Amelia Yip

Anna Taddio

Herpreet Soin

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C J H P – Vol. 58, No. 3 – June 2005 J C P H – Vol. 58, no 3 – juin 2005148
DRUG INFORMATION NOTE
Review of a New Topical Anesthetic, 
Liposomal Lidocaine, for Procedural 
Pain in Children
Amelia Yip, Herpreet Soin, and Anna Taddio
The introduction of the topical local anesthetic creamEMLA (a eutectic mixture of the local anesthetics
lidocaine and prilocaine) revolutionized the management
of procedural pain in children. Since lidocaine–
prilocaine was first launched over 10 years ago, several
other topical anesthetics have become commercially
available for use in children, including liposomal 
lidocaine, the subject of this article. The pharmacologic
profile of liposomal lidocaine offers several advantages
over lidocaine–prilocaine, including faster onset of
action and fewer adverse effects. This drug is currently
available in Canada and the United States under the
trade names Maxilene 4 (RGR Pharma, Windsor,
Ontario) and LMX (formerly ELA-Max; Ferndale 
Laboratories, Ferndale, Michigan), respectively.
Maxilene 4 is a liposomal encapsulated formula
containing 4% lidocaine. Liposomal encapsulation
involves the use of lipid bilayers to rapidly deliver the
lidocaine into the dermis of the skin. The liposome 
protects the lidocaine molecule from metabolic processes
and from removal by blood circulation and acts as a
depot in the epidermis for prolonged release of the
drug.1 The rate at which lidocaine is released into the
dermis depends on the stability and permeability of the
lipid bilayer in the skin environment. After release, the
lidocaine accumulates in the vicinity of pain receptors
and nerve endings, where it exerts its local anesthetic
action. It stabilizes neuronal membranes by inhibiting
the ionic fluxes required for the initiation and conduction
of impulses. The onset, depth, and duration of 
dermal analgesia depend primarily on the duration of
application.1
Effective analgesia is achieved within 30 min of
application of liposomal lidocaine and persists beyond
30 min after removal of the cream.1 The usual dose for
adults and children is about 2.5 g, applied to the skin as
a small mound, with or without an occlusive dressing.2
For a child of less than 10 kg the cream should not be
applied to an area greater than 100 cm2 (maximum dose
area) (roughly the size of a child’s abdomen).3 The 
manufacturer states that use in children under the age of
2 years should be carefully monitored2; however, 
liposomal lidocaine can potentially be used in neonates
with a maximum dosage similar to lidocaine–prilocaine
(1 g per day for infants from 37 weeks gestational age
to 3 months).4 Liposomal lidocaine can be stored at
room temperature for up to 3 years.2
The documented adverse effects of liposomal 
lidocaine are localized skin reactions, which may occur
during or immediately after treatment. These include
erythema, edema, and mild irritation. Allergic reactions
due to liposomal lidocaine cream may include urticaria,
angioedema, bronchospasm, and shock. In pediatric
studies, the incidence of local skin reactions was 12.1%5
and 43%6 for skin blanching in 2 separate studies and
1.7% for erythema.5 Systemic reactions after topical use
of liposomal lidocaine have not been reported. However,
if a sufficient quantity were absorbed into the systemic
circulation, systemic reactions might include central 
nervous system excitation and/or depression, as well as
cardiovascular manifestations including bradycardia,
hypotension, and cardiovascular collapse and arrest.7,8
A key advantage of liposomal lidocaine over 
lidocaine–prilocaine is the absence of prilocaine. 
Lidocaine–prilocaine consists of 2.5% lidocaine and 2.5% 
prilocaine,5 and it is the latter that is primarily responsible
for increased methemoglobin concentrations in infants, a
systemic toxic effect that can occur with overdose or in
susceptible populations.9,10 Increased methemoglobin
149C J H P – Vol. 58, No. 3 – June 2005 J C P H – Vol. 58, no 3 – juin 2005
concentrations have not been observed with liposomal
lidocaine.11 In addition, products such as lidocaine–
prilocaine cause vasoconstriction, which may lead to
increased difficulty in performing procedures such as IV
cannulation. Lidocaine has fewer vasoconstrictive
