Global prescribing info for EMLA Patch
1. NAME OF THE MEDICINAL PRODUCT
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
3. PHARMACEUTICAL FORM
4. CLINICAL PARTICULARS
5. PHARMACOLOGICAL PROPERTIES
6. PHARMACEUTICAL PARTICULARS
Please consult full local prescribing information before using EMLA cream or EMLA patch.
1. NAME OF THE MEDICINAL PRODUCT
EMLA® Patch
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Active constituents:
One EMLA Patch contains lidocaine 25 mg, prilocaine 25 mg.
EMLA Patch is a unit-dose formulation of EMLA in the form of an occlusive dressing. An absorbent cellulose disc, saturated with 1 g of EMLA emulsion, is affixed to a laminate backing equipped with an adhesive tape frame. The contact surface area of the EMLA saturated disc is approx. 10 cm2.
EMLA emulsion is an oil-in-water emulsion system in which the oil phase consists of a eutectic mixture of the base forms of lidocaine and prilocaine in the ratio 1:1.
4. CLINICAL PARTICULARS
4.1 Therapeutic indications
Topical anaesthesia of intact skin in connection with minor procedures, such as needle insertion and surgical treatment of localized lesions (refs 1,2,3,4).
4.2 Posology and method of administration
Adults and children over 1 year of age
One or more patch(es) are applied to the skin area(s) selected.
Minimum application time: 1 hour. After a longer application time than 5 hours the anaesthesia decreases. (Refs 5,6,8,9,10,11,12,13,16)
Maximum dose for children aged 1-5 years is 10 patches.
Maximum dose for children aged 6-11 years is 20 patches. (Ref 14)
Prior to curettage of mollusca in children with atopic dermatitis, an application time of 30 minutes is recommended (refs 19,38).
Infants aged 3 - 11 months
The patch is applied to the skin area selected. Approximate application time: 1 hour. Not more than two EMLA Patches should be applied at the same time (ref 15). No clinically significant increase in methaemoglobin levels has been observed following the application of 2 g EMLA Cream for up to 4 hours (refs 15,17).
Neonates under 3 months of age
The patch is applied to the skin area selected. Approximate application time: 1 hour, not more. A longer application time than 1 hour has not been documented.
Not more than one EMLA Patch should be applied at the same time (ref 14).
The size of the patch makes it less suitable for use on certain parts of the body in neonates and infants.
Until further clinical data is available, EMLA should not be used in infants between 0 and 12 months of age receiving treatment with methaemoglobin inducing agents (refs 14,15,17).
4.3 Contraindications
Hypersensitivity to local anaesthetics of the amide type or to any other component of the product.
4.4 Special warnings and special precautions for use
Patients with glucose-6-phosphate dehydrogenase deficiency or congenital or idiopathic methaemoglobinaemia are more susceptible to drug-induced methaemoglobinaemia (ref 57).
Due to insufficient data on absorption, EMLA should not be applied to open wounds.
Studies have been unable to demonstrate the efficacy of EMLA for heel lancing in neonates (refs 39-41).
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). Prior to currettage of mollusca in children with atopic dermatitis, an application time of 30 minutes is recommended (refs 18,19,38).
Care should be taken not to allow EMLA to come in contact with the eyes as it may cause eye irritation (see section 5.3). Also the loss of protective reflexes may allow corneal irritation and potential abrasion. If eye contact occurs, immediately rinse the eye in water or sodium chloride solution and protect it until sensation returns (ref 20).
In children/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 (ref 14).
Lidocaine and prilocaine have bacteriocidal and antiviral properties in concentrations above 0.5 2%. For this reason, although one clinical study suggests that the immunization response is not affected when EMLA is used prior to BCG vaccination, the results of intracutaneous injections of live vaccines should be monitored (refs 21,54,55).
Until further clinical data is available, EMLA should not be used in the following cases:
(a) in infants between 0 and 12 months of age receiving treatment with methaemoglobin-inducing agents (see section 4.8) (refs 14,15,17).
(b) in preterm infants with a gestational age less than 37 weeks (ref 14).
