LIDOCAINE (Generic for ANECREAM)

General Administration Information
For storage information, see the specific product information within the How Supplied section.

Route-Specific Administration

Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Intravenous Administration
-Monitor blood pressure and ECG during IV administration.

IV Push
-During cardiopulmonary resuscitation (CPR): Administer IV push.
-Non-CPR indications: Administer bolus injection at a rate of 0.35 to 0.7 mg/kg/minute (25 to 50 mg/minute).

Continuous IV Infusion
-ASHP Recommended Standard Concentrations for Pediatric Continuous Infusions: 4 mg/mL or 8 mg/mL.
-The maximum concentration for continuous IV infusion is 8 mg/mL.
-Use an infusion pump to administer by continuous infusion.

Other Injectable Administration
Intradermal Administration (Zingo)
-Each device contains 0.5 mg of sterile lidocaine hydrochloride monohydrate powder.
-Only use on skin locations where an adequate seal can be maintained. Do not use around the eyes, on body orifices, on mucous membranes, or on areas with a compromised skin barrier.
-Press the device against an intact area of skin. Ensure an adequate seal between the device and the skin. Pressing the device against the skin will release the safety interlock. Press the button to actuate the device.
-A popping sound like a burst balloon is heard when the device is actuated. Lidocaine is delivered to the dermis by a needle-free, helium-pressurized delivery system.
-Multiple administrations at the same location are not recommended.

Intraosseous Administration
NOTE: Lidocaine is not FDA-approved for intraosseous administration.
-During cardiopulmonary resuscitation, the same dosage may be given via the intraosseous route when IV access is unsuccessful or not feasible.




Topical Administration
-Have resuscitative equipment and drugs for the management of adverse reactions immediately available while administering local anesthetics to mucous membranes.
-Use topical lidocaine products with extreme caution if the mucosa in the area of application has been traumatized, as this may enhance the potential for rapid systemic absorption and adverse effects.
-Application to mouth or throat area: Instruct patients to avoid eating, drinking, and chewing gum for at least 60 minutes after application and until numbness has resolved. Topical anesthesia may increase the risk of biting trauma and impair swallowing, which increases the risk of aspiration.
Cream/Ointment/Lotion Formulations
Ointment
-Skin: If used on broken skin, apply using a sterile gauze pad.
-Dental use: Apply to 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. For denture fitting, apply to all denture surfaces contacting the mucosa.
-Intubation: Apply to the tube prior to intubation. Be sure to avoid putting ointment into the lumen of the tube.

Lotion
-Apply to clean and dry skin. Clothing may be worn over the area of application.
-If irritation or burning occurs, wash the lotion off the skin and do not reapply until the irritation subsides.

Transdermal Patch Formulations
Dermal Patch 5% (Lidoderm or therapeutic equivalents)

-Ensure the prescribed dosage is applied. The prescribed dosage may differ from the dosage on the product's label.
-Keep the patches in their sealed envelopes until immediately before use.
-After removing the patch from the protective envelope, immediately apply to intact skin to cover the most painful area. Do not expose the eyes.
-Patches may be cut into smaller sizes prior to removal of the release liner.
-Adherence of the patch may be affected by contact with water; advise patients to avoid activities such as bathing, swimming, or showering while wearing the patch.
-Wash hands after handling the patches. Fold the sticky side of used patches together, and dispose of in such a way as to prevent accidental exposure to children or pets.

Dermal Topical System (ZTlido)
-Keep the system in the sealed envelope until immediately before use.
-Systems may be cut into smaller sizes prior to removal of the release liner.
-After removing the system from the protective envelope, immediately apply to intact skin to cover the most painful area. Avoid contact with eyes.
-Advise patients to avoid contact with water, such as bathing, swimming, or showering while wearing the system; the system may not stick if it gets wet.
-Do not apply external heat sources, such as heating pads and electric blankets, directly to the system. The system can be applied to the administration site after moderate heat exposure (e.g., 15 minutes of heating pad exposure on a medium setting). The system may be used during moderate exercise (e.g., biking for 30 minutes).
-If irritation or burning occurs, advise patients to remove the system and do not reapply until the irritation subsides.
-If a system comes off completely and will not stick to the skin, it should be thrown away and a new system should be applied for a total duration of 12 hours of used and new topical system together.
-Wash hands immediately after handling the system. To discard, fold the system so that the adhesive side sticks to itself. Safely dispose used systems where children or pets cannot get to them.

Transoral Delivery System
-Isolate the procedure area with cotton rolls; use suction as appropriate
-Dry area of application with air or gauze for 30 seconds. Drying time may be reduced when administering palatal injections.
-Remove protective liner and apply the system with firm finger pressure. Hold in place for 30 seconds. This allows the patch to properly conform and adhere to the gingiva and mucosa.
-An application time of 5 minutes was used in a small pharmacokinetic study in children (n = 11, age 2 to 7 years). Confirm the level of anesthesia by probing the site prior to beginning the procedure.
-The product labeling recommends removal of the system in adults when desired anesthetic effect is produced, but within 15 minutes, using cotton pliers or fingers and disposing of properly. Based on a 15 minute application of the system in adults, 30 to 40 minutes of continued anesthesia can be achieved.

Other Topical Formulations
Topical Sterile Solution
-Topical solution may be sprayed or applied using cotton applicators or packs. When used as a spray, transfer topical solution from its original container to an atomizer.

Viscous Solution
-For use in the mouth: Swish around in the mouth and spit out. For infants and children 3 years and younger, apply the solution to the affected area using a cotton-tipped applicator. Do NOT use for the treatment of teething pain in infants and young children due to the risk of serious adverse reactions; 2% viscous lidocaine has been associated with seizures, severe brain injury, heart problems, and even death.
-For use in the pharynx: Gargle with the undiluted solution and either swallow or spit out the solution.

Jelly
-For use in endotracheal intubation: Apply a moderate amount to the external surface of the tube. Be careful to avoid getting any of the jelly into the lumen of the tube to prevent occlusion. Do not use jelly to lubricate endotracheal stylettes.

Gel
-Apply a thin film to the affected area.
-The gel is supplied in an airless pump bottle; one pump is intended to cover an area 2 x 2 inches.

Single-use Foam Applicator
-Apply using gloved hands.
-Swirl the applicator tip prior to removing the swab from the pouch.
-Apply to the area 3 to 5 minutes prior to the procedure not more than 4 times daily.
-Do not use in large quantities over raw or blistered skin.



Ophthalmic Administration
-For ophthalmic administration under the direct supervision of a health care provider. The product is NOT intended for patient self-administration.
-Do not touch the tip of the tube to the eye, fingertips, or other surface.


Other Administration Route(s)
Endotracheal Administration
NOTE: Lidocaine is not FDA-approved for endotracheal (ET) administration.
-Consider ET administration only when other access is not available. ET administration is the least-preferred administration due to its association with unpredictable (but generally low) drug concentrations and lower rates of ROSC and survival.
-If CPR is in progress, stop chest compressions briefly and administer the medication.
-Dilute the dose in 1 to 5 mL of saline or follow drug administration with a saline flush (5 mL or more) and 5 consecutive positive-pressure ventilations.

