Summary of Product Characteristics

1. NAME OF THE MEDICINAL PRODUCT

EMLA 5% w/w Cream

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

1 g cream contains 25 mg lidocaine and 25 mg prilocaine.
Excipient with known effect: Macrogolglycerol hydroxystearate (19 mg/g).
For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM
Cream
White, homogeneous cream.

4. CLINICAL PARTICULARS
4.1 Therapeutic indications
EMLA Cream is indicated for:
• Topical anaesthesia of the skin in connection with:
o needle insertion, e.g. intravenous catheters or blood sampling;
o superficial surgical procedures;
in adults and in the paediatric population.

• Topical anaesthesia of the genital mucosa, e.g. prior to superficial surgical

procedures or infiltration anaesthesia; in adults and adolescents ≥ 12 years.

• Topical anaesthesia of leg ulcers to facilitate mechanical cleansing/ debridement

in adults only.

4.2 Posology and method of administration

Posology

Adults and adolescents

The details of the Indications or Procedures for use, with Dosage and Application
Time are provided in Tables 1 and 2.

For further guidance on the appropriate use of the product in such procedures,
please refer to Method of administration.

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Summary of Product Characteristics

Table 1 Adults and adolescents 12 years of age and above

Indication/Procedure Dosage and Application Time
Skin
Minor procedures, e.g. needle insertion 2 g (approx. half a 5 g tube) or
and surgical treatment of localised approx. 1.5 g/10 cm2 for 1 to 5
lesions. hours1).
Dermal procedures on newly shaven skin Maximum recommended dose: 60 g.
of large body areas, e.g. laser hair Maximum recommended treated
removal (self application by patient) area: 600 cm2 for a minimum of 1
hour, maximum 5 hours.1)
Dermal surgical procedures on larger Approx. 1.5-2 g/10 cm2 for 2 to 5
areas in a hospital setting e.g. split skin hours1)
grafting.
Skin of male genital organs 1 g/10 cm2 for 15 minutes
Prior to injection of local
anaesthetics

Skin of female genital organs 1-2 g/10 cm2 for 60 minutes

Prior to injection of local
anaesthetics2)

Genital mucosa
Surgical treatment of localised lesions, Approx. 5-10 g of cream for 5-10
e.g. removal of genital warts minutes1) 3) 4).
(condylomata acuminata) and prior to
injection of local anaesthetics.
Prior to cervical curettage. 10 g of cream should be administered
in the lateral vaginal fornices for 10
minutes.
Leg ulcer(s)
Adults only Approx. 1-2 g/10 cm2 up to a total of
Mechanical cleansing/debridement 10 g to the leg ulcer(s) 3) 5).
Application time: 30 - 60 minutes.
1)
After a longer application time anaesthesia decreases.
2)
On female genital skin, EMLA alone applied for 60 or 90 minutes does not
provide sufficient anaesthesia for thermocautery or diathermy of genital warts.
3)
Plasma concentrations have not been determined in patients treated with doses of
>10 g (see also section 5.2).
4)
In adolescents weighing less than 20 kg the maximum dose of EMLA on genital
mucosa should be proportionally reduced.
5)
EMLA has been used for the treatment of leg ulcers up to 15 times over a period
of 1 to 2 months without loss of efficacy or increased number or severity of adverse
events.

Paediatric population

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Summary of Product Characteristics

Table 2 Paediatric patients 0-11 years of age

Age group Procedure Dosage and Application time

Minor procedures, e.g. needle Approx. 1g/10 cm2 for one

insertion and surgical hour (see details below)
treatment of localised lesions.
Newborn infants Up to 1 g and 10 cm2 for one
and infants 0-2 hour4)
months1) 2) 3)
Infants 3-11 Up to 2 g and 20 cm2 for one
months1)2) hour5)
Toddlers and Up to 10 g and 100 cm2 for 1-
children 1-5 years 5 hours6)
Children 6-11 Up to 20 g and 200 cm2 for 1-
years 5 hours6)
Paediatric patients Prior to removal of mollusca Application time: 30 minutes
with atopic
dermatitis
1)
In term newborn infants and infants below 3 months, only one single dose should
be applied in any 24-hour period. For children aged 3 months and above, a
maximum of 2 doses, separated by at least 12 hours can be given within any 24-
hour period, see sections 4.4 and 4.8.
2)
EMLA should not be used in infants up to 12 months of age receiving treatment
with methaemoglobin-inducing agents, because of safety concerns, see sections 4.4
and 4.8.
3)
EMLA should not be used at less than 37 weeks gestational age, because of safety
concerns, see section 4.4.
4)
Application for > 1 hour has not been documented.
5)
No clinically significant increase in methaemoglobin levels has been observed
after an application time of up to 4 hours on 16 cm2.
6)
After longer application time anaesthesia decreases.

