Lidocaine

1 INDICATIONS AND USAGE Lidocaine Hydrochloride Injection is indicated in adult and pediatric patients for the production of local or regional anesthesia or analgesia for surgery, dental, and oral surgery procedures, diagnostic and therapeutic procedures, and for obstetrical procedures. Specific concentrations and presentations of Lidocaine Hydrochloride Injection is recommended for each type of block indicated to produce local or regional anesthesia or analgesia [see Dosage and Administration (2.2) ]. Lidocaine Hydrochloride Injection contains lidocaine, an amide local anesthetic is indicated in adult and pediatric patients for the production of local or regional anesthesia or analgesia for surgery, dental, and oral surgery procedures, diagnostic and therapeutic procedures, and for obstetrical procedures. For each type of block indicated to produce local or regional anesthesia or analgesia, specific concentrations and presentations are recommended. ( 1 , 2.2 )

2 DOSAGE AND ADMINISTRATION See Full Prescribing Information for recommended dosages and administration information for adult and pediatric patients 2.1 Important Dosage and Administration Information Lidocaine Hydrochloride Injection is not recommended for intrathecal use. Avoid use of Lidocaine Hydrochloride Injection solutions containing antimicrobial preservatives (i.e., multiple-dose vials) for epidural or caudal anesthesia [see Warnings and Precautions (5.3) ]. Discard unused portions of solution not containing preservatives, i.e., those supplied in single-dose vials, following initial use. Visually inspect this product for particulate matter and discoloration prior to administration whenever solution and container permit. Lidocaine Hydrochloride Injection is clear, colorless solution. Do not administer solutions which are discolored or contain particulate matter. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever the solution and container permit. Solutions which are discolored (e.g., pinkish or darker than slightly yellow) or which contain particulate matter or precipitate should not be administered. Mixing or the prior or intercurrent use of any other local anesthetic with Lidocaine Hydrochloride Injection is not recommended because of insufficient data on the clinical use of such mixtures. Administration Precautions Lidocaine Hydrochloride Injection is to be administered in carefully adjusted dosages by or under the supervision of experienced clinicians who are well versed in the diagnosis and management of dose related toxicity and other acute emergencies which might arise from the block to be employed. Use Lidocaine Hydrochloride Injection only if the following are immediately available: oxygen, cardiopulmonary resuscitative equipment and drugs, and the personnel resources needed for proper management of toxic reactions and related emergencies [see Warnings and Precautions (5.1) , Adverse Reactions (6) , Overdosage (10) ]. 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 Lidocaine Hydrochloride Injection [see Warnings and Precautions (5.1) , Drug Interactions (7.1) , Overdosage (10) ]. Aspirate for blood or cerebrospinal fluid (where applicable) prior to injecting Lidocaine Hydrochloride Injection, both the initial dose and all subsequent doses, to avoid intravascular or intrathecal injection. However, a negative aspiration for blood or cerebrospinal fluid does not ensure against an intravascular or intrathecal injection [see Warnings and Precautions (5.7) ]. Avoid rapid injection of a large volume of Lidocaine Hydrochloride Injection and use fractional (incremental) doses when feasible. During major regional nerve blocks, such as those of the brachial plexus or lower extremity, the patient should have an indwelling intravenous catheter to assure adequate intravenous access. The lowest dosage of Lidocaine Hydrochloride Injection that results in effective anesthesia should be used to avoid high plasma levels and serious adverse reactions. Perform careful and constant monitoring of cardiovascular and respiratory (adequacy of oxygenation and ventilation) vital signs and the patient’s level of consciousness after each local anesthetic injection. Use Lidocaine Hydrochloride Injection in carefully restricted quantities in areas of the body supplied by end arteries or having otherwise compromised blood supply such as digits, nose, external ear, or penis [see Warnings and Precautions (5.10) ]. 2.2 Recommended Concentrations and Dosages of Lidocaine Hydrochloride Injection in Adults The dosage of Lidocaine Hydrochloride Injection administered varies with the anesthetic procedure, the area to be anesthetized, the vascularity of the tissues, the number of neuronal segments to be blocked, the depth …

3 DOSAGE FORMS AND STRENGTHS Lidocaine Hydrochloride Injection, USP is a clear, colorless solution available as: 1% (10 mg/mL): 2 mL Multiple Dose Vials packaged in 25s 20 mL Multiple Dose Vials packaged in 10s 30 mL Multiple Dose Vials packaged in 10s 50 mL Multiple Dose Vials packaged in 10s 2% (20 mg/mL): 2 mL Multiple Dose Vials packaged in 25s 20 mL Multiple Dose Vials packaged in 10s 50 mL Multiple Dose Vials packaged in 10s Lidocaine Hydrochloride Injection, USP - Preserved: 1%, 2%

CONTRAINDICATIONS Lidocaine Hydrochloride Injection, USP is contraindicated in patients with a known history of hypersensitivity to local anesthetics of the amide type. Lidocaine Hydrochloride Injection, USP should not be used in patients with STOKES-ADAMS syndrome, Wolff-Parkinson-White syndrome, or with severe degrees of sinoatrial, atrioventricular or intraventricular block.

