XYLOCAINE® TOPICAL 5%
Oral Topical Anesthetic
Action And Clinical Pharmacology: Mechanism of Action: Lidocaine stabilizes the neuronal membrane by inhibiting the ionic fluxes required for the initiation and conduction of impulses, thereby effecting local anesthetic action. Local anesthetics of the amide type are thought to act within the sodium channels of the nerve membrane.
Onset of Action: The onset of action is 3 to 5 minutes when applied to mucous membrane. Xylocaine Topical 5% is ineffective when applied to intact skin.
Hemodynamics: Lidocaine, like other local anesthetics, may also have effects on excitable membranes in the brain and myocardium. If excessive amounts of drug reach systemic circulation rapidly, symptoms and signs of toxicity will appear, emanating from the central nervous and cardiovascular systems.
CNS toxicity (see Overdose: Symptoms and Treatment) usually precedes the cardiovascular effects since it occurs at lower plasma concentrations. Direct effects of local anesthetics on the heart include slow conduction, negative inotropism and eventually cardiac arrest.
Pharmacokinetics: The rate and extent of absorption depends upon concentration and total dose administered, the specific site of application and duration of exposure. In general, the rate of absorption of local anesthetic agents, following topical application to wound surfaces and mucous membranes is high, and occurs most rapidly after intratracheal and bronchial administration. Lidocaine is also well absorbed from the gastrointestinal tract, although little intact drug may appear in the circulation because of biotransformation in the liver.
Lidocaine readily crosses the placenta, and equilibrium in regard to free, unbound drug will be reached. Because the degree of plasma protein binding in the fetus is less than in the mother, the total plasma concentration will be greater in the mother, but the free concentrations will be the same.
The plasma binding of lidocaine is dependent on drug concentration, and the fraction bound decreases with increasing concentration. At concentrations of 1 to 4 g of free base per mL, 60 to 80% of lidocaine is protein bound. Binding is also dependent on the plasma concentration of the alpha-1-acid glycoprotein.
Lidocaine has a total plasma clearance of 0.95 L/min, a volume of distribution at steady state of 91 L, an elimination half-life of 1.6 hours and an estimated hepatic extraction ratio of 0.65. The clearance of lidocaine is almost entirely due to liver metabolism, and depends both on liver blood flow and the activity of metabolizing enzymes.
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. Only 2% of lidocaine is excreted unchanged. Most of it is metabolized first to monoethylglycinexylidide (MEGX) and then to glycinexylidide (GX) and 2,6-xylidine. Up to 70% appears in the urine as 4-hydroxy-2,6-xylidine.
The elimination half-life of lidocaine following an i.v. bolus injection is typically 1.5 to 2.0 hours. The elimination half-life in neonates (3.2 hours) is approximately twice that of adults. 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.
Acidosis increases the systemic toxicity of lidocaine while the use of CNS depressants may increase the levels of lidocaine required to produce overt CNS effects. Objective adverse manifestations become increasingly apparent with increasing venous plasma levels above 6.0 g free base per mL.
Indications And Clinical Uses: To provide relief of pain and discomfort in connection with irritated or inflamed mucous membranes of the mouth and for anesthesia of these membranes for the performance of minor dental surgical procedures.
Contra-Indications: In patients with a known history of hypersensitivity to local anesthetics of the amide type or to other components of the solution.
Manufacturers’ Warnings In Clinical States: Excessive dosage, or short intervals between doses, can result in high plasma levels of lidocaine or its metabolites and serious adverse effects. Patients should be instructed to strictly adhere to the recommended dosage. This is especially important in children where doses vary with weight. The management of serious adverse reactions may require the use of resuscitative equipment, oxygen and other resuscitative drugs (see Overdose: Symptoms and Treatment).
Lidocaine should be used with caution in patients with sepsis and/or traumatized mucosa at the area of application, since under such conditions there is the potential for rapid systemic absorption.