Safety and efficacy for the use of EMLA on genital skin and genital mucosa have
not been established in children younger than 12 years.

Available paediatric data do not demonstrate adequate efficacy for circumcision.

Elderly
No dose reduction is necessary in elderly patients (see sections 5.1 and 5.2).

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Summary of Product Characteristics

Hepatic impairment
A reduction of a single dose is not necessary in patients with impaired hepatic
function (see section 5.2).

Renal impairment
A dose reduction is not necessary among patients with restricted renal function.

Method of administration

Cutaneous use

The protective membrane of the tube is perforated by applying the cap.

One gram of EMLA pressed out of a tube of 30 g is approximately 3.5 cm. If high
levels of accuracy in dosing are required to prevent overdose (i.e. at doses
approaching the maximum in newborn infants or if two applications may be
required in a 24-hour period), a syringe can be used where 1 mL = 1 g.

A thick layer of EMLA should be applied to the skin, including genital skin, under
an occlusive dressing. For application to larger areas, such as split-skin grafting, an
elastic bandage should be applied on top of the occlusive dressing to give an even
distribution of cream and protect the area. In the presence of atopic dermatitis, the
application time should be reduced.

For procedures related to genital mucosa, no occlusive dressing is required. The

procedure should be commenced immediately after removal of the cream.

For procedures related to leg ulcers, a thick layer of EMLA should be applied under
an occlusive dressing. Cleansing should start without delay after removal of the
cream.

The EMLA tube is intended for single use when used on leg ulcers: The tube with
any remaining contents should be discarded after each occasion that a patient has
been treated.
4.3 Contraindications
Hypersensitivity to lidocaine and/or prilocaine or local anaesthetics of the amide-
type or to any of the excipients listed in section 6.1.

4.4 Special warnings and precautions for use

Patients with defective glucose-6-phosphate dehydrogenase hereditary or idiopathic
methaemoglobinaemia are more susceptible to active-substance-induced signs of
methaemoglobinaemia. In glucose-6-phosphate dehydrogenase deficient patients
the antidote methylene blue is ineffective at methaemoglobin reduction, and is
capable of oxidising haemoglobin itself, and therefore methylene blue therapy
cannot be given.

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Summary of Product Characteristics

Due to insufficient data on absorption, EMLA should not be applied to open

wounds (excluding leg ulcers).

Due to the potentially enhanced absorption on the newly shaven skin, it is important
to adhere to the recommended dosage, area and time of application (see section
4.2).

Care should be taken when applying EMLA to patients with atopic dermatitis. A
shorter application time, 15-30 minutes, may be sufficient (see section 5.1).
Application times of longer than 30 minutes in patients with atopic dermatitis may
result in an increased incidence of local vascular reactions, particularly application
site redness and in some cases petechia and purpura (see section 4.8). Prior to
removal of mollusca in children with atopic dermatitis it is recommended to apply
cream for 30 minutes.

When applied in the vicinity of the eyes, EMLA should be used with particular care
since it may cause eye irritation. Also the loss of protective reflexes may allow
corneal irritation and potential abrasion. If eye contact occurs, the eye should
immediately be rinsed with water or sodium chloride solution and protected until
sensation returns.

EMLA should not be applied to an impaired tympanic membrane. Tests on

laboratory animals have shown that EMLA has an ototoxic effect when instilled
into the middle ear. Animals with an intact tympanic membrane, however, show no
abnormality when exposed to EMLA in the external auditory canal.

Patients treated with anti-arrhythmics of class III (e.g. amiodarone) should be

carefully monitored and ECG monitoring considered, as cardiac effects may be
additive.

