Consumer medicine information

LMX4

Lidocaine (lignocaine)

BRAND INFORMATION

Brand name

LMX4

Active ingredient

Lidocaine (lignocaine)

Schedule

S2

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using LMX4.

What is in this leaflet

This leaflet answers some of the common questions people ask about LMX4®. It does not contain all of the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor will have weighed the risks of you or your child using LMX4® against the benefits they expect it will have for you or your child.

If you have any concerns about using this medicine, ask your doctor or pharmacist.

Keep this leaflet. You may need to read it again.

What LMX4® is used for

LMX4® is used for topical anaesthesia of intact skin prior to superficial skin procedures, including insertion of IV catheters and blood sampling.

It belongs to a group of medicines called local anaesthetics.

It works by numbing the area where the cream has been applied.

Ask your doctor if you have any questions about this medicine. Your doctor may have given it for another reason.

LMX4® is not addictive.

This medicine is not expected to affect your ability to drive a car or operate machinery.

Before you use LMX4®

When you must not use it

Do not use LMX4® if you or your child have an allergy to:

  • any medicine containing lignocaine
  • any of the ingredients listed at the end of this leaflet.
  • any other similar medicines (other local anaesthetics, for example those used at the dentist).
  • Adhesives or sticking plasters

Some of the symptoms of an allergic reaction may include:

  • shortness of breath
  • wheezing or difficulty breathing
  • swelling of the face, lips, tongue or other parts of the body
  • rash, itching or hives on the skin

Do not use this medicine on premature babies.

Safety and effectiveness in infants who are not full term, have not been established

Do not use LMX4® after the expiry date printed on the pack or if the packaging is torn or shows signs of tampering. If it has expired or is damaged, return it to your pharmacist for disposal.

If you are not sure whether you should use LMX4®, talk to your doctor.

Before you start to use it

Tell your doctor if you or your child have allergies to any other medicines, foods, preservatives or dyes.

Tell your doctor if you have or have had any of the following medical conditions:

  • you are acutely ill or elderly (you will be more sensitive to lignocaine)
  • you have severe liver (hepatic) disease

Tell your doctor if you are pregnant or plan to become pregnant or are breast-feeding. Your doctor can discuss with you the risks and benefits involved.

The ingredients in LMX4® have been used for many years and no ill effects have been shown if they are used while you are pregnant.

Only very small amounts of LMX4®get into the blood, so even though your baby can take LMX4® from breast milk if you are breast feeding, it is unlikely to cause any problems.

If you have not told your doctor about any of the above, tell him/her before you start using LMX4®.

Taking other medicines

Tell your doctor or pharmacist if you or your child is taking any other medicines, including any that you get without a prescription from your pharmacy, supermarket or health food shop.

Some medicines and LMX4® may interfere with each other. These include:

  • medicines used to treat arrhythmia (irregular heartbeat) such as tocainide, mexiletine and amiodarone.
  • other local anaesthetics

These medicines may be affected by LMX4® or may affect how well it works. You may need different amounts of your medicines, or you may need to take different medicines.

Your doctor and pharmacist have more information on medicines to be careful with or avoid while using this medicine.

How to use LMX4®

Follow all directions given to you by your doctor or pharmacist carefully. They may differ from the information contained in this leaflet.

If you do not understand the instructions on the package leaflet, ask your doctor or pharmacist for help.

How much to use

1g is approximately equal to 5cm length of cream squeezed from the 5g tube and 3.5cm from the 30g tube.

Adults, the elderly and children 1 year of age and older:
Apply 1g – 2.5g of the cream to cover an area of skin 2.5 cm x 2.5 cm.

Full term neonates and infants up to 1 year of age:
No more than 1g of cream should be applied.

How to use it

Apply a small amount of cream and if required or not using an occlusive dressing gently massage it into the skin. Then apply the specified amount of cream (refer above ‘How much to use’) to the area undergoing the procedure. The cream can then be left uncovered or covered with a dressing for the time specified below.

Refer to package leaflet for detailed directions for use.

