ompromise, 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 hydrochloride 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. intra-articular infusions of local anesthetics following arthroscopic and other surgical procedures is an unapproved use, and there have been post-marketing reports of chondrolysis in patients receiving such infusions. the majority of reported cases of chondrolysis have involved the shoulder joint; cases of gleno-humeral chondrolysis have been described in pediatric and adult patients following intra-articular infusions of local anesthetics with and without epinephrine for periods of 48 to 72 hours. there is insufficient information to determine whether shorter infusion periods are not associated with these findings. the time of onset of symptoms, such as joint pain, stiffness and loss of motion can be variable, but may begin as early as the 2nd month after surgery. currently, there is no effective treatment for chondrolysis; patients who experienced chondrolysis have required additional diagnostic and therapeutic procedures and some required arthroplasty or shoulder replacement. to avoid intravascular injection, aspiration should be performed before the local anesthetic solution is injected. the needle must be repositioned until no return of blood can be elicited by aspiration. note, however, that the absence of blood in the syringe does not guarantee that intravascular injection has been avoided. local anesthetic solutions containing antimicrobial preservatives (e.g., methylparaben) should not be used for epidural or spinal anesthesia because the safety of these agents has not been established with regard to intrathecal injection, either intentional or accidental. anaphylactic reactions may occur following administration of lidocaine hydrochloride (see adverse reactions ). in the case of severe reaction, discontinue the use of the drug.

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. lidocaine should also be used with caution in patients with impaired cardiovascular function since they may be less able to compensate for functional changes associated with the prolongation of a-v conduction produced by these drugs. 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). proper tourniquet technique, as described in publications and standard textbooks, is essential in the performance of intravenous regional anesthesia. solutions containing epinephrine or other vasoconstrictors should not be used for this technique. lidocaine hcl should be used with caution in persons with known drug sensitivities. patients allergic to para-aminobenzoic acid derivatives (procaine, tetracaine, benzocaine, etc.) have not shown cross-sensitivity to lidocaine hcl.