Lidocaine crosses the blood brain barrier and can produce significant central nervous system (CNS) toxicity, particularly when high plasma concentrations (more than 6 mcg/mL free base) are achieved. CNS manifestations are excitatory and/or depressant and may be characterized by lightheadedness (dizziness), anxiety (i.e., nervousness or apprehension), restlessness, euphoria, confusion, drowsiness, tinnitus, blurred vision or double vision, vomiting, metallic taste, dysgeusia, sensations of heat (hot flashes), cold or numbness, hyperesthesia, hypoesthesia, asthenia, twitching, tremor, convulsions (seizures), unconsciousness, respiratory depression, and respiratory arrest. Headache has also been reported. Agitation, paresthesias, dysarthria, oral hypoesthesia, and disorientation have also been reported with systemic use. 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 after the administration of lidocaine is usually an early sign of a high blood concentration of the drug and may occur as a consequence of rapid absorption. In some patients, the symptoms of CNS toxicity are minor and transient.

There have been reported cases of permanent injury to extraocular muscles requiring surgical repair following retrobulbar administration of lidocaine. Additionally, small doses of local anesthetics injected into the head and neck area may produce an adverse reaction similar to systemic toxicity after unintentional intravascular injection. Confusion, convulsions, respiratory depression and/or arrest, and cardiovascular stimulation or depression have been reported. These reactions may be due to potential intraarterial injection of the local anesthetic with retrograde flow to the cerebral circulation. Monitor the ventilatory and circulatory systems of these patients closely. Do not exceed recommended doses in these patients. An injection site reaction consisting of transient burning can occur. Preexisting inflammation or infection increases the risk of developing serious skin side effects.

Arrhythmias associated with the use of lidocaine continuous infusion for the treatment of seizures in premature and term neonates occurred in 4.8% of patients in a retrospective study (n = 207). Arrhythmias included bradycardia (associated with a prolonged QRS complex in 1 case), AV block, ventricular extrasystole, premature ventricular contraction, tachycardia (after bolus administration), and irregular heart rate. The arrhythmia resolved spontaneously in 1 patient and in 7 others resolution occurred with discontinuation of lidocaine. Two patients died prior to lidocaine discontinuation due to their underlying disease. Cardiac effects of local anesthetics such as lidocaine are due to the interference of conduction within the myocardium. Cardiac effects are seen at very high systemic doses and usually occur after the onset of central nervous system (CNS) toxicity. Systemic adverse cardiovascular reactions include myocardial depression, sinus bradycardia, hypotension, ventricular fibrillation, ventricular tachycardia, ventricular arrhythmia, asystole, cardiovascular collapse, and cardiac arrest. These effects typically occur with high plasma drug concentrations but have occurred with smaller doses in rare instances. Treat cardiovascular and CNS adverse reactions resulting from lidocaine administration with general supportive physiologic measures such as oxygen therapy, assisted ventilation, and IV fluids. Monitor blood pressure and the electrocardiogram during intravenous lidocaine administration. If cardiovascular adverse reactions such as hypotension, arrhythmia exacerbation, or excessive depression of cardiac conduction occur (e.g., prolonged PR interval or widened QRS complex), discontinue lidocaine administration and re-evaluate treatment options.

Systemic adverse reactions after appropriate application of topical or transdermal lidocaine are unlikely because of the small amount of lidocaine absorbed; however, systemic effects including nausea (2%) and vomiting (1%) have been reported with lidocaine intradermal powder (Zingo). Nausea has also been reported with the use of IV lidocaine. The skin at the site of treatment may develop erythema, swelling, or dysesthesia (abnormal sensation). Erythema (53% vs. 27%), petechiae (44% vs. 5%), and swelling (8% vs. 3%) occurred more frequently in pediatric patients receiving lidocaine via an intradermal system (Zingo) compared to those receiving placebo via a sham device during clinical trials; pruritus occurred in 1% of patients in both treatment groups. Application site reactions including ecchymosis, burning, pain, contusion, and bleeding were reported in 4% of patients (both groups). Application site reactions may occur during or immediately after treatment with the lidocaine transdermal patch. Blisters, ecchymosis, depigmentation (skin discoloration), skin erosion, exfoliation, flushing, skin irritation (including burning sensation and dermatitis), papules, petechiae, pruritus, or vesicles may develop on the skin at the site of application. These reactions are usually mild and transient resolving within a few minutes to hours.

Allergic and anaphylactoid reactions have been infrequently associated with lidocaine administration. If signs of hypersensitivity develop during IV administration, discontinue the infusion immediately. Allergic reactions may manifest as cutaneous lesions, urticaria, edema, angioedema, bronchospasm, dermatitis, dyspnea, laryngospasm, pruritus, or anaphylactic shock. Allergic reactions may occur as a result of sensitivity either to local anesthetic agents or to other components in the formulation. The detection of sensitivity by skin testing is of doubtful value. There have been no reports of cross-sensitivity between lidocaine and para-amino-benzoic acid derivatives (procaine, tetracaine, benzocaine, etc.).

Methemoglobinemia has been reported with local anesthetic use. Signs and symptoms of methemoglobinemia may occur immediately or may be delayed some hours after local anesthetic exposure and are characterized by cyanotic skin discoloration and abnormal coloration of the blood. Other symptoms may include headache, rapid heart rate, shortness of breath, dizziness, and drowsiness. Since methemoglobin concentrations may continue to rise, immediately discontinue lidocaine to avoid serious central nervous system and cardiovascular adverse events including seizures, coma, arrhythmias, and death. Depending on the severity of symptoms, patients may require supportive care, such as oxygen therapy and hydration. More severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.

Local anesthetics such as lidocaine administered by a continuous infusion to a joint space may cause chondrolysis (necrosis and destruction of cartilage). The majority of reports have involved the shoulder joint. Gleno-humeral chondrolysis has been reported in pediatric and adult patients after intra-articular infusions of local anesthetics for 48 to 72 hours. Joint pain, stiffness, and loss of motion were reported as early as the second month after infusion receipt. In more than half of these reports, the patients required additional surgery including arthroscopy or arthroplasty. Local anesthetics are not indicated for continuous intra-articular postoperative infusions or for use with infusion devices such as elastomeric pumps. Health care professionals are advised to NOT use elastomeric infusion devices for continuous intra-articular infusion of local anesthetics after orthopedic surgery. Of importance, single intra-articular injections of local anesthetics in orthopedic procedures have been used for many years without any reported occurrence of chondrolysis. If a patient has received a continuous intra-articular postoperative infusion of a local anesthetic, monitor the patient for the emergence of the signs and symptoms of chondrolysis such as joint pain, stiffness, and loss of motion. Also, instruct the patient to report any such symptoms. The appearance of these symptoms can be variable and may begin two or more months after surgery.

Systemic adverse reactions after appropriate application of lidocaine ophthalmic gel are unlikely because of the small amount of lidocaine absorbed. After instillation of lidocaine ophthalmic gel, the most common reported side effects included conjunctival hyperemia, corneal epithelial changes, headache, and ocular irritation (burning upon instillation). Lidocaine ophthalmic gel, when used over a prolonged period, may cause permanent corneal opacification and ulceration leading to visual impairment.