4.5 Interaction with other medicinal products and other forms of interaction
Prilocaine in high doses may cause an increase in the methaemoglobin level particularly in conjunction with methaemoglobin-inducing agents (eg sulphonamides) (ref 22).
With large doses of EMLA, consideration should be given to the risk of additional systemic toxicity in patients receiving other local anaesthetics or agents structurally related to local anaesthetics, since the toxic effects are additive.
4.6 Pregnancy and lactation
Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development.
In both animal and humans, 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 potential. No specific disturbances to the reproductive process have so far been reported, eg an increased incidence of malformations or other directly or indirectly harmful effects on the foetus. However, caution should be exercised when used in pregnant women. (Refs 23,24,63)
Lidocaine and, in all probability, 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 (ref 25).
4.7 Effects on ability to drive and use machines
Not applicable at the recommended dosage.
4.8 Undesirable effects
FREQUENCY OF ADVERSE EVENTS
Intact skin
| Common Events (>1%) | Skin: Transient local reactions at the application site such as paleness, erythema (redness) and oedema |
| Uncommon Events (>0.1% and <1%) | Skin: Skin sensations (an initial mild burning or itching sensation at the application site). |
| Rare Events (< 0.1%) | General: Methaemoglobinaemia in children. 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 (see 4.5 and 4.9). Corneal irritation after accidental eye exposure. In rare cases, local anaesthetic preparations have been associated with allergic reactions (in the most severe instances anaphylactic shock). |
4.9 Overdose
Rare cases of clinically significant methaemoglobinaemia in connection with treatment with EMLA cream (see section 4.8) have been reported in children. Prilocaine in high doses may cause an increase in the methaemoglobin level particularly in conjunction with methaemoglobin-inducing agents (eg sulphonamides) (ref 22). Clinically significant methaemoglobinaemia should be treated with a slow intravenous injection of methylene blue.
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.
5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Local anaesthetic of the amide-type, ATC code: N01B B20
EMLA Patch, applied to intact skin, provides dermal anaesthesia through the release of lidocaine and prilocaine into the epidermal and dermal layers of the skin and the accumulation of lidocaine and prilocaine in the vicinity of dermal pain receptors and nerve endings. Lidocaine and prilocaine are amide-type local anaesthetic agents. 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 (refs 5,8). The time needed to achieve reliable anaesthesia of intact skin is at least 60 minutes (refs 10,11).
In clinical studies of EMLA on intact skin, no differences in safety or efficacy (including anaesthetic onset time) were observed between geriatric patients (aged 65-96 years) and younger patients (refs.58,59).
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 min and 3 mm after 120 min of EMLA treatment (ref 45). 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) (ref 56).
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 immunization, as compared to placebo treated patients (refs 54,55,60,61).
The EMLA emulsion produces a biphasic vascular response involving initial vasoconstriction followed by vasodilatation at the application site (see section 4.8) (refs 10,13,27,32). Irrespective of the vascular response, EMLA facilitates the needle procedure compared to placebo (refs 46-75).
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) (ref 18).
5.2 Pharmacokinetic properties
The systemic absorption of lidocaine and prilocaine from EMLA is dependent upon the dose, area of application, application time, thickness of the skin, which varies in different areas of the body, and other conditions of the skin (refs 7,33-37).
The available pharmacokinetic data refer to the application of EMLA cream 5% to intact skin. Following application to the thigh in adults (60 g cream/400 cm2 for 3 hours), the extent of absorption of lidocaine and prilocaine was approx. 5%. Maximum plasma concentrations (mean 0.12 and 0.07 µg/ml) were reached approx. 2-6 hours after application (ref 37).
The extent of systemic absorption was approx. 10% following application to the face (10 g/100 cm2 for 2 hours). Maximum plasma levels (mean 0.16 and 0.06 µg/ml) were reached after approx 1.5-3 hours (ref 34).
Plasma levels 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 (ref 62).
Children: Following the application of 1.0 g EMLA cream in neonates below 3 months of age, to approx 10 cm2 for one hour, the maximum plasma concentrations of lidocaine and prilocaine were 0.135 µg/ml and 0.107 µg/ml respectively. Following the application of 2.0 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 µg/ml and 0.131 µg/ml respectively. Following the application of 10.0 g 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 µg/ml and 0.215 µg/ml respectively. Following the application of 10.0-16.0 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 µg/ml and 0.110 µg/ml respectively. (Ref 14.)
