as an anesthetic lubricant for intubation and for the temporary relief of pain associated with minor burns, including sunburn, abrasions of the skin, and insect bites.

WARNINGS EXCESSIVE DOSAGE, OR SHORT INTERVALS BETWEEN DOSES, CAN RESULT IN HIGH PLASMA LEVELS AND SERIOUS ADVERSE EFFECTS, PATIENTS SHOULD BE INSTRUCTED TO STRICTLY ADHERE TO THE RECOMMENDED DOSAGE AND ADMINISTRATION GUIDELINES AS SET FORTH IN THIS PACKAGE INSERT. THE MANAGEMENT OF SERIOUS ADVERSE REACTIONS MAY REQUIRE THE USE OF RESUSCITATIVE EQUIPMENT, OXYGEN, AND OTHER RESUSCITATIVE DRUGS. Lidocaine Ointment 5% should be used with extreme caution in the presence of sepsis or severely traumatized mucosa in the area of application, since under such conditions there is the potential for rapid systemic absorption. 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 Lidocaine Ointment USP, 5% 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.

PRECAUTIONS General The safety and effectiveness of lidocaine depend on proper dosage, correct technique, adequate precautions, and readiness for emergencies. (See WARNINGS and ADVERSE REACTIONS ). The lowest dosage that results in effective anesthesia should be used to avoid high plasma levels and serious adverse effects. Repeated doses of lidocaine may cause significant increases in blood levels with each repeated dose because of slow accumulation of the drug and/or its metabolites. Tolerance to elevated blood levels varies with the status of the patient. Debilitated, elderly patients, acutely ill patients, and children should be given reduced doses commensurate with their age and physical condition. Lidocaine should also be used with caution in patients with severe shock or heart block. Lidocaine Ointment 5% should be used with caution in patients with known drug sensitivities. Patients allergic to paraaminobenzoic acid derivatives (procaine, tetracaine, benzocaine, etc.) have not shown cross sensitivity to lidocaine. Many drugs used during the conduct of anesthesia are considered potential triggering agents for familial malignant hyperthermia. Since it is not known whether amide-type local anesthetics may trigger this reaction and since the need for supplemental general anesthesia cannot be predicted in advance, it is suggested that a standard protocol for the management of malignant hyperthermia should be available. Early unexplained signs of tachycardia, tachypnea, labile blood pressure and metabolic acidosis may precede temperature elevation. Successful outcome is dependent on early diagnosis, prompt discontinuance of the suspect triggering agent(s) and institution of treatment, including oxygen therapy, indicated supportive measures and dantrolene (consult dantrolene sodium intravenous package insert before using). Information for Patients Inform patients that use of local anesthetics may cause methemoglobinemia, a serious condition that must be treated promptly. Advise patients or caregivers to 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. When topical anesthetics are used in the mouth, the patient should be aware that the production of topical anesthesia may impair swallowing and thus enhance the danger of aspiration. For this reason, food should not be ingested for 60 minutes following the use of local anesthetic preparations in the mouth or throat area. This is particularly important in children because of their frequency of eating. Numbness of the tongue or buccal mucosa may enhance the danger of unintentional biting trauma. Food and chewing gum should not be taken while the mouth or throat area is anesthetized. Repackaged By / Distributed By: RemedyRepack Inc.

area. This is particularly important in children because of their frequency of eating. Numbness of the tongue or buccal mucosa may enhance the danger of unintentional biting trauma. Food and chewing gum should not be taken while the mouth or throat area is anesthetized. Repackaged By / Distributed By: RemedyRepack Inc. 625 Kolter Drive, Indiana, PA 15701 (724) 465-8762 Drug Interactions 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 Carcinogenesis, mutagenesis, impairment of fertility Studies of lidocaine in animals to evaluate the carcinogenic and mutagenic potential or the effect on fertility have not been conducted. Use in Pregnancy Teratogenic Effects. Reproduction studies have been performed in rats at doses up to 6.6 times the human dose and have revealed no evidence of harm to the fetus caused by lidocaine. There are, however, no adequate and well-controlled studies in pregnant women. Animal reproduction studies are not always predictive of human response. General consideration should be given to this fact before administering lidocaine to women of childbearing potential, especially during early pregnancy when maximum organogenesis takes place. Labor and Delivery Lidocaine is not contraindicated in labor and delivery. Should Lidocaine Ointment 5% be used concomitantly with other products containing lidocaine, the total dose contributed by all formulations must be kept in mind. Nursing Mothers It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when lidocaine is administered to a nursing woman. Pediatric use Dosage in children should be reduced, commensurate with age, body weight and physical condition. Caution must be taken to avoid overdosage when applying Lidocaine Ointment 5% to large areas of injured or abraded skin, since the systemic absorption of lidocaine may be increased under such conditions. See DOSAGE and ADMINISTRATION.

<table cellspacing="0" cellpadding="0" border="0" width="100%"><col width="35.46%"/><col width="64.54%"/><tbody><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"><content styleCode="bold">Class</content> </td><td styleCode="Rrule" valign="top"><content styleCode="bold">Examples</content> </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top">Nitrates/Nitrites </td><td styleCode="Rrule" valign="top">nitric oxide, nitroglycerin, nitroprusside, nitrous oxide </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top">Local anesthetics </td><td styleCode="Rrule" valign="top">articaine, benzocaine, bupivacaine, lidocaine, mepivacaine, prilocaine, procaine, ropivacaine, tetracaine </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top">Antineoplastic Agents </td><td styleCode="Rrule" valign="top">cyclophosphamide, flutamide, hydroxyurea, ifosfamide, rasburicase </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top">Antibiotics </td><td styleCode="Rrule" valign="top">dapsone, nitrofurantoin, para-aminosalicylic acid, sulfonamides </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top">Antimalarials </td><td styleCode="Rrule" valign="top">chloroquine, primaquine </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top">Anticonvulsants </td><td styleCode="Rrule" valign="top">Phenobarbital, phenytoin, sodium valproate </td></tr><tr><td styleCode="Lrule Rrule" valign="top">Other drugs </td><td styleCode="Rrule" valign="top">acetaminophen, metoclopramide, quinine, sulfasalazine </td></tr></tbody></table>

General The safety and effectiveness of lidocaine depend on proper dosage, correct technique, adequate precautions, and readiness for emergencies. (See WARNINGS and ADVERSE REACTIONS ). The lowest dosage that results in effective anesthesia should be used to avoid high plasma levels and serious adverse effects. Repeated doses of lidocaine may cause significant increases in blood levels with each repeated dose because of slow accumulation of the drug and/or its metabolites. Tolerance to elevated blood levels varies with the status of the patient. Debilitated, elderly patients, acutely ill patients, and children should be given reduced doses commensurate with their age and physical condition. Lidocaine should also be used with caution in patients with severe shock or heart block. Lidocaine Ointment 5% should be used with caution in patients with known drug sensitivities. Patients allergic to paraaminobenzoic acid derivatives (procaine, tetracaine, benzocaine, etc.) have not shown cross sensitivity to lidocaine. Many drugs used during the conduct of anesthesia are considered potential triggering agents for familial malignant hyperthermia. Since it is not known whether amide-type local anesthetics may trigger this reaction and since the need for supplemental general anesthesia cannot be predicted in advance, it is suggested that a standard protocol for the management of malignant hyperthermia should be available. Early unexplained signs of tachycardia, tachypnea, labile blood pressure and metabolic acidosis may precede temperature elevation. Successful outcome is dependent on early diagnosis, prompt discontinuance of the suspect triggering agent(s) and institution of treatment, including oxygen therapy, indicated supportive measures and dantrolene (consult dantrolene sodium intravenous package insert before using).

Information for Patients Inform patients that use of local anesthetics may cause methemoglobinemia, a serious condition that must be treated promptly. Advise patients or caregivers to 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. When topical anesthetics are used in the mouth, the patient should be aware that the production of topical anesthesia may impair swallowing and thus enhance the danger of aspiration. For this reason, food should not be ingested for 60 minutes following the use of local anesthetic preparations in the mouth or throat area. This is particularly important in children because of their frequency of eating. Numbness of the tongue or buccal mucosa may enhance the danger of unintentional biting trauma. Food and chewing gum should not be taken while the mouth or throat area is anesthetized. Repackaged By / Distributed By: RemedyRepack Inc. 625 Kolter Drive, Indiana, PA 15701 (724) 465-8762

Drug Interactions 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

Use in Pregnancy Teratogenic Effects. Reproduction studies have been performed in rats at doses up to 6.6 times the human dose and have revealed no evidence of harm to the fetus caused by lidocaine. There are, however, no adequate and well-controlled studies in pregnant women. Animal reproduction studies are not always predictive of human response. General consideration should be given to this fact before administering lidocaine to women of childbearing potential, especially during early pregnancy when maximum organogenesis takes place.

Labor and Delivery Lidocaine is not contraindicated in labor and delivery. Should Lidocaine Ointment 5% be used concomitantly with other products containing lidocaine, the total dose contributed by all formulations must be kept in mind.

Nursing Mothers It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when lidocaine is administered to a nursing woman.

Pediatric use Dosage in children should be reduced, commensurate with age, body weight and physical condition. Caution must be taken to avoid overdosage when applying Lidocaine Ointment 5% to large areas of injured or abraded skin, since the systemic absorption of lidocaine may be increased under such conditions. See DOSAGE and ADMINISTRATION.

ADVERSE REACTIONS Adverse experiences following the administration of lidocaine are similar in nature to those observed with other amide local anesthetic agents. These adverse experiences are, in general, dose-related and may result from high plasma levels caused by excessive dosage or rapid absorption, or may result from a hypersensitivity, idiosyncrasy or diminished tolerance on the part of the patient. Serious adverse experiences are generally systemic in nature. The following types are those most commonly reported: Central nervous system: CNS manifestations are excitatory and/or depressant and may be characterized by 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. The excitatory manifestations may be very brief or may not occur at all, in which case the first manifestation of toxicity may be drowsiness merging into unconsciousness and respiratory arrest. Drowsiness following the administration of lidocaine is usually an early sign of a high blood level of the drug and may occur as a consequence of rapid absorption. Cardiovascular system: Cardiovascular manifestations are usually depressant and are characterized by bradycardia, hypotension, and cardiovascular collapse, which may lead to cardiac arrest. Allergic: Allergic reactions are characterized by cutaneous lesions, urticaria, edema or anaphylactoid reactions. Allergic reactions may occur as a result of sensitivity either to the local anesthetic agent or to other components in the formulation. 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.

OVERDOSAGE Acute emergencies from local anesthetics are generally related to high plasma levels encountered during therapeutic use of local anesthetics. (see ADVERSE REACTIONS, WARNINGS , and PRECAUTIONS ). Management of local anesthetic emergencies : The first consideration is prevention, best accomplished by careful and constant monitoring of cardiovascular and respiratory vital signs and the patient's state of consciousness after each local anesthetic administration. At the first sign of change, oxygen should be administered. The first step in the management of convulsions consists of immediate attention to the maintenance of a patent airway and assisted or controlled ventilation with oxygen and a delivery system capable of permitting immediate positive airway pressure by mask. Immediately after the institution of these ventilatory measures, the adequacy of the circulation should be evaluated, keeping in mind that drugs used to treat convulsions sometimes depress the circulation when administered intravenously. Should convulsions persist despite adequate respiratory support, and if the status of the circulation permits, small increments of an ultra-short acting barbiturate (such as thiopental or thiamylal) or a benzodiazepine (such as diazepam) may be administered intravenously. The clinician should be familiar, prior to use of local anesthetics, with these anticonvulsant drugs. Supportive treatment of circulatory depression may require administration of intravenous fluids and, when appropriate, a vasopressor as directed by the clinical situation (e.g., ephedrine). If not treated immediately, both convulsions and cardiovascular depression can result in hypoxia, acidosis, bradycardia, arrhythmias and cardiac arrest. If cardiac arrest should occur, standard cardiopulmonary resuscitative measures should be instituted. Dialysis is of negligible value in the treatment of acute overdosage with lidocaine. The oral LD 50 of lidocaine HCI in non-fasted female rats is 459 (346-773) mg/kg (as the salt) and 214 (159-324) mg/kg (as the salt) in fasted female rats.

