Lidocaine Cream

Overview of Lidocaine Cream

Dosage Strengths of Lidocaine Cream

2.5% 30 mL Pump
5% 30 mL Pump
7.5% 30 mL Pump

General Information

Lidocaine is a widely used antiarrhythmic and amide-type local anesthetic. As an anesthetic agent, it is available as an ointment, jelly, patch, or aerosol for topical use, as an oral solution, and as an injection. Lidocaine is classified as a class Ib antiarrhythmic. It may be considered for ventricular fibrillation (VF) and pulseless ventricular tachycardia (pVT) that is unresponsive to cardiopulmonary resuscitation (CPR), defibrillation, and vasopressor therapy. Evidence is inadequate regarding the routine use of lidocaine after cardiac arrest or early (within the first hour) after return of spontaneous circulation (ROSC). However, prophylactic use of lidocaine may be considered in certain circumstances (e.g., during emergency medical services transport) when treatment of recurrent VF/pVT may be challenging.12 Due to the potential for serious adverse reactions, including cardiovascular depression, continuous electrocardiogram monitoring is recommended during intravenous lidocaine treatment.3 There is limited evidence suggesting that nebulized lidocaine exhibits steroid-sparing effects when used in corticosteroid-dependent asthmatics.456 However, extreme caution is recommended until long-term safety and efficacy can be established.

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.7 Lidocaine produces its analgesics 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.

Pharmacokinetics

Lidocaine is administered dermally, topically, ophthalmically, and parenterally. It 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. The major metabolic pathway, sequential N-deethylation to MEGX and GX, is primarily mediated by CYP1A2 with a minor role of CYP3A4. After intravenous administration, MEGX and GX concentrations in serum range from 11% to 36% and from 5% to 11%, respectively, of lidocaine concentrations. Serum concentrations of MEGX were about one-third the serum lidocaine concentrations. It is not known if lidocaine is metabolized in the skin. The initial half-life in an otherwise healthy 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.8910 Lidocaine and its metabolites are excreted by the kidneys. More than 98% of an absorbed dose can be recovered in the urine as metabolites or parent drug. Less than 10% is excreted unchanged in adults.

Route-Specific Pharmacokinetics:

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.1112

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 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. The lidocaine concentration does not increase with daily use in patients with normal renal function.13

Lidocaine topical system (ZTlido) 1.8% demonstrated equivalent AUC and Cmax of lidocaine to lidocaine dermal patch 5%. After application of 3 lidocaine topical systems over a 420 cm2 area of intact skin on the backs of 54 healthy volunteers for 12 hours, mean plasma Cmax was 75.1 (+/- 23) ng/mL and mean Tmax was 13.9 (4, 18) hours. Systemic lidocaine concentrations did not increase with daily use. Exposure to external heat source (heating pad at medium setting applied for 20 minutes at time 0 and 8.5 hours) increased lidocaine mean peak plasma concentrations from 97.6 +/- 36.9 ng/mL to 160.3 +/- 100.1 ng/mL. Moderate exercise (cycling at a heart rate of 108 bpm) at time 0, 2.5, 5.5, and 8.5 hours produced no clinically relevant differences in systemic absorption with mean peak plasma concentrations of 90.5 +/- 25.4 ng/mL. There were no significant pharmacokinetic differences when the system was applied to the administration site after external heat exposure (heating pad at medium setting applied for 15 minutes prior to system application) or after moderate walking for approximately 20 minutes beginning approximately 30 minutes prior to system application.14

Local anesthesia starts to occur within 2.5 minutes of application of the transoral patch (DentiPatch) to intact mucous membranes. During 15 minutes of system application, serum concentrations of lidocaine are less than 0.1 mcg/mL. After removal of the patch after 15 minutes of application, local anesthesia continues for approximately 30 minutes. The maximum plasma concentration after the application of the DentiPatch is approximately one-seventh of the concentration achieved by the application of 5% lidocaine ointment.15

Administration of lidocaine into the dermis with Zingo yields local dermal analgesia within 1 to 3 minutes of application. Analgesia diminishes within 10 minutes of administration. In adults, lidocaine plasma concentrations were undetectable (less than 5 ng/mL) after a single dose of Zingo.16

Special Populations:

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.17

Renal Impairment: Lidocaine elimination may be reduced in patients with renal impairment, and accumulation of glycinexylidide (GX), a renally eliminated and active metabolite of lidocaine, may occur. Among adults who received lidocaine 1 mg/kg IV, increased GX concentrations were noted among adults 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.18

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.1920 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.19 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.20

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).21 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%).22 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).23

Geriatric: During intravenous studies, the elimination half-life of lidocaine was statistically significantly longer in elderly patients (2.5 hours) than in younger patients (1.5 hours).