ee of muscular relaxation required, duration of anesthesia required, and the physical condition of the patient. in all cases the lowest concentration and smallest dose that will produce the desired result should be given. dosages should be reduced for children and for the elderly and debilitated patients and patients with cardiac and/or liver disease. the onset of anesthesia, the duration of anesthesia and the degree of muscular relaxation are proportional to the volume and concentration (i.e., total dose) of local anesthetic used. thus, an increase in volume and concentration of lidocaine hydrochloride injection will decrease the onset of anesthesia, prolong the duration of anesthesia, provide a greater degree of muscular relaxation and increase the segmental spread of anesthesia. however, increasing the volume and concentration of lidocaine hydrochloride injection may result in a more profound fall in blood pressure when used in epidural anesthesia. although the incidence of side effects with lidocaine hcl is quite low, caution should be exercised when employing large volumes and concentrations, since the incidence of side effects is directly proportional to the total dose of local anesthetic agent injected. for intravenous regional anesthesia, only the 50 ml single-dose vial containing 0.5% lidocaine hydrochloride injection, usp should be used. epidural anesthesia for epidural anesthesia, only the following available specific products of lidocaine hydrochloride injection by hospira are recommended: 1% 30 ml single-dose teartop vials 1.5% 20 ml single-dose ampuls 2% 10 ml single-dose ampuls although these solutions are intended specifically for epidural anesthesia, they may also be used for infiltration and peripheral nerve block, provided they are employed as single dose units. these solutions contain no bacteriostatic agent. in epidural anesthesia, the dosage varies with the number of dermatomes to be anesthetized (generally 2 to 3 ml of the indicated concentration per dermatome). caudal and lumbar epidural block as a precaution against the adverse experience sometimes observed following unintentional penetration of the subarachnoid space, a test dose such as 2 to 3 ml of 1.5% lidocaine hcl should be administered at least 5 minutes prior to injecting the total volume required for a lumbar or caudal epidural block. the test dose should be repeated if the patient is moved in a manner that may have displaced the catheter. epinephrine, if contained in the test dose (10 to 15 mcg have been suggested), may serve as a warning of unintentional intravascular injection. if injected into a blood vessel, this amount of epinephrine is likely to produce a transient "epinephrine response" within 45 seconds, consisting of an increase in heart rate and systolic blood pressure, circumoral pallor, palpitations and nervousness in the unsedated patient. the sedated patient may exhibit only a pulse rate increase of 20 or more beats per minute for 15 or more seconds. patients on beta-blockers may not manifest changes in heart rate, but blood pressure monitoring can detect an evanescent rise in systolic blood pressure. adequate time should be allowed for onset of anesthesia after administration of each test dose. the rapid injection of a large volume of lidocaine hydrochloride injection through the catheter should be avoided, and, when feasible, fractional doses should be administered. in the event of the known injection of a large volume of local anesthetic solution into the subarachnoid space, after suitable resuscitation and if the catheter is in place, consider attempting the recovery of drug by draining a moderate amount of cerebrospinal fluid (such as 10 ml) through the epidural catheter. maximum recommended dosages note: the products accompanying this insert do not contain epinephrine. adults for normal healthy adults, the individual maximum recommended dose of lidocaine hcl with epinephrine should not exceed 7 mg/kg (3.5 mg/lb) of body weight, and in general it is recommended that the maximum total dose not exceed 500 mg. when used without epinephrine the maximum individual dose should not exceed 4.5 mg/kg (2 mg/lb) of body weight, and in general it is recommended that the maximum total dose does not exceed 300 mg. for continuous epidural or caudal anesthesia, the maximum recommended dosage should not be administered at intervals of less than 90 minutes. when continuous lumbar or caudal epidural anesthesia is used for non-obstetrical procedures, more drug may be administered if required to produce adequate anesthesia. the maximum recommended dose per 90 minute period of lidocaine hydrochloride for paracervical block in obstetrical patients and non-obstetrical patients is 200 mg total. one-half of the total dose is usually administered to each side. inject slowly, five minutes between sides (see also discussion of paracervical block in precautions ). for intravenous regional anesthesia, the dose administered should not exceed 4 mg/kg in adults. 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 over 3 years of age who have a normal lean body mass and normal body development, the maximum dose is determined by the child's age and weight. for example, in a child of 5 years weighing 50 lbs the dose of lidocaine hcl should not exceed 75 to 100 mg (1.5 to 2 mg/lb). the use of even more dilute solutions (i.e., 0.25 to 0.5%) and total dosages not to exceed 3 mg/kg (1.4 mg/lb) are recommended for induction of intravenous regional anesthesia in children. in order to guard against systemic toxicity, the lowest effective concentration and lowest effective dose should be used at all times. in some cases it will be necessary to dilute available concentrations with 0.9% sodium chloride injection in order to obtain the required final concentration. note: parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever the solution and container permit. solutions that are discolored and/or contain particulate matter should not be used. table 1 recommended dosages lidocaine hydrochloride injection, usp (without epinephrine) procedure conc. (%) vol. (ml) total dose (mg) infiltration percutaneous 0.5 or 1 1 to 60 5 to 300 intravenous regional 0.5 10 to 60 50 to 300 peripheral nerve blocks, e.g. brachial 1.5 15 to 20 225 to 300 dental 2 1 to 5 20 to 100 intercostal 1 3 30 paravertebral 1 3 to 5 30 to 50 pudendal (each side) 1 10 100 paracervical obstetrical analgesia (each side) 1 10 100 sympathetic nerve blocks, e.g. cervical (stellate ganglion) 1 5 50 lumbar 1 5 to 10 50 to 100 central neural blocks epidural dose determined by number of dermatomes to be anesthetized (2 to 3 ml/dermatome). thoracic 1 20 to 30 200 to 300 lumbar analgesia 1 25 to 30 250 to 300 anesthesia 1.5 15 to 20 225 to 300 2 10 to 15 200 to 300 caudal obstetrical analgesia 1 20 to 30 200 to 300 surgical anesthesia 1.5 15 to 20 225 to 300 the above suggested concentrations and volumes serve only as a guide. other volumes and concentrations may be used provided the total maximum recommended dose is not exceeded. sterilization, storage and technical procedures disinfecting agents containing heavy metals, which cause release of respective ions (mercury, zinc, copper, etc.) should not be used for skin or mucous membrane disinfection as they have been related to incidents of swelling and edema. when chemical disinfection of multi-dose vials is desired, either isopropyl alcohol (91%) or ethyl alcohol (70%) is recommended. many commercially available brands of rubbing alcohol, as well as solutions of ethyl alcohol not of usp grade, contain denaturants which are injurious to rubber and therefore are not to be used. it is recommended that chemical disinfection be accomplished by wiping the vial stopper thoroughly with cotton or gauze that has been moistened with the recommended alcohol just prior to use.