DOSAGE & ADMINISTRATION When Lidocaine Ointment 5% is used concomitantly with other products containing lidocaine, the total dose contributed by all formulations must be kept in mind. Adult: A single application should not exceed 5 g of Lidocaine Ointment 5%, containing 250 mg of Lidocaine base (equivalent chemically to approximately 300 mg of lidocaine hydrochloride). This is roughly equivalent to squeezing a six (6) inch length of ointment from the tube. In a 70 kg adult this dose equals 3.6 mg/kg (1.6 mg/lb) lidocaine base. No more than one-half tube, approximately 17-20 g of ointment or 850-1000 mg lidocaine base, should be administered in any one day. Although the incidence of adverse effects with Lidocaine Ointment 5% is quite low, caution should be exercised, particularly when employing large amounts, since the incidence of adverse effects is directly proportional to the total dose of local anesthetic agent administered. Dosage for children: It is difficult to recommend a maximum dose of any drug for children since this varies as a function of age and weight. For children less than ten years who have a normal lean body mass and a normal lean body development, the maximum dose may be determined by the application of one of the standard pediatric drug formulas (e.g., Clark's rule). For example a child of five years weighing 50 lbs., the dose of lidocaine should not exceed 75-100 mg when calculated according to Clark's rule. In any case, the maximum amount of lidocaine administered should not exceed 4.5 mg/kg (2 mg/lb) of body weight. Administration: For medical use, apply topically for adequate control of symptoms. The use of a sterile gauze pad is suggested for application to broken skin tissue. Apply to the tube prior to intubation. In dentistry, apply to previously dried oral mucosa. Subsequent removal of excess saliva with cotton rolls or saliva ejector minimizes dilution of the ointment, permits maximum penetration, and minimizes the possibility of swallowing the topical ointment. For use in connection with the insertion of new dentures, apply to all denture surfaces contacting mucosa. IMPORTANT: Patients should consult a dentist at intervals not exceeding 48 hours throughout the fitting period.

HOW SUPPLIED Lidocaine Ointment USP, 5% is White to slight yellow translucent ointment and available in below packs: NDC: 70518-3746-00 PACKAGING: 1 in 1 CARTON, 50 g in 1 TUBE TYPE 0 Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [See USP Controlled Room Temperature]. Repackaged and Distributed By: Remedy Repack, Inc. 625 Kolter Dr. Suite #4 Indiana, PA 1-724-465-8762

SPL Unclassified Section AQUEOUS SOLUTIONS FOR INFILTRATION AND NERVE BLOCK Ampul Plastic Multiple-dose Fliptop Vial Glass Teartop Vial Rx only Distributed by Hospira, Inc., Lake Forest, IL 60045 USA LAB-1118-5.0 Revised: 07/2021

Precautions Section General The safety and effectiveness of lidocaine HCl depend on proper dosage, correct technique, adequate precautions, and readiness for emergencies. Standard textbooks should be consulted for specific techniques and precautions for various regional anesthetic procedures. Resuscitative equipment, oxygen, and other resuscitative drugs should be available for immediate use (see WARNINGS and ADVERSE REACTIONS). The lowest dosage that results in effective anesthesia should be used to avoid high plasma levels and serious adverse effects. Syringe aspirations should also be performed before and during each supplemental injection when using indwelling catheter techniques. During the administration of epidural anesthesia, it is recommended that a test dose be administered initially and that the patient be monitored for central nervous system toxicity and cardiovascular toxicity, as well as for signs of unintended intrathecal administration, before proceeding. When clinical conditions permit, consideration should be given to employing local anesthetic solutions that contain epinephrine for the test dose because circulatory changes compatible with epinephrine may also serve as a warning sign of unintended intravascular injection. An intravascular injection is still possible even if aspirations for blood are negative. Repeated doses of lidocaine HCl may cause significant increases in blood levels with each repeated dose because of slow accumulation of the drug or its metabolites. Tolerance to elevated blood levels varies with the status of the patient. Debilitated, elderly patients, acutely ill patients, and children should be given reduced doses commensurate with their age and physical condition. Lidocaine HCl should also be used with caution in patients with severe shock or heart block. Lumbar and caudal epidural anesthesia should be used with extreme caution in persons with the following conditions: existing neurological disease, spinal deformities, septicemia, and severe hypertension. Local anesthetic solutions containing a vasoconstrictor should be used cautiously and in carefully circumscribed quantities in areas of the body supplied by end arteries or having otherwise compromised blood supply. Patients with peripheral vascular disease and those with hypertensive vascular disease may exhibit exaggerated vasoconstrictor response. Ischemic injury or necrosis may result. Preparations containing a vasoconstrictor should be used with caution in patients during or following the administration of potent general anesthetic agents, since cardiac arrhythmias may occur under such conditions. Careful and constant monitoring of cardiovascular and respiratory (adequacy of ventilation) vital signs and the patient's state of consciousness should be accomplished after each local anesthetic injection. It should be kept in mind at such times that restlessness, anxiety, tinnitus, dizziness, blurred vision, tremors, depression or drowsiness may be early warning signs of central nervous system toxicity. Since amide-type local anesthetics are metabolized by the liver, lidocaine should be used with caution in patients with hepatic disease. Patients with severe hepatic disease, because of their inability to metabolize local anesthetics normally, are at greater risk of developing toxic plasma concentrations.

ons containing epinephrine or norepinephrine to patients receiving monoamine oxidase inhibitors or tricyclic anti-depressants may produce severe, prolonged hypertension. Phenothiazines and butyrophenones may reduce or reverse the pressor effect of epinephrine. Concurrent use of these agents should generally be avoided. In situations when concurrent therapy is necessary, careful patient monitoring is essential. Concurrent administration of vasopressor drugs (for the treatment of hypotension related to obstetric blocks) and ergot-type oxytocic drugs may cause severe, persistent hypertension or cerebrovascular accidents. Drug/Laboratory Test Interactions The intramuscular injection of lidocaine HCl may result in an increase in creatine phosphokinase levels. Thus, the use of this enzyme determination, without isoenzyme separation, as a diagnostic test for the presence of acute myocardial infarction may be compromised by the intramuscular injection of lidocaine HCl. 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: Carcinogenesis, Mutagenesis, Impairment of Fertility Studies of lidocaine HCl in animals to evaluate the carcinogenic and mutagenic potential or the effect on fertility have not been conducted. Pregnancy Teratogenic Effects Reproduction studies have been performed in rats at doses up to 6.6 times the human dose and have revealed no evidence of harm to the fetus caused by lidocaine HCl. There are, however, no adequate and well-controlled studies in pregnant women. Animal reproduction studies are not always predictive of human response. General consideration should be given to this fact before administering lidocaine HCl to women of childbearing potential, especially during early pregnancy when maximum organogenesis takes place. Labor and Delivery Local anesthetics rapidly cross the placenta and when used for epidural, paracervical, pudendal or caudal block anesthesia, can cause varying degrees of maternal, fetal and neonatal toxicity (see CLINICAL PHARMACOLOGY, Pharmacokinetics and Metabolism). The potential for toxicity depends upon the procedure performed, the type and amount of drug used, and the technique of drug administration. Adverse reactions in the parturient, fetus and neonate involve alterations of the central nervous system, peripheral vascular tone and cardiac function. Maternal hypotension has resulted from regional anesthesia. Local anesthetics produce vasodilation by blocking sympathetic nerves. Elevating the patient's legs and positioning her on her left side will help prevent decreases in blood pressure. The fetal heart rate also should be monitored continuously, and electronic fetal monitoring is highly advisable. Epidural, spinal, paracervical, or pudendal anesthesia may alter the forces of parturition through changes in uterine contractility or maternal expulsive efforts. In one study, paracervical block anesthesia was associated with a decrease in the mean duration of first stage labor and facilitation of cervical dilation. However, spinal and epidural anesthesia have also been reported to prolong the second stage of labor by removing the parturient's reflex urge to bear down or by interfering with motor function. The use of obstetrical anesthesia may increase the need for forceps assistance. The use of some local anesthetic drug products during labor and delivery may be followed by diminished muscle strength and tone for the first day or two of life. The long-term significance of these observations is unknown.

How Supplied Lidocaine Hydrochloride Injection, USP is supplied as follows: Single-dose products are preservative-free. Store at 20 to 25°C (68 to 77°F). [see USP Controlled Room Temperature.] Lidocaine Hydrochloride Injection, USP solutions packaged in ampuls and glass teartop vials may be autoclaved one time only. Autoclave at 15 pounds pressure, 121°C (250°F) for 15 minutes. DO NOT AUTOCLAVE PRODUCT IN PLASTIC VIALS. Product repackaged by: Henry Schein, Inc., Bastian, VA 24314 From Original Manufacturer/Distributor's NDC and Unit of Sale To Henry Schein Repackaged Product NDC and Unit of Sale Total Strength/Total Volum (Concentration) per unit NDC 0409-4276-01 Tray of 25 Plastic Multiple-dose Fliptop Vials NDC 0404-9888-20 1 Multiple-dose Fliptop Vial in a bag (Vial bears 0409-4276-16) 1% 200 mg/20 mL (10 mg/mL) NDC 0409-4276-02 Tray of 25 Plastic Multiple-dose Fliptop Vials NDC 0404-9888-50 1 Multiple-dose Fliptop Vial in a bag (Vial bears 0409-4276-17) 1% 500 mg/50mL (10 mg/mL) NDC 0409-4277-01 Tray of 25 Plastic Multiple-dose Fliptop Vials NDC 0404-9895-20 1 Multiple-dose Fliptop Vial in a bag (Vial bears NDC 0409-4277-16) 2% 400 mg/20mL (20 mg/mL) NDC 0409-4278-01 Tray of 25 Glass Single-dose Teartop Vials NDC 0404-9885-50 1 Single-Dose Teartop Vial in a bag (Vial bears NDC 0409-4278-16) 0.5% 250 mg/50mL (5 mg/mL) NDC 0409-4282-01 Bundle of 5 Clamcells containing 5 Single-dose Ampuls per Clamcell NDC 0404-9893-02 1 Ampul in a bag (Ampul bears 0409-4282-11) 2% 40 mg/2mL (20 mg/mL) NDC 0409-4282-02 Carton of 25 Glass Single-dose Ampuls NDC 0404-9893-10 1 Single-dose Ampul in a bag (Ampul bears 0409-4282-12) 2% 200 mg/10mL (20 mg/mL) NDC 0409-4713-32 Bundle of 5 Cartons containing 10 Single-dose Ampuls per Carton NDC 0404-9887-02 1 Single-Dose Ampul in a bag (Ampul bears NDC 0409-4713-42) 1% 20 mg/2 mL (10 mg/mL) Image5.jpg Image6.jpg Image7.jpg

