title: Novel topical formulation of lidocaine provides significant pain relief for intrauterine device insertion: pharmacokinetic evaluation and randomized placebo-controlled trial.
abstract: OBJECTIVE
  To investigate the pharmacokinetics, safety, and analgesic efficacy of a novel topical formulation of lidocaine at insertion of an intrauterine device (IUD).
  
  
  METHODS
  Randomized controlled trial; phase-I and phase-II studies.
  
  
  METHODS
  University and public hospitals.
  
  
  METHODS
  Women aged ≥18 years who wanted to receive an IUD. Four women were parous in phase I; all in phase II were nulliparous.
  
  
  METHODS
  A single, 8.5-mL dose of lidocaine formulation (SHACT) was administered (to the portio, cervix, and uterus) with a specially designed applicator.
  
  
  METHODS
  The phase-I study (single-arm) was designed for pharmacokinetic assessment; the phase-II study (randomized) was intended for investigation of efficacy and safety.
  
  
  RESULTS
  From the phase-I study (15 participants), mean pharmacokinetic values were: maximum plasma concentration: 351 ± 205 ng/mL; time taken to reach maximum concentration: 68 ± 41 minutes; and area under the concentration-time curve from 0 to 180 minutes: 717 ± 421 ng*h/mL. Pain relief was observed with lidocaine vs. placebo in the phase-II study (218 women, randomized). Mean visual analog scale score for maximum pain during the first 10 minutes after IUD insertion was 36% lower with lidocaine than with placebo (28.3 ± 24.6 vs. 44.2 ± 26.0). Pain intensity was also significantly lower in the lidocaine group at 30 minutes. On average, 3 of 4 patients will have less pain with lidocaine than with placebo. Adverse events were similar in the placebo and lidocaine groups. No serious adverse events were reported.
  
  
  CONCLUSIONS
  Lidocaine provides pain relief lasting for 30-60 minutes for women undergoing IUD insertion, without any safety concerns. Further studies of this lidocaine formulation, for IUD insertion and other clinical applications, are planned.
  
  
  BACKGROUND
  2011-005660-18 and 2011-006220-20 (EudraCT).
authors.affiliation: Division of Obstetrics and Gynecology, Department of Woman and Child Health, Karolinska Institute, Stockholm, Sweden.
authors.forename: Sara
authors.initials: S
authors.lastname: Tornblom-Paulander
authors.affiliation: Division of Obstetrics and Gynecology, Department of Woman and Child Health, Karolinska Institute, Stockholm, Sweden.
authors.forename: Berith K
authors.initials: BK
authors.lastname: Tingåker
authors.affiliation: Department of Obstetrics and Gynecology, Norrköping, Sweden.
authors.forename: Agneta
authors.initials: A
authors.lastname: Werner
authors.affiliation: Department of Clinical and Experimental Medicine, Obstetrics and Gynecology, Linköping University, Linköping, Sweden.
authors.forename: Caroline
authors.initials: C
authors.lastname: Liliecreutz
authors.affiliation: Division of Obstetrics and Gynecology, Department of Woman and Child Health, Karolinska Institute, Stockholm, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Conner
authors.affiliation: Division of Obstetrics and Gynecology, Department of Woman and Child Health, Karolinska Institute, Stockholm, Sweden.
authors.forename: Hans
authors.initials: H
authors.lastname: Wessel
authors.affiliation: Division of Obstetrics and Gynecology, Department of Woman and Child Health, Karolinska Institute, Stockholm, Sweden. Electronic address: gunvor.ekman-ordeberg@ki.se.
authors.forename: Gunvor
authors.initials: G
authors.lastname: Ekman-Ordeberg
mesh_terms: D000287:Administration, Topical; D000328:Adult; D000779:Anesthetics, Local / Q000008:administration & dosage*; D002626:Chemistry, Pharmaceutical; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007434:Intrauterine Devices / Q000009:adverse effects*; D008012:Lidocaine / Q000008:administration & dosage*; D010146:Pain / Q000175:diagnosis / Q000453:epidemiology / Q000517:prevention & control*; D059408:Pain Management / Q000379:methods*; D010147:Pain Measurement / Q000187:drug effects* / Q000379:methods; D010865:Pilot Projects; D055815:Young Adult
chemical_list: D000779:Anesthetics, Local; D008012:Lidocaine
keywords: Intrauterine device; lidocaine; pain; pharmacokinetics; topical anesthetic