Ulipristal acetate, sold under the brand name Ella among others, is a

medication A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy ( pharmacotherapy) is an important part of the medical field and ...

used for

emergency contraception Emergency contraception (EC) is a birth control measure, used after sexual intercourse to prevent pregnancy. There are different forms of EC. Emergency contraceptive pills (ECPs), sometimes simply referred to as emergency contraceptives (ECs), o ...

(birth control) and

uterine fibroids Uterine fibroids, also known as uterine leiomyomas or fibroids, are benign smooth muscle tumors of the uterus. Most women with fibroids have no symptoms while others may have painful or heavy periods. If large enough, they may push on the bl ...

. As emergency contraception it should be used within 120 hours of vaginally penetrating intercourse. For fibroids it may be taken for up to six months. It is taken

by mouth Oral administration is a route of administration where a substance is taken through the mouth. Per os abbreviated to P.O. is sometimes used as a direction for medication to be taken orally. Many medications are taken orally because they are i ...

. Common side effects include headache, nausea, feeling tired, and abdominal pain. It should not be used in women who are already pregnant. It is in the

selective progesterone receptor modulator A selective progesterone receptor modulator (SPRM) is an agent that acts on the progesterone receptor (PR), the biological target of progestogens like progesterone. A characteristic that distinguishes such substances from full receptor agonists (e ...

(SPRM) class of medications. It works by preventing the effects of progesterone, therefore preventing

ovulation Ovulation is the release of eggs from the ovaries. In women, this event occurs when the ovarian follicles rupture and release the secondary oocyte ovarian cells. After ovulation, during the luteal phase, the egg will be available to be fertilize ...

but not affecting

fertilization Fertilisation or fertilization (see spelling differences), also known as generative fertilisation, syngamy and impregnation, is the fusion of gametes to give rise to a new individual organism or offspring and initiate its development. Proce ...

or implantation. Ulipristal acetate was approved for medical use in the United States in 2010. It is on the

World Health Organization's List of Essential Medicines The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health s ...

Medical uses

Emergency contraception

For

a 30 mg tablet is used within 120 hours (5 days) after unprotected intercourse or contraceptive failure. It has been shown to prevent about 62–85% of expected pregnancies, and prevents more pregnancies than emergency contraception with levonorgestrel. Ulipristal acetate is available by prescription for emergency contraception in over 50 countries, with access through pharmacists without a prescription being tested in the United Kingdom. In November 2014, the European Medicines Agency (EMA) recommended availability of ellaOne emergency contraceptive without prescription in the European Union. In January 2015 the

European Commission The European Commission (EC) is the executive of the European Union (EU). It operates as a cabinet government, with 27 members of the Commission (informally known as "Commissioners") headed by a President. It includes an administrative body ...

issued an implementing decision amending accordingly the marketing authorization of EllaOne in the EU. Since July 2016, it is available without prescription in Israel.

Uterine fibroids

Ulipristal acetate is used for pre-operative treatment of moderate to severe symptoms of

in adult women of reproductive age. The use of ulipristal acetate to treat fibroids was suspended in the European Union in March 2020. In November 2020, the

Committee for Medicinal Products for Human Use The Committee for Medicinal Products for Human Use (CHMP), formerly known as Committee for Proprietary Medicinal Products (CPMP), is the European Medicines Agency's committee responsible for elaborating the agency's opinions on all issues regardin ...

(CHMP) of the European Medicines Agency (EMA) recommended that ulipristal acetate be used only to treat uterine fibroids in premenopausal women for whom surgical procedures (including uterine fibroid embolization) are not appropriate or have not worked. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged. In addition, the committee stated that ulipristal acetate must not be used for controlling symptoms of uterine fibroids while awaiting surgical treatment. Treatment of uterine fibroids with ulipristal acetate for 13 weeks effectively controlled excessive bleeding due to uterine fibroids and reduced the size of the fibroids. Two intermittent 3-months treatment courses of ulipristal acetate 10 mg resulted in amenorrhea at the end of the first treatment course in 79.5%, at the end of the second course in 88.5% of subjects. Mean myoma volume reduction observed during the first treatment course (−41.9%) was maintained during the second one (−43.7%). After two to four 3-months courses of treatment, UPA-treated fibroids shown about -70% in volume reduction. Volume reduction of uterine fibroid induced by ulipristal acetate was tentatively explained by the combination of multifactorial events involving control of proliferation of the tumor cells, induction of apoptosis and remodeling of the

extracellular matrix In biology, the extracellular matrix (ECM), also called intercellular matrix, is a three-dimensional network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide s ...

