ions that may occur. ask your health care provider if lidorx® 3% may interact with other medicines that you take. 7.1 serious interactions: antiarrhythmic drugs: lidorx® 3% should be used with caution in patients receiving class i antiarrhythmic drugs (such as tocainide and mexiletine) since the toxic effects are additive and potentially synergistic. bupivacaine liposome: lidocaine hydrochloride usp increases toxicity of bupivacaine by increasing the free (unencapsulated)bupiacaine. dofetilide: lidocaine hydrochloride usp increases effects of dofetilide thru pharmacodynamic synergism. lomitapide: lidocaine hydrochloride usp increases levels of lomitapide by affecting hepatic/intestinal enzymes cyp3a4 metabolism. 7.2 general interactions: drug interactions: patients that are administered local anesthetics may be at increased risk of developing methemoglobinemia when concurrently exposed to the following oxidizing agents: class examples nitrates/nitrites nitroglycerin, nitroprusside, nitric oxide, nitrous oxide local anesthetics benzocaine, lidocaine, bupivacaine, mepivacaine, letracaine, prilocaine, procaine, articaine, ropivacaine antincoplastic agents cyclophosphosphamide,flutamide, rasburicase, ifosfamide, hydroxyurea antibiotics dapsone, sulfonamides, nitrofurantoin,paraaminosalicylic acid antimalarials chloroquine,primaquine anticonvulsants phenytoin,sodium valproate,phenobarbital other drugs acetaminophen, metoclopramide, sulfa drugs (i.e, sulfasalazine), quinine drugs metabolized via cyp3a4 enzyme: (ex. antipsychotics, ssris, tcas, many chemotherapeutics, calcium channel bockers, benzodiazopines) lidocaine hydrochloride usp may increase serum levels of many drugs metabolized by hepatic / intestinal cyp3a4 enzymes. drugs that affect hepatic cyp1a2 enzyme: (ex. quinoline antibiotics, cimetidine, barbiturates, benzodiazepines, erythromycin) may increase serum lidocaine hydrochloride usp levels by decreasing lidocaine hydrochloride usp metabolism by cyp1a2 enzyme.

s recommended. signs and symptoms of methemoglobinemia may occur immediately or may be delayed some hours after exposure and are characterized by a cyanotic skin discoloration and abnormal coloration of the blood. methemoglobin levels may continue to rise; therefore, immediate treatment is required to avert more serious central nervous system and cardiovascular adverse effects, including seizures, coma, arrhythmias, and death. discontinue lidorx® and any other oxidizing agents. depending on the severity of the symptoms, patients may respond to supportive care, i.e., oxygen therapy, hydration. more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen for external use only. avoid contact with eyes. if irritation or sensitivity occurs or infection appears, discontinue use and institute appropriate therapy. lidorx® 3% should be used with caution in ill, elderly, debilitated patients and children who may be more sensitive to the systemic effects of lidocaine hydrochloride usp. methemoglobinemia warning: cases of methemoglobinemia have been reported in association with local anesthetic use. although all patients are at risk for methemoglobinernia, patients with glucose-6-phosphate dehydrogenase deficiency, congenital or idiopathic methemoglobinemia, cardiac or pulmonary compromise, infants under 6 months of age, and concurrent exposure to oxidizing agents or their metabolites are more susceptible to developing clinical manifestations of the condition. if local anesthetics must be used in these patients, close monitoring for symptoms and signs of methemoglobinemia is recommended. signs and symptoms of methemoglobinemia may occur immediately or may be delayed some hours after exposure and are characterized by a cyanotic skin discoloration and abnormal coloration of the blood. methemoglobin levels may continue to rise; therefore, immediate treatment is required to avert more serious central nervous system and cardiovascular adverse effects, including seizures, coma, arrhythmias, and death. discontinue lidorx® and any other oxidizing agents. depending on the severity of the symptoms, patients may respond to supportive care, i.e., oxygen therapy, hydration. more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.

to the target area 10 minutes prior to initiation of procedure. 2.1 dosage for children it is difficult to recommend a maximum dose of any drug for children since this varies as a function of age and weight. for children less than ten years who have a normal lean body mass and a normal lean body development, the maximum dose may be determined by the application of one of the standard pediatric drug formulas (e.g., clark’s rule). for example a child of five years weighing 50 lbs., the dose of lidocaine should not exceed 75-100 mg when calculated according to clark’s rule. in any case, the maximum amount of lidocaine hydrochloride usp administered should not exceed 4.3 mg/kg (2.0 mg/lb) of body weight. 2.2 administration apply 1-4 pumps to the affected area three or four times daily not to exceed 16 pumps in twenty-four hours (24 hrs) or as directed by a physician. as a topical anesthesic, apply an adequate amount for the desired procedure to the target area 10 minutes prior to initiation of procedure.

nervousness, apprehension, euphoria, confusion, dizziness, drowsiness, tinnitus, blurred or double vision, vomiting, sensations of heat, cold or numbness, twitching, tremors, convulsions, unconsciousness, respiratory depression and arrest. the excitatory manifestations may be very brief or may not occur at all, in which case the first manifestation of toxicity may be drowsiness merging into unconsciousness and respiratory arrest. drowsiness following the administration of lidocaine hydrochloride usp is usually an early sign of a high blood level of the drug and may occur as a consequence of rapid absorption. 6.2 cardiovascular system cardiovascular manifestations are usually depressant and are characterized by bradycardia, hypotension, and cardiovascular collapse, which may lead to cardiac arrest. 6.3 allergic allergic reactions are characterized by cutaneous lesions, urticaria, edema or anaphylactoid reactions. allergic reactions may occur as a result of sensitivity either to the local anesthetic agent or to other components in the formulation. allergic reactions as a result of sensitivity to lidocaine hydrochloride usp are extremely rare and, if they occur, should be managed by conventional means. the detection of sensitivity by skin testing is of doubtful value.

