Last Updated on eMC 04-05-2017 View medicine  | Aspen Contact details

When a pharmaceutical company changes an SPC or PIL, a new version is published on the eMC.  For each version, we show the dates it was published on the eMC and the reasons for change.

Reasons for adding or updating:

  • Change to section 4.1 - Therapeutic indications
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.3 - Contraindications
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.6 - Fertility, pregnancy and lactation
  • Change to section 4.7 - Effects on ability to drive and use machines
  • Change to section 4.8 - Undesirable effects
  • Change to section 4.8 - Undesirable effects - how to report a side effect
  • Change to section 4.9 - Overdose
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 5.2 - Pharmacokinetic properties
  • Change to section 5.3 - Preclinical safety data
  • Change to section 6.1 - List of excipients
  • Change to section 6.6 - Special precautions for disposal and other handling
  • Change to section 10 - Date of revision of the text

Date of revision of text on the SPC:23-12-2016

Legal Category:P

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



Text in red = new text
Text strikethrough = deleted text

 

 

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.

Posology and method of administration

Administration of EMLA Cream on genital mucosa, genital skin or leg ulcers should only be performed by or under the supervision of a healthcare professional.

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.

 

 

Table 1                 Adults and adolescents 12 years of age and above

 

Indication/Procedure

Dosage and Application Time

Skin

 

 

 

 

Minor procedures, e.g. needle insertion and surgical treatment of localised lesions.

2 g (approx half a 5 g tube) or approx. 1.5g/10cm2 for 1 to 5 hours1).

 

 

Dermal procedures on newly shaven skin of large body areas, e.g. laser hair removal (self-application by patient)

Maximum recommended dose: 60 g. Maximum recommended treated area; 600 cm2 for a minimum of 1 hour, maximum 5 hours1).

 

Dermal surgical procedures on larger areas in a hospital setting, e.g. split-skin grafting.

Approx 1.5-2 g/10 cm2 for 2 to 5 hours1).

 

Skin of male genital organs

Prior to injection of local anaesthetics

Skin of female genital organs

Prior to injection of local anaesthetics2)

 

1 g/10 cm2 for 15 minutes

 

1-2 g/10 cm2 for 60 minutes

Genital mucosa

 

 

Surgical treatment of localised lesions, e.g. removal of genital warts (condylomata acuminata) and prior to injection of local anaesthetics

Approx 5-10 g of cream for 5-10 minutes1) 3) 4).

 

Prior to cervical curettage

10 g of cream should be administered in the lateral vaginal fornices for 10 minutes.

Leg ulcer(s)

 

 

Adults only
Mechanical cleansing/debridement

Approx 1-2 g/10 cm2 up to a total of 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 Cream 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 Cream on genital mucosa should be proportionally reduced.

5        EMLA Cream 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.

 

 

Table 2                 Paediatric patients 0-11 years of age

Age group

Procedure

Dosage and Application time

 

Minor procedures, e.g. needle insertion and surgical treatment of localised lesions.

Approx 1g/10 cm2 for one hour (see details below)

Newborn infants and infants 0‑2 months1)2)3)

 

Up to 1 g and 10 cm2 for one hour4)

Infants 3-11 months1) 2)

 

Up to 2 g and 20 cm2 for one hour5)

Toddlers and children 1-5years

 

Up to 10 g and 100 cm2 for 1‑5 hours6)

Children 6-11 years

 

Up to 20 g and 200 cm2 for 1‑5 hours6)

Paediatric patients with atopic dermatitis

Prior to removal of mollusca

Application time: 30 minutes

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 Cream 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 Cream 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 Cream 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).

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.

 

A thick layer of EMLA Cream 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.

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

The EMLA Cream 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.

 

 

 

Paediatric population
Studies have been unable to demonstrate the efficacy of EMLA Cream 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 Cream within the recommended dosing.

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 Cream 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 Cream 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

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 Cream in pregnant women should be undertaken with care because insufficient data are available concerning the use of EMLA Cream in pregnant women. However, animal studies do not indicate any direct or indirect negative 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).

 

 

Breast-feeding

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 Cream can be used during breast-feeding 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 Cream 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 Cream 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.

 

 

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

 

 

 

 

5.1         Pharmacodynamic properties

Pharmacotherapeutic group: anaesthetics, local; amides

ATC code: N01B B20

Mechanism of action

EMLA Cream 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 stabilise 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 Cream 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 Cream 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 Cream 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 Cream 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.

MLA Cream 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 Cream 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 Cream 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 Cream treatment. 

