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Classification: A

Drug products: Citanest®, Denela, Emla, EMLA®, Fortacin, Lidokain/Prilokain Alternova, Lidokain/Prilokain Ebb, Oraqix, Prilotekal, Takipril, Takipril®, Tapin, Xylonest

ATC code: N01BB04, N01BB20

Substances: prilocaine, prilocaine hydrochloride


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.
One single study reported sex differences of prilocaine for spinal anesthesia and where women were found to have a higher risk for urinary retention.

Additional information

The prevalence of several clinical pain conditions is higher in women than in men. Differences in pharmacokinetics, sex hormones, stress response, or socio-cultural aspects may be of importance [1-3]. Therefore, sex and gender differences of pain medications are difficult to interpret [4].

Pharmacokinetics and dosing

No studies with a clinically relevant sex analysis regarding pharmacokinetics of prilocaine have been found.


All retrieved publications on possible sex differences in efficacy of the local anaesthetic prilocaine refer to the cutaneous ointment which contains 25 mg/g prilocaine and 25 mg/g lidocaine. However, there are conflicting data regarding sex differences on EMLA.

 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 a study of patients undergoing ambulatory lower limb surgery who received spinal anesthesia using hyperbaric prilocaine 2% (60 mg) (49 men, 37 women), the incidence of urinary retention after prilocaine was significantly higher in women (37.8%; 14/37 patients) than in men (12.2%; 6/49). Female sex was an independent risk factor for catheterization with an OR of > 4 [14].

Reproductive health issues

Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (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 [15].

Updated: 2022-12-22

Date of litterature search: 2019-07-20


  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. Bartley EJ, Fillingim RB. Sex differences in pain: a brief review of clinical and experimental findings. Br J Anaesth. 2013;111(1):52-8. PubMed
  3. Sorge RE, Totsch SK. Sex Differences in Pain. J Neurosci Res. 2017;95(6):1271-1281. PubMed
  4. Dance A. Why the sexes don't feel pain the same way. Nature. 2019;567(7749):448-450. PubMed
  5. EMLA (lidocaine/prilocaine). Summary of Product Characteristics. Swedish Medical Products Agency [updated 2018-01-31, cited 2019-07-20]
  6. EMLA (lidocaine/prilocaine). Drugs.com [www]. [updated 2019-05-01, cited 2019-07-20]. länk
  7. Lim S, Julliard K. Evaluating the efficacy of EMLA topical anesthetic in sealant placement with rubber dam. Pediatr Dent. 2004;26:497-500. PubMed
  8. 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
  9. 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
  10. 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
  11. 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
  12. 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
  13. 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
  14. 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
  15. 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
  16. Kreutziger J, Frankenberger B, Luger TJ, Richard S, Zbinden S. Urinary retention after spinal anaesthesia with hyperbaric prilocaine 2% in an ambulatory setting. Br J Anaesth. 2010;104(5):582-6. PubMed
  17. 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
  18. Concise (INSIKT). Kalmar: eHälsomyndigheten. 2018 [cited 2019-03-14.] länk

Authors: Carl-Olav Stiller, Linnéa Karlsson Lind

Reviewed by: Mia von Euler

Approved by: Karin Schenck-Gustafsson