<table width="100%"><caption>Product repackaged by: Henry Schein, Inc., Bastian, VA 24314 </caption><tbody><tr><td>From Original Manufacturer/Distributor&apos;s NDC and Unit of Sale</td><td>To Henry Schein Repackaged Product NDC and Unit of Sale</td><td>Total Strength/Total Volum (Concentration) per unit</td></tr><tr><td>NDC 0409-4276-01 Tray of 25 Plastic Multiple-dose Fliptop Vials</td><td>NDC 0404-9888-20 1 Multiple-dose Fliptop Vial in a bag (Vial bears 0409-4276-16)</td><td>1% 200 mg/20 mL (10 mg/mL)</td></tr><tr><td>NDC 0409-4276-02 Tray of 25 Plastic Multiple-dose Fliptop Vials</td><td>NDC 0404-9888-50 1 Multiple-dose Fliptop Vial in a bag (Vial bears 0409-4276-17)</td><td>1% 500 mg/50mL (10 mg/mL)</td></tr><tr><td>NDC 0409-4277-01 Tray of 25 Plastic Multiple-dose Fliptop Vials</td><td>NDC 0404-9895-20 1 Multiple-dose Fliptop Vial in a bag (Vial bears NDC 0409-4277-16)</td><td>2% 400 mg/20mL (20 mg/mL)</td></tr><tr><td>NDC 0409-4278-01 Tray of 25 Glass Single-dose Teartop Vials</td><td>NDC 0404-9885-50 1 Single-Dose Teartop Vial in a bag (Vial bears NDC 0409-4278-16)</td><td>0.5% 250 mg/50mL (5 mg/mL)</td></tr><tr><td>NDC 0409-4282-01 Bundle of 5 Clamcells containing 5 Single-dose Ampuls per Clamcell</td><td>NDC 0404-9893-02 1 Ampul in a bag (Ampul bears 0409-4282-11)</td><td>2% 40 mg/2mL (20 mg/mL)</td></tr><tr><td>NDC 0409-4282-02 Carton of 25 Glass Single-dose Ampuls</td><td>NDC 0404-9893-10 1 Single-dose Ampul in a bag (Ampul bears 0409-4282-12)</td><td>2% 200 mg/10mL (20 mg/mL)</td></tr><tr><td>NDC 0409-4713-32 Bundle of 5 Cartons containing 10 Single-dose Ampuls per Carton</td><td>NDC 0404-9887-02 1 Single-Dose Ampul in a bag (Ampul bears NDC 0409-4713-42)</td><td>1% 20 mg/2 mL (10 mg/mL)</td></tr></tbody></table>

LIDOCAINE PATCH 5% is comprised of an adhesive material containing 5% lidocaine, which is applied to a non‑woven polyester felt backing and covered with a polyethylene terephthalate (PET) film release liner. The release liner is removed prior to application to the skin. The size of the patch is 10 cm x 14 cm. Lidocaine 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: [Chemical Structure] Each adhesive patch contains 700 mg of lidocaine (50 mg per gram adhesive) in an aqueous base. It also contains the following inactive ingredients: dihydroxyaluminum aminoacetate, disodium edetate, gelatin, glycerin, kaolin, methylparaben, polyacrylic acid, polyvinyl alcohol, propylene glycol, propylparaben, sodium carboxymethylcellulose, sodium polyacrylate, D-sorbitol, tartaric acid, and urea.

Pharmacodynamics Lidocaine is an amide-type local anesthetic agent and is suggested to stabilize neuronal membranes by inhibiting the ionic fluxes required for the initiation and conduction of impulses. The penetration of lidocaine into intact skin after application of LIDOCAINE PATCH 5% is sufficient to produce an analgesic effect, but less than the amount necessary to produce a complete sensory block. Pharmacokinetics Absorption The amount of lidocaine systemically absorbed from LIDOCAINE PATCH 5% is directly related to both the duration of application and the surface area over which it is applied. In a pharmacokinetic study, three LIDOCAINE PATCH 5% patches were applied over an area of 420 cm2 of intact skin on the back of normal volunteers for 12 hours. Blood samples were withdrawn for determination of lidocaine concentration during the application and for 12 hours after removal of patches. The results are summarized in Table 1. Table 1 Absorption of lidocaine from LIDOCAINE PATCH 5% Normal volunteers (n = 15, 12-hour wearing time) Lidocaine Patch 5% Application Site Area (cm2) Dose Absorbed (mg) Cmax (mcg/mL) Tmax (hr) 3 patches (2100 mg) Back 420 64 ± 32 0.13 ± 0.06 11 hr When LIDOCAINE PATCH 5% is used according to the recommended dosing instructions, only 3 ± 2% of the dose applied is expected to be absorbed. At least 95% (665 mg) of lidocaine will remain in a used patch. Mean peak blood concentration of lidocaine is about 0.13 mcg/mL (about 1/10 of the therapeutic concentration required to treat cardiac arrhythmias). Repeated application of three patches simultaneously for 12 hours (recommended maximum daily dose), once per day for three days, indicated that the lidocaine concentration does not increase with daily use. The mean plasma pharmacokinetic profile for the 15 healthy volunteers is shown in Figure 1. Figure 1 Mean lidocaine blood concentrations after three consecutive daily applications of three LIDOCAINE PATCH 5% patches simultaneously for 12 hours per day in healthy volunteers (n = 15). [Figure 1] Distribution When lidocaine is administered intravenously to healthy volunteers, the volume of distribution is 0.7 to 2.7 L/kg (mean 1.5 ± 0.6 SD, n=15). At concentrations produced by application of LIDOCAINE PATCH 5%, lidocaine is approximately 70% bound to plasma proteins, primarily alpha‑1‑acid glycoprotein. At much higher plasma concentrations (1 to 4 mcg/mL of free base), the plasma protein binding of lidocaine is concentration dependent. Lidocaine crosses the placental and blood brain barriers, presumably by passive diffusion.Metabolism It is not known if lidocaine is metabolized in the skin. Lidocaine is metabolized rapidly by the liver to a number of metabolites, including monoethylglycinexylidide (MEGX) and glycinexylidide (GX), both of which have pharmacologic activity similar to, but less potent than that of lidocaine. A minor metabolite, 2, 6-xylidine, has unknown pharmacologic activity but is carcinogenic in rats. The blood concentration of this metabolite is negligible following application of LIDOCAINE PATCH 5%. Following intravenous administration, MEGX and GX concentrations in serum range from 11 to 36% and from 5 to 11% of lidocaine concentrations, respectively.Excretion Lidocaine and its metabolites are excreted by the kidneys. Less than 10% of lidocaine is excreted unchanged.

e following application of LIDOCAINE PATCH 5%. Following intravenous administration, MEGX and GX concentrations in serum range from 11 to 36% and from 5 to 11% of lidocaine concentrations, respectively.Excretion Lidocaine and its metabolites are excreted by the kidneys. Less than 10% of lidocaine is excreted unchanged. The half-life of lidocaine elimination from the plasma following IV administration is 81 to 149 minutes (mean 107 ± 22 SD, n = 15). The systemic clearance is 0.33 to 0.90 L/min (mean 0.64 ± 0.18 SD, n = 15).

Single-dose treatment with LIDOCAINE PATCH 5% was compared to treatment with vehicle patch (without lidocaine), and to no treatment (observation only) in a double‑blind, crossover clinical trial with 35 post‑herpetic neuralgia patients. Pain intensity and pain relief scores were evaluated periodically for 12 hours. LIDOCAINE PATCH 5% performed statistically better than vehicle patch in terms of pain intensity from 4 to 12 hours. Multiple-dose, two-week treatment with LIDOCAINE PATCH 5% was compared to vehicle patch (without lidocaine) in a double-blind, crossover clinical trial of withdrawal-type design conducted in 32 patients, who were considered as responders to the open-label use of LIDOCAINE PATCH 5% prior to the study. The constant type of pain was evaluated but not the pain induced by sensory stimuli (dysesthesia). Statistically significant differences favoring LIDOCAINE PATCH 5% were observed in terms of time to exit from the trial (14 versus 3.8 days at p-value <0.001), daily average pain relief, and patient’s preference of treatment. About half of the patients also took oral medication commonly used in the treatment of post-herpetic neuralgia. The extent of use of concomitant medication was similar in the two treatment groups.

Risk of 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 LIDOCAINE PATCH 5% 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. Accidental Exposure in Children Even a used LIDOCAINE PATCH 5% patch contains a large amount of lidocaine (at least 665 mg). The potential exists for a small child or a pet to suffer serious adverse effects from chewing or ingesting a new or used LIDOCAINE PATCH 5% patch, although the risk with this formulation has not been evaluated. It is important for patients to store and dispose of LIDOCAINE PATCH 5% out of the reach of children, pets and others. (See HANDLING AND DISPOSAL) Excessive Dosing Excessive dosing by applying LIDOCAINE PATCH 5% to larger areas or for longer than the recommended wearing time could result in increased absorption of lidocaine and high blood concentrations, leading to serious adverse effects (see ADVERSE REACTIONS, SYSTEMIC REACTIONS). Lidocaine toxicity could be expected at lidocaine blood concentrations above 5 mcg/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 patches, smaller patients, or impaired elimination may all contribute to increasing the blood concentration of lidocaine. With recommended dosing of LIDOCAINE PATCH 5%, the average peak blood concentration is about 0.13 mcg/mL, but concentrations higher than 0.25 mcg/mL have been observed in some individuals.

General 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, LIDOCAINE PATCH 5% 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. LIDOCAINE PATCH 5% is only recommended for use on intact skin. External Heat Sources Placement of external heat sources, such as heating pads or electric blankets, over LIDOCAINE PATCH 5% patches is not recommended as this has not been evaluated and may increase plasma lidocaine levels. Eye Exposure The contact of LIDOCAINE PATCH 5% 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 Antiarrhythmic Drugs LIDOCAINE PATCH 5% 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 LIDOCAINE PATCH 5% 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 LIDOCAINE PATCH 5% 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 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis A minor metabolite, 2, 6-xylidine, has been found to be carcinogenic in rats. The blood concentration of this metabolite is negligible following application of LIDOCAINE PATCH 5%. Mutagenesis Lidocaine HCl is not mutagenic in Salmonella/mammalian microsome test nor clastogenic in chromosome aberration assay with human lymphocytes and mouse micronucleus test.

een found to be carcinogenic in rats. The blood concentration of this metabolite is negligible following application of LIDOCAINE PATCH 5%. Mutagenesis Lidocaine HCl is not mutagenic in Salmonella/mammalian microsome test nor clastogenic in chromosome aberration assay with human lymphocytes and mouse micronucleus test. Impairment of Fertility The effect of LIDOCAINE PATCH 5% on fertility has not been studied. Pregnancy Teratogenic Effects Pregnancy Category B. LIDOCAINE PATCH 5% has not been studied in pregnancy. Reproduction studies with lidocaine have been performed in rats at doses up to 30 mg/kg subcutaneously and have revealed no evidence of harm to the fetus due to lidocaine. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, LIDOCAINE PATCH 5% should be used during pregnancy only if clearly needed. Labor and Delivery LIDOCAINE PATCH 5% has not been studied in labor and delivery. Lidocaine is not contraindicated in labor and delivery. Should LIDOCAINE PATCH 5% be used concomitantly with other products containing lidocaine, total doses contributed by all formulations must be considered. Nursing Mothers LIDOCAINE PATCH 5% has not been studied in nursing mothers. Lidocaine is excreted in human milk, and the milk: plasma ratio of lidocaine is 0.4. Caution should be exercised when LIDOCAINE PATCH 5% is administered to a nursing woman. Pediatric Use Safety and effectiveness in pediatric patients have not been established.