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 compounds were shown to have a low oral acute toxicity, providing a good safety margin in the event that EMLA is inadvertently swallowed. No drug-related adverse effects were seen in the reproduction toxicity studies, using either compound separately or together.
Neither local anaesthetic showed a mutagenic potential in either in vitro or in vivo mutagenicity 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 drugs.
Genotoxicity tests with lidocaine showed no evidence of mutagenic potential. A metabolite of lidocaine, 2,6-xylidine, showed weak evidence of activity in some genotoxicity tests. The metabolite 2,6-xylidine has 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, with the exposure used in preclinical studies, indicate a wide margin of safety for clinical use. (ref 65)
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. (Ref 63.)
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 (ref 20). This is the same concentration of local anaesthetics and a similar formulation as for EMLA cream and patch. 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.
Preclinical studies on the adhesive used in the patch did not raise any concerns.
6. PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Carboxypolymethylene, polyoxyl hydrogenated castor oil, sodium hydroxide to pH 8.7-9.7, purified water.
Contains no preservative.
6.2 Incompatibilities
Not applicable.
6.3 Shelf-life
2 years
6.4 Special precautions for storage
Do not store above 30°C. Do not refrigerate or freeze (ref.64)
6.5 Nature and contents of container
The patch consists of an occlusive dressing (user part) and a protective liner (closure part). The user part is composed of an aluminium/plastic backing laminate, an absorbent cellulose disc and a foam tape ring. The tape is a polyethylene foam coated with acrylate adhesive. The closure part is an aluminium/plastic laminate. A peel-off seal between the backing and closure laminates encloses the disc, which is impregnated with EMLA emulsion.
EMLA Patch is available in cardboard boxes containing 2 and 20 patches per box.
6.6 Instructions for use, handling and disposal
See "EMLA Patch. Directions for use", 22 June 1994.
Date of text: August 2005
REFERENCES
1. Tamsen A. Expert Report on the clinical documentation of EMLA Patch.Astra Report No. 802-540-LC-0005-01, 1991-03-22.
2. Eriksson G. Expert Report on the human pharmacological and clinical documentation. Addendum to Clinical Expert Report no. 802-540-LC-0005-01.Astra Report No. 802-540-LC-0052-01, 1994-01-27.
3. Uppfeldt A, Haegerstam G. EMLA Cream 5% Summary of clinical data.Astra Report No. 802-10 AC 018-2, 1983-09-29.
4. Minor B, Grafford K. EMLA Cream 5% Summary and evaluation of clinical data.Astra Report No. 802-10 AC 073, 1988-02-25.
5. Evers H, Danielson K, Vinnars E. Dermal analgesia and local circulatory effects in volunteers after epicutaneous application of EMLA Cream. Influence of applied dose and size of test area.Astra Report No. 802-10 AC 050-1, 1987-07-29.
6. Ohlsén L, Lähteenmäki T, Olenius M, Strömbeck J-O, Lillieborg S. Comparison of two doses of EMLA Cream as local analgesia for cutting split skin grafts. A multicentre study.Astra Report No. 802-10 AC 046, 1986-11-28.
7. Haugstvedt S, Friman A-M, Danielson K. EMLA Cream 5% for removal of mollusca. A clinical study of plasma concentrations of lidocaine and prilocaine and analgesic effect in children.Astra Report No. 802-10 AC 070-1, 1988-02-26.
8. Oranje AP, de Waard-van der Spek FB, Stolz E, Lillieborg S. Analgesia for the surgical removal of mollusca contagiosa in children: A double-blind, placebo-controlled, time-response study of EMLA® (lidocaine/prilocaine) cream.Astra Report No. 802-10 AC 082-1, 1990-02-05.
9. Rosdahl I, Edmar B, Gisslén H, Nordin P, Lillieborg S. Topical analgesia with EMLA Cream for curettage of mollusca contagiosa in children.Astra Report No. 802-10 AC 054-2, 1986-12-18.
