XYLOCAINE® DENTAL SOLUTIONS
Lidocaine HCl – Epinephrine
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 sodium channels of the nerve membrane.
Onset of Action: When used for infiltration anesthesia in dental patients, the onset of action is rapid and on average is 2 to 3 minutes. Lidocaine 2% with epinephrine 1:100 000 provides anesthesia of about 1 hour, with postoperative soft tissue anesthesia of approximately 2.5 hours. Lidocaine 2% with epinephrine 1:50 000 provides, on average, pulp anesthesia in excess of 1 hour and is recommended for oral surgery requiring prolonged duration of anesthesia and pronounced hemostasis.
When used for nerve blocks in dental patients, the onset of action for lidocaine 2% with epinephrine 1:50 000 is 2 to 4 minutes. Mandibular block requires 5 minutes or more to take full effect. The average approximate duration of pulp anesthesia is at least 1.5 hours, with postoperative soft tissue anesthesia of approximately 3 to 3.25 hours.
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 and Metabolism: Lidocaine is completely absorbed following parenteral administration. The rate of absorption depends on the dose, route of administration and the vascularity of the injection site. The highest peak plasma levels are obtained following intercostal nerve block (approximately 1.5 g/mL/100 mg injected) while abdominal s.c. injections give the lowest (approximately 0.5 g/mL/100 mg injected). Epidural and major nerve blocks are intermediate.
Absorption is considerably slowed by the addition of epinephrine, although it also depends on the site of injection. Peak plasma concentrations are reduced by 50% following s.c. injection, by 30% following epidural injection and by 20% following intercostal block if epinephrine 5 g/mL is added.
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 h 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.
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/mL, 60 to 80% of lidocaine is protein bound. Binding is also dependent on the plasma concentration of the alpha-1-acid glycoprotein.
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.
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 i.v. bolus injection is typically 1.5 to 2 hours. The elimination half-life in neonates (3.2 hours) is approximately twice that of adults. The half-life may be prolonged 2-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/mL.
Indications And Clinical Uses: For the production of local anesthesia by nerve block or infiltration injection.
Contra-Indications: In patients with a known history of hypersensitivity to local anesthetics of the amide type or to other components of the solution, i.e., epinephrine, sodium metabisulfite. tag_WarningWarnings
Manufacturers’ Warnings In Clinical States: Local anesthetics should only be employed by clinicians who are well versed in diagnosis and management of dose-related toxicity and other acute emergencies that might arise from the block to be employed and then only after ensuring the immediate availability of oxygen, other resuscitative drugs, cardiopulmonary equipment and the personnel needed for proper management of toxic reactions and related emergencies (see also Adverse Effects and Precautions). Delay in proper management of dose-related toxicity, underventilation from any cause, and/or altered sensitivity may lead to the development of acidosis, cardiac arrest and possibly, death.
It is essential that aspiration for blood or cerebrospinal fluid (where applicable) be done prior to injecting any local anesthetics, both the original and all subsequent doses, to avoid intravascular or subarachnoid injection. However, a negative aspiration does not ensure against an intravascular or subarachnoid injection.
Lidocaine with epinephrine contains sodium metabisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic people.
Precautions: The safety and effectiveness of lidocaine with epinephrine depend on proper dosage, correct technique, adequate precautions and readiness for emergencies. Standard textbooks should be consulted for specific techniques and precautions for various regional anesthetic procedures.
Resuscitative equipment, oxygen, and other resuscitative drugs should be available for immediate use (see Warnings and
Repeated doses of lidocaine may cause significant increases in blood levels with each repeated dose because of slow accumulation of the drug or its metabolites. 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 function and in severe shock.
Because amide-type local anesthetics such as lidocaine are metabolized by the liver, these drugs, especially repeat 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.
Local anesthetic procedures should not be used when there is inflammation and/or sepsis in the region of the proposed injection.