The use of EMLA Cream 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 Cream 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 Cream reduces the postoperative pain for up to 4 hours after debridement. EMLA Cream 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

Altogether, data from elevenClinical 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 Cream 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 Cream versus placebo for liquid nitrogen cryotherapy of common warts. No adequate efficacy for circumcision could be demonstrated.

 

 

5.2 Pharmacokinetic properties

SAbsorption, distribution, biotransformation and elimination

he systemic absorption of lidocaine and prilocaine from EMLA Cream 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 bodyIntact skin), 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 Cream 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 Atopical application of EMLA Cream 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 Cream, 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.

 

 

 

 

 

In studies of split-skin grafting in adults: Absorption f 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

 

 

Leg ulcer 

Following thea single application of 5 to 10 g of EMLA Cream Following the application of 2 g EMLA Cream in infants between 3 and 12 monthsto leg ulcers with an area of up to 64 cm2 for 30 minutes, the maximum plasma concentrations of lidocaine (range 0.05-0.25 µg/ml, one individual value of 0.84 µg/ml) and of prilocaine (0.02-0.08 µg/ml) were Following the application of 10 g of EMLA Cream in children between 2 and 3 years of age,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.

 

repeated application of 2-10 g EMLA Cream 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 Cream 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 Cream 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 Cream 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 cream

Application time of the cream on the skin

Plasma concentration

[ng/ml]

Lidocaine Prilocaine

0 - 3 months

1 g/10 cm2

1 hour

135 107

3 - 12 months

2 g/16 cm2

4 hours

155 131

2 - 3 years

10 g/100 cm2

2 hours

315 215

6 - 8 years

10 - 16 g/100-160 cm2 (1 g/ 10 cm2)

2 hours

299 110

 

 

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 Cream 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, σ-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 Cream. This ocular reaction may have been influenced by the high pH of the formulation of the emulsion (approximately 9), but is probably also partly a result of the irritative potential of the local anaesthetics themselves.

 

 

 

6.1         List of excipients

Macrogolglycerol hydroxystearate, Carbomer 974P, sodium hydroxide and water purified.

 

 

 

6.5         Nature and contents of container

“Pre-medication pack” containing 5 x 5 g tubes EMLA and 12 occlusive dressings.

Pack containing 1 x 5 g tube of EMLA and 2 occlusive dressings.

1 x 30 g tube with enclosed spatula

1 x 5 g tube

Not all pack sizes may be marketed.

 

6.6         Special precautions for disposal

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.

 

 

10.         DATE OF REVISION OF THE TEXT

23/12/2016  Nov 2016

 

Reasons for adding or updating:

  • Change to section 7 - Marketing authorisation holder
  • Change to section 8 - Marketing authorisation number(s)
  • Change to section 10 - Date of revision of the text

Date of revision of text on the SPC:30-11-2016

Legal Category:P

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



Text in red = new text
Text strikethrough = deleted text

 

 

Marketing Authorisation holder

AstraZeneca UK Limited

600 Capability Green

Luton

LU1 3LU, UK

 

Aspen Pharma Trading Limited,

3016 Lake Drive,

Citywest Business Campus,

Dublin 24

 

 

Marketing authorisation number(s)

PL 17901/0120

PL 39699/0088

 

Date of revision of the text

25th March 2013

November 2016

 

Reasons for adding or updating:

  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 10 - Date of revision of the text

Date of revision of text on the SPC:25-03-2013

Legal Category:P

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



Section 4.2:         Align wording with CSP. Include footnote “Until further clinical data are available, EMLA should not be used at less than 37 weeks gestational age.”

Section 4.5:         Amend wording around methaemoglobin-inducing agents to align with CSP.

Section 10:          Update to "Date of Revision"

Reasons for adding or updating:

  • Change to section 4.1 - Therapeutic indications
  • Change to section 10 date of revision of the text

Date of revision of text on the SPC:30-10-2012

Legal Category:P

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



Section 4.1
 
Modified to state the age groups in which the product is indicated, specifying the age limit for paediatric indication.



Section 10

Date of revision updated to 30th October 2012.

Reasons for adding or updating:

  • Change to section 4.1 - Therapeutic indications
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.3 - Contraindications
  • Change to section 4.4 - Special warnings and precautions for Use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.6 - Pregnancy and Lactation
  • Change to section 4.7 - Effects on Ability to Drive and Use Machines
  • Change to section 4.8 - Undesirable Effects
  • Change to section 4.9 - Overdose
  • Change to section 10 date of revision of the text

Date of revision of text on the SPC:14-07-2011

Legal Category:P

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



Section 4.1

 

Text added:

 

-                      dermal procedures on newly shaven skin of large body areas e.g. laser hair removal
-           Topical anaesthesia of the genital mucosa, e.g. prior to superficial surgical procedures or prior to infiltration anaesthesia of mucosa.