10. Evers H, Danielson K, Vinnars E. Dermal analgesia and local circulatory effects in volunteers after epicutaneous application of EMLA Cream. Influence of application time.Astra Report No. 802-10 AC 052-1, 1987-07-29.
11. Ehrenström-Reiz G, Reiz S, Stockman O. Topical anaesthesia with EMLA, a new lidocaine-prilocaine cream and the cusum technique for detection of minimal application time.Acta Anaesth Scand 1983;27:510-2.
12. Hallen B, Olsson G, Uppfeldt A. Determination of a minimum application time for efficacy of a 5% lidocaine-prilocaine cream, EMLA (Eutectic Mixture of Local Anaesthetics), used for relief of venipuncture pain in children.Astra Report No. 802-10 AC 015-2, 1983-03-31.
13. Evers H, Danielson K, Vinnars E. Dermal analgesia and local circulatory effects in volunteers after epicutaneous application of EMLA Cream. Influence of application time.Astra Report No. 802-10 AC 051-1, 1987-07-29.
14. Larsson L. EMLA in children; use in neonates and recommended doses for children of all age groups.Clinical Expert Report No. 802-540-LC-0105-01, 1997-04-28.
15. Engberg G, Henneberg S, Nilsson A, Danielson K. Plasma concentrations of prilocaine and lidocaine and Methemoglobin formation in infants after dermal application of a 5% lidocaine-prilocaine cream (EMLA).Astra Report No. 802-10 AC 026-5, 1986-01-31.
16. Lähteenmäki T, Lillieborg S, Ohlsén L et al. Topical analgesia for the cutting of split skin grafts. A multicentre comparison of two doses of a lidocaine-prilocaine cream.Plastic Reconstr Surg 1988;82:458-62.
17. Nilsson A, Danielson K, Enberg G, Henneberg S. A clinical study of plasma concentrations of lidocaine and prilocaine and methaemoglobin formation after dermal application of EMLA in infants. (part B).Astra Report No. 802-10 AC 071-1, 1988-02-26.
18. Juhlin L, Rollman O. Vascular effects of a local anaesthetic mixture in atopic dermatitis.Acta Derm Venereol (Stockh) 1984;64:439-40.
19. Rönnerfält L, Fransson J, Minor BG. EMLA Cream for the removal of mollusca contagiosa on patients with atopic dermatitis.Astra Report No. 802-10 AC 080-1, 1990-05-05.
20. Astra Toxicology Laboratories, Södertälje, Sweden. Eye irritation in rabbits after single administration of Xylocain®/Citanest® emulsion.Astra Report No. 802-10 T1018, 1980-01-15.
21. Böttiger M. Statement; Evaluation of possible negative effects of the application of an anaesthetic cream (EMLA ™) on the immunogenicity of vaccinations. Jan 22, 1996.
22. Jakobson, Nilsson. Methemoglobinemia associated with a prilocaine-lidocaine cream and trimethoprim-sulphamethoxazole. A case report.Acta Anaesthesiol Scand 1985;29:453-5.
23. Astra Safety Assessment, Södertälje, Sweden. Effects upon pregnancy in rats of a lidocaine HCl (LEA151): prilocaine HCl (LEA154) (1:1 w/w) mixture given subcutaneously - a dose finding study.Astra Report No. 802-40 T2412, 1991-06-24.
24. Astra Safety Assessment, Södertälje, Sweden. Effects upon pregnancy in rats of a lidocaine HCl (LEA151): prilocaine HCl (LEA154) (1:1 w/w) mixture given subcutaneously.Astra Report No. 802-40 T2413, 1991-06-24.
25. Zeisler, Gaarder, De Mesquita. Lidocaine excretion in breast milk.Drug Intelligence and Clinical Pharmacy 1986;20:691-3.
26. Haegerstam. G. EMLA Cream 5% summary of human-pharmacological data.Astra Report No. 802-10 AC 058-2, 1985-05-31.
27. Minor B. EMLA Cream 5% summary and evaluation of human pharmacological data.Astra Report No. 802-10 AC 072, 1988-02-25.
28. Norrbrink L, Waldenlind L. Periodic drug-safety update lidocaine 25 mg/g and prilocaine 25 mg/g. EMLA Patch.Astra Report No. 802-540-LC-0075-01, 1995-09-05.