Drugs used to administer anesthesia have been associated with malignant hyperthermia. Although it is unknown whether local anesthetics, such as lidocaine, trigger this reaction, it is recommended that a standard protocol for management be available when lidocaine is administered in hospital environments. Early unexplained symptoms such as tachycardia, tachypnea, labile blood pressure, and metabolic acidosis may precede temperature elevation. Successful management includes prompt discontinuation of suspected triggering agents and institution of treatment.

Lidocaine application to oral mucosa can interfere with swallowing and increase the risk of aspiration. Numbness of the tongue or buccal mucosa may also increase the risk of unintentional biting trauma. Advise patients to not ingest food for at least 1 hour after the use of anesthetic agents in the mouth or throat and to avoid chewing food or gum while the mouth and throat are anesthetized.

Intravenous lidocaine should not be added to blood transfusion assemblies due to the risk of pseudoagglutination or hemolysis.

Lidocaine is contraindicated in patients with amide local anesthetic hypersensitivity. There have been no reports of cross-sensitivity between lidocaine and either procainamide or quinidine.

Lidocaine does not provide adequate anesthesia in patients with collagen-vascular disease, such as Ehlers Danlos Type III. Use lidocaine cautiously in these patients; increased monitoring to ensure adequate analgesia throughout procedures may be necessary.

Methemoglobinemia has been reported with local anesthetic use. Although all patients are at risk for methemoglobinemia, patients with glucose-6-phosphate dehydrogenase deficiency (G6PD deficiency), preexisting (congenital or idiopathic) methemoglobinemia, cardiac or pulmonary compromise (cardiac disease or pulmonary disease), those younger than 6 months, and those with concurrent exposure to oxidizing agents or their metabolites are more susceptible to developing methemoglobinemia. Monitor such patients closely for signs and symptoms of methemoglobinemia if a local anesthetic must be used. Signs of methemoglobinemia may occur immediately or may be delayed hours after exposure. Immediately discontinue the local anesthetic to avoid serious central nervous system and cardiovascular adverse events, as methemoglobin concentrations may continue to rise. Patients may require supportive care such as oxygen therapy and hydration. More severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. Lidocaine cream is recommended for topical anesthesia prior to newborn circumcision due to a lower risk of methemoglobinemia compared to lidocaine; prilocaine cream.

Use lidocaine with caution in patients at increased risk of adverse reactions. Conditions that reduce hepatic blood flow such as hepatic disease and congestive heart failure may reduce hepatic metabolism and lead to drug accumulation, increasing the risk of developing systemic toxicity. The immediate availability of oxygen, cardiopulmonary resuscitative equipment and drugs, and the appropriate support personnel for the management of toxic reactions or emergencies must be ensured during administration of parenteral lidocaine or topical lidocaine to mucous membranes. Repeated doses of topical or parenteral lidocaine may cause a significant increase in blood concentrations with each successive dose. These increases may be poorly tolerated, particularly by debilitated patients or the acutely ill. The dosage may need to be adjusted in at risk patients.

Although specific forms of parenteral lidocaine are indicated for the treatment of some cardiac arrhythmias, it can worsen others. Intravenous (IV) lidocaine for the treatment of ventricular arrhythmias is contraindicated in patients with Adams-Stokes syndrome, Wolff-Parkinson-White syndrome, or severe SA block, AV block, or intraventricular heart block unless an artificial pacemaker is present. The administration of IV lidocaine for the elimination of ventricular ectopic beats to patients with bradycardia or incomplete heart block without prior acceleration of heart rate may cause a more serious ventricular arrhythmia or complete heart block. Lidocaine can increase the ventricular rate in patients with atrial fibrillation or atrial flutter. Use lidocaine with caution in patients with hypovolemia. Monitor blood pressure and the electrocardiogram during IV lidocaine administration. Reduce the infusion rate of lidocaine if patients experience signs of excessive depression of cardiac electrical activity or aggravation of arrhythmias; discontinuation of therapy may be necessary. Use both parenteral and topical formulations of lidocaine with caution in patients with severe shock (including cardiogenic shock and hemorrhagic shock) and heart block. Patients with impaired cardiac function, particularly AV block, may be less able to compensate for functional changes associated with prolonged AV conduction (i.e., PR or QT prolongation) caused by local anesthetics. Topical ocular application of lidocaine is not expected to result in systemic exposure.

Patients with renal impairment may be at increased risk for toxicity because lidocaine is excreted by the kidneys. Use lidocaine with caution in patients with severe renal impairment. The elimination of lidocaine was reduced in a study of adult subjects with severe renal impairment or renal failure (CrCl less than 30 mL/minute/1.73m2) not receiving hemodialysis compared to subjects with normal renal function. Also the AUC and Cmax of one of the major active metabolites of lidocaine, glycinexylidide, were significantly higher in subjects with renal impairment (CrCl 60 mL/minute/1.73m2 or less) and subjects receiving hemodialysis compared to subjects with normal renal function.

Applying dermal, transdermal, or oromucosal lidocaine preparations to severely traumatized skin (e.g., mucosal or skin abrasion, eczema, burns), to large surface areas, or to warm skin (i.e., exercise or application of thermal heat wraps or a heating pad immediately before or during topical lidocaine use) can increase its absorption, possibly increasing the risk of systemic toxicity. Also, applying large amounts of lidocaine or using an occlusive dressing (skin wraps) can increase absorption. At least 2 reports of deaths exist in adult females after application of compounded topical anesthetics containing high amounts of lidocaine and tetracaine prior to cosmetic procedures. In both instances, the women applied the topical anesthetic to their legs and wrapped the treated area, as directed, in plastic wrap to enhance the numbing effect of the cream. In order to reduce the risk of toxicity due to increased absorption of topical anesthetic, the FDA recommends patients use a topical anesthetic containing the lowest amount of medication needed to relieve pain, apply the medication sparingly, and only treat known or anticipated areas of pain. Further, do not apply the anesthetic to broken or irritated skin, be aware of potential adverse reactions, and that covering or applying heat to the treated area could increase the risk of systemic toxicity. Only administer transdermal patches/systems and intradermal injection (Zingo) to intact skin, and transoral delivery systems to intact mucosa. Excessive dosing by applying patches to larger areas or for longer than the recommended wearing time could result in increased absorption of lidocaine. Application of 1 additional intradermal injection (Zingo) at a new location is acceptable after a failed attempt at venous access. However, multiple injections at the same location are not recommended. Multiple intradermal applications could result in plasma concentrations that could produce systemic toxicity.

Avoid unintended ocular exposure of lidocaine dermal, oromucosal, and transdermal products. Severe eye irritation has been reported in animals treated with similar products. If eye contact occurs, immediately wash the eye with water or saline and protect the eye until sensation returns. Lidocaine ophthalmic gel is intended for application to the eye surface under the direct supervision of a health care provider; it is NOT intended for patient self-administration. Prolonged use may produce permanent corneal opacification and ulceration with accompanying visual loss. Use with caution in patients with pre-existing cataracts or ocular trauma or ulceration.

