igns 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 lidocaine ointment usp, 5% and any other oxidizing agents. depending on the severity of the symptoms, patients may respond to supportive care, i.e., oxygen therapy, hydration. a more severe clinical presentation may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. lidocaine ointment 5% should be used with extreme caution in the presence of sepsis or severely traumatized mucosa in the area of application, since under such conditions there is the potential for rapid systemic absorption.

oss sensitivity to lidocaine. many drugs used during the conduct of anesthesia are considered potential triggering agents for familial malignant hyperthermia. since it is not known whether amide-type local anesthetics may trigger this reaction and since the need for supplemental general anesthesia cannot be predicted in advance, it is suggested that a standard protocol for the management of malignant hyperthermia should be available. early unexplained signs of tachycardia, tachypnea, labile blood pressure and metabolic acidosis may precede temperature elevation. successful outcome is dependent on early diagnosis, prompt discontinuance of the suspect triggering agent(s) and institution of treatment, including oxygen therapy, indicated supportive measures and dantrolene (consult dantrolene sodium intravenous package insert before using). drug interactions patients that are administered local anesthetics may be at increased risk of developing methemoglobinemia when concurrently exposed to the following oxidizing agents: examples of drugs associated with methemoglobinemia class examples nitrates/nitrites nitroglycerin, nitroprusside, nitric oxide, nitrous oxide local anesthetics benzocaine, lidocaine, bupivacaine, mepivacaine, tetracaine, prilocaine, procaine, articaine antineoplastic agents cyclophosphamide, flutamide, rasburicase, isofamide, hydroxyurea antibiotics dapsone, sulfonamides, nitrofurantoin, para-aminosalicylic acid antimalarials chloroquine, primaquine anticonvulsants phenytoin, sodium valproate, phenobarbital other drugs acetaminophen, metoclopramide, sulfa drugs (i.e., sulfasalazine), quinine

ommend 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 administered should not exceed 4.5 mg/kg (2.0 mg/lb) of body weight. administration for medical use, apply topically for adequate control of symptoms. the use of a sterile gauze pad is suggested for application to broken skin tissue. apply to the tube prior to intubation. in dentistry, apply to previously 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 the topical ointment. for use in connection with the insertion of new dentures, apply to all denture surfaces contacting mucosa. important: patients should consult a dentist at intervals not exceeding 48 hours throughout the fitting period.

oxicity may be drowsiness merging into unconsciousness and respiratory arrest. drowsiness following the administration of lidocaine is usually an early sign of a high blood level of the drug and may occur as a consequence of rapid absorption. cardiovascular system cardiovascular manifestations are usually depressant and are characterized by bradycardia, hypotension, and cardiovascular collapse, which may lead to cardiac arrest. allergic allergic reactions are characterized by cutaneous lesions, urticaria, edema or anaphylactoid reactions. allergic reactions may occur as a result of sensitivity either to the local anesthetic agent or to other components in the formulation. allergic reactions as a result of sensitivity to lidocaine are extremely rare and, if they occur, should be managed by conventional means. the detection of sensitivity by skin testing is of doubtful value. to report suspected adverse reactions , contact fda at 1-800-fda-1088 or www.fda.gov/medwatch .

curs most rapidly after intratracheal administration. lidocaine is also well-absorbed from the gastrointestinal tract, but little intact drug appears in the circulation because of biotransformation in the liver. lidocaine 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. approximately 90% of lidocaine 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 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 is protein bound. binding is also dependent on the plasma concentration of the alpha-l-acid glycoprotein. lidocaine crosses the blood-brain and placental barriers, presumably by passive diffusion. studies of lidocaine 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 is metabolized, any condition that affects liver function may alter lidocaine kinetics. the half-life may be prolonged two-fold or more in patients with liver dysfunction. renal dysfunction does not affect lidocaine 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 required to produce overt systemic effects. objective adverse manifestations become increasingly apparent with increasing venous plasma levels above 6.0 μ g free base per ml. in the rhesus monkey arterial blood levels of 18-21 μ g/ml have been shown to be threshold for convulsive activity.

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