effects12 and may prove to diminish some of the 
difficulties associated with use of topical anesthetics 
during routine procedures. In addition, the flexibility
associated with not having to use an occlusive dressing
for liposomal lidocaine may prove beneficial, in that
other studies have shown pain and irritation on removal
of the occlusive dressing.3,4
Liposomal lidocaine is preferable to tetracaine 4%
gel (Ametop), another commercially available topical
anesthetic that was launched several years after 
lidocaine–prilocaine. Liposomal lidocaine and tetracaine
both have an onset of action of 30 min and lack the 
systemic adverse effect of methemoglobinemia8; however,
tetracaine requires refrigeration and is more likely to
cause hypersensitivity reactions following repeated
use.13
The efficacy of liposomal lidocaine in adults has
been well established,14-17 but to date only a handful of
studies have been performed in children.4-6,18,19 In 4 of the
5 studies, liposomal lidocaine was compared with 
lidocaine–prilocaine. In the first of these, Eichenfield
and others5 used a blinded crossover trial to compare
the 2 anesthetics during venipuncture. A total of 120 
children 5 to 17 years of age were recruited from the
community for double randomization (treatment 
regimen [application of study medication for either 30 or
60 min] and order of application of the topical 
anesthetics [lidocaine–prilocaine first or liposomal 
lidocaine first]) for 2 separate venipunctures. In all
groups, mean scores on a visual analogue scale ranging
from 0 mm (no pain) to 100 mm (worst possible pain)
were 10 mm or less, and there were no significant 
differences between groups. The investigators concluded
that for venipuncture, application of liposomal lidocaine
for 30 min without occlusion was equivalent to application
of lidocaine–prilocaine for 60 min with occlusion.5 Side
effects that occurred in the group that received liposomal
lidocaine included pallor (12.1%), erythema (1.7%), skin
discomfort (1.7%), and pruritis (1.7%). 
Two other studies compared lidocaine–prilocaine
with liposomal lidocaine, both applied with an occlusive
dressing, in children undergoing IV cannulation. Kleiber
and others4 conducted a randomized crossover trial with
30 pediatric volunteers (7 to 13 years old) who received
both anesthetic treatments, and Koh and others6
conducted a single-treatment design study with 60 
children 1 to 10 years of age who were randomly
assigned to receive lidocaine–prilocaine or liposomal
lidocaine. In both studies there was no difference in
pain scores between the 2 treatment groups. Kleiber and
others4 reported mean pain scores of 20.5 (standard
deviation [SD] 22.7) for lidocaine–prilocaine and 24.0
(SD 17.6) for liposomal lidocaine on the validated 
Oucher pain scale, which ranges from 0 (no pain) to 100
(worst pain). Koh and others6 reported mean pain
scores of 26.8 (SD 27.5) for lidocaine–prilocaine and
25.7 (SD 25.3) for liposomal lidocaine on a visual 
analogue scale ranging from 0 (no pain) to 100 (worst
pain). Koh and others6 also found significantly more
blanching in the group treated with lidocaine–prilocaine
(67% of the subjects treated with lidocaine–prilocaine
but only 43% of those treated with liposomal lidocaine
had blanching; p = 0.04), but this difference did not
make the procedure more difficult for the technician. 
Luhmann and others18 compared application of 
liposomal lidocaine with SC injection of lidocaine
buffered with sodium bicarbonate in 69 children 4 to 17
years old who were undergoing IV cannulation. There
was no difference in pain scores (visual analogue scale)
between the 2 groups. Average pain scores were 3.4 (SD
2.9) for SC lidocaine and 2.6 (SD 2.5) for liposomal 
lidocaine (p = 0.19) on a scale ranging from 1 (no pain)
to 10 (most painful). No side effects were documented.
The findings of this study indicate that liposomal 
lidocaine, a less invasive method of pain control, is
comparable in effect to buffered lidocaine administered
subcutaneously.
Smith and others19 investigated pain during office
meatotomy in children pretreated with liposomal 
lidocaine or lidocaine–prilocaine for 30 min or 45 min.
With the 30-min application time, liposomal lidocaine
was more effective in decreasing pain than lidocaine–
prilocaine. Mean pain scores were 1.1 (SD 2.9) for 