Cardiac Disease: Conditions such as congestive heart failure or myocardial infarction can decrease hepatic blood flow and decrease lidocaine clearance. Terminal half-lives in patients with cardiac failure is 115 minutes.

Contraindications/Precautions

Lidocaine application to oral mucosa can interfere with swallowing and increase the risk of aspiration. Patients should not ingest food for at least 1 hour after the use of anesthetic agents in the mouth or throat.

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.

Lidocaine is contraindicated in patients with amide local anesthetic hypersensitivity. Parenteral preparations containing preservatives should not be used for spinal or epidural anesthesia. Solutions containing dextrose may be contraindicated in patients with known allergy to corn or corn products. There have been no reports of cross-sensitivity between lidocaine and either procainamide or quinidine.3

Lidocaine does not provide adequate anesthesia in patients with collagen-vascular disease, such as Ehlers Danlos Type III. Lidocaine is relatively contraindicated in these conditions.24

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 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.252627

Use lidocaine with caution in patients at increased risk of adverse events. 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, particularly with parenteral, prescription topical jelly, or transdermal patch use.328162712 Resuscitative equipment and facilities should be readily available in case of an emergency when using parenteral products. Repeated doses of parenteral lidocaine may cause a significant increase in blood concentrations with each successive dose; these increases may be poorly tolerated, particularly by those who are debilitated, pediatric patients, geriatric patients, or the acutely ill.328162712 Excessive dosing by applying lidocaine transdermal patches to larger areas or for longer than the recommended wearing time could result in increased absorption of lidocaine and high blood concentrations, leading to serious systemic adverse effects. Lidocaine toxicity could be expected at lidocaine blood concentrations above 5 mcg/mL. The blood concentration of lidocaine is determined by the rate of systemic absorption and elimination. Longer duration of transdermal application, application of more than the recommended number of patches, smaller patients, or impaired elimination may all contribute to increasing the blood concentration of lidocaine.1329 The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities. The OBRA guidelines caution that antiarrhythmics can have serious adverse effects (e.g., impairment of mental function, appetite, behavior, heart function, or falls) in older individuals.30

Lidocaine is classified as FDA pregnancy category B. Reproductive studies conducted in rats have not demonstrated lidocaine-induced fetal harm; however, animal studies are not always predictive of human response. There are no adequate or well controlled studies of lidocaine in pregnant women.3 Local anesthetics are known to cross the placenta rapidly and, when administered for epidural, paracervical, pudendal, or caudal block anesthesia, and to cause fetal toxicity. The frequency and extent of toxicity are dependent on the procedure performed. Maternal hypotension can result from regional anesthesia, and elevating the feet and positioning the patient on her left side may alleviate this effect. Topical ocular application of lidocaine is not expected to result in systemic exposure.31 When lidocaine is used for dental anesthesia, no fetal harm has been observed; lidocaine is generally the dental anesthetic of choice during pregnancy and guidelines suggest the second trimester is the best time for dental procedures if they are necessary.32 A study by the American Dental Association provides some evidence that, when needed, the use of dental local or topical anesthetics at 13 weeks to 21 weeks of pregnancy or later is likely safe and does not raise incidences of adverse pregnancy outcomes or other adverse events; the study analyzed data from the Obstetrics and Periodontal Therapy (OPT) trial, a multicenter study of over 800 pregnant patients in the early to mid second trimester who received required dental procedures.33

According to the manufacturers, caution should be exercised when lidocaine is administered to breast-feeding women (regardless of dosage formulation). Lidocaine is excreted in breast milk with a milk:plasma ratio of 0.4. Many specific dosage forms, including Lidoderm brand lidocaine transdermal patches, have not been studied in breast-feeding women.13 The American Academy of Pediatrics lists lidocaine as usually compatible with breast-feeding.34 When lidocaine is used for dental or short-term, limited local anesthesia, the healthy term infant can generally safely nurse as soon as the mother is awake and alert.3532 Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternal drug exposure, healthcare providers are encouraged to report the adverse effect to the FDA.

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 with severe SA block, AV block, or intraventricular heart block. 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. Promptly discontinue the infusion if signs of excessive depression of cardiac conductivity occur, such as prolongation of the PR interval, widening of the QRS interval, or appearance or aggravation of arrhythmias.336 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.327371238 Topical ocular application of lidocaine is not expected to result in systemic exposure.31

No lidocaine dosage adjustment needed in patients with renal impairment. However, the elimination of glycine xylidide (major active metabolite) is eliminated renally, and accumulation of the metabolite in severe renal failure (renal disease) theoretically could result in neurotoxicity.