29. Floderus E, Waldenlind L. Periodic drug-safety update lidocaine 25 mg/g and prilocaine 25 mg/g. EMLA Patch.Astra Report No. 802-540-LC-0081-01, 1996-04-15.
30. Floderus E, Waldenlind L. Periodic drug-safety update lidocaine 25 mg/g and prilocaine 25 mg/g. EMLA Patch.Astra Report No. 802-540-LC-0108-01, 1997-05-30.
31. Floderus E, Waldenlind L. Periodic drug-safety update lidocaine 25 mg/g and prilocaine 25 mg/g. EMLA Patch, EMLA Anesthetic Disc.Astra Report No. 802-540-LC-0126-01, 1998-05-29.
32. Covino BG, Vassallo HG. Local anesthetics. Mechanisms of action and clinical use.Ed. Grune & Stratton, New York 1976, 134-6.
33. Evers H, Vinnars E. Experimental study of local analgesic effect and plasma concentrations of lidocaine and prilocaine after epicutaneous application of EMLA Cream 5%.Astra Report No. 802-10 AC 007-3, 1984-10-17.
34. Evers H, Vinnars E. Plasma concentrations of lidocaine and prilocaine after epicutaneous application of EMLA 5% cream to the facial skin and to the lower arms, in volunteers.Astra Report No. 802-10 AC 061-1, 1988-02-29.
35. Haugstvedt S, Friman A-M, Danielson K. Open clinical investigation of plasma levels of prilocaine and lidocaine after the dermal application of EMLA to children aged between 2 and 3 years.Astra Report No. 802-10 AC 069-1, 1988-02-26.
36. Ohlsén L, Englesson S, Evers H. An anaesthetic lidocaine/prilocaine cream (EMLA) for epicutaneous application tested for cutting split skin grafts.Scand J Plast Reconstr Surg 1985;19:201-209.
37. Wahlén A, Evers H, Vinnars E. Systemic absorption of lidocaine and prilocaine after topical administration of EMLA 5% cream.Astra Report No. 802-10 AC 035-3, 1986-03-20.
38. Rönnerfält L, Fransson J, Wahlgren C-F. EMLA Cream provides rapid pain relief for the curettage of mollusca contagiosa in children with atopic dermatitis without causing serious application-site reactions.Pediatric Dermatology 1998;15(4):309-312.
39. Larsson BA, Jylli L, Lagercrantz H, Olsson GL. Does a local anaesthetic cream (EMLA) alleviate pain from heel-lancing in neonates?Acta Anaesthesiol Scand 1995;23:1028-1031.
40. Ramaioli F, Amici De D, Guzinska K et al. EMLA Cream and the premature infant.Int Monitor (European Society of Regional Anaesthesia) 1993; 59. Abstract.
41. Stevens B, Johnston C, Taddio A et al. The safety and efficacy of EMLA for heel lance in preterm neonates. Vancouver, Canada: International Association for the study of pain, 8th World Congress on Pain;1996:181-182. Abstract 239.
42. Calobrisi SD, Drolet BA, Esterly NB: Petechial eruption after the application of EMLA Cream.Pediatrics, 1998; 101(3Pt1): 471-3.
43. Rosdahl, Edmar, Gisslen, Nordin, Lillieborg. Curettage of mollusca contagiosa in children: analgesia by topical application of a lidocaine/prilocaine cream (EMLA).Acta Derm Venereol 1988;68:149-153.
44. de Waard-van der Spek FB, Oranje AP. Purpura caused by EMLA is of toxic origin.Contact Dermatitis 1997;36:11-13.
45. Wahlgren C-F, Quiding H, Nilsson M. Standardised dermal sensitivity measures in subjects treated with EMLA for 60 and 120 minutes - An exploratory study.Astra Report 802-540-LC-0128-01.
46. Möller C. A lignocaine-prilocaine cream reduces venipuncture pain.Ups J Med Sci 1985;90:239-98.
47. Cooper CM, Gerrish SP, Hardwick M, Kay R. EMLA Cream reduces the pain of venepuncture in children.Eur J Anaesthesiol 1987;4:441-8.
