![]() ![]() ![]() The Applicant's proposed amendments to the Poisons Standard were: In this section: Applicant's scheduling proposal and reasons for the proposal | Current scheduling status | Scheduling history | Australian regulations | International regulations | Summary of pre-meeting public submissions | Summary of ACMS advice/recommendations to the Delegate | Delegate's considerations | Reasons for the interim decision Applicant's scheduling proposal and reasons for the proposalĪn application to amend the Schedule 2 entry for lidocaine in the Poisons Standard was considered. Proposed date of effect of the proposed amendmentġ June 2020 Reasons for the interim decision (including findings on material questions of fact) in divided preparations containing 200 mg or less of total local anaesthetic substances, except in lozenges containing 30 mg or less of total local anaesthetic substances per dosage unit.in aqueous sprays for oromucosal use containing 0.6 per cent or less of total local anaesthetic substances or.in dermal preparations containing 2 per cent or less of total local anaesthetic substances or.containing 10 per cent or less of total local anaesthetic substances, except:.In the rhesus monkey arterial blood levels of 18-21 g/mL have been shown to be threshold for convulsive activity.LIDOCAINE in preparations for topical use other than eye drops: Objective adverse manifestations become increasingly apparent with increasing venous plasma levels above 6 g free base per mL. Factors such as acidosis and the use of CNS stimulants and depressants affect the CNS levels of lidocaine required to produce overt systemic effects. Renal dysfunction does not affect lidocaine kinetics but may increase the accumulation of metabolites. The half-life may be prolonged two-fold or more in patients with liver dysfunction. ![]() Because of the rapid rate at which lidocaine is metabolized, any condition that affects liver function may alter lidocaine kinetics. Studies of lidocaine metabolism following intravenous bolus injections have shown that the elimination half-life of this agent is typically 1.5 to 2 hours. Lidocaine crosses the blood-brain and placental barriers, presumably by passive diffusion. Binding is also dependent on the plasma concentration of the alpha-1-acid-glycoprotein. At concentration of 1 to 4 g of free base per mL, 60 to 80 percent of lidocaine is protein bound. The plasma binding of lidocaine is dependent on drug concentration, and the fraction bound decreases with increasing concentration. The primary metabolite in urine is a conjugate of 4-hydroxy-2, 6-dimethylaniline. Approximately 90% of lidocaine administered is excreted in the form of various metabolites, and less than 10% is excreted unchanged. The pharmacological/toxicological actions of these metabolites are similar to, but less potent than, those of lidocaine. N-dealkylation, a major pathway of biotransformation, yields the metabolites monoethylglycinexylidide and glycinexlidide. ![]() Biotransformation includes oxidative N-dealkylation, ring hydroxylation, cleavage of the amide linkage, and conjungation. Lidocaine is metabolized rapidly by the liver, and metabolites and unchanged drug are excreted by the kidneys. Lidocaine is also well-absorbed from the gastrointestinal tract, but little intact drug appears in the circulation because of biotransformation of the liver. In general, the rate of absorption of local anesthetic agents following topical application occurs most rapidly after intratracheal administration. Lidocaine may be absorbed following topical administration to mucous membranes, its rate and extent of absorption depending upon the specific site of application, duration of exposure, concentration, and total dosage. ![]()
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