To avoid accidental exposure and/or ingestion, advise patients and/or their caregivers to store and dispose of all lidocaine products out of the reach of any pediatric-age person and pets. It is important to note that whether new or used, lidocaine patches (Lidoderm) contain a large amount of lidocaine (at least 665 mg post-use). The potential exists for small kids or pets to suffer serious adverse reactions from unintended lidocaine exposure including chewing or ingesting a new or used lidocaine system.

When local anesthetics, like lidocaine, are used for retrobulbar block during ocular surgery, do not rely upon lack of corneal sensation to determine whether or not the patient is ready for surgery. Lack of corneal sensation usually precedes clinically acceptable external ocular muscle akinesia.

Parenteral use of lidocaine requires an experienced clinician and requires a specialized care setting. Local anesthetics, like lidocaine, should only be administered by a clinician trained in the diagnosis and management of drug-related toxicity and other acute emergencies that might arise from the administration of a regional anesthetic block. The immediate availability of oxygen, cardiopulmonary resuscitative equipment and drugs, and the appropriate support personnel for the management of toxic reactions or emergencies must be ensured. Any delay in appropriate management may lead to the development of acidosis, cardiac arrest, and possibly death. Do not use lidocaine preparations containing preservatives for epidural anesthesia or spinal anesthesia. Spinal anesthesia is contraindicated in patients with severe bleeding, infection at the injection site, and sepsis. Administer spinal anesthesia to patients with the following conditions with caution: pre-existing central nervous system disorders such as poliomyelitis, pernicious anemia, paralysis from nerve injuries or syphilis; disturbances in blood morphology (e.g., thrombocytopenia) and/or anticoagulant therapy; pediatric patients younger than 16 years; chronic backache; preoperative headache; hypotension; hypertension; arthritis or spinal deformity; technical problems (persistent paresthesias, persistent bloody tap); psychotic or uncooperative patients. Consult standard references for specific techniques and precautions for spinal anesthetic procedures. Use lumbar and caudal epidural anesthesia with extreme caution in patients with existing neurological disease, spinal deformities, sepsis, and severe hypertension. Use caution when applying topical lidocaine to mucous membranes in the presence of sepsis due to the potential for rapid systemic absorption. Patients with platelet disorders or those with bleeding tendencies may be at risk for superficial dermal bleeding when lidocaine is administered intradermally for topical anesthesia.

Lidocaine is not approved for continuous intraarticular infusion administration. Infusion of local anesthetics into a joint space may have caused chondrolysis. Local anesthetics are not indicated for continuous intraarticular postoperative infusions or for use with infusion devices such as elastomeric pumps.

Use lidocaine with caution in patients with a genetic predisposition to malignant hyperthermia. Although it is unknown whether lidocaine triggers this reaction, it is recommended that a standard protocol for management be available when lidocaine is administered in hospital environments.

Lidocaine dosages in pediatric patients should be reduced, commensurate with age, body weight and physical condition. When multiple formulations of lidocaine are used at once, the amount systemically absorbed from all formulations must be considered. Certain products, such as lidocaine transdermal patches, have not been FDA-approved for application to pediatric patients. Non-prescription (OTC) products should not be used without healthcare professional advice in those under 2 years of age, or as directed on the product label. Do not use lidocaine viscous solution for the treatment of teething pain in infants and young children due to the risk of serious adverse reactions, including seizures, cardiopulmonary arrest, severe brain injury, and death. The FDA reviewed 22 cases of serious adverse events that occurred in infants and young children between 5 months and 3.5 years of age after receiving lidocaine viscous solution for the treatment of mouth pain due to teething or stomatitis or who had accidental ingestions. Of the 22 cases, 6 cases resulted in death, 3 were categorized as life-threatening, 11 required hospitalization, and 2 required medical intervention without hospitalization. The FDA recommends against the use of topical pain relievers for teething pain due to the fact that they wash out of the mouth within minutes of application and can cause serious adverse reactions if they are swallowed in excessive amounts. Advise parents and caregivers with teething pain concerns to follow the American Academy of Pediatrics recommendations for the management of teething pain, which include using a teething ring chilled in the refrigerator (not frozen) and gently rubbing or massaging the gums with a finger. For other conditions, the use of viscous lidocaine in neonates, infants, and children 3 years of age and younger should be limited to those situations where safer alternatives are not available or have failed. To ensure safety, doses should be measured by an accurate device, administered no more often than every 3 hours, used only for the prescribed indication, and stored safely out of the reach of children immediately after use. When topical anesthetics are used in the mouth, the topical anesthesia may impair swallowing and thus enhance the danger of aspiration. For this reason, food should not be ingested for 60 minutes after use of local anesthetic preparations in the mouth or throat area. This is particularly important in children because of their frequency of eating.

In utero exposure secondary to unintended fetal intracranial injection of local anesthetics, such as lidocaine, after intended paracervical or pudendal block for obstetrical anesthesia may cause neonatal depression and seizures. Supportive measures and forced urinary excretion of lidocaine have been used to manage this complication.

Description: Lidocaine is a widely used antiarrhythmic and local anesthetic. It is classified as an Ib antiarrhythmic. Administered intravenously, lidocaine is used for the treatment of acute, life-threatening ventricular arrhythmias. PALS guidelines recommend either lidocaine or amiodarone for shock-refractory ventricular fibrillation (VF) or pulseless ventricular tachycardia (pVT). Pediatric observational data has shown improved return of spontaneous circulation (ROSC) with the use of lidocaine as compared with amiodarone. In addition, use of lidocaine compared with no lidocaine was significantly associated with an increased likelihood of ROSC. Neither lidocaine nor amiodarone has been shown to improve survival to hospital discharge. Lidocaine can be safely delivered in patients with long QT syndrome or other channelopathies, whereas amiodarone may precipitate torsades de pointes. Lidocaine is also used intravenously for the second- or third-line treatment of refractory seizures and status epilepticus in neonatal and pediatric patients. Due to the potential for serious adverse reactions, including central nervous system and cardiovascular depression, continuous monitoring of blood pressure and electrocardiogram are recommended during intravenous lidocaine treatment. Lidocaine is an amide-type local anesthetic agent and is available as various topical formulations and as an injection for local anesthesia to skin and mucous membranes. Oropharyngeal application of topical lidocaine should NOT be used for the treatment of teething pain in infants and young children due to the risk of serious adverse reactions, including seizures, cardiopulmonary arrest, severe brain injury, and death; use in other situations should be also be limited in this population. The different formulations of lidocaine for topical or local anesthesia are FDA-approved for use in patients of varying ages depending on the specific product; intravenous lidocaine for the treatment of ventricular arrhythmias and seizures has been used in pediatric patients as young as neonates.

