glydo

1 INDICATIONS AND USAGE GLYDO (lidocaine HCl jelly) 2% is an amide local anesthetic indicated: for prevention and control of pain in procedures involving the male and female urethra for topical treatment of painful urethritis as an anesthetic lubricant for oral and nasal endotracheal intubation GLYDO (lidocaine HCl jelly) 2% contains lidocaine, an amide local anesthetic, and is indicated in adult patients: for prevention and control of pain in procedures involving the male and female urethra ( 1 ) for topical treatment of painful urethritis ( 1 ) as an anesthetic lubricant for oral and nasal endotracheal intubation ( 1 )

2 DOSAGE AND ADMINISTRATION The toxic effects of local anesthetics are additive. When using this product concomitantly with other lidocaine-containing products, consider the total dose of lidocaine and monitor patients for cardiovascular and respiratory vital signs. ( 2.1 ) For surface anesthesia of male adult urethra: 15 mL (300 mg lidocaine HCl) followed by additional 15 mL if needed ( 2.2 ) For surface anesthesia of female adult urethra: 3 mL to 5 mL (60 mg to 100 mg lidocaine HCl) ( 2.3 ) For lubrication for endotracheal intubation: sufficient amount to coat the external surface of endotracheal tube ( 2.4 ) For pediatric patients: Not more than 4.5 mg/kg body weight of lidocaine HCl ( 2.5 ) 2.1 Important Dosage and Administration Information Administration Precautions The toxic effects of local anesthetics are additive. Monitor for neurologic and cardiovascular effects related to local anesthetic systemic toxicity when additional local anesthetics are administered with GLYDO (lidocaine HCl jelly) 2% [see Warnings and Precautions ( 5.1 ), Adverse Reactions ( 6 ), Overdosage ( 10 )] . The dosage varies and depends upon the area to be anesthetized, vascularity of the tissues, individual tolerance, and the technique of anesthesia. The lowest dosage needed to provide effective anesthesia should be administered. Dosages should be reduced for children and for elderly and debilitated patients. Although the incidence of adverse effects with GLYDO (lidocaine HCl jelly) 2% 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. No more than 600 mg of lidocaine HCl should be given in any 12 hour period. 2.2 For Surface Anesthesia of the Male Adult Urethra Slowly instill approximately 15 mL (300 mg of lidocaine HCl) into the urethra. Apply a penile clamp for several minutes at the corona. An additional dose of not more than 15 mL (300 mg) can be instilled if needed. Prior to sounding or cystoscopy, a penile clamp should be applied for 5 to 10 minutes to obtain adequate anesthesia. A total dose of 30 mL (600 mg) is usually required to fill and dilate the male urethra. Prior to catheterization, 5 mL to 10 mL (100 mg to 200 mg) are recommended for lubrication. 2.3 For Surface Anesthesia of the Female Adult Urethra Slowly instill approximately 3 mL to 5 mL (60 mg to 100 mg of lidocaine HCl) into the urethra. In order to obtain adequate anesthesia, wait for several minutes prior to performing urological procedures. If desired, some jelly may be deposited on a cotton swab and introduced into the urethra. 2.4 Lubrication for Endotracheal Intubation Apply a sufficient amount of jelly to coat the external surface of the endotracheal tube shortly before use. Care should be taken to avoid introducing the product into the lumen of the tube. Do not use the jelly to lubricate endotracheal stylettes. (see WARNINGS and ADVERSE REACTIONS concerning rare reports of inner lumen occlusion). It is also recommended that use of endotracheal tubes with dried jelly on the external surface be avoided for lack of lubricating effect. 2.5 Dosing for Pediatric Patients A maximum dose of GLYDO (lidocaine HCl jelly) 2% for children varies based on age and weight. The maximum dose should not exceed 4.5 mg/kg of body weight. For children over 3 years of age, the maximum dose is determined by the child's age and weight. For example, in a child of 5 years weighing approximately 23 kg, the dose of lidocaine hydrochloride should not exceed approximately 75 mg to 100 mg (3.3 mg/kg to 4.4 mg/kg). The lowest effective dose should be used.

4 CONTRAINDICATIONS Known hypersensitivity to any local anesthetic agent of the amide-type or to other components of GLYDO 2% Jelly ( 4.1 ) Infected and/or Severely Traumatized Mucosa ( 4.2 ) Severe shock or heart block ( 4.3 ) 4.1 Hypersensitivity GLYDO 2% Jelly is contraindicated in patients with a known history of hypersensitivity to lidocaine or to any local anesthetics of the amide type or to other components of GLYDO 2% Jelly. 4.2 Use on Infected and/or Severely Traumatized Mucosa GLYDO 2% Jelly should not be used on infected and/or severely traumatized mucosa in the area of application. 4.3 Use in Severe Shock or Heart Block GLYDO 2% Jelly should not be used in patients with severe shock or heart block.

