Zingo

------------------INDICATIONS AND USAGE------------------- ZINGO is an amide local anesthetic indicated for use on intact skin to provide local analgesia prior to venipuncture or peripheral intravenous cannulation in children 3–18 years of age. (1) ZINGO is indicated for use on intact skin to provide topical local analgesia prior to venipuncture in adults. (1) Important Limitations : For use on intact skin only (1, 2) For external use only (5) 1 INDICATIONS AND USAGE ZINGO is indicated for use on intact skin to provide topical local analgesia prior to venipuncture or peripheral intravenous cannulation, in children 3–18 years of age. ZINGO is indicated for use on intact skin to provide topical local analgesia prior to venipuncture in adults.

---------------DOSAGE AND ADMINISTRATION--------------- Apply one ZINGO (0.5 mg lidocaine hydrochloride monohydrate) to the site planned for venipuncture or intravenous cannulation, one to three minutes prior to needle insertion. (2.1) Perform the procedure within 10 minutes after ZINGO administration. (2) Use ZINGO only on intact skin. (2) 2 DOSAGE AND ADMINISTRATION Apply one ZINGO (0.5 mg lidocaine hydrochloride monohydrate) to the site planned for venipuncture or intravenous cannulation, one to three minutes prior to needle insertion. Perform the procedure within 10 minutes after ZINGO administration. Use ZINGO only on intact skin. Application of one additional ZINGO at a new location is acceptable after a failed attempt at venous access. Multiple administrations of ZINGO at the same location are not recommended. When ZINGO is used concomitantly with other products containing local anesthetic agents, the amount absorbed from all sources should be considered, as local anesthetics are thought to have at least additive toxicities. 2.1 Instructions for Use Prepare the Treatment Site and Device : Examine the treatment site to ensure that the skin is intact. Clean the site, according to standard practice. Visually inspect the pouch. Do not use if the pouch has been torn, or damaged or if the device has been dropped. Tear open the pouch using the notch provided (Figure 1a). Remove ZINGO from the pouch, being careful not to touch the purple outlet (open end) to avoid contamination (Figure 1b). Position ZINGO : Grip ZINGO and place on the application site, with one hand, as illustrated in Figure 2, or with both hands, as shown in Figure 3. Ensure that the patient’s treatment site is supported to prevent movement. Seal the purple ZINGO outlet against the patient’s skin. Hold the device perpendicular to the skin, making sure that your thumb can reach the green start button. Avoid gaps between the skin and the ZINGO outlet, like the one illustrated in Figure 4, as gaps will impede drug delivery. Release the Safety Interlock : Apply adequate downward pressure to release the safety interlock, while maintaining the seal between ZINGO and the skin. ZINGO is ready for administration when the green start button has moved into the upward position, as illustrated in Figure 5a. ZINGO cannot be actuated without releasing the internal safety interlock, as illustrated in Figure 5b. Administer ZINGO : While maintaining downward pressure, administer the dose by pressing the green start button, as illustrated in Figure 6. Do not move ZINGO during administration. Actuation is accompanied by a “popping” sound, indicating that the dose has been discharged. Remove ZINGO : Remove ZINGO from the application site and dispose. Begin Procedure : Start the venipuncture or intravenous cannulation procedure 1–3 minutes after ZINGO administration. Figure 1a Figure 1b Figure Figure 3 Figure 4 Figure 5a Figure 5b Figure 6

---------------------CONTRAINDICATIONS--------------------- ZINGO is contraindicated in patients with a known history of sensitivity to local anesthetics of the amide type. (4) 4 CONTRAINDICATIONS ZINGO is contraindicated in patients with a known history of sensitivity to local anesthetics of the amide type.

---------------WARNINGS AND PRECAUTIONS--------------- Methemoglobinemia : Cases of methemoglobinemia have been reported in association with local anesthetic use. (5.1) Use on intact skin only (2.1, 5) Avoid contact with the eye (2.1, 5) Do not use if device is dropped or the pouch is damaged or torn (2.1) Patients with bleeding tendencies or platelet disorders could have a higher risk of superficial dermal bleeding (5) 5 WARNINGS AND PRECAUTIONS Do not use around the eyes. Do not use ZINGO on body orifices, mucous membranes, or on areas with a compromised skin barrier. Only use ZINGO on skin locations where an adequate seal can be maintained. Patients with severe hepatic disease or pseudocholinesterase deficiency, because of their inability to metabolize local anesthetics normally, are at a greater risk of developing toxic plasma concentrations of lidocaine. Patients with bleeding tendencies or platelet disorders could have a higher risk of superficial dermal bleeding. 5.1 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 ZINGO 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. 5.1 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 ZINGO 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.

