CLINICAL PHARMACOLOGY
MECHANISM OF ACTION
LidoRx 3% releases Lidocaine Hydrochloride USP from a mild acidic vehicle to stabilize the neuronal membrane by inhibiting the ionic fluxes required for initiation and conduction of impulses, thereby effecting local anesthetic action. A mild acidic vehicle lowers pH to increase protection against alkaline irritations and to provide a favorable environment for healing.
Onset of anesthesia
LidoRx 3% effects local, topical anesthesia. The onset of action is 3-5 minutes.
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.
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 g 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 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 g free base per mL. In the rhesus monkey arterial blood levels of 18-21 g/mL have been shown to be threshold for convulsive activity.
INDICATIONS AND USAGE
Anesthetic for relief of pruritus, pruritic eczemas, abrasions, minor burns, insect bites, pain, soreness and discomfort due to pruritus ani, pruritus vulvae,hemorrhoids, anal fissures, and similar conditions of the skin and mucous membranes.