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Lidocaine - topical

Classification: A

Drug products: Denela, Emla, EMLA®, Instillagel®, Lidocaine Accord, Lidocaine Hydrochloride, Lidocaine Hydrochloride oral topical solution, USP (viscous) 2%, Lidocaine Viscous 2%, Lidodan Viscous, Lidoderm, Lidokain APL, Lidokain Ebb, Lidokain Mylan, Lidokain/Prilokain Alternova, Lidokainhydroklorid i Oral Cleaner APL, Lidokainhydroklorid APL, Maxilene, Oraqix, pms-Lidocaine Viscous 2%, Tapin, Versatis, Versatis®, Xylocain, Xylocain Pumpspray, Xylocain®, Xylocain® utan konserveringsmedel, Xylocain® viskös, Xylocaine, Xylocaine 2% Viscous, Xylocaine visqueuse, XYLOCAINE® VISCOUS 2%, Xyloproct®

ATC code: C05AA01, D04AB01, N01BB02, N01BB20

Summary

A number of studies report an effect comparison between men and women for the local treatment of lidocaine in combination with prilocaine. In some studies women have better effect than men, while other report the opposite and in some studies no sex difference is noticed.

Additional information

The scientific literature indicates that pain behavior and pain perception may vary between men and women. This could be influenced by differences in pharmacokinetics, sex hormones, differences in stress response, or type of pain test. Also, many variables other than a person’s sex/gender account for individual differences in pain sensitivity. The prevalence of several clinical pain conditions is higher in women than in men, which suggests that either different clinical pain mechanisms may operate in men vs. women, or different or additional risk factors are relevant in one sex, or a combination of differences [1]. Therefore, sex differences of pain releasing medication might thus be difficult to interpret [2].

Pharmacokinetics and dosing

A study in 52 volunteers (20 men, 32 women) measuring S-lidocaine levels after a standardized application of 23% lidocaine/7% tetracaine compounded anesthetic to the face found higher concentrations in men and also in persons with greater facial surface and non-white ethnicity [14]. In contrast to this, a study in persons with mild to moderate asthma, the lidocaine concentration after local administration in the upper airways before bronchoscopy (21 men, 30 women) was similar in men and women [15].

Effects

Studies analyzing sex differences in reduced pain after topical lidocaine treatment (alone or in combination) report contradictory results.

A chart review of patients undergoing phacoemulsification (40 men, 84 women) found a reduction in fentanyl requirements with the addition of intracameral lidocaine to topical anesthesia during cataract surgery independent of patient’s sex [16].  A randomized study in patients being subjected to peripheral i.v. cannulation (149 men, 141 women) showed less patient discomfort, measured with a visual analogue scale (VAS), in both men and women after administration of 0.1 mL of intradermal 1% lidocaine [17].  There are two small studies showing sex differences in the groups treated with topical lidocaine but not in the placebo groups. One randomized study used an algometer to test pressure pain in healthy volunteers (23 men, 21 women) and found men but not women to experience less pain in the lidocaine but not in the placebo group [18]. Together with age above 40 years and lower anxiety level before procedure, male sex was found to be associated with lower estimated pain on the VAS scale over-all in a randomized double-blind placebo-controlled study of the effect of local lidocaine before gastroscopy (119 men, 79 women) [19].

 Lidocaine/prilocaine combination

Studies report conflicting results regarding sex differences in pain scores from EMLA.

In a randomized trial in children 6-12 years (13 boys, 18 girls), EMLA (2.5% each of lidocaine and prilocaine [3, 4]) treatment before dental dam placement was found to be more effective than placebo in both boys and girls regardless of age [5]. Another placebo controlled pediatric study on the effect of EMLA to reduce pain during intravenous catheter insertion (26 boys, 31 girls aged 4-12) found a positive effect, regardless of patient’s age or sex [6]. In children with cerebral palsy (31 boys, 19 girls) undergoing botulinum toxin injections,no significant correlations were found between the patient’s sex and the pain rating scale CHEOPS Max [7].

Topical anaesthesia with EMLA or placebo during cardiac biopsy after cardiac transplantation (50 men, 19 women) did not affect pain differently in men vs women [8]. In a double-blind, placebo-controlled clinical trial the effect on 2,5 g of EMLA administration to patients undergoing fine needle aspiration of the thyroid nodules was evaluated (44 men, 6 women). EMLA treated patients experienced less pain regardless of patient’s sex. Although the male group was small, women reported more pain overall [9]. Similarly, a double-blind placebo controlled, randomized, prospective study on the effect of EMLA before digital ring block for surgery for ingrown big toenail (42 men, 39 women) found no effect of EMLA treatment over all but less pain in men in the EMLA group [10].

The opposite was found in a study of the effect of EMLA before cryotherapy for Human papillomavirus (HPV) (20 men, 20 women) where men reported higher pain scores in the EMLA group [11]. Also, in a cross-over study (20 women, 20 men) women treated with EMLA had significantly lower VAS for pain in association with insertion of a 30G needle and injection of a local anaesthetic compared to men [12]. Women demonstrated lower pain scores with EMLA than men in a double-blind randomized study (40 men, 24 women) over a 6-month period on pain caused by hair removal with a Nd:YAG 1,064 nm laser [13].

Adverse effects

In the pharmacokinetic study mentioned above (20 men, 32 women) cutaneous side effects after a standardized application of 23% lidocaine/7% tetracaine compounded anesthetic to the face was also evaluated. No difference between men and women in reporting of side effects was found [14].