Solutions containing epinephrine should be used with caution in patients whose medical history and physical evaluation suggest the existence of untreated hypertension, poorly controlled thyrotoxicosis, diabetes, ischemic heart disease, heart block, cerebral vascular insufficiency and peripheral vascular disorder. These solutions should also be used cautiously in areas of the body supplied by end arteries, such as digits, or otherwise having a compromised blood supply (see also Drug Interactions).
Careful and constant monitoring of cardiovascular and respiratory (adequacy of ventilation) vital signs and the patient’s state of consciousness should be performed after each local anesthetic injection. It should be kept in mind at such times that restlessness, anxiety, incoherent speech, lightheadedness, numbness and tingling of the mouth and lips, metallic taste, tinnitus, dizziness, blurred vision, tremors, twitching, depression or drowsiness may be early warning signs of CNS toxicity.
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.
Head and Neck Area: Small doses of local anesthetics injected into the head and neck area, including retrobulbar, dental and stellate ganglion blocks, may produce adverse reactions caused by inadvertent injection to an artery. These reactions may be similar to systemic toxicity seen with unintentional intravascular injections of larger doses. Inadvertent injections into an artery can cause cerebral symptoms even at low doses. Confusion, convulsions, respiratory depression and/or respiratory arrest, and cardiovascular stimulation or depression leading to cardiac arrest have been reported. Patients receiving these blocks should have their circulation and respiration monitored and be constantly observed.
Drug Interactions: Lidocaine should be used with caution in patients receiving other agents structurally related to amide-type local anesthetics, since the toxic effects are additive.
Lidocaine with epinephrine or other vasopressors should not be used concomitantly with ergot-type oxytocic drugs, because a severe persistent hypertension may occur and cerebrovascular and cardiac accidents are possible. Likewise, lidocaine with epinephrine or solutions containing lidocaine and another vasoconstrictor should be used with extreme caution in patients receiving MAO inhibitors or antidepressants of the triptyline or imipramine types, because severe prolonged hypertension may result. In situations when concurrent therapy is necessary, careful patient monitoring is essential. Phenothiazines and butyrophenones may reduce or reverse the pressor effect of epinephrine.
If sedatives are employed to reduce patient apprehension, they should be used in reduced doses, since local anesthetic agents, like sedatives, are CNS depressants which in combination may have an additive effect.
Solutions containing epinephrine should be used with caution in patients undergoing general anesthesia with inhalation agents such as halothane, due to the risk of serious cardiac arrhythmias.
Information for the Patient: The patients should be informed that they may experience temporary loss of sensation and motor activity after infiltration or nerve block injections. The patients should be advised to exert caution to avoid inadvertent trauma to the lips, tongue, cheek mucosa or soft palate when these structures are anesthetized. The ingestion of food should therefore be postponed until normal function returns. The patient should be advised to consult the dentist if anesthesia persists or if a rash develops.
Pregnancy : It is reasonable to assume that a large number of pregnant women and women of child-bearing 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 of the effect of lidocaine on the developing fetus.
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. It is not known whether epinephrine enters breast milk, but it is unlikely to affect the breast-fed infant.
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, rapid absorption, or inadvertent intravascular injection, or may result from a hypersensitivity, idiosyncrasy or diminished tolerance on the part of the patient.
Reactions to Xylocaine dental solutions are very rare in the doses used in dental procedures. Psychogenic reactions to anticipation of or during the dental procedures, are however, common and may mimic the symptoms of a generalized systemic reaction to local anesthetics.
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 instances, anaphylactic shock. Allergic reactions of the amide type are extremely rare and may occur as a result of sensitivity either to the local anesthetic agent or to other components in the formulation.
Neurologic: The incidence of adverse neurological reactions, e.g., persistent neurological deficit, associated with the use of local anesthetics is very low. Neurological reactions may be dependent upon the particular drug used, the route of administration and the physical status of the patient. Many of these effects may be linked to the injection technique, with or without a contribution by the drug. Neurological reactions following regional nerve blocks have included persistent paresthesia and sensory disturbances.