Lidocaine and prilocaine have bacteriocidal and antiviral properties in

concentrations above 0.5-2%. For this reason, although one clinical study suggests
that the immunisation response, as assessed by local wheal formation, is not
affected when EMLA is used prior to BCG vaccination, the results of
intracutaneous injections of live vaccines should be monitored.

EMLA contains macrogolglycerol hydroxystearate, which may cause skin reactions.

Paediatric population
Studies have been unable to demonstrate the efficacy of EMLA for heel lancing in
newborn infants.

In newborn infants/infants younger than 3 months a transient, clinically

insignificant increase in methaemoglobin levels is commonly observed up to 12
hours after an application of EMLA within the recommended dosing.

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Summary of Product Characteristics

If the recommended dose is exceeded the patient should be monitored for system
adverse reactions secondary to methaemoglobinaemia (see sections 4.2, 4.8 and
4.9).

EMLA should not be used

- in newborn infants/infants up to 12 months of age receiving concomitant treatment

with methaemoglobin inducing agents
- in preterm newborn infants with a gestational age less than 37 weeks as they are at
risk of developing increased methaemoglobin levels.

Safety and efficacy for the use of EMLA on genital skin and genital mucosa have
not been established in children younger than 12 years.

Available paediatric data do not demonstrate adequate efficacy for circumcision.

4.5 Interaction with other medicinal products and other forms of

interaction
Prilocaine in high doses may cause an increase in methaemoglobin levels
particularly in conjunction with methaemoglobin-inducing medicinal products (e.g.
sulphonamides, nitrofurantoin, phenytoin, phenobarbital). This list is not
exhaustive.

With large doses of EMLA, consideration should be given to the risk of additional
systemic toxicity in patients receiving other local anaesthetics or medicinal products
structurally related to local anaesthetics, since the toxic effects are additive.

Specific interaction studies with lidocaine/prilocaine and anti-arrhythmics class III

(e.g. amiodarone) have not been performed, but caution is advised (see also section
4.4).

Medicinal products that reduce the clearance of lidocaine (e.g. cimetidine or

betablockers) may cause potentially toxic plasma concentrations when lidocaine is
given in repeated high doses over a long time period.

Paediatric population
Specific interaction studies in children have not been performed. Interactions are
likely to be similar to the adult population.

4.6 Fertility, pregnancy and lactation

Pregnancy
Although topical application is associated with only a low level of systemic
absorption, the use of EMLA in pregnant women should be undertaken with care
because insufficient data are available concerning the use of EMLA in pregnant
women. However, animal studies do not indicate any direct or indirect negative

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Summary of Product Characteristics

effects on pregnancy, embryo-foetal development, parturition or postnatal

development. Reproduction toxicity has been shown with
subcutaneous/intramuscular administration of high doses of lidocaine or prilocaine
much exceeding the exposure from topical application (see section 5.3).

Lidocaine and prilocaine cross the placental barrier and may be absorbed by the
foetal tissues. It is reasonable to assume that lidocaine and prilocaine have been
used in a large number of pregnant women and women of childbearing age. No
specific disturbances to the reproductive process have so far been reported, e.g. an
increased incidence of malformations or other directly or indirectly harmful effects
on the foetus.

Breastfeeding
Lidocaine and, in all probability, prilocaine are excreted into breast milk, but in
such small quantities that there is generally no risk of the child being affected at
therapeutic dose levels. EMLA can be used during breastfeeding if clinically
needed.

Fertility
Animal studies have shown no impairment of the fertility of male or female rats
(see section 5.3).

4.7 Effects on ability to drive and use machines

EMLA has no or negligible influence on the ability to drive and use machines when
used at the recommended doses.

4.8 Undesirable effects

Summary of the safety profile
The most frequently observed adverse drug reactions (ADRs) are related to
administration site conditions (transient local reactions at the application site),
reported as common.

Tabulated list of adverse reactions

The incidences of the Adverse Drug Reactions (ADRs) associated with EMLA
therapy is tabulated below. The table is based on adverse events reported during
clinical trials, and/or post-marketing use. Their frequency of Adverse Reactions is
listed by MedDRA System Organ Class (SOC) and at the preferred term level.

Within each System Organ Class, adverse reactions are listed under frequency
categories of: very common (≥1/10), common (≥1/100 to <1/10), uncommon
(≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000). Within
each frequency grouping, adverse reactions are presented in order of decreasing
seriousness.

