INFORMATION FOR HEALTH PROFESSIONALS
Home | Consumers | Health Professionals | Regulatory | Other | Hot Topics | Search
Home | Consumers | Health Professionals | Regulatory | Other | Hot Topics | Search
XYLOCAINE 4% TOPICAL is clear colourless solution contained in a brown glass bottle. The vehicle for the active ingredient consists of water with a dissolved preservative, methyl parahydroxybenzoate. The pH is 6.5-6.7.
The active ingredient in XYLOCAINE 4% TOPICAL is lignocaine, which provides prompt and profound anaesthesia of mucous membranes. Absorption occurs most rapidly after intratracheal administration. Anaesthesia usually occurs rapidly (within 1-5 minutes depending upon the area of application) and lasts for approximately 15-30 minutes.
Lignocaine like other local anaesthetics, causes a reversible blockade of impulse propagation along nerve fibres by preventing the inward movement of sodium ions through the nerve membrane. Local anaesthetics of the amide type are thought to act within the sodium channels of the nerve membrane.
Local anaesthetic drugs may also have similar effects on excitable membranes in the brain and myocardium. If excessive amounts of drug reach the systemic circulation rapidly, symptoms and signs of toxicity will appear, emanating from the central nervous and cardiovascular systems.
Central nervous system toxicity (See OVERDOSAGE) usually precedes the cardiovascular effects since it occurs at lower plasma concentrations. Direct effects of local anaesthetics on the heart include slow conduction, negative inotropism and eventually cardiac arrest.
Lignocaine is absorbed following topical administration to mucous membranes,
its rate and extent of absorption being dependent upon the concentration and
total dose administered, the specific site of application, and the duration of
exposure. In general, the rate of absorption of local anaesthetic agents
following topical application is most rapid after intratracheal and bronchial
administration. Lignocaine is also well-absorbed from the gastrointestinal
tract, although little of the intact drug appears in the circulation because of
biotransformation in the liver.
The plasma protein binding of lignocaine is dependent on the drug concentration,
and the fraction bound decreases with increasing concentration. At
concentrations of 1 to 4 µg of free base per mL, 60% to 80% of lignocaine is
protein-bound. Binding is also dependent on the plasma concentration of the
alpha-1-acid glycoprotein.
Lignocaine crosses the blood-brain and placental barriers, presumably by passive diffusion.
Lignocaine is metabolised 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 lignocaine. Approximately 90% of lignocaine 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 elimination half-life of lignocaine following an intravenous bolus injection is typically 1.5 to 2.0 hours. Because of the rapid rate at which lignocaine is metabolised, any condition that affects liver function may alter lignocaine kinetics. The half-life may be prolonged two-fold or more in patients with liver dysfunction. Renal dysfunction does not affect lignocaine 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 lignocaine 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.
XYLOCAINE 4% TOPICAL provides surface anaesthesia for the oropharyngeal and tracheal areas to reduce reflex activity, attenuate haemodynamic responses and facilitate insertion of the tube or the passage of instruments during endotracheal intubation and endoscopic procedures of the oropharyngeal, tracheal and bronchial areas, e.g.:
- In bronchography, bronchoscopy, laryngoscopy, oesophagoscopy and endotracheal intubation.
The active ingredient in XYLOCAINE 4% TOPICAL is lignocaine, which provides prompt and profound anaesthesia of mucous membranes. Absorption occurs most rapidly after intratracheal administration. Anaesthesia usually occurs rapidly (within 1-5 minutes depending upon the area of application) and lasts for approximately 15-30 minutes.
As with any local anaesthetic, the safety and effectiveness of lignocaine depends on the proper dosage, the correct technique, adequate precautions and readiness for emergencies.
Surface anaesthesia may be achieved by instillation into a cavity or by spraying, e.g. using an atomizer or nebulizer. XYLOCAINE 4% TOPICAL may also be applied from a sterile swab which is discarded after single use.
The following dosage recommendations should be regarded as a guide. The clinician's experience and knowledge of the patient's physical status are of importance in calculating the required dose.
The degree of absorption from mucous membranes is variable but especially high from the bronchial tree. Application only to areas below the vocal cords may result in excessive plasma concentrations because of less transfer to the intestine and less first-pass loss. When inhaled from a nebulizer, the resulting plasma concentrations are lower than following spray applications.
The recommended dosage for a procedure in adults is 1-7.5 mL XYLOCAINE 4% TOPICAL (40-300 mg lignocaine HCl). During prolonged procedures (>5 min) up to 400 mg lignocaine may be administered. In addition, when combined with other lignocaine products, the total does should not exceed 400 mg. With applications mainly to the larynx, trachea and bronchi, the dose should not exceed 5 mL (200 mg lignocaine HCl). When inhaled from a nebulizer, 5-10 mL (200-400 mg lignocaine HCl) may be used.
Debilitated or elderly patients, children over 12 years of age, acutely ill patients or patients with sepsis should be given doses commensurate with their age, weight and physical condition.
In children less than 12 years the dose should not exceed 3 mg/kg.
Known history of hypersensivity to local anaesthetics of the amide type or other components of the solution, e.g. methyl parahydroxybenzoate.