For the treatment of perfusing ventricular arrhythmias including ventricular fibrillation (VF) and ventricular tachycardia (VT) that may result during acute myocardial infarction or cardiac manipulation (e.g., cardiac surgery):
Intravenous dosage:
Neonates: 1 mg/kg IV load then 20 to 50 mcg/kg/minute IV. May repeat bolus if the infusion is initiated more than 15 minutes after the initial bolus. Max IV load: 3 mg/kg administered over a 1-hour period. A maximum infusion rate of 20 mcg/kg/minute IV has been recommended in patients with shock, heart failure, or cardiac arrest. Monitor blood pressure and the electrocardiogram (ECG) during IV lidocaine administration. Terminate IV infusion as soon as the cardiac rhythm stabilizes or if toxicity occurs. It is rarely necessary to continue IV infusions for longer than 24 hours. Due to reduced clearance of lidocaine after prolonged infusions, a 50% reduction in the infusion rate is necessary to avoid toxicity if therapy longer than 24 hours is required. When feasible, switch to an oral antiarrhythmic agent for maintenance therapy.
Infants, Children, and Adolescents: 1 mg/kg (Max: 100 mg) IV load then 20 to 50 mcg/kg/minute IV. May repeat bolus if the infusion is initiated more than 15 minutes after the initial bolus. Max IV load: 3 mg/kg or 300 mg, whichever is less, administered over a 1-hour period. A maximum infusion rate of 20 mcg/kg/minute IV has been recommended in patients with shock, heart failure, or cardiac arrest. Monitor blood pressure and the electrocardiogram (ECG) during IV lidocaine administration. Terminate IV infusion as soon as the cardiac rhythm stabilizes or if toxicity occurs. It is rarely necessary to continue IV infusions for longer than 24 hours. Due to reduced clearance of lidocaine after prolonged infusions, a 50% reduction in the infusion rate is necessary to avoid toxicity if therapy longer than 24 hours is required. When feasible, switch to an oral antiarrhythmic agent for maintenance therapy.

For the treatment of ventricular arrhythmias during cardiopulmonary resuscitation* (CPR):
Continuous Intravenous or Intraosseous* Infusion dosage:
Neonates: 1 mg/kg IV or IO load then 20 to 50 mcg/kg/minute continuous IV infusion. May repeat bolus if the infusion is initiated more than 15 minutes after the initial bolus. Max load: 3 mg/kg administered over a 1-hour period. A maximum infusion rate of 20 mcg/kg/minute has been recommended in patients with shock, heart failure, or cardiac arrest. Either lidocaine or amiodarone can be used for shock-refractory ventricular fibrillation (VF) or pulseless ventricular tachycardia (pVT). Pediatric observational data has shown improved return of spontaneous circulation (ROSC) with the use of lidocaine as compared with amiodarone. In addition, use of lidocaine compared with no lidocaine was significantly associated with an increased likelihood of ROSC. Neither lidocaine nor amiodarone has been shown to improve survival to hospital discharge.
Infants, Children, and Adolescents: 1 mg/kg IV or IO load then 20 to 50 mcg/kg/minute continuous IV infusion. May repeat bolus if the infusion is initiated more than 15 minutes after the initial bolus. Max load: 3 mg/kg or 300 mg, whichever is less, administered over a 1-hour period. A maximum infusion rate of 20 mcg/kg/minute has been recommended in patients with shock, heart failure, or cardiac arrest. Either lidocaine or amiodarone can be used for shock-refractory ventricular fibrillation (VF) or pulseless ventricular tachycardia (pVT). Pediatric observational data has shown improved return of spontaneous circulation (ROSC) with the use of lidocaine as compared with amiodarone. In addition, use of lidocaine compared with no lidocaine was significantly associated with an increased likelihood of ROSC. Neither lidocaine nor amiodarone has been shown to improve survival to hospital discharge. Lidocaine is also recommended by the PALS algorithm to prevent arrhythmias secondary to myocardial infarction in patients with cocaine overdose.
Endotracheal dosage:
NOTE: Consider ET administration only when other access is not available. ET administration is the least-preferred administration due to its association with unpredictable (but generally low) drug concentrations and lower rates of ROSC and survival.
Neonates: 2 to 3 mg/kg/dose via ET tube.
Infants, Children, and Adolescents: 2 to 3 mg/kg/dose via ET tube.