Table 3 Adverse reactions

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Summary of Product Characteristics

System Organ Common Uncommon Rare

Class
Blood and Methaemoglobinaemia1
lymphatic
system
disorders
Immune system Hypersensitivity1, 2, 3
disorders
Eye disorders Corneal irritation1

Skin and Purpura1, Petechiae1

subcutaneous (especially after longer
tissue disorders application times in
children with atopic
dermatitis or mollusca
contagiosa)
General Burning sensation2, 3 Burning sensation1
disorders and Application site Application site
administration pruritus 2, 3 irritation3
site conditions Application site Application site
erythema1, 2, 3 pruritus1
Application site Application site
oedema 1, 2, 3 paraesthesia2 such as
Application site tingling
warmth 2, 3 Application site
Application site warmth1
pallor 1, 2, 3

1
Skin
2
Genital mucosa
3
Leg ulcer

Paediatric population
Frequency, type and severity of adverse reactions are similar in the paediatric and
adult age groups, except for methaemoglobinaemia, which is more frequently
observed, often in connection with overdose (see Section 4.9), in newborn infants
and infants aged 0 to 12 months.

Reporting of suspected adverse reactions

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Summary of Product Characteristics

Reporting suspected adverse reactions after authorisation of the medicinal product

is important. It allows continued monitoring of the benefit/risk balance of the
medicinal product. Healthcare professionals are asked to report any suspected
adverse reactions via:

HPRA Pharmacovigilance
Earlsfort Terrace
IRL - Dublin 2
Tel: +353 1 6764971
Fax: +353 1 6762517
Website: www.hpra.ie
e-mail: [email protected]

4.9 Overdose
Rare cases of clinically significant methaemoglobinaemia have been reported.
Prilocaine in high doses may cause an increase in methaemoglobin levels
particularly in susceptible individuals (section 4.4), with too frequent dosing in
newborn infants and infants below 12 months of age (section 4.2) and in
conjunction with methaemoglobin-inducing medicinal products (e.g.
sulphonamides, nitrofurantoin, phenytoin and phenobarbital). Consideration should
be given to the fact that pulse oximeter values may overestimate the actual oxygen
saturation in case of increased methaemoglobin fraction; therefore, in cases of
suspected methaemoglobinaemia, it may be more helpful to monitor oxygen
saturation by co-oximetry.

Clinically significant methaemoglobinaemia should be treated with a slow

intravenous injection of methylene blue (see also section 4.4).

Should other 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 of administration. 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
anticonvulsive medicinal products, circulatory signs are treated in line with
recommendations for resuscitation.

Since the rate of absorption from intact skin is slow, a patient showing signs of
toxicity should be kept under observation for several hours following emergency
treatment.

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Summary of Product Characteristics

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: anaesthetics, local; amides
ATC code: N01B B20

Mechanism of action
EMLA provides dermal anaesthesia through the release of lidocaine and prilocaine
from the cream into the epidermal and dermal layers of the skin and the vicinity of
dermal pain receptors and nerve endings.

Lidocaine and prilocaine are amide-type local anaesthetics. They both stabilize
neuronal membranes by inhibiting the ionic fluxes required for the initiation and
conduction of impulses, thereby producing local anaesthesia. The quality of
anaesthesia depends upon the application time and the dose.

Skin
EMLA is applied to intact skin under an occlusive dressing. The time needed to
achieve reliable anaesthesia of intact skin is 1 to 2 hours, depending on the type of
procedure. The local anaesthetic effect improves with longer application times from
1 to 2 hours in most parts of the body, with the exception of the skin of the face and
the male genitals. Because of thin facial skin and high tissue blood flow, maximal
local anaesthetic effect is obtained after 30-60 minutes on the forehead and on the
cheeks. Similarly, local anaesthesia of the male genitals is achieved after 15
minutes. The duration of anaesthesia following the application of EMLA for 1 to 2
hours is at least 2 hours after removal of the dressing, except in the face where the
duration is shorter. EMLA is equally effective and has the same anaesthetic onset
time across the range of light to dark pigmented skin (skin types I to VI).

In clinical studies of EMLA on intact skin, no differences in safety or efficacy

(including anaesthetic onset time) were observed between geriatric patients (aged
65 to 96 years) and younger patients.

