title: Instability of misoprostol tablets stored outside the blister: a potential serious concern for clinical outcome in medical abortion.
abstract: BACKGROUND
  Misoprostol (Cytotec) is recognised to be effective for many gynaecological indications including termination of pregnancy, management of miscarriage and postpartum haemorrhage. Although not licensed for such indications, it has been used for these purposes by millions of women throughout the world. Misoprostol tablets are most often packaged as multiple tablets within an aluminium strip, each within an individual alveolus. When an alveolus is opened, tablets will be exposed to atmospheric conditions.
  
  
  OBJECTIVE
  To compare the pharmaco technical characteristics (weight, friability), water content, misoprostol content and decomposition product content (type A misoprostol, type B misoprostol and 8-epi misoprostol) of misoprostol tablets Cytotec (Pfizer) exposed to air for periods of 1 hour to 720 hours (30 days), to those of identical non exposed tablets.
  
  
  METHODS
  Four hundred and twenty (420) tablets of Cytotec (Pfizer) were removed from their alveoli blister and stored at 25°C/60% relative humidity. Water content, and misoprostol degradation products were assayed in tablets exposed from 1 to 720 hours (30 days). Comparison was made with control tablets (N=60) from the same batch stored in non-damaged blisters. Statistical analyses were carried out using Fisher's exact test for small sample sizes.
  
  
  RESULTS
  By 48 hours, exposed tablets demonstrated increased weight (+4.5%), friability (+1 300%), and water content (+80%) compared to controls. Exposed tablets also exhibited a decrease in Cytotec active ingredient dosage (-5.1% after 48 hours) and an increase in the inactive degradation products (+25% for type B, +50% for type A and +11% for 8-epi misoprostol after 48 hours) compared to controls.
  
  
  CONCLUSIONS
  Exposure of Cytotec tablets to 'typical' European levels of air and humidity results in significant time-dependent changes in physical and biological composition that could impact adversely upon clinical efficacy. Health professionals should be made aware of the degradation of misoprostol with inappropriate storage of misoprostol tablets.
authors.affiliation: ICB - CNRS, Division MaNaPI, Département Nanosciences, Université de Bourgogne, Dijon, France.
authors.forename: Veronique
authors.initials: V
authors.lastname: Berard
authors.affiliation: Gynmed Clinic, Vienna, Austria; Department of Women's and Children's Health, Division of Obstetrics and Gynecology, Karolinska Institute and Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Christian
authors.initials: C
authors.lastname: Fiala
authors.affiliation: Chalmers Centre, NHS Lothian, Edinburgh, Scotland.
authors.forename: Sharon
authors.initials: S
authors.lastname: Cameron
authors.affiliation: Obstetric Service, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.
authors.forename: Teresa
authors.initials: T
authors.lastname: Bombas
authors.affiliation: San Filippo Neri Hospital, Rome, Italy.
authors.forename: Mirella
authors.initials: M
authors.lastname: Parachini
authors.affiliation: Department of Women's and Children's Health, Division of Obstetrics and Gynecology, Karolinska Institute and Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Kristina
authors.initials: K
authors.lastname: Gemzell-Danielsson
mesh_terms: D000020:Abortifacient Agents, Nonsteroidal / Q000737:chemistry*; D000028:Abortion, Induced; D004355:Drug Stability; D004356:Drug Storage; D005260:Female; D006801:Humans; D006813:Humidity; D016595:Misoprostol / Q000737:chemistry*; D011247:Pregnancy; D013607:Tablets
chemical_list: D000020:Abortifacient Agents, Nonsteroidal; D013607:Tablets; D016595:Misoprostol