For topical anesthesia of skin and mucous membranes or stomatitis:
Topical dosage (ointment, jelly, gel, solution):
Infants, Children, and Adolescents: Dosage required varies depending on the area to be anesthetized, vascularity of the tissue, individual tolerance, and anesthetic technique. Apply to affected area as needed for adequate control of symptoms, not to exceed a total lidocaine dose of 4.5 mg/kg. Use of a sterile gauze pad is recommended for application of the ointment to broken skin tissue. For the lidocaine 3% gel, apply a thin film to the affected area 2 to 3 times daily (maximum 12 pumps from the airless pump bottle/day; 1 pump covers an area 2 x 2 inches); do not exceed 4.5 mg/kg of lidocaine.
Topical dosage (GEN7T 3.5% lotion):
Children and Adolescents 12 to 17 years: Apply to intact skin of the affected area up to 4 times daily.
Topical dosage (rectal cream):
Children and Adolescents 12 to 17 years: Apply to affected area up to 6 times per day.
Topical dosage (OTC cream, gel, ointment, spray, solution):
Children and Adolescents 2 to 17 years: Apply to affected area of skin no more than 3 to 4 times per day. Avoid application of large quantities especially over raw or blistered areas.
Topical dosage (OTC 4% spray):
Adolescents: Apply to affected area of skin no more than 3 to 4 times per day. Avoid application of large quantities especially over raw or blistered areas.
Topical dosage (Alocane Emergency Burn Pads):
Children and Adolescents 2 to 17 years: Clean the burn area with mild soap and water. Apply the pad over the burn or wound and cover with adhesive tape or gauze. Avoid application of large quantities, especially over raw or blistered areas.
Topical dosage (2% viscous solution):
Infants and Children 1 month to 3 years: 1.2 mL (24 mg) applied to the affected area with a cotton-tipped applicator. Separate doses by at least 3 hours (maximum 4 doses/12 hours). Limit use to those situations where safer alternatives are not available or have failed. Do NOT use to treat teething pain in infants and young children due to the risk of serious adverse reactions, including seizures, severe brain injury, heart problems, and death.
Children and Adolescents 4 to 17 years: A single dose of lidocaine should not exceed 4.5 mg/kg (Max: 300 mg); swish and spit solution for use in the mouth or gargle and swallow for use in the pharynx. Separate doses by at least 3 hours (Max: 8 doses/day). Do NOT use to treat teething pain in young children due to the risk of serious adverse reactions, including seizures, severe brain injury, heart problems, and death.
-for bronchoscopy:
Topical dosage:
Infants and Children: An initial dose of 5 mg/kg of 1.5% lidocaine solution diluted with 0.9% Sodium Chloride Injection to a final volume of 10 to 20 mL was used in a small study (n = 15, age 3 months to 9.5 years) during bronchoscopy. The dose was administered to various parts of the airway via the bronchoscope. The mean dose required to provide anesthesia throughout the procedure was 5.7 mg/kg (range 3.2 to 8.5 mg/kg). Higher doses (7 mg/kg or more) were only used in patients undergoing longer procedures and were given over 20 to 45 minutes. The mean lidocaine maximum concentration was 2.5 mcg/mL (range 1 to 3.5 mcg/mL); no patients had toxic serum concentrations (6 mcg/mL or more).
Nebulized dosage*:
Infants, Children, and Adolescents: 4 to 8 mg/kg of 2% lidocaine solution was administered via nebulization in a small study (n = 20, age 1.5 months to 16 years) of patients immediately before bronchoscopy. Doses with a volume less than 3 mL were further diluted with 0.9% Sodium Chloride Injection. Supplemental doses were administered via syringe into the nose or via the bronchoscope at the discretion of bronchoscopist. The total dose range required during the procedure was 4 to 19.6 mg/kg; 10 patients did not require any supplemental lidocaine. The maximum serum lidocaine concentration observed was 2.27 mcg/mL after a total dose of 16.9 mg/kg; no patients experienced toxic serum concentrations.
-for endotracheal intubation:
Topical dosage (4% solution):
Neonates*, Infants, Children, and Adolescents: 4 mg/kg of 4% lidocaine solution was administered via 2 different methods to 490 patients (ages 0 to 16 years) undergoing elective endotracheal intubation. Lidocaine was administered to 1 group via a spray onto the vocal cords using an atomizer under direct laryngoscopy (n = 254). The other group received lidocaine dripped out of a syringe over the base of the tongue blindly into the pharynx (n = 236). There were no differences in respiratory adverse reactions during the perioperative period between the 2 methods of administration; however, patients who received lidocaine before intubation had significantly more desaturations (SpO2 less than 95%) during induction and recovery compared to patients who did not receive lidocaine (n = 510, 14.7% vs. 9.2%, p less than 0.01).
Topical dosage (jelly):
Infants, Children, and Adolescents: Apply a moderate amount of jelly to the external surface of the endotracheal tube shortly before use. Do not exceed a maximum lidocaine dose of 4.5 mg/kg. Avoid getting any of the jelly into the lumen of the tube in order to prevent occlusion. Do not use jelly to lubricate endotracheal stylettes.
-for prevention of dental pain* and for topical anesthesia of mucous membranes:
Transmucosal dosage (DentiPatch system):
Children 11 years and younger*: An application time of 5 minutes was used in small pharmacokinetic study in children (n = 11, ages 2 to 7 years). Apply patch to the local area of gingiva or mucosa before palatal injection, then remove the patch. Do not inject through the patch. Before scaling and root planing, apply to the buccal and lingual side of the molar, then to the premolar areas in the quadrant being worked on. Allow 5 to 10 minutes after applying the system before beginning any procedures. In adult patients, anesthesia continues for 30 to 40 minutes after the patch is applied for 15 minutes then removed.
Children and Adolescents 12 to 17 years: Isolate the procedure area with cotton rolls; dry the tissue with air or gauze. Apply the patch to the desired area using firm pressure. Allow the patch to remain in place until the desired anesthetic effect is produced but for no longer than 15 minutes. Anesthesia usually occurs within 2.5 minutes of application, is present for the duration of a 15 minute application period, and persists for approximately 30 minutes after patch removal.
-for nonurgent painful procedures including IV cannulation, venipuncture, lumbar puncture, or arterial puncture:
Topical dosage (4% cream; e.g., LMX 4):
Neonates* and Infants*: Apply 1 g for 20 to 40 minutes before procedure and cover with an occlusive dressing (maximum application time is 1 hour).
Children and Adolescents: Apply 2 to 2.5 g for 20 to 60 minutes before procedure and cover with an occlusive dressing (maximum application time is 2 hours).
Topical dosage (Zingo):
Children and Adolescents 3 to 17 years: 0.5 mg (1 actuation) to intact skin 1 to 3 minutes before venipuncture or peripheral IV cannulation. After administration, perform the procedure within 10 minutes. Application of 1 additional actuation (0.5 mg) at a new location is acceptable after a failed attempt at venous access. Multiple administrations of a dose at the same location are not recommended.
Topical dosage (LidoDose):
Children and Adolescents 2 to 17 years: Apply to area 3 to 5 minutes prior to procedure not more than 4 times daily.
-for neonatal circumcision*:
Topical dosage (4% cream; e.g., LMX 4):
Neonates: Apply 2 g topically to the foreskin for 20 minutes before the procedure and cover with an occlusive dressing. Topical 4% lidocaine is the preferred topical local anesthetic for neonatal circumcision because it has a faster onset of action, no risk of methemoglobinemia, and less risk of minor skin reactions or blistering as compared with lidocaine; prilocaine cream.
-for the treatment of stage 1 thru 4 pressure ulcers, venous stasis ulcers, ulcerations of mixed vascular etiologies, diabetic skin ulcers, first and second degree burns, and post-surgical incisions, cuts, and abrasions:
Topical dosage (LDO Plus 4% Hydrogel Wound Dressing):
Children and Adolescents 2 to 17 years: Apply a thin layer of gel to the wound surface and the immediate surrounding skin 3 to 4 times daily.

For the treatment of neuropathic pain*:
Transdermal dosage (Lidoderm 5% patch or therapeutic equivalents):
Children and Adolescents 11 to 17 years: Initially, 1 patch for smaller patients (25 to 27 kg) and 2 patches for larger patients (40 to 56 kg) applied for 12 hours in a 24-hour period was used in a small case series (n = 5, ages 11 to 18 years) of patients with neuropathic pain secondary to surgery. Pain control was achieved in 4 out of the 5 patients. Apply patches to intact skin to cover the most painful area. Patches may be cut into smaller sizes with scissors before removal of the release liner.

For ophthalmic anesthesia:
Ophthalmic dosage:
Children and Adolescents: 2 drops applied to the ocular surface in the area of the planned procedure. Additional doses may be used to maintain anesthesia. Administer under the direct supervision of a health care provider.

For local anesthesia* including peripheral nerve block* anesthesia prior to circumcision (dorsal penile nerve block):
Subcutaneous dosage:
Neonates*: 0.4 to 1 mL of 1% lidocaine subcutaneously given as 2 injections into the base of the penis 3 to 8 minutes before the procedure.

For the attenuation of increased intracranial pressure* during rapid-sequence intubation*:
Intravenous dosage:
Infants, Children, and Adolescents: 1 to 3 mg/kg IV given 30 seconds to 5 minutes before laryngoscopy has been recommended as an optional adjunct for rapid sequence intubation (RSI) in patients with increased intracranial pressure. Maximum efficacy occurs 3 to 5 minutes after injection. When a neuroprotective agent (e.g., etomidate) is used for RSI, lidocaine is not likely to provide additional benefit.