6 ADVERSE REACTIONS The following clinically significant adverse reactions have been reported and described in the Warnings and Precautions section of the labeling: Dose-Related Toxicity [see Warnings and Precautions (5.1) ] Methemoglobinemia [see Warnings and Precautions (5.2) ] Chondrolysis with Intra-Articular Infusion [see Warnings and Precautions (5.4) ] Severe, Persistent Hypertension, Cerebrovascular Accidents, and Bradycardia Due to Drug Interactions [see Warnings and Precautions (5.5) ] Allergic-Type Reactions [see Warnings and Precautions (5.6) ] Systemic Toxicities with Unintended Intravascular or Intrathecal Injection [see Warnings and Precautions (5.7)] Respiratory Arrest Following Retrobulbar Block [see Warnings and Precautions (5.14)] The following adverse reactions from voluntary reports or clinical studies have been reported with lidocaine or lidocaine and epinephrine. Because many 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 reactions to Lidocaine Hydrochloride Injection are characteristic of those associated with other amidetype local anesthetic. A major cause of adverse reactions to this group of drugs is excessive plasma levels, which may be due to overdosage, unintentional intravascular injection, 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 reactions were generally dose-related and due to high plasma levels which may have resulted from overdosage, rapid absorption from the injection site, diminished tolerance, or from unintentional intravascular injection of the local anesthetic solution. In addition to systemic does-related toxicity, unintentional intrathecal injection of drug during the intended performance of caudal or lumbar epidural block or nerve blocks near the vertebral column (especially in the head and neck region) has resulted in underventilation or apnea (“Total or High Spinal”). Also, hypertension due to loss of sympathetic tone and respiratory paralysis or underventilation due to cephalad extension of the motor level of anesthesia have occurred. This has led to secondary cardiac arrest when untreated. When used for dental injections, paresthesia of the lips, tongue, and oral tissues have been reported. Persistent paresthesia lasting weeks to months and, in some instances, lasting greater than one year, have also been reported. 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 incidences of adverse reactions associated with the use of local anesthetics may be related to the total dose of local anesthetic administered and are also dependent upon the particular drug used, the route of administration and the physical status of the patient. In a prospective review of 10,440 patients who received lidocaine hydrochloride for spinal anesthesia, the incidences of adverse reactions were reported to be about 3 percent each for positional headaches, hypotension and backache; 2 percent for shivering; and less than 1 percent each for peripheral nerve symptoms, nausea, respiratory inadequacy and double vision. Persistent motor, sensory and/or autonomic (sphincter control) deficit of some lower spinal segments with slow recovery (several months) or incomplete recovery have been reported in rare instances when caudal or lumbar epidural block has been attempted. Backache and headache have also been noted following use of these anesthetic procedures. There have bee …