Application Site Reactions During or immediately after treatment with LIDOCAINE PATCH 5%, 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. Allergic Reactions Allergic and anaphylactoid reactions associated with lidocaine, although rare, can occur. They are characterized by angioedema, bronchospasm, dermatitis, dyspnea, hypersensitivity, laryngospasm, pruritus, shock, and urticaria. If they occur, they should be managed by conventional means. The detection of sensitivity by skin testing is of doubtful value. Other Adverse Events Due to the nature and limitation of spontaneous reports in postmarketing 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 LIDOCAINE PATCH 5% are unlikely, due to the small dose absorbed (see CLINICAL PHARMACOLOGY, PHARMACOKINETICS). Systemic adverse effects of lidocaine are 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.

Lidocaine overdose from cutaneous absorption is rare, but could occur. If there is any suspicion of lidocaine overdose (see ADVERSE REACTIONS, SYSTEMIC REACTIONS), drug blood concentration should be checked. 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 of symptoms of toxicity should include consideration of other etiologies for the clinical effects, or overdosage from other sources of lidocaine or other local anesthetics. The oral LD50 of lidocaine HCl is 459 (346-773) mg/kg (as the salt) in non-fasted female rats and 214 (159-324) mg/kg (as the salt) in fasted female rats, which are equivalent to roughly 4000 mg and 2000 mg, respectively, in a 60 to 70 kg man based on the equivalent surface area dosage conversion factors between species.

Apply LIDOCAINE PATCH 5% to intact skin to cover the most painful area. Apply the prescribed number of patches (maximum of 3), only once for up to 12 hours within a 24 hour period. Patches may be cut into smaller sizes with scissors prior to removal of the release liner. (See HANDLING AND DISPOSAL) Clothing may be worn over the area of application. Smaller areas of treatment are recommended in a debilitated patient, or a patient with impaired elimination. If irritation or a burning sensation occurs during application, remove the patch(es) and do not reapply until the irritation subsides. When LIDOCAINE PATCH 5% is used concomitantly with other products containing local anesthetic agents, the amount absorbed from all formulations must be considered. LIDOCAINE PATCH 5% may not stick if it gets wet. Avoid contact with water, such as bathing, swimming or showering.

Hands should be washed after the handling of LIDOCAINE PATCH 5%, and eye contact with LIDOCAINE PATCH 5% should be avoided. Do not store patch outside the sealed envelope. Apply immediately after removal from the protective envelope. Fold used patches so that the adhesive side sticks to itself and safely discard used patches or pieces of cut patches where children and pets cannot get to them. LIDOCAINE PATCH 5% should be kept out of the reach of children.

LIDOCAINE PATCH 5% is available as the following: Carton of 30 patches, packaged into individual child-resistant envelopes Store at 25oC (77oF); excursions permitted to 15o-30oC (59o-86oF). [See USP Controlled Room Temperature]. For more information, call Par Pharmacutical at 1-800-828-9393. Manufactured for: Par Pharmaceutical Chestnut Ridge, NY 10977 Printed in U.S.A. Revised: January 2019

<table width="100%"><col width="85%" align="left" valign="top"/><col width="15%" align="right" valign="bottom"/><tbody><tr><td>Dosage and Administration ( <linkHtml href="#S2.1">2.1</linkHtml>) </td><td>4/2021</td></tr></tbody></table>

1 INDICATIONS AND USAGE 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 ).

2 DOSAGE AND ADMINISTRATION 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) ] .

rly 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.

4 CONTRAINDICATIONS 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 )

5 WARNINGS AND PRECAUTIONS Accidental Exposure : Even a used ZTLIDO topical system contains residual lidocaine after use. It is important for patients to store and dispose of ZTLIDO properly and keep out of the reach of children, pets, and others. ( 5.1 ) Excessive Dosing/Overexposure : Applying ZTLIDO to larger surface areas or for a longer duration than recommended could lead to increased absorption and high blood concentrations of lidocaine, leading to adverse effects. ( 5.2 ) Increased Absorption on Non-Intact Skin : May result in higher blood concentrations of lidocaine. ( 5.2 ) Risk of Overexposure with External Heat Sources : Applying external heat sources to ZTLIDO may result in increased drug exposure. ( 5.2 ) Methemoglobinemia : Cases of methemoglobinemia have been reported in association with local anesthetic use. ( 5.3 ) Application Site Reactions : During or immediately after treatment with ZTLIDO, application site reactions may develop. ( 5.4 ) Hypersensitivity Reactions : Cross sensitivity to ZTLIDO in patients with a history of drug sensitivity to para-aminobenzoic acid (PABA) derivatives is possible. ( 5.5 ) Eye Exposure : Immediately wash out the eye with water or saline and protect the eye until sensation returns. ( 5.6 ). 5.1 Accidental Exposure A used ZTLIDO 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 a new or used ZTLIDO. It is important for patients to store and dispose of ZTLIDO properly, and keep out of the reach of children, pets, and others [see Dosage and Administration (2.1) ]. 5.2 Excessive Dosing/Overexposure to Lidocaine Lidocaine toxicity can be expected at lidocaine blood concentrations above 5 mcg/mL. The blood concentration of lidocaine is determined by the rate and extent of lidocaine absorption and elimination. Longer duration of application, application of more than the recommended number of ZTLIDO, 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 ZTLIDO or applying ZTLIDO 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 reactions. Advise patients on proper application and duration. 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. Use on Non-Intact Skin : Application to broken or inflamed skin, although not tested, may result in higher blood concentrations of lidocaine from increased absorption. ZTLIDO is only recommended for use on intact skin. Advise patients not to apply ZTLIDO to non-intact skin. External Heat Sources : External heat sources may increase drug exposure, leading to overexposure to lidocaine. Advise patients not to apply external heat sources to ZTLIDO during administration [see Clinical Pharmacology (12.3) ].

ommended for use on intact skin. Advise patients not to apply ZTLIDO to non-intact skin. External Heat Sources : External heat sources may increase drug exposure, leading to overexposure to lidocaine. Advise patients not to apply external heat sources to ZTLIDO during administration [see Clinical Pharmacology (12.3) ]. 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 ZTLIDO 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 ZTLIDO, 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 ZTLIDO 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 ZTLIDO 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 (such as, eye glasses/eye wear) until sensation returns.

6 ADVERSE REACTIONS 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.

7 DRUG INTERACTIONS 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.

<table width="80%"><col width="50%" align="left" valign="top"/><col width="50%" align="left" valign="top"/><thead><tr><th styleCode="Lrule Rrule">Class</th><th styleCode="Rrule">Examples</th></tr></thead><tbody><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Nitrates/Nitrites</td><td styleCode="Rrule">nitric oxide, nitroglycerin, nitroprusside, nitrous oxide</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Local anesthetics</td><td styleCode="Rrule">articaine, benzocaine, bupivacaine, lidocaine, mepivacaine, prilocaine, procaine, ropivacaine, tetracaine</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Antineoplastic agents</td><td styleCode="Rrule">cyclophosphamide, flutamide, hydroxyurea, ifosfamide, rasburicase</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Antibiotics</td><td styleCode="Rrule">dapsone, nitrofurantoin, para-aminosalicyclic acid, sulfonamides</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Antimalarials</td><td styleCode="Rrule">chloroquine, primaquine</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Anticonvulsants</td><td styleCode="Rrule">phenobarbital, phenytoin, sodium valproate</td></tr><tr><td styleCode="Lrule Rrule">Other drugs</td><td styleCode="Rrule">acetaminophen, metoclopramide, quinine, sulfasalazine</td></tr></tbody></table>

8 USE IN SPECIFIC POPULATIONS Lactation : Lidocaine is excreted into human milk. Caution should be exercised when ZTLIDO is administered to a nursing mother, especially when administered with other local anesthetics. ( 8.2 ) 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 ZTLIDO 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 45 times the maximum recommended daily dose (MRDD) of 108 mg in ZTLIDO 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 0.5 times the MRDD on Gestation Day 11 resulted in developmental delays in neonates (see Data ) . The estimated 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 (2.7 times the maximum recommended daily dose [MRDD] of 108 mg from ZTLIDO 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 45 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 0.5 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. 8.2 Lactation Risk Summary Lidocaine is excreted into human milk.

al 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. 8.2 Lactation Risk Summary Lidocaine is excreted into human milk. When lidocaine was used as an epidural anesthetic for cesarean section in 27 women, a milk:plasma ratio of 1.07 was observed using AUC values. Lactating women undergoing a dental procedure had a 0.4 milk:plasma ratio. In another dental procedure study, a single patient was administered 20 mg of lidocaine and the milk:plasma ratio was reported as 1.1 at five to six hours after injection. These data, and the low concentrations of lidocaine in the plasma after topical administration of ZTLIDO in recommended doses, suggest that a small amount of lidocaine would be ingested orally by a suckling infant. However, caution should be exercised when ZTLIDO is administered to a nursing mother, especially when administered with other local anesthetics. 8.4 Pediatric Use Safety and effectiveness in pediatric patients have not been established. 8.5 Geriatric Use Clinical studies of ZTLIDO did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be done with caution, usually starting at the low end of the dosing range (e.g., a single topical system), reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

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 ZTLIDO 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 45 times the maximum recommended daily dose (MRDD) of 108 mg in ZTLIDO 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 0.5 times the MRDD on Gestation Day 11 resulted in developmental delays in neonates (see Data ) . The estimated 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 (2.7 times the maximum recommended daily dose [MRDD] of 108 mg from ZTLIDO 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 45 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 0.5 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.

8.5 Geriatric Use Clinical studies of ZTLIDO did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be done with caution, usually starting at the low end of the dosing range (e.g., a single topical system), reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

10 OVERDOSAGE Lidocaine overdose from cutaneous absorption is rare, but could occur. If there is any suspicion of lidocaine overdose, check drug blood concentration. 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 of symptoms of toxicity should include consideration of other etiologies for the clinical effects, or overdosage from other sources of lidocaine or other local anesthetics.

11 DESCRIPTION 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

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Lidocaine is an amide local anesthetic. Lidocaine blocks sodium ion channels required for the initiation and conduction of neuronal impulses. 12.2 Pharmacodynamics The penetration of lidocaine into intact skin after application of ZTLIDO is sufficient to produce an analgesic effect, but less than the amount necessary to produce a complete sensory block. 12.3 Pharmacokinetics ZTLIDO has different bioavailability compared to Lidoderm. In a single-dose, crossover study conducted in 53 healthy volunteers, ZTLIDO (lidocaine topical system) 1.8% demonstrated equivalent exposure (AUC) and peak concentration (C max ) of lidocaine to Lidoderm (lidocaine patch 5%). Absorption The amount of lidocaine systemically absorbed from ZTLIDO is directly related to both the duration of application and the surface area over which it is applied. In a pharmacokinetic study, three ZTLIDO topical systems were applied over an area of 420 cm 2 of intact skin on the backs of normal healthy volunteers for 12 hours. Blood samples were drawn for determination of lidocaine concentration during the topical system application and for 12 hours after removal of topical systems. The results are summarized in Table 1 . Table 1 Mean ± SD Absorption of lidocaine from ZTLIDO Healthy Volunteers (n = 54, 12-hour application time) Topical System Application Site Area (cm 2 ) C max (ng/mL) T max (hr) median (min, max) 3 Topical systems of ZTLIDO (108 mg) Back 420 75.1 ± 28.0 13.9 (4.0, 18.0) Repeated application of three Lidoderm patches simultaneously for 12 hours (recommended maximum daily dose), once per day for three days, indicated that the lidocaine concentration does not increase with daily use. The mean plasma pharmacokinetic profile for the 15 healthy volunteers is shown in Figure 1 . Figure 1 Mean lidocaine blood concentrations after three consecutive daily applications of three Lidoderm patches simultaneously for 12 hours per day in healthy volunteers (n = 15). The pharmacokinetics of ZTLIDO (n = 3 topical systems) was assessed in 12 healthy volunteers with exposure to external heat source (heating pad at medium setting applied for 20 minutes at Time 0 and 8.5 hours) or undergoing moderate exercise (cycling for 30 minutes at a heart rate of 108 bpm at Time 0, 2.5, 5.5 and 8.5 hours) and compared to pharmacokinetics of ZTLIDO at rest. Exposure to external heat at 0 and 8.5 hours results in increased peak plasma levels of lidocaine with a mean (SD) of 160.3 ± 100.1 ng/mL versus the peak plasma levels observed at rest with a mean (SD) of 97.6 ± 36.9 ng/mL. For this reason, instruct patients not to apply heating pads directly to ZTLIDO. Concentrations returned to normal within 4 hours after the heat was removed. No clinically relevant differences in systemic absorption were observed under exercise conditions with a mean (SD) peak plasma concentration of 90.5 ± 25.4 ng/mL. A separate study in 12 healthy volunteers showed that there was no effect on ZTLIDO pharmacokinetics when the topical system is applied to the administration site after external heat exposure (heating pad at medium setting applied for 15 minutes prior to the topical system application) or after engagement in exercise (walking at a moderate pace on a treadmill for approximately 20 minutes beginning approximately 30 minutes prior to the topical system application).