-           Topical anaesthesia of leg ulcers to facilitate mechanical cleansing/debridement.

 

Text removed

 

-           on genital mucosa prior to surgical treatment of localised lesions.

 

In adult men, EMLA is indicated for local anaesthesia on genital skin prior to injection of local anaesthetics.

 

Section 4.2

 

Table updated and new lines added relating to procedures on newly shaven areas, paediatric, adult genital organs and leg ulcers.

 

New footnotes added to table:

 

1)         After > 5 hours application time anaesthesia decreases.

2)         Application for >1 hour has not been documented.
3)         Until further clinical data are available, EMLA should not be used in infants up to 12 months of age receiving treatment with methaemoglobin-inducing 
            agents.
4)         No clinically significant increase in plasma methaemoglobin levels has been observed after an application time of up to 4 hours on 16 cm2.
5)         EMLA has been used for the treatment of leg ulcers up to 15 times over a period of 1-2 months without loss of efficacy or increased number or severity of 
            adverse events.
6)         Plasma levels have not been determined in patients treated with doses of >10 g, (See also Section 5.2).
7)         On female genital skin, EMLA alone applied for 60 or 90 min does not provide sufficient anaesthesia for thermocautery or diathermy of genital warts.

 

Paediatric population and methods of dose estimation updated

 

Table 2: Dose, application time and dose interval by age and weight removed. Data incorporated into new table

 

Section 4.3

 

Text amended to:

 

Hypersensitivity to the amide-type local anaesthetics or to any other component of the product.

 

Section 4.4

 

Text amended (12 months to 3 months)

 

In infants/neonates younger than 3 months a transient, clinically insignificant increase in methaemoglobin level is commonly observed up to 12 hours after an application of EMLA.

 

Text added

 

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

 

Studies have been unable to demonstrate the efficacy of EMLA for heel lancing in neonates.

EMLA should not be applied to the genital mucosa of children owing to insufficient data on absorption of active substances. However, when used in neonates for circumcision, a dose of 1.0 g EMLA on the prepuce has been proven to be safe.

 

Text amended re atopic dermatitis.

 

Text amended re eye contact.

 

Text amended re middle ear.

 

Following text added

 

EMLA Cream contains polyoxyethylene hydrogenated castor oil which may cause skin reactions.

 

Section 4.5

 

Text amended re systemic toxicity

 

Section 4.6

 

Text removed

 

For EMLA Cream no adequate clinical data on exposed pregnancies are available. 

 

Text re Pregnancy updated and new text added.

 

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.

 

Text added and amended re lactation

 

Section 4.7

 

Text ameded to EMLA has no influence on driving ability and the ability to operate machines when used at the recommended doses.

 

Section 4.8

 

Text removed

 

EMLA has no influence on driving ability and the ability to operate machines when used at the recommended doses.

 

Table updated, text removed and new text added.

 

Common
(>1/100)

Skin

Transient local reactions at the application site such as paleness, erythema (redness) and oedema. 1,2,3)

An initial and usually mild sensation of burning, itching or warmth at the application site2,3)

Uncommon
(1/1000 to 1/100)

 Skin

An initial mild burning, itching sensation or warmth at the application site1)

Local paresthesia at the application site, e.g. tingling sensation2)

Skin irritation at the application site3)

Rare
(<1/1000)

 General

Methaemoglobinaemia.1)

Rare cases of discrete local lesions at site of administration such as purpuric or petechial, especially at longer application time in children with atopic dermatitis or mollusca contagiosa1)

Corneal irritation after accidental eye exposure1)

In rare cases, local anaesthetic preparations have been associated with allergic reactions (in the most severe cases anaphylactic shock)1,2,3)

 

1) Intact skin

2) Genital Mucosa

3) Leg ulcer

 

Section 4.9

 

Text amended and following new text added

 

; 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.

 

Section10

 

Date of revision of the text amended to 14th July 2011.

Reasons for adding or updating:

  • Change to section 4.8 - Undesirable Effects
  • Change to section 4.9 - Overdose
  • Change to section 10 date of revision of the text

Date of revision of text on the SPC:04-12-2009

Legal Category:P

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

Section 4.8

Change to paragraph before table so now reads:

Undesirable effects are detailed in the following tables in order of system organ class and frequency:

Change to frequencies in adverse events table:

Intact skin

 

 

System Organ Class

Frequency

Description

Blood and Lymphatic System Disorders:

Rare
(>1/10,000; <1/1,000)

Methaemoglobinaemia (see sections 4.5 and 4.9)

Immune System Disorders:

Rare
(>1/10,000; <1/1,000)

In rare cases, local anaesthetic preparations have been associated with allergic reactions (in the most severe instances anaphylactic shock).

