Ella one

• Ulipristal acetate (ellaOne)
  • is a selective progesterone-receptor modulator that seems to be as effective as levonorgestrel for prevention of pregnancy. Ulipristal acetate may be used up to 120h after unprotected sexual intercourse or contraceptive failure
  • it is orally active and taken as a single dose

Mechanism of Action

• ulipristal acetate (also known as CDB-2914 and VA2914) is a synthetic steroid derived from 19-norprogesterone
  • is a selective progesterone receptor modulator (SPRM), a class of compounds that exert tissue-selective full agonist, antagonist or partial agonist effects at the progesterone receptor
  • ulipristal has been described as a second-generation SPRM. In vivo, ulipristal has much weaker antiglucocorticoid activity than mifepristone as a result of differences in their active metabolites
• primary mechanism of action is thought to be inhibition or delay of ovulation. A single midfollicular dose has been shown to suppress growth of lead follicles
  • administration just before, or in some cases just after, the luteinising hormone surge can inhibit follicular rupture
• endometrial changes may also play a role. Early luteal administration of ulipristal results in delayed endometrial maturation and alterations in progesterone-dependent markers of implantation
  • a mid-luteal dose has been shown to induce early endometrial bleeding in a dose-dependent manner
  • postulated that alterations to the endometrium may inhibit implantation by rendering the uterus less receptive to the trophoblast. However, it is not known if ulipristal has a direct endometrial effect or if the observed changes are a result of an ovarian effect

Dose and frequency of administration (4)

• One tablet (30mg) as a single dose taken as soon as possible up to 120 hours after UPSI.

Duration of Treatment (4)

• A single dose is permitted
• If vomiting occurs within 3 hours of ulipristal being taken a repeat dose can be supplied
• Repeated doses can be given within the same cycle. Please note:
  • If within 7 days of previous levonorgestrel offer levonorgestrel again (not ulipristal)
  • If within 5 days of ulipristal then offer ulipristal again (not levonorgestrel)

Criteria for exclusion (4)

Cautions including any actions to be taken (4):

• All individuals should be informed that insertion of a copper intrauterine device (Cu-IUD) within five days of UPSI or within five days from earliest estimated ovulation is the most effective method of emergency contraception. If a Cu-IUD is appropriate and acceptable supply oral EC and refer to the appropriate health service provider
  
  
• Ulipristal is ineffective if taken after ovulation
  
  
• If individual vomits within three hours from ingestion, arepeat dose may be given
  
  
• Body Mass Index (BMI) >26kg/m2 or weight >70kg - individuals should be advised that though oral EC methods may be safely used, a high BMI may reduce the effectiveness. A Cu-IUD should be recommended as the most effective method of EC
  
  
• Consideration should be given to the current disease status of those with severe malabsorption syndromes, such as acute/active inflammatory bowel disease or Crohn's disease. Although the use of ulipristal is not contra-indicated it may be less effective and so these individuals should be advised that insertion of Cu-IUD would be the most effective emergency contraception for them and referred accordingly if agreed
  
  
• Breast feeding - advise to express and discard breast milk for 7 days after ulipristal dose
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• The effectiveness of ulipristal can be reduced by progestogen taken in the following 5 days and individuals must be advised not to take progestogen containing drugs for 5 days after ulipristal
  
  
• If the individual is less than 16 years of age an assessment based on Fraser guidelines must be made and documented
  
  
• If the individual is less than 13 years of age the healthcare professional should speak to local safeguarding lead and follow the local safeguarding policy
  
  
• If the individual has not yet reached menarche consider onward referral for further assessment or investigation

Side effects or safety issues:

• most commonly reported side effects are abdominal pain and menstrual disorders (irregular vaginal bleeding, premenstrual syndrome, uterine cramps)
• study data have shown that the post-treatment cycle length is on average 2.9 days longer than the expected length
• some 7% of women reported a shortened cycle, and 19.2% reported an increase in cycle length of more than 7 days
• have been no associated adverse outcomes in the small numbers of inadvertent pregnancies that have occurred to date. The manufacturer has put a variety of measures in place to monitor outcomes of exposure during pregnancy

Drug interactions:

• Ulipristal is metabolised via cytochrome P450, in particular CYP3A4 Liver enzyme inducers Liver enzyme inhibitors Drugs that increase gastric pH Other contraceptives
  • CYP3A4 inducers (e.g. rifampicin, phenytoin, carbamazepine, ritonavir, St John's wort) may reduce plasma concentrations of ulipristal and may reduce efficacy - see linked item below for further information
    
    
  • The effect of CYP3A4 inhibitors (e.g. ketoconazole, itraconazole, clarithromycin) may increase exposure to ulipristal, but the significance is uncertain
    
    
  • Use of ulipristal with antacids, proton pump inhibitors and H2 receptor antagonists, or any other drugs that increase gastric pH, may reduce absorption of ulipristal and decrease efficacy
    
    
  • Ulipristal binds to progesterone receptors and so may reduce the efficacy of progestogen-containing contraceptives.

Reference:

• 1)Creinin MD et al. Progesterone receptor modulator for emergency contraception: a randomized controlled trial. Obstet Gynecol 2008;108:1089-1097
• 2) Fine P et al. Ulipristal acetate taken 48-120 hours after intercourse for emergency contraception. Obstet Gynecol. 2010 Feb;115(2 Pt 1):257-63.
• 3) FSRH (October 2009). Ulipristal Acetate (ellaOne®) - product review
• 4) Patient Group Direction (PGD) (NHS Specialist Pharmacy Service). Supply and/or administration of ulipristal acetate 30mg tablet for emergency contraception (Accessed 17th March 2021).