nistration site after external heat exposure (heating pad at medium setting applied for 15 minutes prior to the topical system application) or after engagement in exercise (walking at a moderate pace on a treadmill for approximately 20 minutes beginning approximately 30 minutes prior to the topical system application). Chemical Structure Distribution When lidocaine is administered intravenously to healthy volunteers, the volume of distribution is 0.7 to 2.7 L/kg (mean 1.5 ± 0.6 SD, n = 15). At concentrations produced by application of ZTLIDO, lidocaine is approximately 70% bound to plasma proteins, primarily alpha-1-acid glycoprotein. At much higher plasma concentrations (1 to 4 µg/mL of free base), the plasma protein binding of lidocaine is concentration dependent. Lidocaine crosses the placental and blood brain barriers, presumably by passive diffusion. Elimination Metabolism: It is not known if lidocaine is metabolized in the skin. Lidocaine is metabolized rapidly by the liver to a number of metabolites, including monoethylglycinexylidide (MEGX) and glycinexylidide (GX), both of which have pharmacologic activity similar to, but less potent than that of lidocaine. A minor metabolite, 2,6-xylidine, has unknown pharmacologic activity. The blood concentration of this metabolite is negligible following application of ZTLIDO. Following intravenous administration, MEGX and GX concentrations in serum range from 11 to 36% and from 5 to 11% of lidocaine concentrations, respectively. Excretion: Lidocaine and its metabolites are excreted by the kidneys. Less than 10% of lidocaine is excreted unchanged. The half-life of lidocaine elimination from the plasma following IV administration is 81 to 149 minutes (mean 107 ± 22 SD, n = 15). The systemic clearance is 0.33 to 0.90 L/minute (mean 0.64 ± 0.18 SD, n = 15).

12.2 Pharmacodynamics The penetration of lidocaine into intact skin after application of ZTLIDO is sufficient to produce an analgesic effect, but less than the amount necessary to produce a complete sensory block.

12.3 Pharmacokinetics ZTLIDO has different bioavailability compared to Lidoderm. In a single-dose, crossover study conducted in 53 healthy volunteers, ZTLIDO (lidocaine topical system) 1.8% demonstrated equivalent exposure (AUC) and peak concentration (C max ) of lidocaine to Lidoderm (lidocaine patch 5%). Absorption The amount of lidocaine systemically absorbed from ZTLIDO is directly related to both the duration of application and the surface area over which it is applied. In a pharmacokinetic study, three ZTLIDO topical systems were applied over an area of 420 cm 2 of intact skin on the backs of normal healthy volunteers for 12 hours. Blood samples were drawn for determination of lidocaine concentration during the topical system application and for 12 hours after removal of topical systems. The results are summarized in Table 1 . Table 1 Mean ± SD Absorption of lidocaine from ZTLIDO Healthy Volunteers (n = 54, 12-hour application time) Topical System Application Site Area (cm 2 ) C max (ng/mL) T max (hr) median (min, max) 3 Topical systems of ZTLIDO (108 mg) Back 420 75.1 ± 28.0 13.9 (4.0, 18.0) Repeated application of three Lidoderm patches simultaneously for 12 hours (recommended maximum daily dose), once per day for three days, indicated that the lidocaine concentration does not increase with daily use. The mean plasma pharmacokinetic profile for the 15 healthy volunteers is shown in Figure 1 . Figure 1 Mean lidocaine blood concentrations after three consecutive daily applications of three Lidoderm patches simultaneously for 12 hours per day in healthy volunteers (n = 15). The pharmacokinetics of ZTLIDO (n = 3 topical systems) was assessed in 12 healthy volunteers with exposure to external heat source (heating pad at medium setting applied for 20 minutes at Time 0 and 8.5 hours) or undergoing moderate exercise (cycling for 30 minutes at a heart rate of 108 bpm at Time 0, 2.5, 5.5 and 8.5 hours) and compared to pharmacokinetics of ZTLIDO at rest. Exposure to external heat at 0 and 8.5 hours results in increased peak plasma levels of lidocaine with a mean (SD) of 160.3 ± 100.1 ng/mL versus the peak plasma levels observed at rest with a mean (SD) of 97.6 ± 36.9 ng/mL. For this reason, instruct patients not to apply heating pads directly to ZTLIDO. Concentrations returned to normal within 4 hours after the heat was removed. No clinically relevant differences in systemic absorption were observed under exercise conditions with a mean (SD) peak plasma concentration of 90.5 ± 25.4 ng/mL. A separate study in 12 healthy volunteers showed that there was no effect on ZTLIDO pharmacokinetics when the topical system is applied to the administration site after external heat exposure (heating pad at medium setting applied for 15 minutes prior to the topical system application) or after engagement in exercise (walking at a moderate pace on a treadmill for approximately 20 minutes beginning approximately 30 minutes prior to the topical system application). Chemical Structure Distribution When lidocaine is administered intravenously to healthy volunteers, the volume of distribution is 0.7 to 2.7 L/kg (mean 1.5 ± 0.6 SD, n = 15). At concentrations produced by application of ZTLIDO, lidocaine is approximately 70% bound to plasma proteins, primarily alpha-1-acid glycoprotein. At much higher plasma concentrations (1 to 4 µg/mL of free base), the plasma protein binding of lidocaine is concentration dependent.

o 2.7 L/kg (mean 1.5 ± 0.6 SD, n = 15). At concentrations produced by application of ZTLIDO, lidocaine is approximately 70% bound to plasma proteins, primarily alpha-1-acid glycoprotein. At much higher plasma concentrations (1 to 4 µg/mL of free base), the plasma protein binding of lidocaine is concentration dependent. Lidocaine crosses the placental and blood brain barriers, presumably by passive diffusion. Elimination Metabolism: It is not known if lidocaine is metabolized in the skin. Lidocaine is metabolized rapidly by the liver to a number of metabolites, including monoethylglycinexylidide (MEGX) and glycinexylidide (GX), both of which have pharmacologic activity similar to, but less potent than that of lidocaine. A minor metabolite, 2,6-xylidine, has unknown pharmacologic activity. The blood concentration of this metabolite is negligible following application of ZTLIDO. Following intravenous administration, MEGX and GX concentrations in serum range from 11 to 36% and from 5 to 11% of lidocaine concentrations, respectively. Excretion: Lidocaine and its metabolites are excreted by the kidneys. Less than 10% of lidocaine is excreted unchanged. The half-life of lidocaine elimination from the plasma following IV administration is 81 to 149 minutes (mean 107 ± 22 SD, n = 15). The systemic clearance is 0.33 to 0.90 L/minute (mean 0.64 ± 0.18 SD, n = 15).

<table width="75%"><caption>Table 1 Mean &#xB1; SD Absorption of lidocaine from ZTLIDO Healthy Volunteers (n = 54, 12-hour application time)</caption><col width="20%" align="center" valign="middle"/><col width="20%" align="center" valign="middle"/><col width="20%" align="center" valign="middle"/><col width="20%" align="center" valign="middle"/><col width="20%" align="center" valign="middle"/><thead><tr><th styleCode="Lrule Rrule">Topical System</th><th styleCode="Rrule">Application Site</th><th styleCode="Rrule">Area (cm ²) </th><th styleCode="Rrule">C _max(ng/mL) </th><th styleCode="Rrule">T _max(hr) <footnote ID="K1545">median (min, max)</footnote></th></tr></thead><tbody><tr><td styleCode="Lrule Rrule">3 Topical systems of ZTLIDO (108 mg) </td><td styleCode="Rrule">Back</td><td styleCode="Rrule">420</td><td styleCode="Rrule">75.1 &#xB1; 28.0</td><td styleCode="Rrule">13.9 (4.0, 18.0)</td></tr></tbody></table>

13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis Long-term studies in animals specifically designed to evaluate the carcinogenic potential of lidocaine or ZTLIDO have not been conducted. A metabolite, 2,6-xylidine, has been found to be carcinogenic in rats. The clinical significance is not known. Mutagenesis Lidocaine HCl was not mutagenic in the in vitro bacterial reverse mutagenicity assay (Ames test). Lidocaine HCl was not clastogenic in the in vitro chromosome aberration assay with human lymphocytes or in the in vivo mouse micronucleus test. Impairment of Fertility In a published study, female Sprague-Dawley rats were treated subcutaneously with lidocaine via osmotic pumps starting two weeks prior to mating, and reproductive effects were assessed. Rats dosed up to the high dose of 500 mg/kg/day (approximately 45 times the MRDD on a mg/m 2 basis) showed no effects on copulatory rate, pregnancy rate, or the numbers of corpora lutea or implantations.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis Long-term studies in animals specifically designed to evaluate the carcinogenic potential of lidocaine or ZTLIDO have not been conducted. A metabolite, 2,6-xylidine, has been found to be carcinogenic in rats. The clinical significance is not known. Mutagenesis Lidocaine HCl was not mutagenic in the in vitro bacterial reverse mutagenicity assay (Ames test). Lidocaine HCl was not clastogenic in the in vitro chromosome aberration assay with human lymphocytes or in the in vivo mouse micronucleus test. Impairment of Fertility In a published study, female Sprague-Dawley rats were treated subcutaneously with lidocaine via osmotic pumps starting two weeks prior to mating, and reproductive effects were assessed. Rats dosed up to the high dose of 500 mg/kg/day (approximately 45 times the MRDD on a mg/m 2 basis) showed no effects on copulatory rate, pregnancy rate, or the numbers of corpora lutea or implantations.

14 CLINICAL STUDIES Single-dose treatment with lidocaine patch (currently preferred dosage form term for a patch is topical system) was compared to treatment with vehicle patch (without lidocaine), and to no treatment (observation only) in a double-blind, crossover clinical trial with 35 post-herpetic neuralgia patients. Pain intensity and pain relief scores were evaluated periodically for 12 hours. Lidocaine patch performed statistically better than vehicle patch in terms of pain intensity from 4 to 12 hours. Multiple-dose, two-week treatment with lidocaine patch was compared to vehicle patch (without lidocaine) in a double-blind, crossover clinical trial of withdrawal-type design conducted in 32 patients, who were considered as responders to the open-label use of lidocaine patch prior to the study. The constant type of pain was evaluated but not the pain induced by sensory stimuli (dysesthesia). Statistically significant differences favoring lidocaine patch were observed in terms of time to exit from the trial (14 versus 3.8 days at p-value <0.001), daily average pain relief, and patient's preference of treatment. About half of the patients also took oral medication commonly used in the treatment of post-herpetic neuralgia. The extent of use of concomitant medication was similar in the two treatment groups. Based on a clinical study in 54 subjects with ZTLIDO, 47 subjects (87%) had adhesion scores of 0 (≥ 90% adhered) for all evaluations performed every 3 hours during the 12 hours of administration, 7 subjects (13%) had adhesion scores of 1 (≥ 75% to < 90% adhered) for at least one evaluation, and no subjects had scores of 2 or greater (< 75% adhered).