EMLA produces a biphasic vascular response involving initial vasoconstriction

followed by vasodilatation at the application site (see section 4.8). Irrespective of
the vascular response, EMLA facilitates the needle procedure compared to placebo
cream. In patients with atopic dermatitis, a similar but shorter vascular reaction is
seen, with erythema occurring after 30-60 minutes, indicating more rapid absorption
through the skin (see section 4.4). EMLA may cause a transient increase in skin
thickness, partly caused by hydration of the skin under the occlusive dressing. The
skin thickness decreases over the course of 15 minutes air exposure.

The depth of cutaneous anaesthesia increases with application time. In 90% of

patients the anaesthesia is sufficient for the insertion of a biopsy punch (4 mm
diameter) to a depth of 2 mm after 60 minutes and 3 mm after 120 minutes EMLA
treatment.

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Summary of Product Characteristics

The use of EMLA prior to measles-mumps-rubella or intramuscular diphtheria-

pertussis-tetanus-inactivated poliovirus-Haemophilus influenzae b or Hepatitis B
vaccines does not affect mean antibody titres, rate of seroconversion, or the
proportion of patients achieving protective or positive antibody titres post
immunisation, as compared to placebo treated patients.

Genital mucosa
Absorption from the genital mucosa is more rapid and onset time is shorter than
after application to the skin.

After a 5-10 minute application of EMLA to female genital mucosa the average
duration of effective analgesia to an argon laser stimulus, which produced a sharp,
pricking pain was 15-20 minutes (individual variations in the range 5-45 minutes).

Leg ulcers
Reliable anaesthesia for the cleansing of leg ulcers is achieved after an application
time of 30 minutes in most patients. An application time of 60 minutes may
improve the anaesthesia further. The cleansing procedure should start within 10
minutes of removal of the cream. Clinical data from a longer waiting period are not
available. EMLA reduces the postoperative pain for up to 4 hours after
debridement. EMLA reduces the number of cleansing sessions required to achieve a
clean ulcer compared to debridement with placebo cream. No negative effects on
ulcer healing or bacterial flora have been observed.

Paediatric population
Clinical studies involved more than 2,300 paediatric patients of all age groups and
demonstrated efficacy for needle pain (venipuncture, cannulation, s.c. and i.m.
vaccinations, lumbar puncture), laser treatment of vascular lesions, and curettage of
molluscum contagiosum. EMLA diminished the pain of both needle insertion and
injection of vaccines. Analgesic efficacy increased from 15 to 90 minutes
application on normal skin but on vascular lesions 90 minutes provided no benefit
over 60 min. There was no benefit of EMLA versus placebo for liquid nitrogen
cryotherapy of common warts. No adequate efficacy for circumcision could be
demonstrated.

Eleven clinical studies in newborn infants and infants showed that peak
methaemoglobin concentrations occur about 8 hours after epicutaneous EMLA
administration, are clinically insignificant with recommended dosage, and return to
normal values after about 12-13 hours. Methaemoglobin formation is related to the
cumulative amount of prilocaine percutaneously absorbed, and may therefore
increase with prolonged application times of EMLA.

The use of EMLA prior to measles-mumps-rubella or intramuscular diphtheria-

pertussis-tetanus-inactivated poliovirus-Haemophilus influenzae b or Hepatitis B
vaccines did not affect mean antibody titres, rate of seroconversion, or the
proportion of patients achieving protective or positive antibody titres post-
immunisation, as compared to placebo-treated patients.
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Summary of Product Characteristics

5.2 Pharmacokinetic properties

Absorption, distribution, biotransformation and elimination

The systemic absorption of lidocaine and prilocaine from EMLA is dependent upon
the dose, area of application and application time. Additional factors include
thickness of the skin (which varies in different areas of the body), other conditions
such as skin diseases, and shaving. Following application to leg ulcers, the
characteristics of the ulcers may also affect the absorption. Plasma concentrations
after treatment with EMLA are 20-60% lower for prilocaine than for lidocaine,
because of a larger volume of distribution and more rapid clearance. The major
elimination pathway of lidocaine and prilocaine is via hepatic metabolism and
metabolites are renally excreted. However, the rate of metabolism and elimination
of the local anaesthetics after topical application of EMLA are governed by the rate
of absorption. Therefore, a decrease in clearance, such as in patients with severely
impaired liver function, has limited effects on the systemic plasma concentrations
after a single dose of EMLA, and after single doses repeated once daily short term
(up to 10 days).