48. Watson AR, Szymkiw P, Morgan AG. Topical anaesthesia for fistula cannulation in heamodialysis patients.Nephrol Dial Transplant 1988;3:800-2.
49. Young SS, Schwartz R, Sheridan MJ. EMLA Cream as a topical anesthetic before office phlebotomy in children.Southern Med J 1996;89(12):1184-7.
50. Halperin DL, Koren G, Attias D, Pellegrini E, Greenberg ML, Wyss M. Topical skin anesthesia for venous subcutaneous drug reservoir and lumbar punctures in children.Pediatrics;84(2):281-4.
51. Rice LJ, Cravero J. Relieveing the pain and anxiety of needle injections - experience with EMLAâ Cream (lidocaine 2.5% and prilocaine 2.5%) dermal anesthetic.
52. Miser A, Goh TS, Dose AM et al. Trial of a topically administered local anesthtic (EMLA Cream) for pain relief during central venous port accesses in children with cancer.J Pain and Symptom Management 1994;9(4):259-264.
53. Koren G. Use of the eutectic mixture of local anesthetics in young children for procedure-related pain.J Pediatrics 1993;122:30-5.
54. Dohlwitz A, Hellenberg L, Svedmyr J, Tober L, Wigertz A. No negative influence of EMLA application prior to B.C.G. vaccination.Acta Paedriatr 1998;87:480-481.
55. Halperin et al. A randomized ,double-blind, placebo-controlled trial to measure the antibody response to immunization with Measles-Mumps-Rubella vaccines using EMLA® Patch for the reduction of pain associated with subcutaneous injection in twelve months old infants.Astra Report 802-540-LC-0122-01, December 18, 1998.
56. Riendeau L, Scavone J, Black Noller G, Ondrasik J. A randomized double-blind study to evaluate the efficacy of EMLA(R) cream in skin types IV-V and VI undergoing the venipuncture procedure.Astra Report 93-EML-16, Nov. 17, 1994.
57. Coleman MD, Coleman NA. Drug-induced methaemoglobinaemia. Treatment issues.Drug Safety 1996; 14:394-405
58. Lillieborg S. Integrated Summary of Effectiveness Data. EMLA® Cream as a Topical Anesthetic of Intact Skin in Geriatric Patients.Astra Report 802-540-LC-0141, August 20, 1999.
59. Lillieborg S, Floderus E. Integrated Summary of Safety. EMLA® Cream and EMLA® Anesthetic Disc as Topical Anesthetics of Intact Skin in Geriatric Patients.Astra Report 802-540-LC-0142, August 19, 1999.
60. Wahlgren C-F. Expert Report. Clinical documentation for reclassification of EMLA® cream 5% and EMLA® patch from medical prescription products to non-prescription products.Astra Report No. 802-540-LC-0137, June 16, 1999.
61. Halperin SA. A randomised, double-blind, placebo-controlled trial to evaluate the antibody response to immunisation with diphteria-tetanus-pertussis-inactivated poliovirus-Haemophilus influenzae b and hepatitis B vaccines using EMLA® patch for the reduction of pain associated with intramuscular injection in infants from birth to six months of age.Astra Report No. 802-540-LC-0145-01, November 11, 1999.
62. Huledal G. Summary on pharmacokinetics of lidocaine and prilocaine following topical application of EMLA® to intact skin in geriatric patients.Astra Report No. 802-540-LC-0140-01, August 20, 1999.
63. Björkheden CA. Nonclinical safety data on local anaesthetics (bupivacaine, ropivacaine, mepivacaine, lidocaine, prilocaine, lidocaine and prilocaine combination).Astra Report No. 98373-01, December 4, 1998
64. Barret M, Major M, Gasslander U. Stability Report for EMLA® Patch 5% with Carbopol 974P. Up to 9 months data.Document No. A004320, November 28, 2001.
65. Jansson J-R, Bolcsfoldi G. Justification Document Clinical Risk Assessment of Genotoxic or Carcinogenic effect of 2,6-xylidine from the Medical use of AstraZeneca Lidocaine containing Local Anaesthetic products in Man. April 2005 [PAIN.000-079-847]
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