16 HOW SUPPLIED/STORAGE AND HANDLING ZTLIDO (lidocaine topical system) 1.8% is available as the following: Carton of 30 topical systems, packaged into individual child-resistant envelopes. NDC 69557-111-30 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) ] .

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) ] .

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use). Accidental Exposure and Disposal Advise patients to store ZTLIDO out of the reach of children, pets, and others. Advise patients to dispose of used ZTLIDO by folding used ZTLIDO so that the adhesive side sticks to itself and safely discarding used ZTLIDO or pieces of cut ZTLIDO where children, pets, and others cannot come in contact with them [see Warnings and Precautions (5.1) ] . Proper Application Advise patients: not to apply more than the prescribed number (up to 3 ZTLIDO) [see Dosage and Administration (2.2) , Warnings and Precautions (5.2) ]. not to wear ZTLIDO longer than the recommended wearing time (12 hours of every 24 hours) [see Dosage and Administration (2.2) , Warnings and Precautions (5.2) ]. to apply ZTLIDO to intact skin [see Warnings and Precautions (5.2) ]. to reattach by pressing firmly on the edges of ZTLIDO that are lifting. If a ZTLIDO topical system comes off completely and will not stick to patient's skin, it should be removed and properly disposed of and a new ZTLIDO topical system should be applied for a total duration of 12 hours of used and new topical system together [see Dosage and Administration (2.1 , 2.2) ] . 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 [see Warnings and Precautions (5.3) ]. Application Site Reactions Inform patients that skin irritation and other skin reactions may occur at the site of ZTLido application. If skin reactions occur during wear, instruct patients to remove ZTLido and not to reapply until the skin reaction subsides [see Warnings and Precautions (5.4) ] Eye Exposure Advise patients to wash hands immediately after handling ZTLIDO and to avoid contact with eyes. Instruct patients to, if eye contact should occur, immediately wash out the eye with water or saline and protect the eye until sensation returns [see Dosage and Administration (2.1) , Warnings and Precautions (5.6) ] .

Manufactured for: Scilex Pharmaceuticals Inc. Palo Alto, CA 94303 USA ZTLIDO ® is a trademark owned by Scilex Pharmaceuticals Inc. Patented. See: www.scilexpharma.com/patents © 2021 Scilex Pharmaceuticals Inc. All rights reserved. SCILEX ® PHARMACEUTICALS SCILEX ® and ZTLIDO ® are registered trademarks of Scilex Pharmaceuticals Inc.

This Patient Information has been approved by the U.S. Food and Drug Administration. Issued: 4/2021 PATIENT INFORMATION ZTLIDO ® (ZEE-TEE-LIE-DOH) (lidocaine topical system) What is ZTLIDO? ZTLIDO is a prescription medicine used for relief of pain from damaged nerves (neuropathic pain) that follows healing of shingles. It is not known if ZTLIDO is safe and effective in children. Do not use ZTLIDO if you: have a history of allergic reactions to numbing medicines (anesthetics). Ask your healthcare provider if you are not sure. are allergic to any of the ingredients in ZTLIDO. See the end of this leaflet for a complete list of ingredients in ZTLIDO. Before using ZTLIDO, tell your healthcare provider about all your medical conditions, including if you: have liver problems have heart or lung problems are allergic to para-aminobenzoic acid (PABA) medicines such as procaine, tetracaine, or benzocaine have been told that you have glucose-6-phosphate dehydrogenase deficiency were born with (congenital) methemoglobinemia or have had methemoglobinemia from an unknown cause are pregnant or plan to become pregnant. It is not known if ZTLIDO will harm your unborn baby. are breastfeeding or plan to breastfeed. ZTLIDO can pass into your breast milk. Talk to your healthcare provider about the best way to feed your baby if you use ZTLIDO. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Especially, tell your healthcare provider if you are using other lidocaine containing products or anesthetic medicines. How should I use ZTLIDO? Read the Instructions for Use at the end of this Patient Information leaflet for information about how to apply the ZTLIDO topical system. Use ZTLIDO exactly as your healthcare provider tells you to use it. Do not apply more than your prescribed number of ZTLIDO. You may apply up to 3 ZTLIDO topical systems at one time. A ZTLIDO may be worn only 1 time for up to 12 hours within a 24-hour period (12 hours on and 12 hours off). Apply ZTLIDO to intact skin only. Do not apply ZTLIDO to skin that is not intact, such as skin that is cut, scraped, burned, or irritated. ZTLIDO topical systems that come off completely or are lifting at the edges may be reattached by firmly pressing down on the topical system or on the lifted areas. If ZTLIDO lifts off the skin or detaches more than 1 time, do not try to reattach it. Throw it away as described below. If the ZTLIDO you are wearing comes off completely, and will not stick to your skin, throw it away as described below. In either of these cases, you may apply a replacement (a new) ZTLIDO topical system. Take off the replacement ZTLIDO at your usual removal time. The total time you may wear the used and replacement ZTLIDO is 12 hours . You may wear clothing over the ZTLIDO application site. Do not apply external heat sources, such as heating pads or electric blankets, directly on ZTLIDO. This may cause increased levels of lidocaine in your blood. You may apply ZTLIDO to a treatment site after moderate heat exposure, such as after 15 minutes of heating pad use on a medium setting. ZTLIDO may be used during moderate exercise, such as biking for 30 minutes. ZTLIDO may be worn in water such as showering for 10 minutes or bathing for 15 minutes. After ZTLIDO is exposed to water, pat the topical system dry. Do not rub the topical system.

uch as after 15 minutes of heating pad use on a medium setting. ZTLIDO may be used during moderate exercise, such as biking for 30 minutes. ZTLIDO may be worn in water such as showering for 10 minutes or bathing for 15 minutes. After ZTLIDO is exposed to water, pat the topical system dry. Do not rub the topical system. After using ZTLIDO, fold the used ZTLIDO so that the sticky sides stick together. Safely throw away used ZTLIDO and any pieces of cut ZTLIDO where children and pets cannot get to them. Wash your hands right away after handling ZTLIDO (after you apply ZTLIDO, when you try to re-attach it, or when you remove it.) If you start feeling irritation or burning when applying ZTLIDO, remove the ZTLIDO. Do not reapply ZTLIDO until the irritation or burning goes away. If you apply more than 3 ZTLIDO topical systems or apply ZTLIDO for longer than 12 hours of a 24-hour period, call your healthcare provider. What should I avoid while using ZTLIDO? Avoid contact of your hands and fingers with your eyes while handling ZTLIDO. See " Contact of ZTLIDO with your eyes " below. What are the possible side effects of ZTLIDO? ZTLIDO may cause serious side effects, including: Lidocaine overdose can happen if you apply more than the prescribed number of ZTLIDO, applying ZTLIDO for longer than 12 hours, have liver problems, use ZTLIDO on skin that is not intact, or if you apply external heat sources directly on ZTLIDO. This can result in increased levels of lidocaine in your blood. Do not apply more than the prescribed number of ZTLIDO. Do not wear ZTLIDO longer than 12 hours. Do not apply ZTLIDO on skin that is not intact, such as skin that is cut, scraped, burned, or irritated. Do not apply external heat sources directly to ZTLIDO. See " How should I use ZTLIDO? " for more information about how to properly use external heat sources when using ZTLIDO. A serious blood problem called methemoglobinemia. Methemoglobinemia is a serious blood problem where to much methemoglobin is produced in the blood. Methemoglobinemia can happen with the use of local anesthetics and may not let enough oxygen reach the organs and tissues in your body. Anyone who uses or receives local anesthetics is at risk for methemoglobinemia, but certain people are more likely to have serious medical problems and need to be closely monitored by their healthcare provider during treatment with ZTLIDO, including: people with glucose-6-phosphate dehydrogenase deficiency people with heart of lung problems babies under 6 months of age people who were born with (congenital) or who have had methemoglobinemia from an unknown cause people exposed to certain chemicals at the same time that they use or receive a local anesthetic Signs of methemoglobinemia can happen right away or they may not happen for some hours after your have used or received a local anesthetic. It is important to get medical treatment right away to help prevent more serious side effects including seizures, coma, abnormal heart rhythms, and death. You or your caregiver should stop using ZTLIDO and get medical help right away if you develop any of the following signs or symptoms: pale, gray, or blue colored skin headache rapid heart beat shortness of breath lightheadedness tiredness Application site reactions. Skin irritation and other skin reactions at the ZTLIDO application site are common and are usually mild. These reactions can happen during or right after treatment with ZTLIDO. Application site reactions will usually go away within a few minutes to hours.

of breath lightheadedness tiredness Application site reactions. Skin irritation and other skin reactions at the ZTLIDO application site are common and are usually mild. These reactions can happen during or right after treatment with ZTLIDO. Application site reactions will usually go away within a few minutes to hours. Symptoms of application site reactions may include: blisters bruising burning or abnormal sensation change or loss of color of your skin swelling, redness, and pain of the skin peeling or flaking of skin irritation pimple-like raised skin itching If you develop a skin reaction while wearing ZTLIDO, remove it. Do not reapply ZTLIDO until the site reaction goes away. Allergic reactions can happen if you have a history of allergic reactions to numbing medicines (anesthetics). Tell your healthcare provider right away if you have any symptoms of an allergic reaction such as swelling or shortness of breath. Contact of ZTLIDO with your eyes can happen if you touch your eyes while handling the topical system and can cause severe eye irritation. Avoid eye contact with your hands and fingers while handling ZTLIDO. Wash your hands right away after handling ZTLIDO. If the medicine in ZTLIDO comes in contact with your eye, wash out your eye with water or saline right away. Protect the eye (for example eye glasses or eye wear) until the numbness goes away. These are not all the possible side effects of ZTLIDO. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. How should I store ZTLIDO? Store ZTLIDO at room temperature between 68°F to 77°F (20°C to 25°C). Keep ZTLIDO topical system in the original packaging unit until ready for use. Each ZTLIDO topical system comes in a child-resistant envelope. Keep ZTLIDO and all medicines out of the reach of children, pets, and others. General information about the safe and effective use of ZTLIDO. Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use ZTLIDO for a condition for which it was not prescribed. Do not give ZTLIDO to other people, even if they have the same symptoms you have. It may harm them. You can ask your pharmacist or healthcare provider for information about ZTLIDO that is written for health professionals. What are the ingredients in ZTLIDO? Active ingredient: lidocaine Inactive ingredients: butylated hydroxytoluene, dipropylene glycol, isostearic acid, mineral oil, polyisobutylene, silicone dioxide, styrene/isoprene/styrene block copolymer, and terpene resin. Manufactured for: Scilex Pharmaceuticals Inc., Palo Alto, CA 94303 ZTLIDO ® is a trademark owned by Scilex Pharmaceuticals Inc. © 2021 Scilex Pharmaceuticals Inc. All rights reserved. SCILEX ® PHARMACEUTICALS For more information call [1-844-SCILEX1] or visit www.ZTLIDO.com.