For the treatment of refractory seizures* or status epilepticus*:
Intravenous dosage:
Neonates: 2 mg/kg IV loading dose over 10 minutes followed by an infusion of 6 mg/kg/hour IV for 6 hours, then 4 mg/kg/hour IV for 12 hours, then 2 mg/kg/hour IV for 12 hours has been recommended as a second- or third-line treatment. Regimens using a short duration of infusion are recommended in order to reduce accumulation of lidocaine and its metabolites and reduce toxicity. If seizures persist during treatment, this may be a sign of accumulation, and dose reduction may be necessary. This regimen was effective in 78% of the treatment courses in a small study (n = 15). Although premature neonates were included in this study (n = 4, gestational age 27 to 33 weeks), these patients experienced higher plasma lidocaine concentrations compared to term neonates. An initial infusion rate of 4 mg/kg/hour IV for 24 hours then tapered by 1 mg/kg/hour IV every 24 hours for 4 days was used in a small study of premature (n = 5, gestational age 29 to 35 weeks) and term (n = 8) neonates. This regimen was effective in 85% of the patients. However, due to reduced clearance seen in premature neonates compared to term neonates, lower initial doses may be warranted in this population.
Infants, Children, and Adolescents: 1 to 2 mg/kg IV loading dose over 10 minutes followed by a continuous infusion of 2 to 6 mg/kg/hour IV has been reported. The mean duration of infusion in various studies ranged from 14.6 to 105.7 hours.

Therapeutic Drug Monitoring:
Usual target serum concentration (ventricular arrhythmias): 1.5 to 6 mcg/mL
-Toxicity of lidocaine is plasma concentration-dependent and is usually associated with concentrations higher than 9 mcg/mL. However, serious adverse reactions have occurred at plasma concentrations within the therapeutic range. Central nervous system reactions become apparent with increasing plasma concentrations above 6 mcg/mL free base.
-Monitoring of plasma concentrations of lidocaine for the treatment of seizures is recommended when accumulation is suspected. The efficacy of lidocaine for the treatment of seizures does not appear to correlate with plasma concentrations; however a goal concentration of lower than 9 mcg/mL has been suggested to minimize adverse reactions.

Maximum Dosage Limits:
-Neonates
1 mg/kg IV loading dose, up to 3 mg/kg IV total loading dose, and 50 mcg/kg/min IV continuous infusion for ventricular arrhythmias; 2 mg/kg IV loading dose and 6 mg/kg/hour IV continuous infusion for status epilepticus; maximum dosage for use as a topical or local anesthetic is dependent on the indication, route, and formulation used.
-Infants
1 mg/kg IV loading dose, up to 3 mg/kg IV total loading dose, and 50 mcg/kg/min IV continuous infusion for ventricular arrhythmias; 2 mg/kg IV loading dose and 6 mg/kg/hour IV continuous infusion for status epilepticus; maximum dosage for use as a topical or local anesthetic is dependent on the indication, route, and formulation used.
-Children
1 mg/kg IV loading dose (Max: 100 mg IV), up to 3 mg/kg IV total loading dose, and 50 mcg/kg/min IV continuous infusion for ventricular arrhythmias; 2 mg/kg IV loading dose and 6 mg/kg/hour IV continuous infusion for status epilepticus; maximum dosage for use as a topical or local anesthetic is dependent on the indication, route, and formulation used.
-Adolescents
1 mg/kg IV loading dose (Max: 100 mg IV), up to 3 mg/kg IV total loading dose, and 50 mcg/kg/min IV continuous infusion for ventricular arrhythmias; 2 mg/kg IV loading dose and 6 mg/kg/hour IV continuous infusion for status epilepticus; maximum dosage for use as a topical or local anesthetic is dependent on the indication, route, and formulation used.

Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; however, dosage adjustment may be required. Administer IV lidocaine at a lower maintenance infusion rate and monitor for toxicity. Hepatic dysfunction may decrease the clearance and increase the exposure of lidocaine.

Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; however, dosage adjustment may be required. Administer IV lidocaine at a lower maintenance infusion rate and monitor for toxicity. The elimination of lidocaine may be reduced in patients with severe renal impairment and accumulation of glycinexylidide (a major active metabolite) may occur, increasing the risk of toxicity.

*non-FDA-approved indication

Monograph content under development

Mechanism of Action: Lidocaine's antiarrhythmic effects result from its ability to inhibit the influx of sodium through the "fast" channels of the myocardial cell membrane, thereby increasing the recovery period after repolarization. Lidocaine suppresses automaticity and decreases the effective refractory period and the action potential duration in the His-Purkinje system at concentrations that do not suppress automaticity at the SA node. The drug suppresses spontaneous depolarizations in the ventricles by inhibiting reentry mechanisms, and it appears to act preferentially on ischemic tissue. Lidocaine shortens the refractory period, unlike procainamide, which lengthens it. Also, lidocaine does not possess vagolytic properties.

Lidocaine stabilizes neuronal membranes by inhibiting the ionic fluxes required for the initiation and conduction of impulses, thereby effecting local anesthetic action. Lidocaine produces its analgesic effects through a reversible nerve conduction blockade by diminishing nerve membrane permeability to sodium, just as it affects sodium permeability in myocardial cells. This action decreases the rate of membrane depolarization, thereby increasing the threshold for electrical excitability. The blockade affects all nerve fibers in the following sequence: autonomic, sensory and motor, with effects diminishing in reverse order. Loss of nerve function clinically is as follows: pain, temperature, touch, proprioception, skeletal muscle tone. Direct nerve membrane penetration is necessary for effective anesthesia, which is achieved by applying the anesthetic topically or injecting it subcutaneously, intradermally, or submucosally around the nerve trunks or ganglia supplying the area to be anesthetized.

The anticonvulsant mechanism of lidocaine for the management of seizures is unknown; however, it is thought to be similar to the local anesthetic mechanism. Lidocaine acts in the central nervous system to stabilize membranes and restrict the movement of sodium and potassium, thereby decreasing membrane excitability.

Pharmacokinetics: Lidocaine is administered dermally, topically, ophthalmically, and parenterally. Lidocaine is bound to plasma protein, specifically alpha-1-acid glycoprotein, with binding dependent on plasma protein and drug concentrations; the fraction of drug bound decreases with increasing drug concentrations. At concentrations of 1 to 4 mcg/mL free base, 60% to 80% of lidocaine is protein bound. Lidocaine readily crosses the blood-brain barrier. Lidocaine is extensively metabolized in the liver into 2 active compounds, monoethylglycinexylidide (MEGX) and glycinexylidide (GX), which possess 100% and 25% of the potency of lidocaine, respectively. After intravenous administration, MEGX and GX concentrations in serum range from 11% to 36% and from 5% to 11%, respectively, of lidocaine concentrations. It is not known if lidocaine is metabolized in the skin. The initial half-life of lidocaine in an otherwise healthy adult individual is 7 to 30 minutes, followed by a terminal half-life of 1.5 to 2 hours. The half-life of MEGX is 0.5 to 3.3 hours. Lidocaine and its metabolites are excreted by the kidneys. Approximately 90% of an absorbed dose can be recovered in the urine as metabolites or parent drug. Less than 10% of lidocaine is excreted unchanged in adults.

Affected cytochrome P450 isoenzymes: CYP1A2 and CYP3A4
The major metabolic pathway, sequential N-deethylation to MEGX and GX, is primarily mediated by CYP1A2 with a minor role of CYP3A4.