Adults, the elderly and children 12 years of age and older:
Do not leave on the skin for longer than 5 hours

Full term neonates, infants and children under 12 years of age:
Do not leave on the skin for longer than 1 hour.

Do not apply to large areas of the body except on advice of a healthcare practitioner.

When to use it

Apply LMX4® at least 30 minutes before you are due for the procedure.

Depending on the procedure, your doctor may advise for the cream to be left on for a longer time if you choose not to occlude the cream with a dressing. Refer to package leaflet for more information.

If you forget to use it

Apply LMX4® as soon as you realise you have forgotten. If it is less than 30 minutes before your procedure, talk to your doctor.

If you use too much (overdose)

Immediately telephone your doctor or the Poisons Information Centre (telephone 13 11 26 in Australia, and 0800 764 766 in New Zealand) for advice, or go to Accident and Emergency at the nearest hospital, if you think that you or anyone else may have used too much LMX4®. Do this even if there are no signs of discomfort or poisoning.

Overdose with LMX4® cream is unlikely. However, if you use too much you may feel nervous, dizzy, have blurred vision and shaky hands.

When you are using LMX4®

Things you must do

Remember to apply LMX4® on intact skin at least half an hour (30 minutes) before your procedure is due. Depending on your procedure this time may vary and your doctor will advise you of this.

If you do not, you or your child’s appointment may have to be delayed, or the procedure may hurt more than it would otherwise.

Be sure to follow the instructions in the package leaflet on how to apply LMX4® cream carefully.

Make sure the dressing covering the cream is firmly fixed, especially on young children.

If skin irritation occurs, discontinue use and seek advice from your doctor or pharmacist.

Things you must not do

Do not apply LMX4® to damaged or diseased skin. LMX4® is for external use only.

Do not use LMX4® to treat any other complaints unless your doctor tells you to.

Do not give your medicine to anyone else, even if they have the same condition as you.

Things to be careful of

Be careful not to let LMX4® get into your eyes. It may cause eye irritation. If LMX4® does get into your eyes, immediately rinse them with large amounts of water and contact your doctor or pharmacist for advice.

Be careful not to inadvertently injure the anaesthetised area where LMX4® has been applied.

Be careful not scratch, rub or accidently expose the treated area to extreme cold or heat until complete sensation has returned.

Side effects

Tell your doctor or pharmacist as soon as possible if you or your child do not feel well while using LMX4®.

This medicine helps most people during superficial skin procedures, including insertion of IV catheters and blood sampling, but it may have unwanted side effects in a few people. All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical attention if you get some of the side effects.

Do not be alarmed by the following lists of side effects. You may not experience any of them.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor or pharmacist if you notice any of the following and they worry you:

  • any local reaction such as itching, swelling, paleness, redness or a burning sensation

The above list includes the more common side effects of your medicine. They are usually mild and short-lived

If any of the following happen, remove LMX4® and tell your doctor immediately or go to Accident and Emergency at your nearest hospital:

  • a rash at a spot where LMX4® is not being used
  • difficulty breathing

The above list includes very serious side effects. You or your child may need urgent medical attention or hospitalisation. These side effects are very rare.

Tell your doctor or pharmacist if you notice anything that is making you or your child feel unwell.

Other side effects not listed above may also occur in some people.

After using LMX4®

Storage

Keep the cream in the carton until it is time to use it.

Keep it in a cool dry place where the temperature stays below 25°C. Do not freeze, do not refrigerate.

Do not store LMX4® or any other medicine in the bathroom or near a sink. Do not leave it on a window sill or in the car. Heat and dampness can destroy some medicines.

Keep it where children cannot reach it. A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Disposal

Ask your pharmacist what to do with any LMX4® that is left over, or you find it has expired.

Product description

What it looks like

LMX4® is a white to off-white, yellowish cream

LMX4® cream is registered with the following packs:

  • carton containing one 5g tube
  • carton containing 5x5g tubes
  • carton containing one 15g tube
  • carton containing one 30g tube
  • carton containing 5x5g tubes with 10 occlusive dressings

Some packs may not be currently marketed.