Eye Disorders:

Rare
(>1/10,000; <1/1,000)

Corneal irritation after accidental eye exposure

General Disorders and Administration Site Conditions:

Common
(>1/100; <1/10)

Transient local reactions at the application site

such as paleness, erythema (redness) and

oedema.

 

Uncommon
(>1/1,000; <1/100)

Skin sensations (an initial mild burning or

itching sensation at the application site).

 

Rare
(>1/10,000; <1/1,000)

Rare cases of discrete local lesions at the application site, described as purpuric or petechial, have been reported, especially after longer application times in children with atopic dermatitis or mollusca contagiosa

Genital mucosa

 

 

System Organ Class

Frequency

Description

Immune System Disorders

Rare
(>1/10,000; <1/1,000)

In rare cases, local anaesthetic preparations have been associated with allergic reactions (in the most severe instances anaphylactic shock).

General Disorders and Administration Site Conditions

Common
(>1/100; <1/10)

Application site: Transient local reactions such as erythema (redness), oedema and paleness. Local sensations (an initial, usually mild, burning sensation, itch or warmth at the application site).

 

Uncommon
(>1/1,000; <1/100)

Application site: Local paraesthesia such as tingling.



Section 4.9

Removal of 'in children' from first sentence so now reads:

Rare cases of clinically significant methaemoglobinaemia have been reported.

Section 10

Change of date to :

4th December 2009

Reasons for adding or updating:

  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 10 date of revision of the text

Date of revision of text on the SPC:28-09-2009

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Section 4.5

Additional new text last paragraph.

Drugs that reduce the clearance of lidocaine (eg, cimetidine or betablockers) may cause potentially toxic plasma concentrations when lidocaine is given in repeated high doses over a long time period. Such interactions should therefore be of no clinical importance following short term treatment with lidocaine (eg, EMLA cream) at recommended doses.

Section 10

Revision date of text: 28 September 2009

Reasons for adding or updating:

  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for Use
  • Change to section 5.1 - Pharmacodynamic Properties
  • Change to section 10 date of revision of the text

Date of revision of text on the SPC:19-11-2008

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Section 4.2- Paragraph 5 after table 2:

Addition of text-
'Prior to curettage of mollusca in children with atopic dermatitis, an application time of 30 minutes is recommended.'

Section 4.4- Paragraph 8:


Addition of text-

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

Paragraph 9:

Change of text-
'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 Pharmacodynamic properties). Prior to curettage of mollusca in children with atopic dermatitis, an application time of 30 minutes is recommended.'

Section 5.1- Paragraph 3:

Addition of text-

'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 4.5 Special precautions and special warnings for use).'

Section 10:


Change of date-

'19th November 2008'

Reasons for adding or updating:

  • Change to section 4.4 - Special warnings and precautions for Use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 5.1 - Pharmacodynamic Properties
  • Change to section 5.2 - Pharmacokinetic Properties
  • Change to section 4.1 - Therapeutic indications
  • Change to section 10 date of revision of the text
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.8 - Undesirable Effects
  • Change to section 6. 5 - Nature and Contents of Container

Date of revision of text on the SPC:15-09-2008

Legal Category:P

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

Red text is new text, and strike through is deleted text.

Section 4.1


In adults, EMLA is indicated for local anaesthesia

-        on intact skin prior to minor dermatological procedures (e.g. needle insertion and surgical treatment of localised lesions) and prior to dermal procedures on larger areas e.g. split skin grafting.

-            on genital mucosa prior to surgical treatment of localised lesions.

In adult men, EMLA is indicated for local anaesthesia on genital skin prior to injection of local anaesthetics.

In term newborn infants and children under the age of 18 years, EMLA is indicated for local anaesthesia on intact skin prior to minor dermatological procedures. Studies have failed to demonstrate efficacy of EMLA for heel lancing in newborn infants.

Local anaesthetic for topical use to produce surface anaesthesia of the skin.

For topical use on the genital mucosa to facilitate the removal of warts in adults.

Section 4.2

Paediatric population

Adolecents ³ 12 years:

As for adults (approximately 2 g EMLA applied under an occlusive dressing for a minimum of 60 minutes, maximum 5 hours).

Term newborn infants, infants and children
£ 11 years:


For dose, application area, application time and dose interval by age and weight see T
able 2 below.