Symptoms And Treatment Of Overdose: Acute emergencies are, in general, dose-related and may result from high plasma levels caused by excessive dosage, rapid absorption (i.e., rate of increase of plasma concentration) or unintentional intravascular injection, or may result from hypersensitivity or diminished tolerance on the part of the patient.Symptoms: Acute Systemic Toxicity: CNS reactions are excitatory or depressant and may be characterized by nervousness, tinnitus, twitching, euphoria, drowsiness, blurred or double vision, dizziness, convulsions, unconsciousness and possibly respiratory arrest. The excitatory reactions may be very brief or may not occur at all, in which case the first manifestation of toxicity is drowsiness merging into unconsciousness and even respiratory arrest.
Cardiovascular reactions are depressant and may be characterized by hypotension, myocardial depression, bradycardia and possibly cardiac arrest. Signs and symptoms of depressed cardiovascular function may commonly result from a vasovagal reaction, particularly if the patient is in an upright position. Less commonly, they may occur as a direct effect of the drug. Failure to recognize premonitory signs such as sweating, a feeling of faintness, changes in pulse or sensorium, may result in progressive cerebral hypoxia and seizure or serious cardiovascular collapse.
Cardiovascular effects are usually only seen in the most severe cases and are generally preceded by signs of toxicity in the CNS.
Acidosis or hypoxia in the patient may increase the risk and severity of toxic reactions. Such reactions involve the CNS and the cardiovascular system.
Treatment: Treatment of Acute Toxicity: The immediate treatment of acute systemic toxicity is as follows:
a. Put the patient in a supine position. Raise the legs 30 to 45° above the horizontal level.
b. Ensure a patent airway. If ventilation is inadequate, ventilate the patient, with oxygen if available. This is important since toxicity increases with acidosis.
c. The treatment of convulsions consists in ensuring a patent airway and arresting convulsions. Should convulsions persist despite adequate ventilation, 5 to 15 mg diazepam or 50 to 200 mg thiopental should be administered i.v. to arrest the convulsions. Since this treatment may also depress respiration, the means of mechanically supporting or controlling ventilation should be available.
d. Supportive treatment of circulatory depression may require the administration of i.v. fluids and, when appropriate, a vasopressor (e.g., ephedrine 5 to 10 mg i.v. and repeated, if necessary, after 2 to 3 minutes), as governed by the clinical situation.
e. If the patient is unresponsive and the carotid pulse rate is totally absent, start external cardiac massage and mouth to mouth resuscitation.
Dosage And Administration: When used for local anesthesia in dental procedures the dosage depends on the area of the oral cavity to be anesthetized, the vascularity of the oral tissues, and the technique of anesthesia. The total dose must be adjusted to the age, size and physical status of the patient. The lowest dosage that results in effective local anesthesia should be administered. Injections should be made slowly with careful aspiration before and intermittently during injection to avoid inadvertent intravascular injection, which may have toxic effects. For specific techniques and procedures of a local anesthesia in the oral cavity, refer to standard textbooks.
For most routine dental procedures, lidocaine 2% with epinephrine 1:100 000 is preferred. However, when greater depth and a more pronounced hemostasis are required, a 1:50 000 epinephrine concentration should be used.
Adults: Dosage requirements should be determined on an individual basis. In oral infiltration and/or mandibular block, a dose of 1 to 5 mL (20 to 100 mg lidocaine HCl, 1/2 to 2 1/2 cartridges) of lidocaine 2% with epinephrine 1:50 000 or 1:100 000 is usually effective. A dose of 10 mL (200 mg) should not be exceeded.
Children: In children under 10 years of age it is rarely necessary to administer more than one-half cartridge (0.9 to 1 mL or 18 to 20 mg lidocaine HCl) of lidocaine 2% with epinephrine per procedure to achieve local anesthesia for a procedure involving a single tooth. In maxillary infiltration, this amount will often suffice for the treatment of two or even three teeth. In the mandibular block, however, satisfactory anesthesia achieved with this amount of drug will allow treatment of the teeth in the entire quadrant. In any case, a dose of 2 mL (40 mg) should not be exceeded.