<table width="100%"><col width="3%" align="left" valign="top"/><col width="33%" align="left" valign="top"/><col width="20%" align="left" valign="top"/><col width="15%" align="left" valign="top"/><col width="29%" align="left" valign="top"/><tfoot><tr><td colspan="4" align="left"> This Patient Information has been approved by the U.S. Food and Drug Administration.</td><td align="right">Issued: 4/2021 </td></tr></tfoot><tbody><tr styleCode="Botrule"><td colspan="5" align="center" styleCode="Lrule Rrule"><content styleCode="bold">PATIENT INFORMATION</content> ZTLIDO ^&#xAE;(ZEE-TEE-LIE-DOH) (lidocaine topical system) </td></tr><tr><td colspan="5" styleCode="Lrule Rrule"><content styleCode="bold">What is ZTLIDO?</content></td></tr><tr styleCode="Botrule"><td colspan="5" styleCode="Lrule Rrule">ZTLIDO is a prescription medicine used for relief of pain from damaged nerves (neuropathic pain) that follows healing of shingles. It is not known if ZTLIDO is safe and effective in children.</td></tr><tr><td colspan="5" styleCode="Lrule Rrule"><content styleCode="bold">Do not use ZTLIDO if you:</content></td></tr><tr styleCode="Botrule"><td colspan="5" styleCode="Lrule Rrule"><list listType="unordered" styleCode="Disc"><item>have a history of allergic reactions to numbing medicines (anesthetics). Ask your healthcare provider if you are not sure.</item><item>are allergic to any of the ingredients in ZTLIDO. See the end of this leaflet for a complete list of ingredients in ZTLIDO.</item></list></td></tr><tr><td colspan="5" styleCode="Lrule Rrule"><content styleCode="bold">Before using ZTLIDO, tell your healthcare provider about all your medical conditions, including if you:</content></td></tr><tr><td colspan="5" styleCode="Lrule Rrule"><list listType="unordered" styleCode="Disc"><item>have liver problems</item><item>have heart or lung problems</item><item>are allergic to para-aminobenzoic acid (PABA) medicines such as procaine, tetracaine, or benzocaine</item><item>have been told that you have glucose-6-phosphate dehydrogenase deficiency</item><item>were born with (congenital) methemoglobinemia or have had methemoglobinemia from an unknown cause</item><item>are pregnant or plan to become pregnant. It is not known if ZTLIDO will harm your unborn baby.</item><item>are breastfeeding or plan to breastfeed. ZTLIDO can pass into your breast milk. Talk to your healthcare provider about the best way to feed your baby if you use ZTLIDO.</item></list></td></tr><tr styleCode="Botrule"><td colspan="5" styleCode="Lrule Rrule"><content styleCode="bold">Tell your healthcare provider about all the medicines you take,</content>including prescription and over-the-counter medicines, vitamins, and herbal supplements. <content styleCode="bold">Especially, tell your healthcare provider if you are using other lidocaine containing products or anesthetic medicines.</content></td></tr><tr><td colspan="5" styleCode="Lrule Rrule"><content styleCode="bold">How should I use ZTLIDO?</content></td></tr><tr><td colspan="5" styleCode="Lrule Rrule"><content styleCode="bold">Read the Instructions for Use at the end of this Patient Information leaflet for information about how to apply the ZTLIDO topical system.</content></td></tr><tr styleCode="Botrule"><td colspan="5" styleCode="Lrule Rrule"><list listType="unordered" styleCode="Circle"><item>Use ZTLIDO exactly as your healthcare provider tells you to use it.</item><item>Do not apply more than your prescribed number of ZTLIDO.

on about how to apply the ZTLIDO topical system.</content></td></tr><tr styleCode="Botrule"><td colspan="5" styleCode="Lrule Rrule"><list listType="unordered" styleCode="Circle"><item>Use ZTLIDO exactly as your healthcare provider tells you to use it.</item><item>Do not apply more than your prescribed number of ZTLIDO. You may apply up to 3 ZTLIDO topical systems at one time.</item><item>A ZTLIDO may be worn only 1 time for up to 12 hours within a 24-hour period (12 hours on and 12 hours off).</item><item>Apply ZTLIDO to intact skin only. Do not apply ZTLIDO to skin that is not intact, such as skin that is cut, scraped, burned, or irritated.</item><item>ZTLIDO topical systems that come off completely or are lifting at the edges may be reattached by firmly pressing down on the topical system or on the lifted areas. <list listType="unordered" styleCode="Circle"><item>If ZTLIDO lifts off the skin or detaches more than 1 time, <content styleCode="bold">do not</content>try to reattach it. Throw it away as described below. </item><item>If the ZTLIDO you are wearing comes off completely, and will not stick to your skin, throw it away as described below.</item></list><paragraph>In either of these cases, you may apply a replacement (a new) ZTLIDO topical system. Take off the replacement ZTLIDO at your usual removal time. The <content styleCode="bold">total time</content>you may wear the used and replacement ZTLIDO <content styleCode="bold">is 12 hours</content>. </paragraph></item><item>You may wear clothing over the ZTLIDO application site.</item><item><content styleCode="bold">Do not</content>apply external heat sources, such as heating pads or electric blankets, directly on ZTLIDO. This may cause increased levels of lidocaine in your blood. You may apply ZTLIDO to a treatment site after moderate heat exposure, such as after 15 minutes of heating pad use on a medium setting. </item><item>ZTLIDO may be used during moderate exercise, such as biking for 30 minutes.</item><item>ZTLIDO may be worn in water such as showering for 10 minutes or bathing for 15 minutes.</item><item>After ZTLIDO is exposed to water, pat the topical system dry. <content styleCode="bold">Do not</content>rub the topical system. </item><item>After using ZTLIDO, fold the used ZTLIDO so that the sticky sides stick together. Safely throw away used ZTLIDO and any pieces of cut ZTLIDO where children and pets cannot get to them.</item><item>Wash your hands right away after handling ZTLIDO (after you apply ZTLIDO, when you try to re-attach it, or when you remove it.)</item><item>If you start feeling irritation or burning when applying ZTLIDO, remove the ZTLIDO. <content styleCode="bold">Do not</content>reapply ZTLIDO until the irritation or burning goes away. </item><item>If you apply more than 3 ZTLIDO topical systems or apply ZTLIDO for longer than 12 hours of a 24-hour period, call your healthcare provider.</item></list></td></tr><tr><td colspan="5" styleCode="Lrule Rrule"><content styleCode="bold">What should I avoid while using ZTLIDO?</content></td></tr><tr styleCode="Botrule"><td colspan="5" styleCode="Lrule Rrule"><list listType="unordered" styleCode="Circle"><item>Avoid contact of your hands and fingers with your eyes while handling ZTLIDO. <content styleCode="bold">See &quot; <linkHtml href="#Contact">Contact of ZTLIDO with your eyes</linkHtml>&quot; below.

d></tr><tr styleCode="Botrule"><td colspan="5" styleCode="Lrule Rrule"><list listType="unordered" styleCode="Circle"><item>Avoid contact of your hands and fingers with your eyes while handling ZTLIDO. <content styleCode="bold">See &quot; <linkHtml href="#Contact">Contact of ZTLIDO with your eyes</linkHtml>&quot; below. </content></item></list></td></tr><tr><td colspan="5" styleCode="Lrule Rrule"><content styleCode="bold">What are the possible side effects of ZTLIDO?</content></td></tr><tr><td colspan="5" styleCode="Lrule Rrule"><content styleCode="bold">ZTLIDO may cause serious side effects, including:</content></td></tr><tr><td colspan="5" styleCode="Lrule Rrule"><list listType="unordered" styleCode="Circle"><item><content styleCode="bold">Lidocaine overdose</content>can happen if you apply more than the prescribed number of ZTLIDO, applying ZTLIDO for longer than 12 hours, have liver problems, use ZTLIDO on skin that is not intact, or if you apply external heat sources directly on ZTLIDO. This can result in increased levels of lidocaine in your blood. <list listType="unordered" styleCode="Circle"><item>Do not apply more than the prescribed number of ZTLIDO.</item><item>Do not wear ZTLIDO longer than 12 hours.</item><item>Do not apply ZTLIDO on skin that is not intact, such as skin that is cut, scraped, burned, or irritated.</item><item>Do not apply external heat sources directly to ZTLIDO. See &quot; <content styleCode="bold"><linkHtml href="#How">How should I use ZTLIDO?</linkHtml></content>&quot; for more information about how to properly use external heat sources when using ZTLIDO. </item></list></item><item><content styleCode="bold">A serious blood problem called methemoglobinemia.</content>Methemoglobinemia is a serious blood problem where to much methemoglobin is produced in the blood. Methemoglobinemia can happen with the use of local anesthetics and may not let enough oxygen reach the organs and tissues in your body. Anyone who uses or receives local anesthetics is at risk for methemoglobinemia, but certain people are more likely to have serious medical problems and need to be closely monitored by their healthcare provider during treatment with ZTLIDO, including: <list listType="unordered" styleCode="Circle"><item>people with glucose-6-phosphate dehydrogenase deficiency</item><item>people with heart of lung problems</item><item>babies under 6 months of age</item><item>people who were born with (congenital) or who have had methemoglobinemia from an unknown cause</item><item>people exposed to certain chemicals at the same time that they use or receive a local anesthetic</item></list>Signs of methemoglobinemia can happen right away or they may not happen for some hours after your have used or received a local anesthetic. <content styleCode="bold">It is important to get medical treatment right away to help prevent more serious side effects including seizures, coma, abnormal heart rhythms, and death.</content> <content styleCode="bold">You or your caregiver should stop using ZTLIDO and get medical help right away if you develop any of the following signs or symptoms:</content></item></list></td></tr><tr><td styleCode="Lrule"/><td><list listType="unordered"><item>pale, gray, or blue colored skin</item><item>headache</item></list></td><td colspan="2"><list listType="unordered"><item>rapid heart beat</item><item>shortness of breath</item></list></td><td styleCode="Rrule"><list listType="unordered"><item>lightheadedness</item><item>tiredness</item></list></td></tr><tr><td colspan="5" styleCode="Lrule Rrule"><list listType="unordered"><item><content styleCode="bold">Application site reactions.</content>Skin irritation and other skin reactions at the ZTLIDO application site are common and are usually mild.

