Ulirpsital acetate is most commonly taken as an emergency contraceptive, and in smaller doses it is also used to treat uterine fibroids. It is sold under the brand name Ella in the United States and EllaOne in Europe. Emergency contraceptives are distinct from both daily contraceptives and abortion pills; they are neither used as everyday birth control nor for the complete termination of a pregnancy. Clinical trials indicate that ulipristal can prevent between 62 and 85 percent of expected pregnancies, making it more effective than earlier emergency contraceptives such as levonorgestrel.
Ulipristal is a selective progesterone receptor modulator (SPRM); it binds to the receptors of the hormone progesterone. A characteristic of selective modulator drugs is that they behave differently in certain tissues, agonizing (stimulating) the receptors in some and antagonizing (attenuating) them in others. Ulipristal's exact mechanism of action is in fact not thoroughly understood, although it was clear to the research pharmacists responsible for its development that progesterone is essential to the initiation of a pregnancy, and extensive clinical trials confirmed their hypothesis that ulipristal and other SPRMs can be effective contraceptives.
Twenty to eighty percent of women of childbearing age develop uterine fibroids, though the condition is often symptomless and typically abates on its own following menopause. They are a benign tumor of the uterus, but in some cases can cause particularly heavy periods, sometimes even leading to anemia if enough blood is lost. Uterine fibroids can also cause back or stomach pain, pain during menstruation or intercourse, and if they grow large enough, they may press against the bladder and cause a frequent need to urinate. They are a common cause of hysterectomies, but several drugs, including ulipristal, show great promise in nonsurgical treatment. Small doses of ulipristal are shown to reduce the size of uterine fibroids by often 70%, and in some cases it alone is used to manage the condition's symptoms. Clinical trials of women who were awaiting surgery for uterine fibroids indicated that over 90% of them found at least some relief from ulipristal. Ulipristal is effective in treating uterine fibroids because of its influence on the hormone progesterone, which is critical in determining the growth of the lining of the womb. The low dose version of ulipristal used to treat uterine fibroids is currently only available in Europe.
Ulipristal was first approved by the European Medicines Agency in 2009, then the American Food and Drug Administration a year later. Although various types of emergency contraceptives have been available since the 1960s and 70s, it was the first SPRM drug on the market. It is available by prescription only in the United States, but in the over 50 countries where ulipristal can now be found, many don't require a prescription, including the United Kingdom and Israel.
Ulipristal acetate is marketed for emergency contraception by Actavis, a child company of the multinational Teva Pharmaceuticals. A 5 mg version for treating uterine fibroids is sold as Esmya, but as of 2017 it is not yet approved for sale in the United States.
Although it's still a relatively new drug, ulipristal has been placed by the World Health Organization on its list of Essential Medicines, meaning that it's critical to public health; drugs on this list are regarded as thoroughly safe and effective if used as intended, and many governments around the world use this annually published list as a guide to shape their medical infrastructure. However, contraceptives remain an often controversial class of medicines, and many communities and societies continue to restrict access to them.
The most common side effects of ulipristal are flushing, headache, fatigue, lightheadedness, and nausea; about ten percent of users reported flushing during clinical trials. Users should call their doctor immediately if they experience sharp pains in their belly, especially if the pain is radiating from one side.
Many women using ulipristal or other emergency contraception find that their period begins earlier than expected, experience bleeding between periods, or have a particularly heavy period. If a woman's period is more than seven days late after using emergency contraception, she should take a pregnancy test and follow up with her doctor.
During clinical trials, a small number of patients experienced dizziness or lightheadedness after taking ulipristal that was itself negligible but impacted their ability to drive for several hours.
Allergic reactions to ulipristal are rare, but the manufacturer warns that they can occur. If users develop rashes, hives, or other symptoms of anaphylaxis after taking ulipristal, they should seek immediate medical attention.
For emergency contraception, women should take one 30 mg tablet as soon as possible after unprotected sex or a suspected failure of regular contraception, for up to five days. It can be taken with or without food, at any point in the woman's menstrual cycle. Users should never take more than a single dose.