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) Monoamine Oxidase Inhibitors and Tricyclic Antidepressants: Administration of Lidocaine Hydrochloride Injection to patients receiving monoamine oxidase inhibitors or tricyclic antidepressants may produce severe, prolonged hypertension. Concurrent use of these agents should generally be avoided ( 5.5 , 7.2 ) Ergot-type Oxytocic drugs: Concurrent administration of Lidocaine Hydrochloride Injection and ergot-type oxytocic drugs may cause severe, persistent hypertension or cerebrovascular accidents (5.5 , 7.3) Nonselective Beta-Adrenergic Antagonists: Administration of Lidocaine Hydrochloride Injection in patients receiving nonselective beta-adrenergic antagonist may cause severe hypertension and bradycardia. Concurrent use of these agents should generally be avoided. (5.5 , 7.4) 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 (7.5). Potent Inhalation Anesthetics: Serious dose-related cardiac arrhythmias may occur if preparations containing epinephrine are used in patients during or following the administration of potent inhalation anesthetics ( 5.11 , 7.6) Geriatric Use: Elderly patients should be given reduced doses commensurate with their age and physical condition (8.5) 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 lidocaine hydrochloride cannot be avoided, monitor patients for neurologic and cardiovascular effects related to local anesthetic systemic toxicity [see Warnings and Precautions (5.1) ]. 7.2 Monoamine Oxidase Inhibitors and Tricyclic Antidepressants The administration of Lidocaine Hydrochloride Injection to patients receiving monoamine oxidase inhibitors or tricyclic antidepressants may produce severe, prolonged hypertension. Concurrent use of these agents should generally be avoided. In situation when concurrent therapy is necessary, careful monitoring of the patient’s hemodynamic status is essential [see Warnings and Precautions (5.5) ]. 7.3 Ergot-Type Oxytocic Drugs 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. Avoid use of Lidocaine Hydrochloride Injection concomitantly with ergot-type oxytocic drugs [see Warnings and Precautions (5.5)] . 7.4 Nonselective Beta-Adrenergic Antagonists Administration of Lidocaine Hydrochloride Injection in patients receiving nonselective beta-adrenergic antagonists may cause severe hypertension and bradycardia. Concurrent use of these agents should generally be avoided. In situations when concurrent therapy is necessary, careful monitoring of the patient’s blood pressure and heart rate is essential [see Warnings and Precautions (5.5) ]. 7.5 Drugs Associated with Methemoglobinemia Patients that are administered local anesthetics may be at increased risk of developing methemoglobinemia when concurrently exposed to the following oxidizing agents: Class Examples Nitrates/Nitrites nitroglycerin, nitroprusside, nitric oxide, nitrous oxide Local anesthetics articaine, benzocaine, bupivacaine, lidocaine, mepivacaine, prilocaine, procaine, ropivacaine, tetracaine Antineoplastic agents cyclophosphamide, flutamide, rasburicase, ifosfamide, hydroxyurea Antibiotics dapsone, sulfonamides, nitrofurantoin, para-aminosalicylic acid Antimalarials chloroquine, primaquine Anticonvulsants phenytoin, sodium valproat …

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary Available published data and decades of clinical use with lidocaine hydrochloride 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) . In a published animal reproduction study, pregnant rats administered lidocaine by continuous subcutaneous infusion at a dose approximately 9.6 times the maximum recommended human dose (MRHD) of 500 mg in lidocaine hydrochloride during the period of organogenesis resulted in lower fetal body weights [see Data ]. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defects, loss, or other adverse outcomes. In the United States 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 Maternal hypotension has resulted from regional anesthesia. Local anesthetics produce vasodilation by blocking sympathetic nerves. Therefore, during treatment of systemic toxicity, maternal hypotension or fetal bradycardia following regional block, 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 when used for epidural, paracervical, pudendal or caudal block anesthesia, 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 spinal anesthesia are much lower than dosage recommendations for other major blocks. Spinal anesthesia may alter the forces of parturition through changes in uterine contractility or maternal expulsive efforts. Spinal anesthesia has 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. Data Animal Data 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 hydrochloride. 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 9.6 times the maximum recommended human dose [MRHD] of 500 mg lidocaine on a mg/m2 basis) in the absence of maternal toxicity. 8.2 Lactation Risk Summary Published data report the presence of lidocaine and its metabolites in human milk in low amounts, along with poor oral bioavailability. There are no data on the effect of lidocaine on the breastfed infant or the effect on milk production. The developmental and health benefits of b …

Mechanism of action Lidocaine stabilizes the neuronal membrane by inhibiting the ionic fluxes required for the initiation and conduction of nerve impulses, thereby effecting local anesthetic action.

DESCRIPTION Sterile isotonic solutions containing a local anesthetic agent, Lidocaine Hydrochloride, and a vasoconstrictor, epinephrine (as bitartrate) and are administered parenterally by injection. Both solutions are available in single dose cartridges of 1.7 mL (See INDICATIONS AND USAGE for specific uses). Solutions contain lidocaine hydrochloride which is chemically designated as acetamide, 2-(diethylamino)-N-(2,6-dimethylphenyl)-monohydrochloride, and has the following structural formula: C 14 H 22 N 2 0 • HCl • H 2 0 M.W. 288.8 Epinephrine is ( - )-3, 4-Dihydroxy-α-[(Methylamino) methyl] benzyl alcohol and has the following structural formula: C 9 H 13 N0 3 M.W. 183.21 COMPOSITION OF LIDOCAINE HYDROCHLORIDE AND EPINEPHRINE INJECTION, USP BRAND NAME PRODUCT IDENTIFICATION FORMULA SINGLE DOSE CARTRIDGE Lidocaine hydrochloride Epinephrine (as the bitartrate) Sodium Chloride Potassium metabisulfite Edetate Disodium USP (as dihydrate) Concentration % Dilution (mg/mL) (mg/mL) (mg/mL) LIDOCAINE HCl 2% and EPINEPHRINE 1:50,000 2 1:50,000 6.5 1.2 0.25 LIDOCAINE HCl 2% and EPINEPHRINE 1:100,000 2 1:100,000 6.5 1.2 0.25 The pH of the lidocaine hydrochloride and epinephrine injection, USP solutions are adjusted to USP limits with Sodium Hydroxide or Hydrochloric Acid q.s. to adjust pH. lidocaine hydrochloride Epinephrine

