Prescription Drug Information: LIDOCAINE

LIDOCAINE — lidocaine hydrochloride and epinephrine bitartrate injection, solution
Patterson Dental

Rx only

Solutions for local anesthesia in Dentistry

DESCRIPTION

Lidocaine Hydrochloride and Epinephrine, USP is a sterile isotonic solution containing a local anesthetic agent, Lidocaine Hydrochloride, and a vasoconstrictor, Epinephrine (as bitartrate) and are administered parenterally by injection. Both solutions are available in single dose cartridges of 1.7 mL (See INDICATIONS AND USAGE for specific uses). The solutions contain lidocaine hydrochloride which is chemically designated as acetamide, 2-(diethylamino)-N-(2,6-dimethylphenyl)-monohydrochloride, and has the following structural formula :

Chemical Structure

C14 H22 N2 0 • HCl • H2 0 M.W. 288.8

Epinephrine is ( — )-3,4-Dihydroxy-α-[(Methylamino) methyl] benzyl alcohol and has the following structural formula :

Chemical Structure

C9 H13 NO3 M.W. 183.21

COMPOSITION OF AVAILABLE SOLUTIONS
PRODUCT IDENTIFICATIONFORMULA
SINGLE DOSE CARTRIDGE
Lidocaine hydrochlorideEpinephrine
(as the bitartrate)
Sodium ChloridePotassium metabisulfiteEdetate Disodium
Concentration %Dilution(mg/mL)(mg/mL)(mg/mL)
The pH of all solutions are adjusted to USP limits with sodium hydroxide.
21:50,0006.51.20.25
21:100,0006.51.20.25

CLINICAL PHARMACOLOGY

Mechanism of action

Lidocaine stabilizes the neuronal membrane by inhibiting the ionic fluxes required for the initiation and conduction of nerve impulses, thereby effecting local anesthetic action.

Onset and duration of anesthesia

When used for infiltration anesthesia in dental patients, the time of onset averages less than two minutes for Lidocaine and Epinephrine Injections. Lidocaine and Epinephrine Injections provide an average pulp anesthesia of at least 60 minutes with an average duration of soft tissue anesthesia of approximately 2½ hours. When used for nerve blocks in dental patients, the time of onset for both forms of Lidocaine and Epinephrine Injections averages 2 — 4 minutes. Lidocaine and Epinephrine Injections provide pulp anesthesia averaging at least 90 minutes with an average duration of soft tissue anesthesia of 3 to 3½ hours.

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 and/or the beta-adrenergic receptor stimulating action of epinephrine when present.

Pharmacokinetics and metabolism

Information derived from diverse formulations, concentrations and usages reveals that lidocaine is completely absorbed following parenteral administration, its rate of absorption depending, for example, upon various factors such as the site of administration and the presence or absence of a vasoconstrictor agent. Except for intravascular administration, the highest blood levels are obtained following intercostal nerve block and the lowest after subcutaneous administration.

The plasma binding of lidocaine is dependent on drug concentration, and the fraction bound decreases with increasing concentration. At concentration 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.

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.

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 μg free base per mL. In the rhesus monkey, arterial blood levels of 18 — 21 μg/mL have been shown to be the threshold for convulsive activity.

INDICATIONS AND USAGE

Lidocaine and Epinephrine Injection, USP is indicated for the production of local anesthesia for dental procedures by nerve block or infiltration techniques.

Only accepted procedures for these techniques as described in standard textbooks are recommended.

CONTRAINDICATIONS

Lidocaine and Epinephrine Injections is contraindicated in patients with a known history of hypersensitivity to local anesthetics of the amide type or to any components of the injectable formulations.

WARNINGS

DENTAL PRACTITIONERS WHO EMPLOY LOCAL ANESTHETIC AGENTS SHOULD BE WELL VERSED IN DIAGNOSIS AND MANAGEMENT OF EMERGENCIES WHICH MAY ARISE FROM THEIR USE. RESUSCITATIVE EQUIPMENT, OXYGEN AND OTHER RESUSCITATIVE DRUGS SHOULD BE AVAILABLE FOR IMMEDIATE USE.