5 WARNINGS AND PRECAUTIONS Dose-Related Toxicity : follow dosing instructions carefully. ( 5.1 ) Methemoglobinemia : Cases have been reported in association with local anesthetics use. See full prescribing information for more details on managing these risks. ( 5.2 ) Familial Malignant Hyperthermia : Monitoring of patients is recommended ( 5.3 ) Endotracheal Tube Occlusion : Avoid introduction of jelly into the lumen of the endotracheal tube ( 5.4 ) Risk of Aspiration and Biting Trauma with Oral Use : Food and chewing gum should not be taken while the mouth or throat area is anesthetized ( 5.7 ) 5.1 Dose-Related Toxicity The safety and effectiveness of GLYDO 2% Jelly depends on proper dosage, correct technique, adequate precautions, and readiness for emergencies [see Adverse Reactions ( 6 )]. Careful and constant monitoring of cardiovascular and respiratory (adequacy of ventilation) vital signs and the patient's state of consciousness should be performed after application of GLYDO 2% Jelly. Possible early warning signs of central nervous system (CNS) toxicity are restlessness, anxiety, incoherent speech, lightheadedness, numbness and tingling of the mouth and lips, metallic taste, tinnitus, dizziness, blurred vision, tremors, twitching, CNS depression, or drowsiness. Delay in proper management of dose-related toxicity, underventilation from any cause, and/or altered sensitivity may lead to the development of acidosis, cardiac arrest, and, possibly, death. Use the lowest dosage that results in effective anesthesia 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 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 status. Patients and healthcare providers 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. 5.2 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 [see Drug Interactions ( 7.2 )] . 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 GLYDO 2% Jelly 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. 5.3 Familial Malignant Hyperthermia 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 management 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). 5.4 Endotracheal Tube Occlusion When used for endotracheal tube lubrication, care should be taken to avoid introducing the product into the lumen of the tube. Do not use the jelly to lubricate the endotracheal stylettes. If allowed into the inner lumen, the jelly may dry on the inner surface leaving a residue which tends to clump with flexion, narrowing the lumen. There have been rare reports in which this residue has caused the lumen to occlude [see Adverse Reactions ( 6 ) and Dosage and Administration ( 2 )] . 5.5 Anaphylactic Reactions Anaphylactic reactions may occur following administration of lidocaine hydrochloride [see Adverse Reactions ( 6 )] . Patients allergic to para-aminobenzoic acid derivatives (procaine, tetracaine, benzocaine, etc.) have not shown cross sensitivity to lidocaine. 5.6 Risk of Toxicity in Patients with Hepatic Impairment Because amide local anesthetics such as lidocaine are metabolized by the liver, consider reduced dosing and increased monitoring for lidocaine systemic toxicity in patients with moderate to severe hepatic impairment who are treated with GLYDO 2% Jelly, especially with repeat doses [see Use in Specific Populations ( 8.6 )] . 5.7 Risk of Aspiration and Biting Trauma with Oral Use When used orally (i.e., endotracheal tube lubrication), topical anesthesia may occur to oropharyngeal structures. This may impair swallowing and thus enhance the danger of aspiration. For this reason, food should not be ingested for 60 minutes following 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.

7 DRUG INTERACTIONS Local Anesthetics : The toxic effects of local anesthetics are additive. Monitor for neurologic and cardiovascular effects when additional local anesthetics are administered ( 7.1 ). Drugs Associated with Methemoglobinemia : Patients are at increased risk of developing methemoglobinemia when concurrently exposed to nitrates, nitrites, local anesthetics, antineoplastic agents, antibiotics, antimalarials, anticonvulsants, and other drugs ( 7.2 ). Hepatic Impairment : Consider reduced dosing and increased monitoring for local anesthetic systemic toxicity in patients with hepatic impairment ( 8.6 ) 7.1 Local Anesthetics The toxic effects of local anesthetics are additive. If coadministration of other local anesthetics with GLYDO 2% Jelly cannot be avoided, monitor patients for neurologic and cardiovascular effects related to local anesthetic systemic toxicity [see Warnings and Precautions ( 5.1 )]. 7.2 Drugs Associated with Methemoglobinemia 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 Antineoplastics 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