Symptoms of local anaesthetic toxicity become increasingly apparent at increasing

plasma concentration from 5 to 10 μg/mL of either active substance. It should be
assumed that the toxicity of lidocaine and prilocaine are additive.

Intact skin
Following application to the thigh in adults (60 g cream/400 cm2 for 3 hours), the
extent of absorption was approximately 5% of lidocaine and prilocaine. Maximum
plasma concentrations (mean 0.12 and 0.07 µg/ml) were reached approximately 2-6
hours after application.

The extent of systemic absorption was approximately 10% following application to

the face (10 g/100 cm2 for 2 hours). Maximum plasma concentrations (mean 0.16
and 0.06 µg /ml) were reached after approximately 1.5-3 hours.

In studies of split-skin grafting in adults application for up to 7 hours 40 minutes to

the thigh or upper arm to an area of up to 1,500 cm2 resulted in maximum plasma
concentrations not exceeding 1.1 µg/mL lidocaine and 0.2 µg/mL prilocaine.

Genital mucosa
After the application of 10 g EMLA for 10 minutes to vaginal mucosa, maximum
plasma concentrations of lidocaine and prilocaine (mean 0.18 µg /ml and
0.15 µg/ml respectively) were reached after 20-45 minutes.

Leg ulcer
Following a single application of 5 to 10 g of EMLA to leg ulcers with an area of up
to 64 cm2 for 30 minutes, the maximum plasma concentrations of lidocaine (range

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Summary of Product Characteristics

0.05-0.25 µg/mL, one individual value of 0.84 µg/mL) and of prilocaine (0.02-0.08
µg/mL) were reached within 1 to 2.5 hours.

After an application time of 24 hours to leg ulcers with an area of up to 50-100 cm2,
the maximum plasma concentrations of lidocaine (0.19-0.71 µg/mL) and of
prilocaine (0.06-0.28 µg/mL) were usually reached within 2 to 4 hours.

Following repeated application of 2-10 g EMLA to leg ulcers with an area of up to

62 cm2 for 30-60 minutes 3-7 times a week for up to 15 doses during a period of
one month, there was no apparent accumulation in plasma of lidocaine and its
metabolites monoglycinexylidide and 2,6-xylidine or of prilocaine and its
metabolite ortho-toluidine. The maximum observed plasma concentration for
lidocaine, monoglycinexylidide and 2,6-xylidine were 0.41, 0.03 and 0.01 µg/mL
respectively. The maximum observed plasma concentrations for prilocaine and
ortho-toluidine were 0.08 µg/mL and 0.01 µg/mL respectively.

Following repeated application of 10 g EMLA to chronic leg ulcers with an area

between 62-160 cm2 for 60 minutes once daily during 10 consecutive days, the
mean maximum plasma concentration of the sum of lidocaine and prilocaine
concentrations was 0.6 µg/mL. The maximum concentration does not depend on the
patient’s age but is significantly (p<0.01) related to the size of the ulcer area.
Increasing the ulcer area by 1 cm2 results in an increased Cmax for the sum of
lidocaine and prilocaine concentrations of 7.2 ng/mL. The sum of the maximum
plasma concentrations of lidocaine and prilocaine is less than one-third of those
associated with toxic reactions, with no apparent accumulation over 10 days.

Special populations

Elderly patients
Plasma concentrations of lidocaine and prilocaine in both geriatric and non-geriatric
patients following application of EMLA to intact skin are very low and well below
potentially toxic levels.

Paediatric population
The maximum plasma concentrations of lidocaine and prilocaine after application
of EMLA in paediatric patients of different ages were also below potentially toxic
levels. See table 4.