Table 2: Dose, application time and dose interval by age and
weight

Age and body Weight Requirements

Max. total dose of EMLA Cream

Max. application area

Max. application time

Minimum dose interval

Term newborn infants to 3 months or < 5 kg

1 g

10 cm2

1 hour

24 hours

3 up to 12 months and > 5 kg

2 g

20 cm2

4 hours

12 hours

1 to 6 years and > 10 kg

10 g

100 cm2

5 hours

12 hours

7 to 11 years and > 20 kg

20 g

200 cm2

5 hours

12 hours

For paediatric patients below 12 years of age a maximum of 2 doses, separated by at least 12 hours, can be given within any 24 hour period.

0No clinically significant increase in methaemoglobin levels has been observed after an application time of up to 4 hours on 16 cm2.

A longer application time than 1 hour has not been documented.

Until further clinical data is available, EMLA should not be used in neonates/infants between 0-12 months of age receiving treatment with methaemoglobin-inducing agents.

In term newborn infants and infants < 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. If, based on clinical need, a decision is nevertheless taken to use two applications in children under the age of 3 months, see sections 4.4 and 4.8.

The safety of EMLA in pre-term newborn infants has not been established. Use of EMLA is not recommended in pre-term infants.

Use of EMLA is not recommended in infants less than 12 months of age receiving treatment with methaemoglobin-inducing drugs (see section 4.4).

For all age groups analgesic efficacy may decline if the skin application time is more than 5 hours. Procedures on intact skin should begin soon after the occlusive dressing is removed.

On the genital mucosa analgesic efficacy declines after 10-15 minutes and therefore the procedure should be commenced immediately.

Methods of dose estimation

EMLA is available in 5 g and 30 g tubes. A string of cream can be used to define the quantity of EMLA administered from the 30 g aluminium tube where 1 g = 3.5 cm; however, a string of cream may not be appropriate for all application needs, e.g. when administering a low dose to small surface areas.

An alternative method is tEMLA is available in 5 g and 30 g tubes. To dispense 1 g of EMLA to a circular area, applied from either tube size, apply the cream to a circular area with a diameter of approx. 18 mm (a 1 pence coin) and depth of approx. 4 to 5 mm.

If high levels of accuracy in dosing are required to prevent overdose (i.e. at doses approaching the maximum in neonates or if two applications may be required in a 24 h period), a syringe can be used where 1 ml = 1 g.

EMLA is available in 5 g and 30 g tubes. A string of cream can be used to define the quantity of EMLA administered from the 30 galuminium tube where 1 g = 3.5 cm; however, a string of cream may not be appropriate for all application needs, e.g. when administering a low dose to small surface areas.

Not recommended in infants.

Section 4.4

Until further clinical data are available, EMLA should not be used in the following cases:

(a) in pre-term neonates i.e. gestational age less than 37 weeks.

(b) in infants/neonates between 0 and 12 months of age receiving treatment with

methaemoglobin-inducing agents due to the possible additive effects.

In infants/neonates younger than 123 months a transient, clinically insignificant increase in methaemoglobin level is commonly observed up to 12 hours after an application of EMLA.

Patients with glucose-6-phosphate dehydrogenase deficiency or congenital or idiopathic methaemoglobinaemia are more susceptible to drug induced methaemoglobinaemia.

Clinical studies have been unable to demonstrate the efficacy of EMLA during the heel lancing of neonates.

In term newborn infants, infants and children, EMLA should only be used on intact skin and should not be applied to genital mucosa.

EMLA Cream should not be applied to genital mucosa in children.

Until further clinical experience is available, EMLA Cream should not be applied to wounds or in areas of atopic dermatitis.In term neonates and infants < 3 months, only one single dose should be applied in any 24 hour period. If, based on clinical need, a decision is nevertheless taken to use two applications in children under the age of 3 months, the child should be clinically monitored for systemic adverse reactions (see sections 4.8 and 4.9).

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 monitorcheck oxygen saturation by co-oximetry.

Care must be taken to limit the dose and area of application and to prevent accidental ingestion.

Until further clinical experience is available, EMLA Cream should not be applied to wounds or in areas of atopic dermatitis.

Section 4.5

Methaemoglobinaemia may be accentuated in patients already taking drugs known to induce the condition, e.g. sulphonamides., acetanilid, aniline dyes, benzocaine, chloroquine, dapsone, metoclopramide, naphthalene, nitrates and nitrites, nitrofurantoin, nitroglycerin, nitroprusside, pamaquine, para-aminosalicylic acid, phenacetin, phenobarbital, phenytoin, primaquine, quinine.

Section 4.8

Paediatric population

In clinical trials 298 neonates and infants aged up to 12 months were treated with EMLA (Table 3). A large number of infants and children aged 1 year and older have been treated with EMLA in clinical trials and in clinical practice since 1984.