Ingredients

1g of LMX4® contains 40mg of lignocaine as the active ingredient.

It also contains:

  • benzyl alcohol
  • carbomer 940
  • cholesterol
  • lecithin - hydrogenated
  • polysorbate 80
  • propylene glycol
  • triethanolamine
  • dl-alpha tocopheryl acetate

This medicine does not contain lactose, sucrose, gluten, tartrazine or any other azo dyes.

Manufacturer

Ferndale Laboratories
Michigan 48220
Detroit, USA.

Supplier

LMX4® is suppled in Australia by:
Perrigo Australia
25- 29 Delawney Street,
Balcatta WA 6021 Australia.

This leaflet was prepared in July 2013

Date of last amendment: October 2015.

L.M.X.4® is a registered trademark of Ferndale IP, Inc.

Published by MIMS July 2017

BRAND INFORMATION

Brand name

LMX4

Active ingredient

Lidocaine (lignocaine)

Schedule

S2

 

Name of the medicine

Lignocaine (lidocaine).

Excipients.

Benzyl alcohol, carbomer 940, cholesterol, hydrogenated lecithin, polysorbate 80, propylene glycol, triethanolamine, dl-alpha tocopheryl acetate, purified water.

Description

Chemical name: 2-diethylaminoaceto-2',6'-xylidide. Molecular formula: C14H22N2O. MW: 234.3. CAS: 137-58-6.
A white to off-white yellowish cream.
Each 1 gram of cream contains: active ingredient lignocaine 40 mg.

Pharmacology

Anaesthetics for topical use. Lignocaine is an amide-type local anaesthetic agent which stabilises neuronal membranes by inhibiting the ionic fluxes required for the initiation and conduction of impulses, thereby effecting local anaesthetic action.

Pharmacokinetics.

It has been reported that the amount of lignocaine systemically absorbed is directly related to both the duration of application and to the area over which it is applied. It is not known if it is metabolized in the skin. Lignocaine is metabolized rapidly by the liver to a number of metabolites including monoethylglycinexylidide (MEGX) and glycinexylidide (GX), both of which have pharmacologic activity similar to, but less potent than that of lignocaine. The end metabolite, 2,6-xylidine, has unknown pharmacologic activity but is carcinogenic in rats (Parker et al 1996). Following IV administration, MEGX and GX concentrations in serum range from 11 to 36% and from 5 to 11% of administered lignocaine serum concentrations, respectively. The half-life of lignocaine elimination from the plasma following IV administration is approximately 65 to 150 minutes (mean 110, ± 24 SD, n =13). This half-life may be increased in cardiac or hepatic dysfunction. More than 98% of an absorbed dose of can be recovered in the urine as metabolites or parent drug. The systemic clearance is 10 to 20 mL/min/kg (mean 13, ± 3 SD, n =13) (Benowitz and Meister, 1978).
When applied topically to intact skin, the absorption of lignocaine is very low. Increased absorption is therefore to be expected when applied to mucosa or previously damaged skin. LMX 4 should not be applied to mucosa or previously damaged skin.
The maximum plasma level of active ingredient was very low (0.3 microgram/mL or less) in a study investigating the application of LMX4 in 120 children aged 5-7 years, well below the therapeutic (1.2 microgram/mL) and toxic (> 5 microgram/mL) plasma level (Eichenfield, 2002).
Another study evaluated the potential absorption and clinical toxicity of either 30 g or 60 g of occluded LMX4 lignocaine cream (removed after 60 minutes) in healthy adult volunteers (Nestor, 2006). Blood levels of lignocaine and monoethylglycinexylidide (MEGX) were measured at 1, 2, 6 and 24 hours postapplication. Additionally the volunteers were assessed for any clinical signs of lignocaine toxicity. All blood samples showed less than 0.5 microgram/mL of serum lignocaine and MEGX metabolite. Patients reported no systemic effects and did not show any clinical signs of lignocaine toxicity. This study demonstrates the safety of topically applied 4% lignocaine cream, when up to 60 g of product is applied under occlusion to an area of up to 600 cm2 in healthy subjects.