Due to the specific need for bone penetration, dental local anesthetics contain high concentrations of active drug, e.g., 20 mg/mL lidocaine HCl for Xylocaine dental solutions. A combination of high pressure induced by the use of a dental cartridge system and a rapid rate of injection may lead to complications (see Overdose: Symptoms and Treatment) even after the injection of small amounts of local anesthetic. This is due to the high concentration, especially following accidental intravascular injection, when the injected drug could travel in a retrograde manner along the vessel and, in cases of intra-arterial injection in the head and neck area, reach the brain without the same degree of dilution that occurs with an i.v. injection. It must also be noted that epinephrine, when added to a local anesthetic solution is less active as a localizing agent in the highly vascular oral environment than elsewhere in the body.
Aspiration is recommended since it reduces the possibility of intravascular injection, thereby keeping the incidence of side effects and anesthetic failures to a minimum.
For best results, it is important that cartridges be used with a syringe of appropriate size. The Astra Self-Aspirating Syringe has been designed especially for Astra cartridges.
Sterilization, Storage and Technical Procedures: Cartridges should not be autoclaved, because the rubber plunger will typically be extruded thus compromising container integrity.
If disinfection of the cartridge is desired, its immersion should be avoided due to the risk of undesirable effects on the rubber membrane and aluminum cap, and the risk of contamination of the solution. Disinfection of the rubber membrane or the entire dental cartridge should be accomplished by wiping it with a cotton pledget that has been moistened with a disinfectant. Isopropyl alcohol (91%) or ethyl alcohol (70%) is recommended. Many commercially available brands of rubbing alcohol, as well as solutions of ethyl alcohol not of USP grade, contain denaturants which are injurious to rubber and therefore are not to be used.
Quaternary ammonium salts, such as benzalkonium chloride, are electrolytically incompatible with aluminum. Cartridges which are sealed with aluminum caps should not be immersed in any solution containing these salts.
Anti-rust tablets usually contain sodium nitrate or other similar agents which may be capable of releasing metal ions from syringes, needles and aluminum sealed cartridges. Accordingly, cartridges should not be kept in such solutions.
Adequate precautions should be taken to avoid prolonged contact between local anesthetic solutions containing epinephrine (low pH) and metal surfaces (e.g., needles or metal parts of syringes), since dissolved metal ions, particularly copper ions, may cause severe local irritation (swelling, edema) at the site of injection and accelerate the degradation of epinephrine.
To avoid leakage of solutions during injection, be sure to penetrate the center of the rubber diaphragm perpendicularly with the needle when loading the syringe. An off-center penetration produces an oval shaped puncture that allows leakage around the needle.
In order to avoid traumatic nerve injuries leading to paresthesia in conjunction with dental nerve block, an atraumatic technique should be used. Dental cartridge systems may generate high pressures during injection, however, injected local anesthetics may travel in a retrograde manner along a nerve in cases of intraneural injection. If an accidental traumatic nerve injury has occurred, epinephrine, if present in the anesthetic solution, may aggravate the local neurotoxicity by decreasing the intraneural blood circulation. In order to minimize the risk of intraneural injection as well as fascicular injuries, the needle should always be withdrawn a little if paresthesia is elicited during injection. Furthermore, a short-beveled needle should be considered for regional blocks (in which case a topical anesthetic may be used to reduce the pain of needle insertion), while a sharper (i.e., long-beveled) needle can still be recommended for infiltration.
Store at controlled room temperature (15 to 30°C). Protect from light.
Do not use if solution is pinkish or darker than slightly yellow, or if it contains a precipitate.
Xylocaine dental solutions are preservative-free and are for single use only. Discard unused portion.
Availability And Storage: Each plastic dental cartridge contains: lidocaine HCl 2% and epinephrine 1:100 000 or lidocaine HCl 2% and epinephrine 1:50 000. Nonmedicinal ingredients: sodium chloride, sodium metabisulfite and sodium hydroxide and/or hydrochloric acid to adjust pH to 3.3 to 5.5. Cartridges of 1.8 mL, boxes of 50.
XYLOCAINE® DENTAL SOLUTIONS Astra Lidocaine HCl – Epinephrine Local Anesthetic