Table 3. Number of paediatric patients, up to 12 months old, included in clinical studies with EMLA, by age group

Group

Number of patients

Pre-term neonates

21

Age 0–1 months

148

Age 1–3 months

55

Age 3–12 months

74

Total number

298

     

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, in neonates and infants aged 0 to 12 months.

Rare cases of clinically significant methaemoglobinaemia in children have been reported in literature.  Prilocaine, one of the components of EMLA, may in high doses cause an increase in the methaemoglobin level, particularly in susceptible individuals (Section 4.4) and in conjunction with other methaemoglobin-inducing agents. Clinically significant methaemoglobinaemia should be treated with a slow intravenous injection of methylthioninium chloride (Section 4.9).

Section 5.1

Paediatric populationChildren

Clinical safety studies

Methaemoglobin formation after the use of EMLA in term infants was studied with the aim to establish the safety of 1 g EMLA cream 5%. Forty-seven neonates and infants, aged 0-3 months, with a post conceptual age of ≥37 weeks were included in a double blind, randomized, placebo-controlled study. Methaemoglobin concentrations before treatment with EMLA and placebo were in the range 0.67-1.57%  and 0.50-1.53%, respectively. After treatment with 1 g EMLA/placebo for 60-70 min methaemoglobin concentrations were  0.50-2.53% for EMLA and 0.50-1.53% for placebo. From 3.5 to 13 h after application the concentrations were significantly higher with EMLA than with placebo, but were clinically insignificant. One sample, in the EMLA group (2.53%), had a methaemoglobin concentration above the reference value of 2%.

Altogether, data from eleven clinical studies in neonates 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.

Physiological methaemoglobin concentrations in both paediatric patients and adults are normally maintained below 2%. A major increase (25–30%) in methaemoglobin (to a concentration of 25-30%) will cause signs and symptoms of hypoxaemia. In neonates elevated methaemoglobin levels up to 5–6% are not regarded as clinically significant.

Circumcision:

In two randomized, double-blind, placebo-controlled studies in full-term neonates aged 1 to 4 days EMLA cream (0.5 or 1 g) was applied on the prepuce for one hour before circumcision, covered with an occlusive dressing. In the study using 0.5 g EMLA there was no significant differences with placebo in assessment of pain performed by evaluating facial expressions or heart rate, respiratory rate, oxygen saturation, nor in general skin colour.

EMLA Cream (1 g) significantly reduced the pain during parts of the circumcision procedure, as demonstrated by less facial activity, reduction in duration of cry and lower heart rates. No differences were found for oxygen saturation, respiratory rate and Neonatal Infant Pain Scale (NIPS) – which includes facial expression, cry, breathing pattern and state of arousal.

In the study using a dose of 1 g the average concentrations of methaemoglobin up to 18 hours after administration were 1.31% (range 0-3.1%) in the EMLA group and 1.34% (range 1.0%-1.9%) in the placebo group (not significantly different).

Vaccination:

Two randomized double-blind, placebo-controlled studies in infants and neonates looked at anaesthetic efficacy of EMLA cream in vaccinations and the effect on the immunogenicity of live vaccines.

The first study used EMLA Cream prior to subcutaneous measles-mumps-rubella vaccine, in patients aged 12-15 months, where 1g of cream was applied for 60‑180 minutes. EMLA significantly reduced vaccination pain versus placebo, demonstrated by difference between the pre- and post-vaccination total score on the Modified Behavioural Pain Scale (MBPS - includes measurement of facial expression, cry and body movement). No difference versus placebo was seen with the separate assessment of proportion of patients that cry and duration of cry.

The second used EMLA Cream prior to intramuscular diptheria-pertussis-tetanus-inactivated poliovirus-Haemophilus influenzae b or Hepatitis B vaccines in patients aged 0-6 months, where 1 or 2g of cream was applied to patients aged 0-4 and 6 months respectively, for 60-180 minutes. EMLA significantly reduced vaccination pain versus placebo, demonstrated as above, for the 6 month-old group, however in the 0-4 month old group there was high variation in treatment response. In the 2 and 4 month-old groups, EMLA gave reduced pain versus placebo, however statistical significance was not shown (p=0.120 and 0.225 respectively).

Within both studies, tThe use of EMLA prior to measles-mumps-rubella or intramuscular diptheria-pertussis-tetanus-inactivated poliovirus-Haemophilus influenzae b or Hepatitis B vaccines does did not affect mean antibody titres, rate of seroconversion, or the proportion of patients achieving protective or positive antibody titres post immunization, as compared to placebo treated patients.