Pharmacodynamics/ mechanism of action.

Lignocaine applied to intact skin provides dermal analgesia by a release of lignocaine from the cream into the epidermal and dermal layers of the skin, and by the accumulation of lignocaine in the vicinity of pain receptors and nerve endings. The onset, depth and duration of dermal analgesia provided by lignocaine depend primarily on the duration of application. In clinical trials LMX4 has demonstrated an onset of action after an application of 30 minutes.

Clinical Trials

In clinical trials with children, venipuncture or venous catheterisation was achieved within 30 minutes of application with lower mean main scores, higher IV cannulation success rate, less pain, shorter total procedure time and minor dermal changes.

Clinical trial data in children.

A pivotal randomised, double blind, placebo controlled trial compared the safety and efficacy of LMX4 lignocaine 4% w/w cream to placebo prior to venous cannulation procedures in children (Taddio, 2005). One gram of the proposed product or placebo cream (the base cream without the active) with occlusion was applied for 30 minutes to approximately 2.5 cm2 of each hand.
The study report notes that this corresponds to approximately 0.16 g/cm2 per hand, which complies with the proposed usage of the product. Both hands were treated to give the nurse the choice of the best hand for cannulation.

Patient accountability.

A total of 151 patients aged between 1 month and 17 years old were randomised into the trial, but 9 patients dropped out before cannulation took place. For 5 of these patients their clinical condition had improved and IV cannulation was no longer considered necessary. Of the 142 patients that completed the study, 69 received LMX4, and 73 received placebo. The average age of the LMX4 patients was 6.7 years, with equal numbers of male and female subjects. The average weight of the LMX4 subjects was 29.0 kg.
The primary outcome variable of this study was the cannulation success rate. The procedure duration and the assessment of pain were secondary outcome variables.
Cannulation on the first attempt was significantly higher among children who received LMX4 compared with those who received placebo (74% vs 55% respectively). Additionally, the total procedure time was also shorter for those patients receiving LMX4 compared to those with placebo (6.7 minutes and 8.7 minutes respectively).
Pain was measured using the Faces Pain Scale Revised (FPS-R), with scores ranging from zero (no pain) to five (worst possible pain). The scores were evaluated by three different raters:
1. Pain assessment by the child - this was done only in children ≥ 5 years of age.
2. Pain assessment by the parents - this was planned for all patients, but the assessment was missing for 4 patients on LMX4 lignocaine 4% w/w cream and 6 patients on placebo.
3. Pain assessment by research assistant - assessments were available for all patients.
Pain scores were measured during the first cannulation attempt for each child. Baseline measurements (pain without provocation) were taken 5 minutes before the cream was removed). The primary analysis of pain was pain during cannulation minus the baseline score. The scores from the three different raters were given equal priority. See Table 1.
The results are consistent across all three groups of pain raters, with the treatment groups being balanced at baseline and clear differences of around one point being evident during cannulation. The differences are similar whether raw scores or change from baseline is considered. The p-values are extreme for the parent and research assistant rating scores. The less extreme values for the child's own ratings are most likely due to the smaller patient numbers, as the point estimates for the difference are very similar.
This trial provides evidence that use of LMX4 lignocaine 4% w/w cream for 30 minutes under occlusion reduces pain during IV cannulation.
The authors also reported near identical incidence levels of transdermal reactions for both the LMX4 and placebo groups (16 vs 17 incidences respectively), and concluded that the risk:benefit ratio for using LMX4 in these age groups was therefore favourable.

Indications

Topical anaesthesia of intact skin prior to superficial skin procedures, including insertion of IV catheters and blood sampling.

Contraindications

Hypersensitivity to the active substance, or any of the amide-type local anaesthetics, or any of the excipients.