ordered"><item>lightheadedness</item><item>tiredness</item></list></td></tr><tr><td colspan="5" styleCode="Lrule Rrule"><list listType="unordered"><item><content styleCode="bold">Application site reactions.</content>Skin irritation and other skin reactions at the ZTLIDO application site are common and are usually mild. These reactions can happen during or right after treatment with ZTLIDO. Application site reactions will usually go away within a few minutes to hours. Symptoms of application site reactions may include: </item></list></td></tr><tr><td styleCode="Lrule"/><td><list listType="unordered"><item>blisters</item><item>bruising</item><item>burning or abnormal sensation</item><item>change or loss of color of your skin</item><item>swelling, redness, and pain of the skin</item></list></td><td/><td colspan="2" align="left" styleCode="Rrule"><list listType="unordered"><item>peeling or flaking of skin</item><item>irritation</item><item>pimple-like raised skin</item><item>itching</item></list></td></tr><tr><td styleCode="Lrule"/><td colspan="4" styleCode="Rrule">If you develop a skin reaction while wearing ZTLIDO, remove it. <content styleCode="bold">Do not</content>reapply ZTLIDO until the site reaction goes away. </td></tr><tr><td colspan="5" styleCode="Lrule Rrule"><list listType="unordered" styleCode="Circle"><item><content styleCode="bold">Allergic reactions</content>can happen if you have a history of allergic reactions to numbing medicines (anesthetics). Tell your healthcare provider right away if you have any symptoms of an allergic reaction such as swelling or shortness of breath. </item><item><content styleCode="bold">Contact of ZTLIDO with your eyes</content>can happen if you touch your eyes while handling the topical system and can cause severe eye irritation. Avoid eye contact with your hands and fingers while handling ZTLIDO. Wash your hands right away after handling ZTLIDO. If the medicine in ZTLIDO comes in contact with your eye, wash out your eye with water or saline right away. Protect the eye (for example eye glasses or eye wear) until the numbness goes away. </item></list></td></tr><tr><td colspan="5" styleCode="Lrule Rrule">These are not all the possible side effects of ZTLIDO.</td></tr><tr styleCode="Botrule"><td colspan="5" styleCode="Lrule Rrule">Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.</td></tr><tr><td colspan="5" styleCode="Lrule Rrule"><content styleCode="bold">How should I store ZTLIDO?</content></td></tr><tr><td colspan="5" styleCode="Lrule Rrule"><list listType="unordered" styleCode="Circle"><item>Store ZTLIDO at room temperature between 68&#xB0;F to 77&#xB0;F (20&#xB0;C to 25&#xB0;C).</item><item>Keep ZTLIDO topical system in the original packaging unit until ready for use.</item><item>Each ZTLIDO topical system comes in a child-resistant envelope.</item></list></td></tr><tr styleCode="Botrule"><td colspan="5" styleCode="Lrule Rrule"><content styleCode="bold">Keep ZTLIDO and all medicines out of the reach of children, pets, and others.</content></td></tr><tr><td colspan="5" styleCode="Lrule Rrule"><content styleCode="bold">General information about the safe and effective use of ZTLIDO.</content></td></tr><tr styleCode="Botrule"><td colspan="5" styleCode="Lrule Rrule">Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use ZTLIDO for a condition for which it was not prescribed. Do not give ZTLIDO to other people, even if they have the same symptoms you have. It may harm them.

otrule"><td colspan="5" styleCode="Lrule Rrule">Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use ZTLIDO for a condition for which it was not prescribed. Do not give ZTLIDO to other people, even if they have the same symptoms you have. It may harm them. You can ask your pharmacist or healthcare provider for information about ZTLIDO that is written for health professionals.</td></tr><tr><td colspan="5" styleCode="Lrule Rrule"><content styleCode="bold">What are the ingredients in ZTLIDO?</content></td></tr><tr><td colspan="5" styleCode="Lrule Rrule"><content styleCode="bold">Active ingredient:</content>lidocaine </td></tr><tr><td colspan="5" styleCode="Lrule Rrule"><content styleCode="bold">Inactive ingredients:</content>butylated hydroxytoluene, dipropylene glycol, isostearic acid, mineral oil, polyisobutylene, silicone dioxide, styrene/isoprene/styrene block copolymer, and terpene resin. </td></tr><tr><td colspan="5" styleCode="Lrule Rrule"><content styleCode="bold">Manufactured for:</content>Scilex Pharmaceuticals Inc., Palo Alto, CA 94303 </td></tr><tr><td colspan="5" styleCode="Lrule Rrule">ZTLIDO ^&#xAE;is a trademark owned by Scilex Pharmaceuticals Inc. &#xA9; 2021 Scilex Pharmaceuticals Inc. All rights reserved. </td></tr><tr><td colspan="5" styleCode="Lrule Rrule">SCILEX ^&#xAE; PHARMACEUTICALS </td></tr><tr styleCode="Botrule"><td colspan="5" styleCode="Lrule Rrule">For more information call [1-844-SCILEX1] or visit www.ZTLIDO.com.</td></tr></tbody></table>

Instructions for Use ZTLIDO ® (ZEE-TEE-LIE-DOH) (lidocaine topical system) Read this Instructions for Use before you start using ZTLIDO and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical treatment or condition. Important information: One ZTLIDO (lidocaine topical system) 1.8% provides equivalent lidocaine exposure to one Lidoderm® (lidocaine patch 5%). ZTLIDO is for use on intact skin only. ZTLIDO comes in a child-resistant envelope. Do not open the ZTLIDO envelope until you are ready to use it. Apply the prescribed number of ZTLIDO topical systems at one time. Clothing may be worn over ZTLIDO. You should only use a maximum of 3 ZTLIDO topical systems at a time. Keep your prescribed number of ZTLIDO topical systems on for up to 12 hours within a 24-hour period (12 hours on and 12 hours off). ZTLIDO may be used during moderate exercise, such as biking for 30 minutes. ZTLIDO may be worn in water such as showering for 10 minutes or bathing for 15 minutes. After ZTLIDO is exposed to water, pat the topical system dry. Do no t rub the topical system. ZTLIDO topical systems that have come off completely or are lifting at the edges may be re-attached to the affected area by firmly pressing down on the topical system or on the lifted areas. If ZTLIDO lifts off the skin or detaches more than 1 time, do not try to re-attach it. Throw it away (See Step 6 ). If the ZTLIDO you are wearing comes off completely, and will not stick to your skin, throw it away (see Step 6 ). In either of these cases, you may put on a replacement (a new) ZTLIDO topical system. Take off the replacement ZTLIDO at your usual removal time. The total time that you may wear the used and replacement ZTLIDO is 12 hours. Wash your hands well right away after handling ZTLIDO (when you apply ZTLIDO, when you re-attach it, or when you remove it). Avoid eye contact with your hands and fingers while handling ZTLIDO. Figure A: ZTLIDO Topical System Applying your ZTLIDO topical system: Step 1: Select the application site. ZTLIDO should only be applied to clean, dry, and intact skin to cover the most painful area. Step 2: Using scissors, carefully cut the envelope along the dotted line and open it to remove ZTLIDO. Do not use ZTLIDO if it is damaged. Throw it away and get a new one. ZTLIDO may be cut into smaller sizes with scissors prior to removal of the transparent release liner. Step 3a: Remove the transparent release liner before applying ZTLIDO to the skin. Apply ZTLIDO right away after removing the transparent release liner. Apply ZTLIDO only to intact skin. Step 3b: Place the adhesive side of ZTLIDO to skin, while not touching the sticky side. Smooth the ZTLIDO using your hands and firmly press to make sure it sticks well to skin. Step 4: Wash your hands well right away after applying ZTLIDO. Avoid contact of your hands or fingers with your eyes until after you wash your hands . Removing your ZTLIDO topical system: Step 5: Remove ZTLIDO from your skin after you have worn it for up to 12 hours. Fold the used ZTLIDO so that the sticky sides stick together. Step 6: Throw away the used whole or cut pieces of ZTLIDO where children and pets cannot get to them. Wash your hands well right away after removing ZTLIDO. Avoid contact of your hands and fingers with your eyes until after you wash your hands.

to 12 hours. Fold the used ZTLIDO so that the sticky sides stick together. Step 6: Throw away the used whole or cut pieces of ZTLIDO where children and pets cannot get to them. Wash your hands well right away after removing ZTLIDO. Avoid contact of your hands and fingers with your eyes until after you wash your hands. How to reattach ZTLIDO or apply a replacement ZTLIDO: If the ZTLIDO you are wearing comes off completely or lifts at the edges, reattach to the affected area by pressing firmly on the edges of the topical system or lifted areas. If ZTLIDO lifts off the skin or comes off completely more than 1 time, do not try to re-attach it. Throw away the used ZTLIDO as instructed above in Step 6 . If the ZTLIDO you are wearing comes off completely and will not stick to your skin, throw away the used ZTLIDO as instructed above in Step 6. Pat dry the area of skin if ZTLIDO came off while swimming or showering. Apply a replacement ZTLIDO the same way you would apply a new ZTLIDO as described above in Steps 1 through 6. Remove the replacement ZTLIDO at your usual removal time as described above in Steps 5 and 6. The total time you may wear the used and replacement ZTLIDO is 12 hours . Manufactured for: Scilex Pharmaceuticals Inc. Palo Alto, CA 94303 USA ZTLIDO ® is a trademark owned by Scilex Pharmaceuticals Inc. © 2021 Scilex Pharmaceuticals Inc. All rights reserved. SCILEX ® PHARMACEUTICALS Revised: 4/2021 Figure A Step 2 Step 2 Step 3a Step 3b Step 4 Step 5 Step 6

<table width="100%"><col width="50%" align="left" valign="top"/><col width="50%" align="left" valign="top"/><tbody><tr styleCode="Botrule"><td styleCode="Lrule Rrule"><content styleCode="bold">Step 1:</content>Select the application site. <list listType="unordered" styleCode="Disc"><item>ZTLIDO should only be applied to clean, dry, and intact skin to cover the most painful area.</item></list></td><td styleCode="Rrule"/></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"><content styleCode="bold">Step 2:</content>Using scissors, carefully cut the envelope along the dotted line and open it to remove ZTLIDO. <list listType="unordered" styleCode="Disc"><item>Do not use ZTLIDO if it is damaged. Throw it away and get a new one.</item><item>ZTLIDO may be cut into smaller sizes with scissors prior to removal of the transparent release liner.</item></list></td><td styleCode="Rrule"><paragraph><renderMultiMedia referencedObject="MM4"/><renderMultiMedia referencedObject="MM5"/></paragraph></td></tr><tr><td styleCode="Lrule Rrule"><content styleCode="bold">Step 3a:</content>Remove the transparent release liner before applying ZTLIDO to the skin. Apply ZTLIDO right away after removing the transparent release liner. Apply ZTLIDO only to intact skin. </td><td rowspan="2" styleCode="Rrule"><paragraph><renderMultiMedia referencedObject="MM6"/><renderMultiMedia referencedObject="MM7"/></paragraph></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"><content styleCode="bold">Step 3b:</content>Place the adhesive side of ZTLIDO to skin, while not touching the sticky side. Smooth the ZTLIDO using your hands and firmly press to make sure it sticks well to skin. </td></tr><tr><td styleCode="Lrule Rrule"><content styleCode="bold">Step 4:</content>Wash your hands well right away after applying ZTLIDO. <list listType="unordered" styleCode="Disc"><item><content styleCode="bold">Avoid contact of your hands or fingers with your eyes until after you wash your hands</content>. </item></list></td><td styleCode="Rrule Toprule"><paragraph><renderMultiMedia referencedObject="MM8"/></paragraph></td></tr></tbody></table>

TLIDO. <list listType="unordered" styleCode="Disc"><item><content styleCode="bold">Avoid contact of your hands or fingers with your eyes until after you wash your hands</content>. </item></list></td><td styleCode="Rrule Toprule"><paragraph><renderMultiMedia referencedObject="MM8"/></paragraph></td></tr></tbody></table> <table width="100%"><col width="50%" align="left" valign="top"/><col width="50%" align="left" valign="top"/><tbody><tr styleCode="Botrule"><td styleCode="Lrule Rrule"><content styleCode="bold">Step 5:</content>Remove ZTLIDO from your skin after you have worn it for up to 12 hours. <list listType="unordered" styleCode="Disc"><item>Fold the used ZTLIDO so that the sticky sides stick together.</item></list></td><td styleCode="Rrule"><paragraph><renderMultiMedia referencedObject="MM9"/></paragraph></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"><content styleCode="bold">Step 6:</content>Throw away the used whole or cut pieces of ZTLIDO where children and pets cannot get to them. <list listType="unordered" styleCode="Disc"><item>Wash your hands well right away after removing ZTLIDO. <content styleCode="bold">Avoid contact of your hands and fingers with your eyes until after you wash your hands.</content></item></list></td><td styleCode="Rrule"><paragraph><renderMultiMedia referencedObject="MM10"/></paragraph></td></tr></tbody></table>