Section 5.2

Paediatric populationChildren

Following the application of 1 g EMLA Cream in infants/neonates below 3 months of age, to approx 10 cm2 for one hour, the maximum plasma concentrations of lidocaine and prilocaine were 0.135 micrograms/ml and 0.107 micrograms/ml respectively.

Following the application of 2 g EMLA Cream in infants between 3 and 12 months of age, to approx 16 cm2 for four hours, the maximum plasma concentrations of lidocaine and prilocaine were 0.155 micrograms/ml and 0.131 micrograms/ml respectively.

Following the application of 10 g of EMLA Cream in children between 2 and 3 years of age, to approx 100 cm2 for two hours, the maximum plasma concentrations of lidocaine and prilocaine were 0.315 micrograms/ml and 0.215 micrograms/ml respectively.

Following the application of 10-16 g EMLA Cream in children between 6 and 8 years of age, to approx 100-160 cm2 for two hours, the maximum plasma concentrations of lidocaine and prilocaine were 0.299 micrograms/ml and 0.110 micrograms/ml respectively.

Section 6.5

“Pre-medication pack” containing 5 x 5 g tubes EMLA and 12 occlusive dressings.

Pack containing 10 x 5 g tubes of EMLA and 2 occlusive dressings.

1 x 30 g tube with enclosed spatula

1 x 5 g tube

Section 10
21st June 2007February 15th September 2008.

Reasons for adding or updating:

  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for Use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.6 - Pregnancy and Lactation
  • Change to section 4.8 - Undesirable Effects
  • Change to section 4.9 - Overdose
  • Change to section 5.2 - Pharmacokinetic Properties
  • Change to section 10 date of revision of the text

Date of revision of text on the SPC:01-06-2007

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

Section 4.2 -  Addition and Removal of text from table

Current text

Adults (including elderly) and children > 1 year:

 

Surface

Procedure

Application

Skin (apply a thick layer of cream under an occlusive dressing).

Minor dermatological procedures e.g. needle insertion and surgical treatment of localised lesions.

Approximately 2 g EMLA applied for a minimum of 60 minutes, maximum 5 hours.

 

Dermal procedures on larger areas e.g. split skin grafting.

Approximately 1.5-2 g/10 cm2 EMLA applied for a minimum of 2 hours, maximum 5 hours.

Genital mucosa (adults) (no occlusive dressing required).

Surgical treatment of localised lesions.

Apply up to 10 g EMLA for 5-10 minutes. Commence procedure immediately thereafter.

 

New Text

 

Surface

Age group

Procedure

Application

Skin

Adults (including elderly) and children > 1 year

Minor dermatological procedures e.g. needle insertion and surgical treatment of localised lesions.

Approximately 2 g EMLA applied under an occlusive dressing for a minimum of 60 minutes, maximum 5 hours.

 

 

Dermal procedures on larger areas e.g. split skin grafting.

Approximately 1.5-2 g/10 cm2 EMLA applied under an occlusive dressing for a minimum of 2 hours, maximum 5 hours.

Male genital skin

Adults (including elderly)

Prior to injection of local anaesthetics

Approximately 1g/10cm2 EMLA applied for 15 minutes under an occlusive dressing

Genital mucosa

Adults (including elderly)

Surgical treatment of localised lesions

Approximately 5–10 g EMLA for 5-10 minutes (no occlusive dressing required). Commence procedure immediately thereafter.

 

Section 4.4

Spelling error of the word congenital

Removal of the word muscous membrane form the 2nd paragraph

current text:  ‘applied to wounds, mucous membranes or in areas of atopic dermatitis.’

New text:  ‘applied to wounds or in areas of atopic dermatitis’

 

Addition of the paragraph after the 7th paragraph

Patients treated with anti-arrhythmic drugs class III (e.g. amiodarone) should be under close surveillance and ECG monitoring considered, since cardiac effects may be additive

 

Section 4.5

addition of paragraph after the 3rd paragraph:

‘Specific interaction studies with lidocaine/prilocaine and anti-arrhythmic drugs class III (e.g. amiodarone) have not been performed, but caution is advised (see also section 4.4).’

 

Section 4.6

Addition of the 1st paragrapgh:

For EMLA cream no adequate clinical data on exposed pregnancies are available. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development.

Removal of the first sentence from 2nd and 3rd paragraph

‘Lidocaine and prilocaine cross the placental barrier’

‘However, both drugs have been in widespread clinical use for many years and a large number of women of childbearing age have been exposed to them. No specific effects on the reproductive process have been reported. However,’

Removal of the sentence from the 3rd paragraph

‘Lidocaine and prilocaine are excreted in breast milk in small amounts’

addition of text to 4th paragraph

Lidocaine and prilocaine are excreted in breast milk, but in such small quantities that there is generally no risk of the child being affected at therapeutic dose levels.