Precautions

For external use only.
Avoid contact with eyes. Lignocaine coming in contact with the eye should be avoided because animal studies have demonstrated severe eye irritation. Also the loss of protective reflexes can permit corneal irritation and potential abrasion. Absorption of lignocaine in conjunctival tissues has not been determined. If eye contact occurs, immediately wash out the eye with water or saline and protect the eye until sensation returns.
Do not apply to irritated skin or if excessive irritation develops. If condition worsens, or if symptoms persist unaltered for more than seven days or clear up and occur again within only a few days, discontinue use of this product and consult a doctor. Do not use in large quantities, particularly over raw or blistered areas.
LMX4 should not been applied to wounds, mucous membranes or in areas of atopic dermatitis.
Application of lignocaine to larger areas or for longer times than those recommended could result in sufficient absorption of lignocaine resulting in serious adverse effects.
Repeated doses of lignocaine may increase blood levels of lignocaine. Lignocaine should be used with caution in patients who may be more sensitive to the systemic effects of lignocaine including acutely ill, debilitated, or elderly patients.
Lignocaine should not be used in any clinical situation in which its penetration or migration beyond the tympanic membrane into the middle ear is possible. Studies in laboratory animals (guinea pigs) have shown that lignocaine has an ototoxic effect when instilled into the middle ear. In these same studies, animals exposed to lignocaine in the external auditory canal only showed no abnormality.
Patients allergic to para-aminobenzoic acid derivatives (procaine, tetracaine, benzocaine, etc) have not shown cross sensitivity to lignocaine; however, lignocaine should be used with caution in patients with a history of drug sensitivities, especially if the etiologic agent is uncertain.
Patients with severe hepatic disease, because of their inability to metabolize local anaesthetics normally, are at greater risk of developing toxic plasma concentrations of lignocaine. Patients with severe cardiac or renal impairment are also at greater risk.
When lignocaine is used, the patient should be aware that the production of dermal analgesia may be accompanied by the block of all sensations in the treated skin. For this reason, the patient should avoid inadvertent trauma to the treated area by scratching, rubbing, or exposure to extreme hot or cold temperatures until complete sensation has returned.
Lignocaine has bactericidal and antiviral properties in concentrations above 0.5%. For this reason, the results of intracutaneous injections of live vaccines (such as BCG vaccination) should be monitored.

Preclinical safety data.

Genotoxicity.

The mutagenic potential of lignocaine hydrochloride has been tested in the Ames Salmonella/ mammalian microsome test and by analysis of structural chromosome aberrations in human lymphocytes in vitro, and by mouse micronucleus test in vivo. There was no indication in these tests of any mutagenic effects (Benowitz 1978, Nelson 1978). The mutagenicity of 2,6-xylidine, a metabolite of lignocaine, has been studied in different tests with mixed results (Parker 1996). The compound was found to be weakly mutagenic in the Ames test only under metabolic activation conditions. In addition, 2,6-xylidine was observed to be mutagenic at the thymidine kinase locus, with or without activation, and induced chromosome aberrations and sister chromatic exchanges at concentrations at which the drug precipitated out of the solution (1.2 mg/mL). No evidence of genotoxicity induced by 2,6-xylidine was found in the in vivo assays measuring unscheduled DNA synthesis in rat hepatocytes (Mirsalis et al 1989).

Carcinogenicity.

No chromosome damage by 2,6-xylidine was observed in polychromatic erythrocytes or preferential killing of DNA repair deficient bacteria in liver, lung, kidney, testes and blood extracts from mice (Kerlaan et al 1985). However, covalent binding studies of DNA from liver and ethmoid turbinates in rats indicate that 2,6-xylidine may be genotoxic under certain conditions in vivo (Short et al, 1989).

Effects on ability to drive and use machines.

None known.

Use in children and the elderly.

Do not use in preterm infants.

Pediatrics.

Full term infants and children should be closely observed during and after use of topical anaesthetics, as they are at greater risk than adults for adverse events.
When using LMX4 in younger children, especially infants under the age of 12 months, care must be taken to ensure that the caregiver understands the need to limit the dose and area of application and to prevent accidental ingestion (see Dosage and Administration).