To minimize the likelihood of intravascular injection, aspiration should be performed before the local anesthetic solution is injected. If blood is aspirated, the needle must be repositioned until no return of blood can be elicited by aspiration. Note, however, that the absence of blood in the syringe does not assure that intravascular injection will be avoided.

Local anesthetic procedures should be used with caution when there is inflammation and/or sepsis in the region of the proposed injection.

Lidocaine and Epinephrine Injections contain potassium metabisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic people.

The American Heart Association has made the following recommendations regarding the use of local anesthetics with vasoconstrictors in patients with ischemic heart disease: “Vasoconstrictor agents should be used in local anesthesia solutions during dental practice only when it is clear that the procedure will be shortened or the analgesia rendered more profound. When a vasoconstrictor is indicated, extreme care should be taken to avoid intravascular injection. The minimum possible amount of vasoconstrictor should be used.” (Kaplan, EL, editor: Cardiovascular disease in dental practice, Dallas 1986, American Heart Association.)

Methemoglobinemia: Cases of methemoglobinemia have been reported in association with local anesthetic use. Although all patients are at risk for methemoglobinemia, 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 of methemoglobinemia may occur immediately or may be delayed some hours after exposure and are characterized by a cyanotic skin discoloration and/or 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 and any other oxidizing agents. Depending on the severity of the signs and 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.

PRECAUTIONS

General

The safety and effectiveness of lidocaine depend on proper dosage, correct technique, adequate precautions and readiness for emergencies. Consult standard textbooks 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 ADVERSE REACTIONS).

The lowest dosage that results in effective anesthesia should be used to avoid high plasma levels and serious adverse effects. Repeated doses of lidocaine may cause significant increases in blood levels with each repeated dose due to 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.

If sedatives are employed to reduce patient apprehension, reduced doses should be used since local anesthetic agents, like sedatives, are central nervous system depressants which in combination may have an additive effect. Young children should be given minimal doses of each agent.

Lidocaine should be used with caution in patients with severe shock or heart block. Lidocaine should also be used with caution in patients with impaired cardiovascular function. Local anesthetic solutions containing a vasoconstrictor should be used with caution in areas of the body supplied by end arteries or having otherwise compromised blood supply. Patients with peripheral vascular disease and those with hypertensive vascular disease may exhibit exaggerated vasoconstrictor response. Ischemic injury (such as exfoliating or ulcerating lesions) or necrosis may result. Preparations containing a vasoconstrictor should be used with caution in patients during or following the administration of potent general anesthetic agents, since cardiac arrhythmias may occur under such conditions.

Cardiovascular and respiratory (adequacy of ventilation) vital signs and the patient’s state of consciousness should be monitored after each local anesthetic injection. Restlessness, anxiety tinnitus, dizziness, blurred vision, tremors, depression or drowsiness should alert the practitioner to the possibility of central nervous system toxicity. Signs and symptoms of depressed cardiovascular function may commonly result from a vasovagal reaction, particularly if the patient is in an upright position : placing the patient in the recumbent position is recommended when an adverse response is noted after injection of a local anesthetic (See ADVERSE REACTIONS — Cardiovascular System.) Vasovagal reactions may elicit a range of clinical manifestations, from prodrome signs of pre-syncope (e.g. lightheadedness, pallor, nausea, sweating, visual disturbances, weakness) to brief loss of consciousness (i.e. syncope).

Lidocaine should be used with caution in patients with hepatic disease, since amide-type local anesthetics are metabolized by the liver. Patients with severe hepatic disease, because of their inability to metabolize local anesthetics normally, are at greater risk of developing toxic plasma concentrations.

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 management 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 suspected triggering agent (s) and prompt treatment, including oxygen therapy, dantrolene (consult dantrolene sodium intravenous package insert before using) and other supportive measures.

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.

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