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 hcl 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 local anesthetic agents or to the methylparaben used as a preservative in the multiple dose vials. allergic reactions, including anaphylactic reactions, may occur as a result of sensitivity to lidocaine, but are infrequent. if allergic reactions do occur, they should be managed by conventional means. the detection of sensitivity by skin testing is of doubtful value. there have been no reports of cross sensitivity between lidocaine hydrochloride and procainamide or between lidocaine hydrochloride and quinidine. neurologic 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 hcl 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. many of these observations may be related to local anesthetic techniques, with or without a contribution from the local anesthetic. in the practice of caudal or lumbar epidural block, occasional unintentional penetration of the subarachnoid space by the catheter may occur. subsequent adverse effects may depend partially on the amount of drug administered subdurally. these may include spinal block of varying magnitude (including total spinal block), hypotension secondary to spinal block, loss of bladder and bowel control, and loss of perineal sensation and sexual function. 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 been reported cases of permanent injury to extraocular muscles requiring surgical repair following retrobulbar administration. hematologic methemoglobinemia.

site of administration and the presence or absence of a vasoconstrictor agent. except for intravascular administration, the highest blood levels are obtained following intercostal nerve block and the lowest after subcutaneous administration. the plasma binding of lidocaine hcl is dependent on drug concentration, and the fraction bound decreases with increasing concentration. at concentrations of 1 to 4 mcg of free base per ml 60 to 80 percent of lidocaine hcl is protein bound. binding is also dependent on the plasma concentration of the alpha-1-acid glycoprotein. lidocaine hcl crosses the blood-brain and placental barriers, presumably by passive diffusion. lidocaine hcl 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 hcl. approximately 90% of lidocaine hcl 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 elimination half-life of lidocaine hcl following an intravenous bolus injection is typically 1.5 to 2 hours. because of the rapid rate at which lidocaine hcl is metabolized, any condition that affects liver function may alter lidocaine hcl kinetics. the half-life may be prolonged two-fold or more in patients with liver dysfunction. renal dysfunction does not affect lidocaine hcl 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 hcl required to produce overt systemic effects. objective adverse manifestations become increasingly apparent with increasing venous plasma levels above 6 mcg free base per ml. in the rhesus monkey arterial blood levels of 18 to 21 mcg/ml have been shown to be threshold for convulsive activity.

tes 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 hcl. approximately 90% of lidocaine hcl 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 elimination half-life of lidocaine hcl following an intravenous bolus injection is typically 1.5 to 2 hours. because of the rapid rate at which lidocaine hcl is metabolized, any condition that affects liver function may alter lidocaine hcl kinetics. the half-life may be prolonged two-fold or more in patients with liver dysfunction. renal dysfunction does not affect lidocaine hcl 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 hcl required to produce overt systemic effects. objective adverse manifestations become increasingly apparent with increasing venous plasma levels above 6 mcg free base per ml. in the rhesus monkey arterial blood levels of 18 to 21 mcg/ml have been shown to be threshold for convulsive activity.

y of 25 plastic multiple-dose fliptop vials 0.5% 250 mg/50 ml (5 mg/ml) ndc 0409-4276-01 tray of 25 plastic multiple-dose fliptop vials 1% 200 mg/20 ml (10 mg/ml) ndc 0409-4276-02 tray of 25 plastic multiple-dose fliptop vials 1% 500 mg/50 ml (10 mg/ml) ndc 0409-4277-01 tray of 25 plastic multiple-dose fliptop vials 2% 400 mg/20 ml (20 mg/ml) ndc 0409-4277-02 tray of 25 plastic multiple-dose fliptop vials 2% 1000 mg/50 ml (20 mg/ml) for single-dose vials and ampuls: discard unused portion. 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.