-Route-Specific Pharmacokinetics
Oral Route
If swallowed, lidocaine is nearly completely absorbed, but it undergoes extensive first-pass metabolism in the liver, resulting in a low systemic bioavailability. Although it is not administered orally, some systemic absorption is possible when using oral viscous solutions.

Intravenous Route
After intravenous injection, lidocaine rapidly distributes into tissues. Distribution can be decreased in patients with heart failure. In healthy adults, the volume of distribution is approximately 1.7 L/kg compared to approximately 1 L/kg in adults with heart failure. The elimination half-life of lidocaine increases with prolonged (more than 24 hours) intravenous infusion (3.2 hours vs. 1.4 to 2.1 hours).

Subcutaneous Route
Only minimal amounts of lidocaine enter the circulation after subcutaneous injection, but repeated dosing may result in detectable lidocaine blood concentrations due to gradual accumulation of the drug or its metabolites.

Topical Route
The rate and extent of absorption after topical administration is dependent the concentration, total dose, site of application, and duration of exposure. The most rapid rate of absorption generally occurs after intratracheal administration. After topical administration of ointment or jelly, peak effects typically occur within 3 to 5 minutes.

There is a difference in the bioavailability of lidocaine transdermal systems; one 5% patch (Lidoderm) provides equivalent lidocaine exposure to one 1.8% lidocaine system (ZTlido). Transdermal absorption of lidocaine is related to the duration of application and the surface area over which the patch is applied. When the dermal patch (Lidoderm) is used as directed, only 3 +/- 2% of the dose applied is expected to be absorbed transcutaneously with very little systemic absorption. After application of Lidoderm patches over a 420 cm2 area of intact skin for 12 hours, the absorbed dose of lidocaine was 64 mg resulting in a Cmax of 0.13 mcg/mL. After application of 3 ZTlido systems (108 mg) over a 420 cm2 area of intact skin for 12 hours, a Cmax of 0.075 mcg/mL (75 ng/mL) was attained in approximately 14 hours. The lidocaine concentration does not increase with daily use in patients with normal renal function. Exposure of the ZTlido system to heat at 0 and 8.5 hours results in an increased Cmax (0.16 mcg/mL [160 ng/mL] vs. 0.098 mcg/mL [97.6 ng/mL) at rest). Concentrations returned to normal within 4 hours after the heat was removed. No clinically relevant differences in absorption were seen under exercise conditions.

Mean plasma concentrations of lidocaine in children 2 to 7 years of age (n = 11) after a 5 minute application of the transoral patch (DentiPatch) were 4 to 5 times higher than mean peak plasma concentrations in adult patients after a 15 minute application (82 ng/mL vs. 16.5 to 22.3 ng/mL). Local anesthesia starts to occur within 2.5 minutes of application of the lidocaine patch (DentiPatch) to intact mucous membranes in adults. After removal of the patch after 15 minutes of application, local anesthesia continues for approximately 30 minutes.

Other Route(s)
Ocular Route
Administration of lidocaine on the ocular surface with ophthalmic gel (Akten) yields ocular anesthesia within 20 seconds to 1 minute of application. The duration of anesthesia ranges from 5 to 30 minutes.


-Special Populations
Pediatrics
Premature Neonates and Neonates
The mean clearance of lidocaine was reduced in premature neonates (n = 5, gestational age 29 to 35 weeks) compared to term neonates (n = 8) receiving continuous infusion lidocaine for the treatment of seizures (0.56 to 1.25 L/kg/hour vs. 0.98 to 1.68 L/kg/hour). The mean volume of distribution and elimination half-life were significantly longer in premature neonates (n = 4, gestational age 26 to 36 weeks, postnatal age 9 to 42 days) after administration of single doses of subcutaneous lidocaine compared to adult subjects (n = 10). The mean volume of distribution and elimination half-life were 2.75 L/kg and 3.16 hours, respectively, in the premature neonates versus 1.11 L/kg and 1.8 hours, respectively, in the adult subjects. The total plasma clearance normalized to body weight was not significantly different between premature neonates and adults. The proportion of the lidocaine dose excreted in the urine as unchanged drug was significantly higher in the premature neonates compared to the adult subjects (19.67% vs. 4.27%). The mean percentage of free lidocaine was significantly higher in neonatal patients (47.6%) compared to infants, children, and adolescents (26.3% to 31.5%). Mean serum concentrations of alpha-1-acid glycoprotein, the primary plasma protein that lidocaine is bound to, were also significantly lower in premature and term neonates (8.7 to 17.1 mg/dL) compared to infants (52 mg/dL).

Infants and Children
The pharmacokinetics of lidocaine after single intravenous or caudal injections in infants and children (age 6 months to 9 years) undergoing general anesthesia were similar to those reported in adults. The mean volume of distribution, elimination half-life, and clearance of intravenous lidocaine in infants and children (n = 10, age 6 months to 3 years) were 1.11 L/kg, 58 minutes, 11.1 mL/kg/minute, respectively, compared to 0.71 L/kg, 43 minutes, and 9.8 mL/kg/minute, respectively, in adults. The mean volume of distribution, elimination half-life, and clearance of lidocaine in children 3.5 to 9 years of age after a single caudal injection were 3.05 L/kg, 155 minutes, and 15.4 mL/kg/minute, respectively. Although the half-life in this study was longer than the half-life reported in adult patients after intravenous or extradural lidocaine, the clearance was similar. The increased half-life was attributed to the larger volume of distribution in pediatric patients rather than a difference in the rate of elimination between children and adults.

Hepatic Impairment
Conditions such as liver disease can decrease hepatic blood flow and decrease lidocaine clearance. The half-life may increase by 2-fold or greater (5 hours or more) in patients with liver dysfunction.

Renal Impairment
Lidocaine clearance is decreased by half and the accumulation of glycinexylidide (GX) is increased 1.5-fold in patients with severe renal impairment. Mild or moderate renal impairment does not significantly affect lidocaine kinetics. Increased GX concentrations were noted among adults who received lidocaine 1 mg/kg IV with a CrCl of 30 to 60 mL/minute/1.73m2 (760 +/- 555 ng x hour/mL), those with a CrCl less than 30 mL/minute/1.73m2 (690 +/- 511 ng x hour/mL), and those on hemodialysis (587 +/- 268 ng x hour/mL) as compared with adults with a CrCl more than 80 mL/minute/1.73m2 (274 +/- 150 ng x hour/mL). Also, significantly decreased lidocaine clearance (6.01 +/- 2.54 mL/minute x kg vs. 11.87 +/- 2.97 mL/minute x kg) and increased half-life (4.55 +/- 1.71 hours vs. 2.24 +/- 0.55 hours) were noted among adults with a CrCl less than 30 mL/minute/1.73m2 who were not receiving hemodialysis as compared with data from patients with a CrCl more than 80 mL/minute/1.73m2. Of note, lidocaine concentrations were similar among adults undergoing hemodialysis as compared with data from adults with a CrCl more than 80 mL/minute/1.73m2. Dialyzable uremic toxins may be responsible for inhibition of lidocaine metabolism.