What is ulipristal, used for a female of reproductive age with a history of pregnancy, uterine fibroids, or other gynecological conditions?

What is Ulipristal?

Ulipristal is a selective progesterone receptor modulator (SPRM) that exists in two distinct formulations: ulipristal acetate 30 mg for emergency contraception (ella®) and ulipristal acetate 5 mg for treatment of symptomatic uterine fibroids. 1

Mechanism of Action

Ulipristal works by competing at progesterone receptor binding sites in a tissue-specific manner, producing both agonistic and antagonistic effects depending on the tissue type and receptor isoform (PR-A vs PR-B) present. 1

Key Pharmacological Effects:

• Direct antiproliferative and pro-apoptotic effects on leiomyoma (fibroid) cells 1
• Endometrial changes that reduce bleeding 1
• Inhibition of the pituitary luteinizing hormone surge, resulting in anovulation and amenorrhea 1
• Pharmacologically inhibits endometrial proliferation, which prevents pregnancy when used as emergency contraception 2

Clinical Applications

Emergency Contraception (30 mg formulation - ella®)

• The CDC highlights that ulipristal may be more effective than levonorgestrel formulations after the first 72 hours and for women who are overweight or obese 1
• Must be taken within 102 hours (approximately 5 days) of unprotected intercourse 3
• Important contraindication: Opill® (progestin-only contraceptive) should not be used for 5 days after using ella®, as this might reduce the ability of both medications to prevent pregnancy 4

Treatment of Uterine Fibroids (5 mg formulation)

Ulipristal acetate reduces both bleeding and bulk symptoms from fibroids and can be administered intermittently, allowing for menstruation during medication breaks. 1

Evidence of Efficacy:

• Efficacy of continuous use after 3 months and intermittent use for 2 years has been demonstrated in randomized controlled trials comparing to both placebo and GnRH agonists 1
• Reduces fibroid volume by 33-68% in clinical studies 5
• Faster than leuprolide in reducing fibroid-associated bleeding 6
• Significantly improves hemoglobin and hematocrit levels in anemic patients 6
• Maintains estradiol levels at mid-follicular phase range, thereby reducing hot flushes and having no impact on bone turnover (unlike GnRH agonists) 6

Treatment Protocol:

• Administered as 5 mg daily for periods of three months as a pre-surgical strategy, reducing bleeding and fibroid size and facilitating surgery 3
• A proportion of patients may avoid surgery entirely 3

Critical Safety Concerns

Hepatotoxicity Warning

Reports of hepatotoxicity are a barrier to ulipristal acetate's approval for fibroid treatment in the United States. 1

• Seek medical help immediately if yellowing of skin or whites of eyes develops, especially with fever, tiredness, loss of appetite, or dark-colored urine 4
• This represents a rare but serious medical condition requiring immediate evaluation 4

Contraindications (from FDA labeling):

• Do not use if you have or ever had breast cancer 4
• Do not use if already pregnant or think you may be pregnant 4
• Do not use together with another birth control pill, vaginal ring, patch, implant, injection, or IUD 4
• Do not use as emergency contraception if you are male 4

Important Drug Interactions:

Ulipristal effectiveness may be reduced when taken with medications for seizures (barbiturates, carbamazepine, oxcarbazepine, phenytoin, topiramate, primidone), tuberculosis (rifampin, rifabutin), pulmonary hypertension (bosentan), HIV/AIDS (efavirenz), or St. John's Wort. 4

Common Pitfalls to Avoid

Pregnancy Considerations:

• Despite its contraceptive mechanism, spontaneous pregnancy can occur during ulipristal acetate treatment for fibroids 2
• One documented case exists of spontaneous conception while on ulipristal acetate therapy, resulting in delivery of a healthy baby without drug-related complications 2
• Take a pregnancy test or talk to a doctor if period is late after missing any tablets, if you have not had a period for 2 months, or if you think you may be pregnant 4

Ectopic Pregnancy Risk:

Seek medical help immediately if sudden or severe persistent pain develops in the lower belly, mostly on one side, as this could indicate ectopic pregnancy. 4

Expected Menstrual Changes:

• Periods may become less or more frequent, shorter or longer, lighter or heavier 4
• Some women stop having periods while taking ulipristal 4
• Spotting or bleeding between periods is expected 4
• However, talk to a doctor if periods last more than 8 days or are unusually heavy, or if vaginal bleeding is repeatedly brought on by sex 4

Endometrial Changes:

Ulipristal can cause specific benign and reversible endometrial changes called PAEC (Progesterone Receptor Modulator-Associated Endometrial Changes). 7

Current Regulatory Status

While ulipristal acetate has demonstrated efficacy in randomized controlled trials for fibroid treatment, hepatotoxicity concerns remain a barrier to FDA approval for this indication in the United States. 1 The 30 mg formulation for emergency contraception remains FDA-approved. 1, 4