liposomal lidocaine and 1.8 (SD 2.6) for lidocaine–
prilocaine (p < 0.05) on the Wong-Baker Face pain scale,
which ranges from 0 (no pain) to 10 (worst pain). With
the 45-min application time, the mean pain scores were
0.3 (SD 0.8) for liposomal lidocaine and 0 for lidocaine–
prilocaine (p > 0.05). No side effects were documented. 
Cost comparisons indicate that of the 3 commercially
available topical local anesthetics — lidocaine–
prilocaine, tetracaine gel, and liposomal lidocaine —
lidocaine–prilocaine is the least expensive, with a list
price of $1.00 per gram. Tetracaine costs $2.29 per gram,
and liposomal lidocaine costs $1.16 per gram (all cost
data according to the Hospital for Sick Children Hospital
contract for 2005). Lidocaine–prilocaine is available in 
C J H P – Vol. 58, No. 3 – June 2005 J C P H – Vol. 58, no 3 – juin 2005150
5-g and 30-g tubes or as a 1-g patch. Tetracaine is 
available only in a single-dose tube (1.5 g), and 
liposomal lidocaine is available in a 5-g or a 30-g tube.
For both lidocaine–prilocaine and tetracaine, a 
Tegaderm dressing (3M, St Paul, Minnesota) is distributed
with the cream by the manufacturer;, however, no
dressing is provided with liposomal lidocaine, and the
total cost of administration must be adjusted to account
for the extra cost of the dressing (if occlusion is used).
In summary, liposomal lidocaine is a new topical
anesthetic that offers advantages over previously available
products, including short onset of action, lack of 
systemic adverse effects, infrequent local reactions, and
the option of application without a dressing. Liposomal
lidocaine is therefore a good candidate for routine use
in children undergoing painful cutaneous procedures. 
References
1. Friedman PM, Mafong EA, Friedman ES, Geronemus RG. 
Topical anesthetics update: EMLA and beyond. Dermatol Surg
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2. Ferndale Laboratories, Inc. MaxileneTM-4 product monograph.
Ferndale (MI); 2002 Aug. 
3. Friedman PM, Fogelman JP, Nouri K, Levine VJ, Ashinoff R.
Comparative study of the efficacy of four topical anesthetics.
Dermatol Surg 1999;25:950-4.
4. Kleiber C, Sorenson M, Whiteside K, Gronstal A, Tannous R.
Topical anesthetics for intravenous insertion in children: a 
randomized equivalency study. Pediatrics 2002;110:758-61.
5. Eichenfield LF, Funk A, Fallon-Friedlander S, Cunningham B. A
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lidocaine) as compared with eutectic mixture of local anesthetics
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T. A randomized, double-blind comparison study of EMLA and
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14. Bucalo BD, Mirikitani EJ, Moy RL. Comparison of skin anesthetic
effect of liposomal lidocaine, nonliposomal lidocaine, and EMLA
using 30-minute application time. Dermatol Surg 1998;24:537-41.
15. Finkel JC, Yang CI, Yarvitz JL, Patel KM. Neuroselective sensory
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Anesth Analg 2002;94:1259-62.
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17. Tang MB, Goon AT, Goh CL. Study on the efficacy of ELA-Max
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Amelia Yip, BSc, MSc, is a Clinical Research Assistant, Department of
Pharmacy, The Hospital for Sick Children, and Faculty of Pharmacy, 
University of Toronto, Toronto, Ontario.
Herpreet Soin, BScPhm, is a Pharmacist with the Department of
Pharmacy, The Hospital for Sick Children, Toronto, Ontario. She is also
a Master of Science candidate in the Faculty of Pharmacy, University
of Toronto, Toronto, Ontario.
Anna Taddio, BScPhm, MSc, PhD, is a Scientist with the Department
of Pharmacy and Population Health Sciences, Research Institute, The
Hospital for Sick Children, and Graduate Faculty of Pharmaceutical
Sciences, University of Toronto, Toronto, Ontario.
Address correspondence to:
Dr Anna Taddio
Department of Pharmacy
The Hospital for Sick Children
555 University Avenue
Toronto ON
M5G 1X8
e-mail: anna.taddio@sickkids.ca 


Review of a New Topical Anesthetic, Liposomal Lidocaine, for Procedural Pain in Children

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Review of a New Topical Anesthetic, Liposomal Lidocaine, for Procedural Pain in Children

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