ions that may occur. ask your health care provider if lidorx® 3% may interact with other medicines that you take. 7.1 serious interactions: antiarrhythmic drugs: lidorx® 3% should be used with caution in patients receiving class i antiarrhythmic drugs (such as tocainide and mexiletine) since the toxic effects are additive and potentially synergistic. bupivacaine liposome: lidocaine hydrochloride usp increases toxicity of bupivacaine by increasing the free (unencapsulated)bupiacaine. dofetilide: lidocaine hydrochloride usp increases effects of dofetilide thru pharmacodynamic synergism. lomitapide: lidocaine hydrochloride usp increases levels of lomitapide by affecting hepatic/intestinal enzymes cyp3a4 metabolism. 7.2 general interactions: drug interactions: patients that are administered local anesthetics may be at increased risk of developing methemoglobinemia when concurrently exposed to the following oxidizing agents: class examples nitrates/nitrites nitroglycerin, nitroprusside, nitric oxide, nitrous oxide local anesthetics benzocaine, lidocaine, bupivacaine, mepivacaine, letracaine, prilocaine, procaine, articaine, ropivacaine antincoplastic agents cyclophosphosphamide,flutamide, rasburicase, ifosfamide, hydroxyurea antibiotics dapsone, sulfonamides, nitrofurantoin,paraaminosalicylic acid antimalarials chloroquine,primaquine anticonvulsants phenytoin,sodium valproate,phenobarbital other drugs acetaminophen, metoclopramide, sulfa drugs (i.e, sulfasalazine), quinine drugs metabolized via cyp3a4 enzyme: (ex. antipsychotics, ssris, tcas, many chemotherapeutics, calcium channel bockers, benzodiazopines) lidocaine hydrochloride usp may increase serum levels of many drugs metabolized by hepatic / intestinal cyp3a4 enzymes. drugs that affect hepatic cyp1a2 enzyme: (ex. quinoline antibiotics, cimetidine, barbiturates, benzodiazepines, erythromycin) may increase serum lidocaine hydrochloride usp levels by decreasing lidocaine hydrochloride usp metabolism by cyp1a2 enzyme.

drugs are excreted in human milk, caution should be exercised when lidocaine hydrochloride usp. is administered to a nursing woman. 8.4 pediatric use dosage in children should be reduced, commensurate with age, body weight and physical condition. caution must be taken to avoid over dosage when applying lidorx® 3% to large areas of injured or abraded skin, since the systemic absorption of lidocaine hydrochloride usp may be increased under such conditions. 8.5 geriatric use no overall clinical differences in safety or effectiveness have been observed between the healthy elderly and other adult patients.

age and relative skin condition. 11.3 hemodynamics excessive blood levels may cause changes in cardiac output, total peripheral resistance, and mean arterial pressure. these changes may be attributable to a direct depressant effect of the local anesthetic agent on various components of the cardiovascular system. 11.4 pharmacokinetics and metabolism lidocaine hydrochloride usp may be absorbed following topical administration to mucous membranes or open wounds, its rate and extent of absorption depending upon the specific site of application, duration of exposure, concentration, and total dosage. in general, the rate of absorption of local anesthetic agents following topical application occurs most rapidly after intratracheal administration. lidocaine hydrochloride usp is also well-absorbed from the gastrointestinal tract, but little intact drug appears in the circulation because of biotransformation in the liver. lidocaine hydrochloride usp is metabolized rapidly by the liver, and metabolites and unchanged drug are excreted by the kidneys. biotransformation includes oxidative n-dealkylation, ring hydroxylation, cleavage of the amide linkage, and conjugation. n-dealkylation, a major pathway of biotransformation, yields the metabolites monoethylglycinexylidide and glycinexylidide. the pharmacological/toxicological actions of these metabolites are similar to, but less potent than, those of lidocaine hydrochloride usp. approximately 90% of lidocaine hydrochloride usp administered is excreted in the form of various metabolites, and less than 10% is excreted unchanged. the primary metabolite in urine is a conjugate of 4-hydroxy-2,6-dimethylaniline. the plasma binding of lidocaine hydrochloride usp is dependent on drug concentration, and the fraction bound decreases with increasing concentration. at concentrations of 1 to 4 μg of free base per ml, 60 to 80 percent of lidocaine hydrochloride usp is protein bound. binding is also dependent on the plasma concentration of the alpha-l-acid glycoprotein. lidocaine hydrochloride usp crosses the blood-brain and placental barriers, presumably by passive diffusion. studies of lidocaine hydrochloride usp metabolism following intravenous bolus injections have shown that the elimination half-life of this agent is typically 1.5 to 2.0 hours. because of the rapid rate at which lidocaine hydrochloride usp is metabolized, any condition that affects liver function may alter lidocaine hydrochloride usp kinetics. the half-life may be prolonged two-fold or more in patients with liver dysfunction. renal dysfunction does not affect lidocaine hydrochloride usp kinetics but may increase the accumulation of metabolites. factors such as acidosis and the use of cns stimulants and depressants affect the cns levels of lidocaine hydrochloride usp required to produce overt systemic effects. objective adverse manifestations become increasingly apparent with increasing venous plasma levels above 6.0 μg free base per ml. in the rhesus monkey arterial blood levels of 18-21 μg/ml have been shown to be threshold for convulsive activity.