7 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

---------------------ADVERSE REACTIONS--------------------- The most common adverse reactions (>5%) are skin reactions at the site of administration: erythema, petechiae, edema, and pruritus (6.1) To report SUSPECTED ADVERSE REACTIONS, contact 7T Pharma, LLC, at 1-800-941-2848 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. See 17 for PATIENT COUNSELING INFORMATION. Revised: December 2025 6 ADVERSE REACTIONS 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. The safety of ZINGO has been evaluated in 10 clinical trials, five in adults and five in pediatric patients. The five adult clinical trials consisted of a randomized, double-blind, parallel-arm, sham-placebo controlled Phase 3 trial that enrolled 693 patients, two randomized, double-blind, crossover design, sham-placebo controlled Phase 1 trials that enrolled 455 patients, and two open-label studies that enrolled 44 patients. A total of 742 adults received an active treatment with an active treatment that delivered a 0.5 mg dose of lidocaine, while 775 received placebo. The five pediatric clinical trials consisted of five randomized, double-blind, parallel-arm, sham-placebo controlled trials in which 1761 patients, ages 3 to 18, received either ZINGO or a sham placebo device. A total of 906 pediatric patients received active treatment, while 855 received placebo. Application Site Reaction The application site was specifically assessed for four categories of skin site reaction (erythema, edema, pruritus, and petechiae). In adults, erythema occurred in 67.3% of ZINGO-treated patients, and in 25.0% of placebo-treated patients. Petechiae occurred in 46.4% of ZINGO-treated patients, and in 7.0% of placebo-treated patients. Edema occurred in 4.3% of ZINGOtreated patients, and in 0.8% of placebo-treated patients. Pruritus occurred in 9.4% of ZINGO-treated patients and in 6.2% of placebo-treated patients. In pediatric patients, erythema occurred in 53% of ZINGO-treated patients, and in 27% of placebo-treated patients. Petechiae occurred in 44% of ZINGO-treated patients, and in 5% of placebo-treated patients. Edema occurred in 8% of ZINGO-treated patients, and in 3% of placebo-treated patients. Pruritus occurred in 1% of patients in both treatment groups. Adverse Reactions Amongst the 742 adult patients receiving active treatment and 775 adult patients receiving sham placebo treatment in the 5 adult studies, the percentage of adult patients with any adverse reactions was 3.9% in the active-treated patients and 4.9% in the sham placebo treated patients. Most adverse reactions were application-site related (i.e., hypoaesthesia (0% active, 0.5% sham placebo), burning (0.54% active, 0.4% sham placebo), and venipuncture site hemorrhage (0.4% active, 1.7% sham placebo)). The most common systemic adverse reaction was dizziness, which occurred in 0.9% of active-treated adult patients and in 0.7% of sham placebo treated adult patients. No other systemic adverse events occurred in more than two patients in either treatment group. Amongst the 906 pediatric patients receiving active treatment and 855 pediatric patients receiving sham placebo treatment, the percentage of pediatric patients with any adverse reactions was approximately 9% in each treatment group. Most adverse reactions were application-site related (i.e., bruising, burning, pain, contusion, hemorrhage), occurring in 4% of pediatric patients in each treatment group. The most common systemic adverse reactions were nausea (2%) and vomiting (1%).