Xylocaine Topical 5% is for topical use only and must not be used for injection.
Precautions: The lowest dosage that results in effective anesthesia should be used to avoid high plasma levels and serious adverse effects. Tolerance to elevated blood levels varies with the status of the patient. Debilitated, elderly patients, acutely ill patients, and children should be given reduced doses commensurate with their age and physical condition. Lidocaine should also be used with caution in patients with epilepsy, impaired cardiac conduction, bradycardia, impaired hepatic or renal function, and in severe shock.
Because amide-type local anesthetics such as lidocaine are metabolized by the liver, these drugs, especially repeated doses, should be used cautiously in patients with hepatic disease. Patients with severe hepatic disease, because of their inability to metabolize local anesthetics normally, are at greater risk of developing toxic plasma concentrations.
Lidocaine should also be used with caution in patients with impaired cardiovascular function since they may be less able to compensate for functional changes associated with the prolongation of AV conduction produced by these drugs.
Many drugs used during the conduct of anesthesia are considered potential triggering agents for familial malignant hyperthermia. It has been shown that the use of amide local anesthetics in malignant hyperthermia patients is safe. However there is no guarantee that neural blockade will prevent the development of malignant hyperthermia during surgery. It is also difficult to predict the need for supplemental general anesthesia. Therefore, a standard protocol for the management of malignant hyperthermia should be available.
Lidocaine should be used with caution in persons with known drug sensitivities. Patients allergic to para-aminobenzoic acid derivatives (procaine, tetracaine, benzocaine, etc.) have not shown cross-sensitivity to lidocaine.
Drug Interactions: Lidocaine should be used with caution in patients receiving other local anesthetics or agents structurally related to amide-type local anesthetics, since the toxic effects are additive.
Information for the Patient: When topical anesthetics are used in the mouth, the patient should be aware that the production of topical anesthesia may impair swallowing and thus enhance the danger of aspiration. Numbness of the tongue or buccal mucosa may enhance the danger of unintentional biting trauma. Food or chewing gum should not be taken while the mouth or throat area is anesthetized.
Pregnancy : It is reasonable to assume that a large number of pregnant women and women of childbearing age have been given lidocaine. No specific disturbances to the reproductive process have so far been reported, e.g., no increased incidence of malformations. However, care should be given during early pregnancy when maximum organogenesis takes place.
There are no adequate and well-controlled studies in pregnant women on the effect of lidocaine on the developing fetus.
Labor and Delivery: Lidocaine is not contraindicated in labor and delivery. Should Xylocaine Topical 5% be used concomitantly with other products containing lidocaine, the total dose contributed by all formulations must be kept in mind.
Lactation : Lidocaine is excreted in the breast milk, but in such small quantities that there is generally no risk of affecting the infant at therapeutic dose levels.
Adverse Reactions: Adverse experiences following the administration of lidocaine are similar in nature to those observed with other amide local anesthetic agents. These adverse experiences are, in general, dose-related and may result from high plasma levels caused by overdosage or rapid absorption, or may result from a hypersensitivity, idiosyncrasy or diminished tolerance on the part of the patient.
Serious adverse experiences are generally systemic in nature. The following types are those most commonly reported.
CNS: CNS manifestations are excitatory and/or depressant and may be characterized by circumoral paresthesia, lightheadedness, nervousness, apprehension, euphoria, confusion, dizziness, drowsiness, hyperacusis, tinnitus, blurred 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 is usually an early sign of a high lidocaine plasma level and may occur as a consequence of rapid absorption.
Cardiovascular: Cardiovascular manifestations are usually depressant and are characterized by bradycardia, hypotension, arrhythmia, and cardiovascular collapse, which may lead to cardiac arrest.
Allergic: Allergic reactions are characterized by cutaneous lesions, urticaria, edema or, in the most severe cases, anaphylactic shock. Allergic reactions of the amide type are rare and may occur as a result of sensitivity either to the local anesthetic agent or to other components in the formulation.