6 ADVERSE REACTIONS The following adverse reactions associated with the use of GLYDO 2% Jelly were identified in clinical studies or postmarketing reports. 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. Adverse experiences following the administration of lidocaine are similar in nature to those observed with other amide local anesthetic agents. A major cause of adverse reactions to this group of drugs is excessive plasma levels, which may be due to overdosage or slow metabolic degradation. The most commonly encountered acute adverse reactions that demand immediate counter measures were related to the CNS and the cardiovascular system. 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. There have been rare reports of endotracheal tube occlusion associated with the presence of dried jelly residue in the inner lumen of the tube. Most common adverse reactions are as follows: Central Nervous System : 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. ( 6 ) Cardiovascular System : Bradycardia, hypotension, and cardiovascular collapse. ( 6 ) Allergic : Cutaneous lesions, urticaria, edema or anaphylactoid reactions. ( 6 ) Neurologic : Positional headaches, hypotension and backache. ( 6 ) Hematologic : Methemoglobinemia. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Sagent Pharmaceuticals at 1-866-625-1618 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . Nervous System Disorders Adverse reactions were characterized by excitation and/or depression of the central nervous system and included 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. Cardiac Disorders High doses have led to high plasma levels and related depression of the myocardium, decreased cardiac output, heartblock, hypotension, bradycardia, and cardiovascular collapse, which may lead to cardiac arrest. Immune System Disorders 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.

8.1 Pregnancy Risk Summary Available published data and decades of clinical use with GLYDO 2% Jelly in pregnant women have not identified any drug-associated risk for major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Local anesthetics may cause varying degrees of toxicity to the mother and fetus and adverse reactions include alterations of the central nervous system, peripheral vascular tone and cardiac function [see Clinical Considerations ]. There was no evidence of teratogenicity when lidocaine was administered to pregnant rats and rabbits subcutaneously at 0.8 and 0.16 times, respectively, the maximum recommended human dose (MRHD) of 600 mg during the period of organogenesis. In a published animal reproduction study, pregnant rats administered lidocaine by continuous subcutaneous infusion at 8 times the MRHD during the period of organogenesis resulted in lower fetal body weights [see Data ] . The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Maternal adverse reactions During treatment of systemic toxicity, which may appear as maternal hypotension or fetal bradycardia, the parturient should be maintained in the left lateral decubitus position if possible or manual displacement of the uterus off the great vessels be accomplished. Elevating the patient's legs will also help prevent decreases in blood pressure. The fetal heart rate also should be monitored continuously, and electronic fetal monitoring is highly advisable. Labor or delivery Local anesthetics rapidly cross the placenta and can cause varying degrees of maternal, fetal and neonatal toxicity [see Clinical Pharmacology ( 12.3 )] . The incidence and degree of toxicity depend 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. However, dosage recommendations for local anesthesia are much lower than dosage recommendations for other major blocks. Data Animal Data Reproduction studies for lidocaine have been performed in both rats and rabbits. There was no evidence of harm to the fetus when pregnant rats were given subcutaneous doses of up to 50 mg/kg lidocaine (approximately 0.8 times the MRHD of 600 mg based on body surface area (BSA) comparison) during the period of organogenesis. In addition, there was no evidence of harm to the fetus when pregnant rabbits were given a subcutaneous dose of 5 mg/kg (approximately 0.16 times the MRHD based on BSA comparison) during the period of organogenesis. Treatment of pregnant rabbits with 25 mg/kg (approximately 0.8 times the MRHD based on BSA comparison) produced evidence of maternal toxicity and evidence of delayed fetal development, including a non-significant decrease in fetal weight (7%) and an increase in minor skeletal anomalies (skull and sternebral defect, reduced ossification of the phalanges). The effect of lidocaine on post-natal development was examined in rats by treating pregnant female rats daily subcutaneously at doses of 2, 10, and 50 mg/kg (approximately 0.03, 0.16, and 0.8 times, respectively, the MRHD based on BSA comparison) from Day 15 of pregnancy and up to 20 days postpartum. No signs of adverse effects were seen either in dams or in the pups up to and including the dose of 10 mg/kg; however, the number of surviving pups was reduced at 50 mg/kg, both at birth and the duration of lactation period, the effect most likely being secondary to maternal toxicity. No other effects on litter size, litter weight, abnormalities in the pups and physical developments of the pups were seen in this study. A second study examined the effects of lidocaine on post-natal development in the rat that included assessment of the pups from weaning to sexual maturity. Rats were treated for 8 months with 10 or 30 mg/kg, s.c. lidocaine (approximately 0.8 and 1.6 times, respectively, the MRHD based on BSA comparison). This time period encompassed 3 mating periods. There was no evidence of altered post-natal development in any offspring; however, both doses of lidocaine significantly reduced the average number of pups per litter surviving until weaning of offspring from the first 2 mating periods. 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 8 times the MRHD based on BSA comparison) in the absence of maternal toxicity.