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. Patches and administration via Zingo injection system should only be used on intact skin, and transoral delivery systems should only be applied 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 one additional Zingo at a new location is acceptable after a failed attempt at venous access. However, multiple administrations of Zingo at the same location are not recommended. Multiple Zingo applications could result in plasma concentrations that could produce systemic toxicity.16 At least 2 reports of deaths exist after application of topical anesthetics prior to cosmetic procedures. In both instances, women, aged 22 and 25 years, applied topical anesthetics to their legs and wrapped the treated area, as directed, in plastic wrap to enhance the numbing effect of the cream. Both women died from toxic effects of the topical anesthetic. The preparations used in both cases were compounded in pharmacies and contained high amounts of lidocaine and tetracaine. 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 do not cover or apply heat to the treated area.

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; however, prolonged use may produce permanent corneal opacification and ulceration with accompanying visual loss.31 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 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 patch.13

When parenteral lidocaine is intended as a local anesthetic, avoid intravenous administration, intraarterial administration, or intrathecal administration. Unintended intravenous or intraarterial administration may result in cardiac arrest and may require prolonged resuscitation. Further, do not administer preservative-containing parenteral lidocaine via intrathecal routes. To avoid intravascular administration of lidocaine during local anesthetic procedures, aspiration should be performed before the local anesthetic is injected and after repositioning of the needle. During epidural administration, a test dose should be administered initially and the patient should be monitored for CNS and cardiovascular toxicity, as well as signs of inadvertent intrathecal administration (see Adverse Reactions). Syringe aspiration should also be performed before and during each supplemental injection in continuous catheter techniques. Clinicians should be aware that the absence of blood return does not guarantee that intravascular injection has been avoided.

Patients receiving local head and neck anesthesia including retrobulbar, stellate ganglion, and dental blocks, are at increased risk of CNS toxicity similar to the systemic toxicity seen with unintentional intravascular injections of large doses of lidocaine. These reactions may be due to potential intraarterial injection of the local anesthetic with retrograde flow to the cerebral circulation. Patients receiving these blocks should have their ventilatory and circulatory systems monitored closely. Recommended doses should not be exceeded in these patients.

When local anesthetics, like lidocaine, are used for retrobulbar block during ocular surgery, lack of corneal sensation should not be relied upon 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. Lidocaine preparations containing preservatives should not be used for epidural or spinal anesthesia. Patients with the following conditions should receive spinal anesthesia with caution: pre-existing CNS disorders such as poliomyelitis, pernicious anemia, paralysis from nerve injuries or syphilis; children < 16 years, or elderly patients; chronic backache; preoperative headache; hypotension; hypertension; arthritis or spinal deformity; technical problems (persistent paresthesias, persistent bloody tap); psychotic or uncooperative patients. Consult standard textbooks for specific techniques and precautions for spinal anesthetic procedures. Epidural, local, nerve block and spinal administration of lidocaine are contraindicated in patients with the following: infection or inflammation at the injection site, bacteremia (sepsis), platelet abnormalities, thrombocytopenia less than 100,000/mm3, increased bleeding time, uncontrolled coagulopathy or bleeding, or anticoagulant therapy. Lumbar and caudal epidural anesthesia should be used 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.3712 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.16

During labor and obstetric delivery, local anesthetics, like lidocaine, can cause varying degrees of maternal, fetal, and neonatal toxicities. The potential for toxicity is related to the procedure performed, the type and amount of drug used, and the technique of administration. Appropriate patient positioning during obstetric delivery may decrease maternal hypotension that can result from regional anesthesia. Injection of the local anesthetic should be performed with the patient in the left lateral decubitus position to displace the gravid uterus, thereby minimizing aortocaval compression. Epidural, spinal, paracervical, or pudendal nerve block may alter the forces of parturition. The use of obstetrical anesthesia may alter the duration of various phases of labor and increase the need for forceps assistance. Electronic fetal monitoring for signs of fetal distress is highly recommended.

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

Physicians should weigh the possible risks versus benefits when considering obstetrical paracervical nerve block with parenteral lidocaine in situations of fetal prematurity, toxemia of pregnancy, and fetal distress. Adherence to the recommended dosage is critical during obstetrical paracervical block. Failure to achieve adequate analgesia with recommended doses should arouse suspicion of intravascular or fetal intracranial injection. Use of paracervical block in early pregnancy (i.e., anesthesia for elective abortion) may result in rapid systemic absorption and can result in maternal seizures or cardiovascular collapse. The recommended dose of the local anesthetic should not be exceeded. Injections should be administered slowly with frequent aspirations. Allow a 5-minute interval between administration to each side.