under the action of

matrix metalloproteinase Matrix metalloproteinases (MMPs), also known as matrix metallopeptidases or matrixins, are metalloproteinases that are calcium-dependent zinc-containing endopeptidases; other family members are adamalysins, serralysins, and astacins. The MMPs be ...

s. In May 2018, the European Medicines Agency (EMA) recommended measures to minimize the risk of rare but serious liver injury with ulipristal, including contraindication in women with known liver problems; liver tests before, during and after stopping treatment; a card for women to inform them about the need for liver monitoring and to contact their doctor should they develop symptoms of liver injury. In addition, use of the medicine for more than one treatment course has been restricted to women who are not eligible for surgery.

Contraindications

Ulipristal acetate should not be taken by women with severe liver diseases because of its CYP mediated metabolism. It has not been studied in women under the age of 18. It is also not recommended for women with severe asthma receiving

glucocorticoid Glucocorticoids (or, less commonly, glucocorticosteroids) are a class of corticosteroids, which are a class of steroid hormones. Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor that is present in almost every verteb ...

treatment because it has shown antiglucocorticoid effects in animal studies.

Pregnancy

Unlike levonorgestrel, and like

mifepristone Mifepristone, also known as RU-486, is a medication typically used in combination with misoprostol to bring about a medical abortion during pregnancy and manage early miscarriage. This combination is 97% effective during the first 63 days of ...

, ulipristal acetate is embryotoxic in animal studies. Before taking the drug, a pregnancy must be excluded. The EMA proposed to avoid any allusion to a possible use as an abortifacient in the package insert to avert

off-label use Off-label use is the use of pharmaceutical drugs for an unapproved indication or in an unapproved age group, dosage, or route of administration. Both prescription drugs and over-the-counter drugs (OTCs) can be used in off-label ways, although ...

. It is unlikely that ulipristal acetate could effectively be used as an abortifacient, since it is used in much lower doses (30 mg) than the roughly equipotent mifepristone (600 mg), and since mifepristone has to be combined with a prostaglandin for the induction of abortion. However, data on embryotoxicity in humans are very limited, and it is not clear what the risk for an abortion or for teratogenicity (birth defects) is. Of the 29 women studied who became pregnant despite taking ulipristal acetate, 16 had induced abortions, six had spontaneous abortions, six continued the pregnancies, and one was

lost to follow-up In the clinical research trial industry, loss to follow-up refers to patients who at one point in time were actively participating in a clinical research trial, but have become lost (either by error in a computer tracking system or by being unrea ...

Lactation

It is not recommended to breast feed within seven days of taking the drug since ulipristal acetate is excreted into the breast milk, and possible effects on the infant have not been studied.

Side effects

The most common side effects include headache, nausea (feeling sick), abdominal pain (stomach ache), and dysmenorrhea (period pains).

Interactions

Ulipristal acetate is metabolized by CYP3A4 in vitro. Ulipristal acetate is likely to interact with substrates of CYP3A4, like rifampicin,

phenytoin Phenytoin (PHT), sold under the brand name Dilantin among others, is an anti-seizure medication. It is useful for the prevention of tonic-clonic seizures (also known as grand mal seizures) and focal seizures, but not absence seizures. The in ...

St John's wort ''Hypericum perforatum'', known as St. John's wort, is a flowering plant in the family Hypericaceae and the type species of the genus '' Hypericum''. Possibly a hybrid between '' H. maculatum'' and '' H. attenuatum'', the species can be found ...

carbamazepine Carbamazepine (CBZ), sold under the trade name Tegretol among others, is an anticonvulsant medication used primarily in the treatment of epilepsy and neuropathic pain. It is used as an adjunctive treatment in schizophrenia along with other m ...

ritonavir Ritonavir, sold under the brand name Norvir, is an antiretroviral drug used along with other medications to treat HIV/AIDS. This combination treatment is known as highly active antiretroviral therapy (HAART). Ritonavir is a protease inhibitor ...

, therefore concomitant use with these agents is not recommended. It might also interact with hormonal contraceptives and

progestogens Progestogens, also sometimes written progestagens or gestagens, are a class of natural or synthetic steroid hormones that bind to and activate the progesterone receptors (PR). Progesterone is the major and most important progestogen in the bod ...

such as levonorgestrel and other substrates of the progesterone receptor, as well as with

glucocorticoids Glucocorticoids (or, less commonly, glucocorticosteroids) are a class of corticosteroids, which are a class of steroid hormones. Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor that is present in almost every vertebr ...