OVERDOSAGE Acute emergencies from local anesthetics are generally related to high plasma levels encountered during therapeutic use of local anesthetics or to unintended subarachnoid injection of local anesthetic solution (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 injection. At the first sign of change, oxygen should be administered. The first step in the management of convulsions, as well as underventilation or apnea due to unintended subarachnoid injection of drug solution, 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 the 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. Underventilation or apnea due to unintentional subarachnoid injection of local anesthetic solution may produce these same signs and also lead to cardiac arrest if ventilatory support is not instituted. If cardiac arrest should occur, standard cardiopulmonary resuscitative measures should be instituted. Endotracheal intubation, employing drugs and techniques familiar to the clinician, may be indicated, after initial administration of oxygen by mask, if difficulty is encountered in the maintenance of a patent airway or if prolonged ventilatory support (assisted or controlled) is indicated. Dialysis is of negligible value in the treatment of acute overdosage with lidocaine HCl. The oral LD 50 of lidocaine HCl in non-fasted female rats is 459 (346 to 773) mg/kg (as the salt) and 214 (159 to 324) mg/kg (as the salt) in fasted female rats.

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 injection. At the first sign of change, oxygen should be administered. The first step in the management of convulsions, as well as underventilation or apnea due to unintended subarachnoid injection of drug solution, 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 the use of loca …

HOW SUPPLIED - Lidocaine hydrochloride 2% (34 mg/1.7 mL) (20 mg/mL) and Epinephrine 1:50,000 injection is available in cartons containing 5 blisters of 10 x 1.7 mL single-dose cartridges (NDC 0362-0262-05). - Lidocaine hydrochloride 2% (34 mg/1.7 mL) (20 mg/mL) and Epinephrine 1:100,000 injection is available in cartons containing 5 blisters of 10 x 1.7 mL single-dose cartridges (NDC 0362-0898-05). Store at controlled room temperature, below 25°C (77°F). Protect from light. Do not permit to freeze. BOXES: For protection from light, retain in box until time of use. Once opened, the box should be reclosed by closing the end flap. Do not use if color is pinkish or darker than slightly yellow or if it contains a precipitate. STERILIZATION : STORAGE AND TECHNICAL PROCEDURES Cartridges should not be autoclaved, because the closures employed cannot withstand autoclaving temperatures and pressures. If chemical disinfection of anesthetic cartridges is desired, either isopropyl alcohol (91%) or 70% ethyl alcohol is recommended. Many commercially available brands of rubbing alcohol, as well as solutions of ethyl alcohol not of U.S.P grade, contain denaturants that are injurious to rubber and, therefore, are not to be used. It is recommended that chemical disinfection be accomplished just prior to use by wiping the cartridge cap thoroughly with a pledge of cotton that has been moistened with recommended alcohol. Certain metallic ions (mercury, zinc, copper, etc.) have been related to swelling and edema after local anesthesia in dentistry. Therefore, chemical disinfectants containing or releasing these ions are not recommended. Antirust tablets usually contain sodium nitrite or some similar agents that may be capable of releasing metal ions. Because of this, aluminium sealed cartridges should not be kept in such solutions. Quaternary ammonium salts, such as benzalkonium chloride, are electrolytically incompatible with aluminium. Cartridges of lidocaine hydrochloride and epinephrine injection, USP are sealed with aluminium caps and therefore should not be immersed in any solution containing these salts. To avoid leakage of solutions during injection, be sure to penetrate the center of the rubber diaphragm when loading the syringe. An off-center penetration produces an oval shaped puncture that allows leakage around the needle. Other causes of leakage and breakage include badly worn syringes, aspirating syringes with bent harpoons, the use of syringes not designed to take 1.7 mL cartridges, and inadvertent freezing. Cracking of glass cartridges is most often the result of an attempt to use a cartridge with an extruded plunger. An extruded plunger loses its lubrication and can be forced back into the cartridge only with difficulty. Cartridges with extruded plungers should be discarded. Store at controlled room temperature, below 25°C (77°F).