If vomiting occurs within three hours of taking ulipristal, a doctor should be consulted to decide whether or not the woman should repeat her dose.
When used to treat uterine fibroids, a much lower dose -- 5 mg -- is taken daily for up to three months. Ulipristal treatment for uterine fibroids should begin during the first week of the patient's menstruation and then continue intermittently with at least one full menstrual cycle without ulipristal between each round. Clinical trials have examined this treatment method for up to four rounds. If patients taking ulipristal daily to treat uterine fibroids miss a dose, they should take it as early as they remember, unless the next dose is less than 12 hours away, in which case they should skip the missed dose and continue as usual; patients should not take extra doses to make up for missed ones.
The possibility of overdose on ulipristal is unclear. In clinical trials, single doses of up to 200 mg and daily 50 mg doses taken for ten days did not cause any significant reactions. However, these doses are far beyond what is necessary for either contraception or fibroid treatment.
Ulipristal's most dangerous interactions are with edoxaban, a drug used to treat deep vein thrombosis and pulmonary embolism as well as prevent strokes, and colchicine, used to treat gout; ulipristal can amplify the effects of these drugs to a dangerous degree. Patients using these drugs may need to reduce their dose of these drugs, or stop taking them altogether if using ulipristal, and should discuss this with their doctor.
Ulipristal is metabolized in the body by the enzyme CYP3A4, and it may interact with the wide variety of drugs that are substrates of that enzyme, including St. John's wort, carbamazepine, ritonavir, and phenytoin. Enzymes bond with substrates to change those substrates into new products before releasing them and then accepting new substrates; if two substrates are competing for the same enzyme, neither will work with full efficiency.
The availability of the CYP3A4 enzyme is also why women using ulipristal should not eat grapefruit or drink grapefruit juice; it is known to strongly inhibit the availability of this enzyme and thus impact the metabolism of ulipristal and many other drugs.
Ulipristal may temporarily reduce the effectiveness of hormonal contraceptives, especially those that rely solely on progestogens such as Depo-Provera and Nexplanon.
Ulipristal should never be taken by pregnant women; it is shown in animal studies to be explicitly embryotoxic and could cause severe birth defects. It is unknown whether or not ulipristal or any of its metabolites are secreted in breast milk, so the manufacturer recommends that women should not breastfeed for at least a day and a half after taking it.
Women with severe liver problems should not take ulipristal. Though it has not observed directly through clinical trials, pharmacists believe that since ulipristal is metabolized through an enzyme in the liver, it could either not function properly or exacerbate existing issues in patients with liver problems.
Women who take glucocorticoid steroids -- commonly used to treat severe asthma -- should avoid ulipristal because in animal trials it was shown to reduce the effectiveness of glucocorticoids.
Ulipristal has not been studied in men, children, adolescents under age 18, or postmenopausal women, and it is not intended for any of these groups. The European Medicines Agency has called for further research into its safety for post-pubescent adolescents since ulipristal could potentially be of great benefit to this group.
Like any oral contraceptive, ulipristal will not protect users from sexually transmitted diseases such as HIV or herpes and should never be used for this purpose; it is only to prevent unwanted pregnancies.
Ulipristal should be stored at room temperature, and protected from light. It should be kept dry, and thus not stored in bathrooms that become steamy when bathing. If stored properly, ulipristal should have a shelf life of approximately three years.
It is critically important to keep ulipristal out of reach from children and pets.
In the event that users must discard unused ulipristal, they should ask their pharmacist about proper disposal locations.
One of the newest emergency contraceptives on the market, ulipristal acetate is remarkably safe, clinically proven to be more effective than older drugs, and typically has fewer unpleasant side effects than similar drugs. In addition to emergency contraception, it is also one of the most promising non-surgical treatments for women facing symptomatic uterine fibroids.
Europe has been ahead of the United States in the development and approval of ulipristal; the Food and Drug Administration is still yet to approve its low-dose version for the treatment of uterine fibroids.
Ulipristal acetate has the potential to help millions of women, both with family planning and a common health problem, and hopefully communities around the world will heed the World Health Organization's recommendation and make it available to any woman who, following sound medical advice, decides she needs it.