Table 4 Plasma concentrations of lidocaine and prilocaine in paediatric age groups

from 0 months to 8 years of age

Age Applied amount of Application time of Plasma concentration

cream the cream on the skin [ng/ml]
Lidocaine Prilocaine
0 - 3 months 1 g/10 cm2 1 hour 135 107

3 - 12 2 g/16 cm2 4 hours 155 131

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Summary of Product Characteristics

months

2 - 3 years 10 g/100 cm2 2 hours 315 215

6 - 8 years 10 - 16 g/100-160 cm2 2 hours 299 110

(1 g/ 10 cm2)

5.3 Preclinical safety data

In animal studies the toxicity noted after high doses of either lidocaine or prilocaine,
alone or in combination, consisted of effects on the central nervous and
cardiovascular systems. When lidocaine and prilocaine were combined, only
additive effects were seen, with no indication of synergism or unexpected toxicity.
Both active substances were shown to have a low oral acute toxicity, providing a
good safety margin in the event that EMLA is inadvertently swallowed. In studies
on reproduction toxicity, embryotoxic or fetotoxic effects of lidocaine were
detected at doses of 25 mg/kg s.c. in the rabbit and for prilocaine starting at doses of
100 mg/kg i.m. in the rat. At doses below the maternal toxic range in the rat,
lidocaine has no effect on the postnatal development of the offspring. An
impairment of the fertility of male or female rats by lidocaine or prilocaine was not
observed. Lidocaine crosses the placental barrier by means of simple diffusion. The
ratio of the embryofetal dose to the maternal serum concentration is 0.4 to 1.3.

Neither local anaesthetic showed a genotoxic potential in either in vitro or in vivo

genotoxicity tests. Cancer studies have not been performed with either lidocaine or
prilocaine alone or in combination, due to the indication and duration of therapeutic
use of these active substances.

A metabolite of lidocaine, 2,6-dimethylaniline, and a metabolite of prilocaine, o-

toluidine, showed evidence of genotoxic activity. These metabolites have been
shown to have carcinogenicity potential in preclinical toxicological studies
evaluating chronic exposure. Risk assessments comparing the calculated maximum
human exposure from intermittent use of lidocaine and prilocaine, with the
exposure used in preclinical studies, indicate a wide margin of safety for clinical
use.

Local tolerance studies using a 1:1 (w/w) mixture of lidocaine and prilocaine as an
emulsion, cream or gel indicated that these formulations are well tolerated by intact
and damaged skin and mucosal membranes.

A marked irritative reaction was seen after single ocular administration of a 50

mg/g lidocaine + prilocaine 1:1 (w/w) emulsion, in an animal study. This is the
same concentration of local anaesthetics and a similar formulation as for EMLA.
This ocular reaction may have been influenced by the high pH of the formulation of

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Summary of Product Characteristics

the emulsion (approximately 9), but is probably also partly a result of the irritative
potential of the local anaesthetics themselves.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Carbomers
Macrogolglycerol hydroxystearate
Sodium hydroxide
Purified water

6.2 Incompatibilities
Not applicable.

6.3 Shelf life

3 years.

6.4 Special precautions for storage

Do not freeze.
Keep the tube tightly closed.

6.5 Nature and contents of container

Aluminium tube with a membrane, internally coated with protective epoxy resin
lacquer, with a polypropylene screw cap with a piercing device.

EMLA Cream is available in packs of:

1 tube containing 5 g cream

1 tube containing 5 g cream + 2 dressings
1 tube containing 5 g cream + 3 dressings
3 tubes containing 5 g cream + 8 dressings
5 tubes containing 5 g cream
5 tubes containing 5 g cream + 10 dressings
5 tubes containing 5 g cream + 12 dressings
10 tubes containing 5 g cream + 25 dressings
25 tubes containing 5 g cream
25 tubes containing 5 g cream + 50 dressings
1 tube containing 30 g cream

Not all pack sizes may be marketed.

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Summary of Product Characteristics

6.6 Special precautions for disposal and other handling

Precautions to be taken before handling or administering the medicinal product
Persons frequently applying or removing cream should ensure that contact is
avoided in order to prevent the development of hypersensitivity.

Any unused medicinal product or waste material should be disposed of in

accordance with local requirements.

7. MARKETING AUTHORISATION HOLDER

Aspen Pharma Trading Limited,
3016 Lake Drive,
Citywest Business Campus,
Dublin 24, Ireland.

8. MARKETING AUTHORISATION NUMBER(S)

PA 1691/023/001

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE

AUTHORISATION
Date of first authorisation: 25 January 1988
Date of latest renewal: 28 November 2014

10. DATE OF REVISION OF THE TEXT

September 2017

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