Reproductive health issues

Regarding teratogenic aspects, please consult the Drugs and Birth Defects Database (in Swedish, Janusmed fosterpåverkan).

Other information

In a randomized, blinded study comparing topical amethocaine with EMLA before Port-a-Cath procedures in children (27 boys, 12 girls aged 5-16) no difference between boys or girls were found in their own or their parents pain assessment. However, nurses estimated the pain to be worse for boys and younger children [20].

Updated: 2019-10-07

Date of litterature search: 2019-07-20

References

  1. Greenspan JD, Craft RM, LeResche L, Arendt-Nielsen L, Berkley KJ, Fillingim RB et al. Studying sex and gender differences in pain and analgesia: a consensus report. Pain. 2007;132 Suppl 1:S26-45. PubMed
  2. Dance A. Why the sexes don't feel pain the same way. Nature. 2019;567(7749):448-450. PubMed
  3. EMLA (lidocaine/prilocaine). Summary of Product Characteristics. Swedish Medical Products Agency [updated 2018-01-31, cited 2019-07-20]
  4. EMLA (lidocaine/prilocaine). Drugs.com [www]. [updated 2019-05-01, cited 2019-07-20]. länk
  5. Lim S, Julliard K. Evaluating the efficacy of EMLA topical anesthetic in sealant placement with rubber dam. Pediatr Dent. 2004;26:497-500. PubMed
  6. Cordoni A, Cordoni LE. Eutectic mixture of local anesthetics reduces pain during intravenous catheter insertion in the pediatric patient. Clin J Pain. 2001;17:115-8. PubMed
  7. Brochard S, Blajan V, Lempereur M, Garlantezec R, Houx L, Le Moine P et al. Determining the technical and clinical factors associated with pain for children undergoing botulinum toxin injections under nitrous oxide and anesthetic cream. Eur J Paediatr Neurol. 2011;15(4):310-5. PubMed
  8. Leloudis DH, Kittleson MM, Felker GM, Rosenberg PB, Hernandez AF, Yager JE et al. Topical anesthesia with EMLA reduces pain during endomyocardial biopsy: a randomized trial. J Heart Lung Transplant. 2006;25(9):1164-6. PubMed
  9. Gursoy A, Ertugrul DT, Sahin M, Tutuncu NB, Demirer AN, Demirag NG. The analgesic efficacy of lidocaine/prilocaine (EMLA) cream during fine-needle aspiration biopsy of thyroid nodules. Clin Endocrinol (Oxf). 2007;66:691-4. PubMed
  10. Serour F, Ben-Yehuda Y, Boaz M. EMLA cream prior to digital nerve block for ingrown nail surgery does not reduce pain at injection of anesthetic solution. Acta Anaesthesiol Scand. 2002;46:203-6. PubMed
  11. Mansell-Gregory M, Romanowski B. Randomised double blind trial of EMLA for the control of pain related to cryotherapy in the treatment of genital HPV lesions. Sex Transm Infect. 1998;74:274-5. PubMed
  12. Franz-Montan M, de Paula E, Groppo FC, Silva AL, Ranali J, Volpato MC. Liposomal delivery system for topical anaesthesia of the palatal mucosa. Br J Oral Maxillofac Surg. 2012;50(1):60-4. PubMed
  13. Guardiano RA, Norwood CW. Direct comparison of EMLA versus lidocaine for pain control in Nd:YAG 1,064 nm laser hair removal. Dermatol Surg. 2005;31(4):396-8. PubMed
  14. McCleskey PE, Patel SM, Mansalis KA, Elam AL, Kinsley TR. Serum lidocaine levels and cutaneous side effects after application of 23% lidocaine 7% tetracaine ointment to the face. Dermatol Surg. 2013;39:82-91. PubMed
  15. Langmack EL, Martin RJ, Pak J, Kraft M. Serum lidocaine concentrations in asthmatics undergoing research bronchoscopy. Chest. 2000;117:1055-60. PubMed
  16. Ho AL, Zakrzewski PA, Braga-Mele R. The effect of combined topical-intracameral anaesthesia on neuroleptic requirements during cataract surgery. Can J Ophthalmol. 2010;45:52-7. PubMed
  17. Robinson PA, Carr S, Pearson S, Frampton C. Lignocaine is a better analgesic than either ethyl chloride or nitrous oxide for peripheral intravenous cannulation. Emerg Med Australas. 2007;19:427-32. PubMed
  18. Robinson ME, Riley JL, Brown FF, Gremillion H. Sex differences in response to cutaneous anesthesia: a double blind randomized study. Pain. 1998;77:143-9. PubMed
  19. Froehlich F, Schwizer W, Thorens J, Köhler M, Gonvers JJ, Fried M. Conscious sedation for gastroscopy: patient tolerance and cardiorespiratory parameters. Gastroenterology. 1995;108:697-704. PubMed
  20. Bishai R, Taddio A, Bar-Oz B, Freedman MH, Koren G. Relative efficacy of amethocaine gel and lidocaine-prilocaine cream for Port-a-Cath puncture in children. Pediatrics. 1999;104:e31. PubMed
  21. Concise (INSIKT). Kalmar: eHälsomyndigheten. 2018 [cited 2019-03-14.] länk

Authors: Mia von Euler, Linnéa Karlsson Lind

Reviewed by: Mia von Euler

Approved by: Karin Schenck-Gustafsson