Excessive dosage or short intervals between doses, may result in high plasma
levels and serious adverse effects. Absorption from mucous membranes is variable
but is especially high from the bronchial tree. Lignocaine when sprayed should
be used with caution in patients with wounds or traumatised mucosa in the region
of the proposed application. A damaged mucosa will permit increased systemic
absorption. The management of serious adverse reactions may require the use of
resuscitative equipment, oxygen and other resuscitative drugs. (See OVERDOSAGE).
In paralysed patients under general anaesthesia, higher blood concentrations may
occur than in spontaneously breathing patients. Patients who are not paralysed
are more likely to swallow a large proportion of the dose, which then undergoes
considerable first-pass hepatic metabolism following absorption from the gut.
The oropharyngeal use of topical anaesthetic agents may interfere with swallowing and thus enhance the danger of aspiration. Numbness of the tongue or buccal mucosa may increase the danger of biting trauma.
If the dose or administration is likely to result in high blood levels, some patients require special attention to prevent potentially dangerous side effects:
Patients treated with anti-arrhythmic drugs class III (eg. amiodarone) should be kept under close surveillance and ECG monitoring considered, since cardiac effects may be additive.
The use of XYLOCAINE 4% TOPICAl as a gargle is not indicated. The use of concentrated XYLOCAINE 4% TOPICAL for gargling increases the risk of systemic toxicity due to overdosing and rapid uptake over the mucosa and/or ingestion.
It is reasonable to assume that a large number of pregnant women and women of child-bearing age have been given lignocaine. No specific disturbances to the reproductive process have so far been reported, e.g. no increased incidence of malformations.
Like other local anaesthetics, lignocaine may enter the mother's milk, but in such small amounts that there is generally no risk of this affecting the neonate.
Depending on the dose, local anaesthetics may have a very mild effect on mental function and may temporarily impair locomotion and coordination.
Allergic reactions (in the most severe instances anaphylactic shock) to local anaesthetics of the amide type are rare (<0.1%). Other constituents of the solution e.g. methyl parahydroxybenzoate, may also cause this type of reaction.
Lignocaine may have acute toxic effects if high systemic levels occur due to rapid absorption or overdosage. (See ACTIONS and OVERDOSAGE.)
Lignocaine should be used with caution in patients receiving other local anaesthetics or agents structurally related to amide-type local anaesthetics, e.g. arrhythmics such as mexiletine and tocainide, since the toxic effects are additive.
Specific interaction studies with lignocaine and anti-arrhythmic drugs class III (eg. amiodarone) have not been performed, but caution is advised (see WARNINGS AND PRECAUTIONS).
Drugs that reduce the clearance of lignocaine (eg. cimetidine or betablockers) may cause potentially toxic plasma concentrations when lignocaine is given in repeated high doses over a long period of time. Such interactions should therefore be of no clinical importance following short term treatment with lignocaine (eg. XYLOCAINE 4% TOPICAL) at recommended doses.
Toxic reactions originate mainly in the central nervous system and the cardiovascular system.
Central nervous system toxicity is a graded response with symptoms and signs of escalating severity. The first symptoms are circumoral paraesthesia, numbness of the tongue, light-headedness, hyperacusis and tinnitus. Visual disturbance and muscular tremors are more serious and precede the onset of generalised convulsions. Unconsciousness and grand mal convulsions may follow, which may last from a few seconds to several minutes. Hypoxia and hypercapnia occur rapidly following convulsions due to the increased muscular activity, together with the interference with normal respiration. In severe cases apnoea may occur. Acidosis increases the toxic effects of local anaesthetics.
Recovery is due to redistribution and metabolism of the local anaesthetic drug from the central nervous system. Recovery may be rapid unless large amounts of the drug have been administered.
Cardiovascular effects are only 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 central nervous system, unless the patient is receiving a general anaesthetic or is heavily sedated with drugs such as a benzodiazepine or barbiturate.
Should symptoms of systemic toxicity occur, the signs are anticipated to be similar in nature to those following the administration of local anaesthetics by other routes. Local anaesthetic toxicity is manifested by symptoms of nervous system excitation and, in severe cases, central nervous and cardiovascular depression.
Severe neurological symptoms (convulsions, CNS depression) must be treated symptomatically by respiratory support and the administration of anticonvulsant drugs.
If circulatory arrest should occur, immediate cardiopulmonary resuscitation should be instituted. Optimal oxygenation and ventilation and circulatory support as well as treatment of acidosis are of vital importance.
Not for injection
The solubility of lignocaine is limited at pH>6.5. This must be taken into consideration when alkaline solutions, i.e. carbonates, are added since precipitation might occur.
36 months.
Store below 25°C. Do not freeze.
Prescription Medicine
50 mL bottle made of brown glass with pilfer-proof caps.
In animal studies the toxicity noted after high doses of lignocaine consisted of effects on the central nervous and cardiovascular systems. No drug-related adverse effects were seen in reproduction toxicity studies, neither did lignocaine show a mutagenic potential in either in vitro or in vivo mutagenicity tests. Cancer studies have not been performed with lignocaine, due to the area and duration of therapeutic use for this drug.
AstraZeneca Limited
303 Manukau Road
Epsom, Auckland
New Zealand
Telephone: (09) 623-6300
12 April 2006
CDS December 2005
Copyright - No part may be reproduced by any process without the prior written permission of AstraZeneca Limited