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.38

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. Resuscitative equipment and facilities should be readily available in case of an emergency when using parenteral products. Repeated doses of parenteral lidocaine may cause a significant increase in blood concentrations with each successive dose; these increases may be poorly tolerated by pediatric patients, particularly by those who are debilitated or the acutely ill.328162712 Similar increases in systemic exposure are possible with repeat topical application. Certain products, such as lidocaine transdermal patches, have not been FDA-approved for application to pediatric patients.13 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.39 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.39 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.39 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.40 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 following use of local anesthetic preparations in the mouth or throat area. This is particularly important in children because of their frequency of eating.37

Pregnancy

Lidocaine is classified as FDA pregnancy category B. Reproductive studies conducted in rats have not demonstrated lidocaine-induced fetal harm; however, animal studies are not always predictive of human response. There are no adequate or well controlled studies of lidocaine in pregnant women.3 Local anesthetics are known to cross the placenta rapidly and, when administered for epidural, paracervical, pudendal, or caudal block anesthesia, and to cause fetal toxicity. The frequency and extent of toxicity are dependent on the procedure performed. Maternal hypotension can result from regional anesthesia, and elevating the feet and positioning the patient on her left side may alleviate this effect. Topical ocular application of lidocaine is not expected to result in systemic exposure.31 When lidocaine is used for dental anesthesia, no fetal harm has been observed; lidocaine is generally the dental anesthetic of choice during pregnancy and guidelines suggest the second trimester is the best time for dental procedures if they are necessary.32 A study by the American Dental Association provides some evidence that, when needed, the use of dental local or topical anesthetics at 13 weeks to 21 weeks of pregnancy or later is likely safe and does not raise incidences of adverse pregnancy outcomes or other adverse events; the study analyzed data from the Obstetrics and Periodontal Therapy (OPT) trial, a multicenter study of over 800 pregnant patients in the early to mid second trimester who received required dental procedures.33

Breast-feeding

According to the manufacturers, caution should be exercised when lidocaine is administered to breast-feeding women (regardless of dosage formulation). Lidocaine is excreted in breast milk with a milk:plasma ratio of 0.4. Many specific dosage forms, including Lidoderm brand lidocaine transdermal patches, have not been studied in breast-feeding women.13 The American Academy of Pediatrics lists lidocaine as usually compatible with breast-feeding.34 When lidocaine is used for dental or short-term, limited local anesthesia, the healthy term infant can generally safely nurse as soon as the mother is awake and alert.3532 Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternal drug exposure, healthcare providers are encouraged to report the adverse effect to the FDA.

Adverse Reactions/Side Effects

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. Agitation, 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.31327374011123841 Dizziness and vomiting occurred in 0.9% and 1% of patients, respectively, who were treated with the lidocaine intradermal injection system during clinical trials.16

During caudal or lumbar epidural block, unintentional penetration of the subarachnoid space may occur. Adverse effects depend upon the amount of drug given subdurally and may include spinal block of varying magnitude, low blood pressure secondary to spinal block, fecal incontinence and urinary incontinence, and loss of perineal sensation and sexual function. In a prospective review of 10,440 patients who received lidocaine HCl for spinal anesthesia, positional headaches, low blood pressure and backache were reported in 3% of patients, shivering was reported in 2%, and peripheral nerve symptoms, nausea, respiratory inadequacy and double vision were reported in < 1% of patients. Many of these observations may be related to local anesthetic techniques, with or without a contribution from the local anesthetic. Neurologic effects seen following spinal anesthesia include paresthesias, weakness and paralysis of lower extremities, low blood pressure, high or total spinal block, urinary retention, headache, back pain, septic meningitis, meningismus, arachnoiditis, shivering, cranial nerve palsies due to traction on nerves from loss of cerebrospinal fluid. Persistent motor, sensory, and/or autonomic (sphincter control) deficit of lower spinal segments with slow (several months) or incomplete recovery has been reported rarely.42 Following spinal administration with lidocaine 5% with Dextrose, transient neuropathic pain, developing in the buttocks and radiating to the lateral thighs and calves may be seen. Complete resolution of symptoms usually takes place within 3 days but may persist for up to 2 months. Nausea occurred in 2% of patients who were treated with the lidocaine intradermal injection system during clinical trials.16

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 CNS toxicity. Lidocaine-induced adverse cardiovascular effects include myocardial depression, sinus bradycardia, hypotension, cardiovascular collapse, and cardiac arrest. These effects typically occur with high plasma drug concentrations but have occurred with smaller doses in rare instances. Cardiovascular and CNS side effects resulting from lidocaine administration should be treated 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 side effects 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.73740111343 Combining lidocaine with a vasoconstrictor increases the likelihood of producing anxiety, palpitations, dizziness, headache, restlessness, tremor, angina, and hypertension.