 

Section 4.8

 

Removal of text:

Transient paleness, redness and oedema have been reported.

Prilocaine has been known to cause methaemoglobinaemia in children when given parenterally.

In rare cases local anaesthetics have been associated with allergic reactions including anaphylactic shock.

Rare cases of discrete local lesions at the application site, described as purpuric or petechial, have been reported, especially after longer application times in children with atopic dermatitis or mollusca contagiosa.

Corneal irritation after accidental eye exposure.

 

Addition of text:

Transient local reactions at the application site, most commonly erythema, paleness and/or oedema, may occur in >1% of patients treated with EMLA. Other types of reactions, such as allergic reactions or methaemoglobinaemia, occur in <0.1% of patients.

Intact skin

 

 

Blood and Lymphatic System Disorders:

Rare events
(< 0.1%)

Methaemoglobinaemia in children (see sections 4.5 and 4.9)

Immune System Disorders:

Rare events
(< 0.1%)

In rare cases, local anaesthetic preparations have been associated with allergic reactions (in the most severe instances anaphylactic shock).

Eye Disorders:

Rare events
(< 0.1%)

Corneal irritation after accidental eye exposure

General Disorders and Administration Site Conditions:

Common events
(>1%)

Transient local reactions at the application site

such as paleness, erythema (redness) and

oedema.

 

Uncommon events
(>0.1% and <1%)

Skin sensations (an initial mild burning or

itching sensation at the application site).

 

Rare events
(< 0.1%)

Rare cases of discrete local lesions at the application site, described as purpuric or petechial, have been reported, especially after longer application times in children with atopic dermatitis or mollusca contagiosa

Genital mucosa

 

 

Immune System Disorders

Rare events
(< 0.1%)

In rare cases, local anaesthetic preparations have

been associated with allergic reactions (in the

most severe instances anaphylactic shock).

General Disorders and Administration Site Conditions

Common events
(>1%)

Application site: Transient local reactions such as erythema (redness), oedema and paleness. Local sensations (an initial, usually mild, burning sensation, itch or warmth at the application site).

 

Uncommon events
(>0.1% and <1%)

Application site: Local paraesthesia such as tingling.

 

Prilocaine, one of the components of EMLA, may in high doses cause an increase in the methaemoglobin level, particularly in susceptible individuals (Section 4.4) and in conjunction with other methaemoglobin-inducing agents. Clinically significant methaemoglobinaemia should be treated with a slow intravenous injection of methylthioninium chloride (Section 4.9).

 

Section 4.9

 

Removal of text

Overdosage with EMLA is unlikely but signs of systemic toxicity will be similar in nature to those observed after administration of other local anaesthetics

 

Addition of text

Rare cases of clinically significant methaemoglobinaemia have been reported in children. Prilocaine in high doses may cause an increase in the methaemoglobin level particularly in conjunction with methaemoglobin-inducing agents (e.g. sulphonamides). Clinically significant methaemoglobinaemia should be treated with a slow intravenous injection of methylthioninium chloride.

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. 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 drugs.

 

Section 5.2

Addition of text after the 2nd paragraph

After the application of EMLA cream to intact male genital skin for 15 minutes (median 1 g), plasma concentrations of lidocaine and prilocaine (mean 6.6 nanogram/ml and 4.1 nanogram/ml) were reached after approximately 1.5 hours.

 

Section10  Date of Revision of text changed to 21/06/2007

 

Reasons for adding or updating:

  • Change to section 6. 5 - Nature and Contents of Container

Reasons for adding or updating:

  • Change to section 6. 4 - Special Precautions for Storage
  • Change to section 10 (date of (partial) revision of the text

Reasons for adding or updating:

  • Change to section 9 - Date of Renewal of Authorisation

Reasons for adding or updating:

  • Change to section 4.3 - Contra-indications
  • Change to section 4.4 - Special Warnings and Precautions for Use
  • Change to section 4.6 - Pregnancy and Lactation
  • Change to section 4.8 - Undesirable Effects
  • Change to section 5.1 - Pharmacodynamic Properties

Reasons for adding or updating:

  • Change to section 6. 5 - Nature and Contents of Container

Reasons for adding or updating:

  • Change to section 7 - Marketing Authorisation Holder
  • Change to section 8 - MA number
  • Change to section 9 - Date of Renewal of Authorisation

Reasons for adding or updating:

  • Change to section 7 - Marketing Authorisation Holder

Reasons for adding or updating:

  • New SPC for eMC ie an SPC for an existing product, but one that is new for the eMC

Reasons for adding or updating:

  • No reasons supplied