8 USE IN SPECIFIC POPULATIONS 8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary Available published data and decades of clinical use with lidocaine in pregnant women have not identified any drug-associated risk for major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Lidocaine is not detectable systemically following intradermal administration [see Clinical Pharmacology (12.3)], and maternal use is not expected to result in fetal exposure to the drug. Lidocaine has been previously tested for reproductive toxicity in animal studies. The following ratios are based on the assumption that the applied dose is completely absorbed through the skin. In an 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 a dose of 6 mg/kg at 120-fold the single dermal administration (SDA) of 0.5 mg lidocaine on Gestation Day 11 resulted in developmental delays in neonatal behavior among offspring. In another animal reproduction study, no developmental toxicities were observed in rats administered lidocaine by subcutaneous route at doses up to 1200-fold the SDA or in rabbits up to 600-fold the SDA (see Data). The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies carry some risk of birth defects, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data Lidocaine was not teratogenic in rats given subcutaneous doses up to 60 mg/kg [360 mg/m2 or 1200-fold the single dermal administration (SDA) of 0.5 mg lidocaine in a 60 kg individual (0.3 mg/m2)] or in rabbits up to 15 mg/kg (180 mg/m2 or 600-fold the SDA) during the period of organogenesis. In a published study, lidocaine administered to pregnant rats by continuous subcutaneous infusion during the period of organogenesis at doses of 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 (3000 mg/m2 or 10,000-fold the SDA on a mg/m2 basis) in the absence of maternal toxicity. Lidocaine, containing 1:100,000 epinephrine, at a dose of 6 mg/kg (36 mg/m2 or 120-fold the SDA) injected into the masseter muscle of the jaw or into the gum of the lower jaw of Long-Evans hooded pregnant rats on Gestation Day 11 led to developmental delays in neonatal behavior among offspring. 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 the animal data is uncertain. 8.2 Lactation Risk Summary Published data report the presence of lidocaine and its metabolites in human milk in low amounts following parenteral administration, along with poor oral bioavailability. There are no data on the effect of lidocaine on the breastfed infant or the effect on milk production. There are no detectable plasma concentrations of lidocaine after subdermal administration of ZINGO; therefore, breastfeeding is not expected to result in exposure of the child to lidocaine [see Clinical Pharmacology (12.3)]. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ZINGO and any potential adverse effects on the breastfed child from ZINGO or from the underlying maternal condition. 8.4 Pediatric Use Safety and effectiveness in pediatric patients below the age of 3 years have not been established. 8.5 Geriatric Use Of the 693 patients evaluated in a Phase 3 randomized, double blind, sham-placebo-controlled trial in adults, 17% were of 65 and over. The safety and effectiveness of ZINGO in geriatric patients were similar to that of ZINGO in adults under 65 years of age. 8.1 Pregnancy Risk Summary Available published data and decades of clinical use with lidocaine in pregnant women have not identified any drug-associated risk for major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Lidocaine is not detectable systemically following intradermal administration [see Clinical Pharmacology (12.3)], and maternal use is not expected to result in fetal exposure to the drug. Lidocaine has been previously tested for reproductive toxicity in animal studies. The following ratios are based on the assumption that the applied dose is completely absorbed through the skin. In an 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 a dose of 6 mg/kg at 120-fold the single dermal administration (SDA) of 0.5 mg lidocaine on Gestation Day 11 resulted in developmental delays in neonatal behavior among offspring. In another animal reproduction study, no developmental toxicities were observed in rats administered lidocaine by subcutaneous route at doses up to 1200-fold the SDA or in rabbits up to 600-fold the SDA (see Data). The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies carry some risk of birth defects, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data Lidocaine was not teratogenic in rats given subcutaneous doses up to 60 mg/kg [360 mg/m2 or 1200-fold the single dermal administration (SDA) of 0.5 mg lidocaine in a 60 kg individual (0.3 mg/m2)] or in rabbits up to 15 mg/kg (180 mg/m2 or 600-fold the SDA) during the period of organogenesis. In a published study, lidocaine administered to pregnant rats by continuous subcutaneous infusion during the period of organogenesis at doses of 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 (3000 mg/m2 or 10,000-fold the SDA on a mg/m2 basis) in the absence of maternal toxicity. Lidocaine, containing 1:100,000 epinephrine, at a dose of 6 mg/kg (36 mg/m2 or 120-fold the SDA) injected into the masseter muscle of the jaw or into the gum of the lower jaw of Long-Evans hooded pregnant rats on Gestation Day 11 led to developmental delays in neonatal behavior among offspring. 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 the animal data is uncertain. 8.2 Lactation Risk Summary Published data report the presence of lidocaine and its metabolites in human milk in low amounts following parenteral administration, along with poor oral bioavailability. There are no data on the effect of lidocaine on the breastfed infant or the effect on milk production. There are no detectable plasma concentrations of lidocaine after subdermal administration of ZINGO; therefore, breastfeeding is not expected to result in exposure of the child to lidocaine [see Clinical Pharmacology (12.3)]. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ZINGO and any potential adverse effects on the breastfed child from ZINGO or from the underlying maternal condition. 8.4 Pediatric Use Safety and effectiveness in pediatric patients below the age of 3 years have not been established. 8.5 Geriatric Use Of the 693 patients evaluated in a Phase 3 randomized, double blind, sham-placebo-controlled trial in adults, 17% were of 65 and over. The safety and effectiveness of ZINGO in geriatric patients were similar to that of ZINGO in adults under 65 years of age.