Local anesthetics generally are known to cross the placenta. For obstetric use, fetal heart rate should be monitored continuously because fetal bradycardia has occurred with high plasma levels of lidocaine. Maternal hypotension can result from regional anesthesia. Patient position can alleviate this problem, and the injection should be performed with the patient in the left lateral decubitus position to displace the gravid uterus, thereby minimizing aortocaval compression. Because of the profound motor blockade produced when used epidurally, lidocaine can cause decreased uterine contractility and further decrease maternal expulsive efforts.42 Unintended fetal intracranial injection of local anesthetics has occurred from attempted pudendal or paracervical block. Failure to achieve adequate anesthesia with standard doses should arouse suspicion of intracranial or intravascular injections. Infants so affected often present with unexplained neonatal depression at birth and can develop seizures within 6 hours as a result of high serum concentrations. Fetal bradycardia and fetal acidosis have resulted from paracervical injections.

Systemic adverse reactions after appropriate application of topical or transdermal lidocaine are unlikely because of the small amount of lidocaine absorbed. The skin at the site of treatment may develop erythema, swelling, or dysesthesia (abnormal sensation).4413 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.1341 Preexisting inflammation or infection increases the risk of developing serious skin side effects. There have been reported cases of permanent injury to extraocular muscles requiring surgical repair following retrobulbar administration of lidocaine.27 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.7 During adult and pediatric clinical trials of lidocaine injectable powder (Zingo), erythema (an injection site reaction) occurred in 53% to 67.3% of patients who received active drug, petechiae in 44% to 46.4% of patients, edema in 4.3% to 8% of patients, and pruritus in 1% to 9.4% of patients. Burning and venipuncture site hemorrhage occurred in 0.54% and 0.4% of adults, respectively. A total of 4% of pediatric patients experienced application site reactions that included ecchymosis, burning, pain, contusion, and hemorrhage.16

Allergic and anaphylactoid reactions have been infrequently associated with lidocaine administration. 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 questionable value. There have been no reports of cross-sensitivity between lidocaine and para-amino-benzoic acid derivatives (procaine, tetracaine, benzocaine, etc.).137374011434541

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.464727

Local anesthetics such as lidocaine administered by a continuous infusion to a joint space may cause chondrolysis (necrosis and destruction of cartilage). The FDA has received 35 reports of chondrolysis in patients given continuous intra-articular infusions of local anesthetics with elastomeric infusion devices to control post-surgical pain. Data suggest that the reported cases of chondrolysis are not associated with any single manufacturer of elastomeric infusion devices. In all but 1 patient, chondrolysis occurred after shoulder surgeries. The local anesthetics +/- epinephrine were infused for 48 to 72 hours directly into the intra-articular space using an elastomeric pump. The most commonly reported site of infusion was the glenohumeral (glenoid) space (46%), and bupivacaine was at least 1 of the local anesthetics used in all 35 cases. Joint pain, stiffness, and loss of motion were reported as early as the second month after infusion receipt. Chondrolysis was diagnosed a median of 8.5 months after the infusion. In more than half of these reports, the patients required additional surgery including arthroscopy or arthroplasty. In addition to the 35 bupivicaine-related cases, the FDA has received four additional reports of chondrolysis in patients administered continuous intra-articular infusions of lidocaine in the shoulder. It is not known which specific factor or combination of factors contributed to the development of chondrolysis. The infused local anesthetic drugs, the device materials, and/or other sources may have resulted in the development of chondrolysis. In vitro data do suggest that bupivacaine, lidocaine, and ropivacaine cause chondrolysis.4849 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. The FDA is requiring the drug manufacturers to update their product labels to warn healthcare professionals about the reported cases of chondrolysis after continuous intra-articular infusion with local anesthetics. The FDA is also requiring the manufacturers of pumps that may be used to infuse local anesthetics such as elastomeric infusion devices to have similar warnings for their products. 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.2742

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.31

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.42

Storage

Store this medication at 68°F to 77°F (20°C to 25°C) and away from heat, moisture and light. Keep all medicine out of the reach of children. Throw away any unused medicine after the beyond use date. Do not flush unused medications or pour down a sink or drain.

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