Geriatrics.

Greater sensitivity of some older individuals cannot be ruled out. There are insufficient data to evaluate quantitative differences in systemic plasma levels of lignocaine between geriatric and nongeriatric patients following application of LMX4.
During IV studies, the elimination half-life of lignocaine was statistically significantly longer in elderly patients (2.5 hours) than in younger patients (1.5 hours).

Use in pregnancy.

(Category A)
Category A: Drugs which have been taken by a large number of pregnant women and women of childbearing age without any proven increase in the frequency of malformations or other direct or indirect harmful effects on the fetus having been observed.
Lignocaine should be used during pregnancy only if clearly needed.
Lignocaine is not contraindicated in labour and delivery. Should LMX4 be used concomitantly with other products containing lignocaine, total doses contributed by all formulations must be considered.
Lignocaine can cross the placental barrier.

Use in lactation.

Lignocaine is excreted in human milk. Therefore, caution should be exercised when LMX4 is administered to a nursing mother since the milk:plasma ratio of lignocaine is 0.4.

Interactions

Lignocaine should be used with caution in patients receiving class III and 1b antiarrhythmic drugs (such as amiodorone, tocainide and mexiletine) since the toxic effects are additive and generally synergistic.
The risk of additional systemic toxicity should be considered when large doses of LMX4 are applied to patients already using other local anaesthetics.
Drugs that reduce the clearance of lignocaine, for instance cimetidine or beta-blockers, may cause potentially toxic plasma concentrations when lignocaine is given in repeated high doses over a long time period. Such interactions should not be of clinical importance following short-term treatment of LMX4 at recommended doses.

Adverse Effects

Common side effects (> 1/100) can include irritation, redness, itching, or rash.
In rare cases local anaesthetics have been associated with allergic reactions including anaphylactic shock.
To the best of our knowledge there have been no reports of methaemaglobinaemia directly associated with LMX4.
Corneal irritation after accidental eye exposure.

Dosage and Administration

For cutaneous use only.

Adults, the elderly and children 1 year of age and older.

Apply 1 g to 2.5 g of cream onto the skin to cover a 2.5 cm x 2.5 cm area where venous cannulation or venipuncture will occur.

Full term neonates and infants up to 1 year of age.

Apply up to 1 g of cream onto the skin where venous cannulation or venipuncture will occur. Not more than 1 g of cream should be applied to infants below the age of 1 year.

Adults, the elderly and children 12 years of age and older.

Maximum application time should not exceed 5 hours.

Full term neonates, infants and children under 12 years of age.

Do not leave on skin for longer than 1 hour.
There is insufficient data for neonates under full term age and therefore LMX4 is not recommended in this age group.
1 g of cream equates to approximately 5 cm of cream squeezed from the 5 g tube or 3.5 cm from the 30 g tube.
The cream should remain undisturbed and the area can be covered with an occlusive dressing to prevent disturbance or interference by the patient or other external factors. Adequate anaesthesia should be obtained after 30 minutes at which time the LMX4 cream should be removed using a clean gauze swab and the site for venous cannulation or venipuncture prepared in the usual manner. The procedure should be initiated approximately 5 minutes after the cream has been removed.

Overdosage

In an event of an overdose contact the Poisons Information Centre (telephone 131 126 in Australia). Overdose with LMX4 cream is unlikely, but signs of systemic toxicity would be consistent with those of lignocaine.
An indication of systemic toxicity may include blurred vision, dizziness or drowsiness, difficulty breathing, trembling, chest pain, or irregular heartbeat.

Presentation

Cream (white to off white, yellowish), 4% w/w: 5 g, 5 g x 5's*, 15 g*, 30 g (aluminium tubes fitted with polypropylene cap, packed in carton, AUST R 126095); 5 g x 5's* (aluminium tubes fitted with polypropylene cap, 10 occlusive dressings, packed in carton, AUST R 208815).
*Not currently marketed in Australia.

Storage

Store below 25°C.

Poison Schedule

S2.