ulipristal acetate (ellaOne) postcoital contraception

Last edited 03/2021 and last reviewed 03/2021

• 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)

• Informed consent not given.  Individuals under 16 years old and assessed as lacking capacity to consent using the Fraser Guidelines. Individuals 16 years of age and over and assessed as lacking capacity to consent. This episode of UPSI occurred more than 120 hours ago. N.B. A dose may be given if there have been previous untreated or treated episodes of UPSI within the current cycle if the most recent episode of UPSI is within 120 hours. Known or suspected pregnancy (N.B. a previous episode of UPSI in this cycle is not an exclusion. Consider pregnancy test if more than three weeks after UPSI and no normal menstrual period). Less than 21 days after childbirth. Less than 5 days after miscarriage, abortion, ectopic pregnancy or uterine evacuation for gestational trophoblastic disease (GTD). Known hypersensitivity to the active ingredient or to any component of the product - see Summary of Product Characteristics Use of levonorgestrel or any other progestogen in the previous 7 days (i.e. hormonal contraception, hormone replacement therapy or use for other gynaecological indications). Concurrent use of antacids, proton-pump inhibitors or H2-receptor antagonists. Severe asthma controlled by oral glucocorticoids. Individuals using enzyme-inducing drugs/herbal products or within 4 weeks of stopping. Acute porphyria

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
  .
• 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

  • 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
    
    

  Liver enzyme inhibitors

  • The effect of CYP3A4 inhibitors (e.g. ketoconazole, itraconazole, clarithromycin) may increase exposure to ulipristal, but the significance is uncertain
    
    

  Drugs that increase gastric pH

  • 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
    
    

  Other contraceptives

  • 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).