Pharmacology

Pharmacodynamics

As an SPRM, ulipristal acetate has

partial agonist In pharmacology, partial agonists are drugs that bind to and activate a given receptor, but have only partial efficacy at the receptor relative to a full agonist. They may also be considered ligands which display both agonistic and antagonis ...

ic as well as antagonistic effects on the progesterone receptor. Ulipristal acetate exhibits similar potency to antagonize progesterone receptor as

''in vitro''. It also binds to the androgen receptor and the

glucocorticoid receptor The glucocorticoid receptor (GR, or GCR) also known as NR3C1 (nuclear receptor subfamily 3, group C, member 1) is the receptor to which cortisol and other glucocorticoids bind. The GR is expressed in almost every cell in the body and regulates ...

, but is only a weak

antiandrogen Antiandrogens, also known as androgen antagonists or testosterone blockers, are a class of drugs that prevent androgens like testosterone and dihydrotestosterone (DHT) from mediating their biological effects in the body. They act by blocking the ...

and

antiglucocorticoid An antiglucocorticoid is a drug which reduces glucocorticoid activity in the body. They include direct glucocorticoid receptor antagonists such as mifepristone and synthesis inhibitors such as metyrapone, ketoconazole, and aminoglutethimide. ...

relative to

flutamide Flutamide, sold under the brand name Eulexin among others, is a nonsteroidal antiandrogen (NSAA) which is used primarily to treat prostate cancer. It is also used in the treatment of androgen-dependent conditions like acne, excessive hair grow ...

and

, respectively. Ulipristal acetate has no relevant

affinity Affinity may refer to: Commerce, finance and law * Affinity (law), kinship by marriage * Affinity analysis, a market research and business management technique * Affinity Credit Union, a Saskatchewan-based credit union * Affinity Equity Par ...

to the

estrogen Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal ac ...

and

mineralocorticoid receptor The mineralocorticoid receptor (or MR, MLR, MCR), also known as the aldosterone receptor or nuclear receptor subfamily 3, group C, member 2, (NR3C2) is a protein that in humans is encoded by the ''NR3C2'' gene that is located on chromosome 4q31 ...

s. Phase II

clinical trial Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, diet ...

s suggest that the mechanism might consist of blocking or delaying

and of delaying the maturation of the endometrium.

Pharmacokinetics

In animal studies, the drug was quickly and nearly completely absorbed from the gut. Intake of food delays absorption, but it is not known whether this is clinically relevant. Ulipristal acetate is

metabolized Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cell ...

in the

liver The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it ...

, most likely by CYP3A4, and to a small extent by

CYP1A2 Cytochrome P450 1A2 (abbreviated CYP1A2), a member of the cytochrome P450 mixed-function oxidase system, is involved in the metabolism of xenobiotics in the human body. In humans, the CYP1A2 enzyme is encoded by the ''CYP1A2'' gene. Function ...

and

CYP2D6 Cytochrome P450 2D6 (CYP2D6) is an enzyme that in humans is encoded by the ''CYP2D6'' gene. ''CYP2D6'' is primarily expressed in the liver. It is also highly expressed in areas of the central nervous system, including the substantia nigra. CYP2D ...

. The two main metabolites have been shown to be pharmacologically active, but less than the original drug. The main

excretion Excretion is a process in which metabolic waste is eliminated from an organism. In vertebrates this is primarily carried out by the lungs, kidneys, and skin. This is in contrast with secretion, where the substance may have specific tasks after ...

route is via the feces.

History

Ulipristal acetate was granted marketing authorization by the European Medicines Agency (EMA) in May 2009. In 2014, the EMA recommended ulipristal be made available without a prescription in the European Union. The U.S.

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...

(FDA) approved the drug for use in the United States on 13 August 2010, following the FDA advisory committee's recommendation. Watson Pharmaceuticals announced the availability of ulipristal acetate in the United States on 1 December 2010, in retail pharmacies, clinics, and one on-line pharmacy, KwikMed.

Society and culture

Brand names

Ulipristal acetate is marketed in the United States under the brand name Ella and in Canada under the brand name Fibristal. It is also marketed under the brand names EllaOne and Esmya in many countries including the United Kingdom and Ireland. A few less-widely used brand names also exist.

References

External links

* {{DEFAULTSORT:Ulipristal Acetate Acetate esters Dimethylamino compounds Antiprogestogens Antiglucocorticoids Embryotoxicants Dienes Diketones Hormonal contraception Norpregnanes Selective progesterone receptor modulators World Health Organization essential medicines Wikipedia medicine articles ready to translate