Symptoms And Treatment Of Overdose: Acute systemic toxicity from local anesthetics is generally related to high plasma levels encountered during therapeutic use of local anesthetics and originates mainly in the central nervous and the cardiovascular systems (see Adverse Effects, Warnings, and Precautions).Symptoms: CNS toxicity is a graded response, with symptoms and signs of escalating severity. The first symptoms are circumoral paresthesia, numbness of the tongue, lightheadedness, hyperacusis and tinnitus. Visual disturbance and muscular tremors are more serious and precede the onset of generalized convulsions. Unconsciousness and grand mal convulsions may follow, which may last from a few seconds to several minutes. Hypoxia and hypercarbia occur rapidly following convulsions due to the increased muscular activity, together with the interference with normal respiration. In severe cases apnea may occur. Acidosis increases the toxic effects of local anesthetics.
Recovery is due to redistribution and metabolism of the local anesthetic drug. Recovery may be rapid unless large amounts of the drug have been administered.
Cardiovascular effects may be seen in cases with high systemic concentrations. Severe hypotension, bradycardia, arrhythmia and cardiovascular collapse may be the result in such cases.
Cardiovascular toxic effects are generally preceded by signs of toxicity in the CNS, unless the patient is receiving a general anesthetic or is heavily sedated with drugs such as a benzodiazepine or barbiturate.
Treatment: The first consideration is prevention, best accomplished by careful and constant monitoring of cardiovascular and respiratory vital signs and the patient’s state of consciousness after each local anesthetic administration. At the first sign of change, oxygen should be administered.
The first step in the management of systemic toxic reactions consists of immediate attention to the maintenance of a patent airway and assisted or controlled ventilation with oxygen and a delivery system capable of permitting immediate positive airway pressure by mask. This may prevent convulsions if they have not already occurred.
If necessary, use drugs to control convulsions. An anticonvulsant should be given i.v. if the convulsions do not stop spontaneously in 15 to 20 seconds. Thiopental 100 to 150 mg i.v. will abort the convulsions rapidly. Alternatively, diazepam 5 to 10 mg i.v. may be used, although its action is slower. Succinylcholine will stop the muscle convulsions rapidly, but will require tracheal intubation and controlled ventilation, and should only be used by those familiar with these procedures.
If cardiovascular depression is evident (hypotension, bradycardia), ephedrine 5 to 10 mg i.v. should be given and may be repeated, if necessary, after 2 to 3 minutes.
Should circulatory arrest occur, immediate cardiopulmonary resuscitation should be instituted. Optimal oxygenation and ventilation and circulatory support as well as treatment of acidosis are of vital importance, since hypoxia and acidosis will increase the systemic toxicity of local anesthetics. Epinephrine (0.1 to 0.2 mg as i.v. or intracardial injections) should be given as soon as possible and repeated, if necessary.
Children should be given doses commensurate with their age and weight.
Dosage And Administration: When used concomitantly with other products containing lidocaine, the total dose contributed by all formulations must be kept in mind. Debilitated, elderly and acutely ill patients should be given reduced doses.
Adults: Apply topically to oral mucosa with disposable cotton applicators. 1 to 4 mL (50 to 200 mg lidocaine) of Xylocaine Topical 5% may be applied to a wet or dry oral mucosa.
Children (under 12 years): It is difficult to recommend a maximum dose of any drug for children since this varies as a function of age and weight. The maximum amount of Xylocaine administered should not exceed 4 mg/kg of body weight.
Availability And Storage: Each mL contains: lidocaine base 50 mg. Nonmedicinal ingredients: amaranth (coloring agent), glycerin, propylene glycol, spearmint oil (flavoring agent) and water for injection. Plastic bottles of 50 mL with child-resistant closures. Store between 15 and 30°C. Protect from freezing.
XYLOCAINE® TOPICAL 5% Astra Lidocaine Oral Topical Anesthetic