Ulipristal acetate
Encyclopedia
Ulipristal acetate is a selective progesterone receptor modulator
(SPRM) for emergency contraception
within 120 hours (5 days) after an unprotected intercourse
or contraceptive failure. It has shown to prevent about 60% of expected pregnancies, which is comparable to the emergency contraception scheme with levonorgestrel
. Ulipristal acetate is available by prescription only.
(EMA) in March 2009.
The U.S. Food and Drug Administration approved the drug for use in the United States on August 13, 2010, following the FDA advisory committee's recommendation. Watson Pharmaceuticals
announced the availability of ulipristal acetate in the United States on December 1, 2010, in retail pharmacies, clinics, and one on-line pharmacy, KwikMed
.
Ulipristal acetate is metabolized in the liver, most likely by CYP3A4
, and to a small extent by CYP1A2
and CYP2D6
. The two main metabolites have been shown to be pharmacologically active, but less than the original drug. The main excretion route is via the faeces.
ic as well as antagonistic
effects on the progesterone receptor
. It also binds to the glucocorticoid receptor
, but has no relevant affinity to the estrogen
, androgen
and mineralocorticoid receptor
s. Phase II clinical trial
s suggest that the mechanism might consist of blocking or delaying ovulation
and of delaying the maturation of the endometrium
.
, 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
. It is unlikely that Ellaone 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".
and temporary menstrual disorder
. Headache and nausea were observed under long-term administration (12 weeks), but not after a single dose.
or carbamazepine
, but this might not be clinically relevant because only a single dose of the drug is taken. It might also interact with levonorgestrel and other substrates of the progesterone receptor, as well as with glucocorticoids.
Selective progesterone receptor modulator
A selective progesterone receptor modulator is an agent that acts on the progesterone receptor. A characteristic that distinguishes such substances from receptor full agonists and full antagonists is that their action differs in different tissues...
(SPRM) for emergency contraception
Emergency contraception
Emergency contraception , or emergency postcoital contraception, refers to birth control measures that, if taken after sexual intercourse, may prevent pregnancy.Forms of EC include:...
within 120 hours (5 days) after an unprotected intercourse
Sexual intercourse
Sexual intercourse, also known as copulation or coitus, commonly refers to the act in which a male's penis enters a female's vagina for the purposes of sexual pleasure or reproduction. The entities may be of opposite sexes, or they may be hermaphroditic, as is the case with snails...
or contraceptive failure. It has shown to prevent about 60% of expected pregnancies, which is comparable to the emergency contraception scheme with levonorgestrel
Levonorgestrel
Levonorgestrel is a second generation synthetic progestogen used as an active ingredient in some hormonal contraceptives.-Chemistry:...
. Ulipristal acetate is available by prescription only.
History
Ulipristal acetate was granted marketing authorization by the European Medicines AgencyEuropean Medicines Agency
The European Medicines Agency is a European agency for the evaluation of medicinal products. From 1995 to 2004, the European Medicines Agency was known as European Agency for the Evaluation of Medicinal Products.Roughly parallel to the U.S...
(EMA) in March 2009.
The U.S. Food and Drug Administration approved the drug for use in the United States on August 13, 2010, following the FDA advisory committee's recommendation. Watson Pharmaceuticals
Watson Pharmaceuticals
Watson Pharmaceuticals, Incorporated is the 5th largest pharmaceutical company in the United States based on number of prescriptions dispensed...
announced the availability of ulipristal acetate in the United States on December 1, 2010, in retail pharmacies, clinics, and one on-line pharmacy, KwikMed
KwikMed
KwikMed is an approved online pharmacy in the United States which has been granted regulatory approval to operate and sell medications online. Based in Salt Lake City, Utah, KwikMed's parent company, Phoenix Capital Management, is located in Scottsdale, Arizona...
.
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 in the liver, most likely by CYP3A4
CYP3A4
Cytochrome P450 3A4 , a member of the cytochrome P450 mixed-function oxidase system, is one of the most important enzymes involved in the metabolism of xenobiotics in the body. CYP3A4 is involved in the oxidation of the largest range of substrates of all the CYPs. As a result, CYP3A4 is present in...
, and to a small extent by CYP1A2
CYP1A2
Cytochrome P450 1A2 , a member of the cytochrome P450 mixed-function oxidase system, is involved in the metabolism of xenobiotics in the body...
and CYP2D6
CYP2D6
Cytochrome P450 2D6 , a member of the cytochrome P450 mixed-function oxidase system, is one of the most important enzymes involved in the metabolism of xenobiotics in the body. Also, many substances are bioactivated by CYP2D6 to form their active compounds...
. The two main metabolites have been shown to be pharmacologically active, but less than the original drug. The main excretion route is via the faeces.
Pharmacodynamics
As a SPRM, ulipristal acetate has partial agonistPartial agonist
Partial agonists bind and activate a given receptor, but have only partial efficacy at the receptor relative to a full agonist...
ic as well as antagonistic
Receptor antagonist
A receptor antagonist is a type of receptor ligand or drug that does not provoke a biological response itself upon binding to a receptor, but blocks or dampens agonist-mediated responses...
effects on the progesterone receptor
Progesterone receptor
The progesterone receptor also known as NR3C3 , is an intracellular steroid receptor that specifically binds progesterone...
. It also binds to the glucocorticoid receptor
Glucocorticoid receptor
The glucocorticoid receptor also known as NR3C1 is the receptor to which cortisol and other glucocorticoids bind....
, but has no relevant affinity to the estrogen
Estrogen receptor
Estrogen receptor refers to a group of receptors that are activated by the hormone 17β-estradiol . Two types of estrogen receptor exist: ER, which is a member of the nuclear hormone family of intracellular receptors, and the estrogen G protein-coupled receptor GPR30 , which is a G protein-coupled...
, androgen
Androgen receptor
The androgen receptor , also known as NR3C4 , is a type of nuclear receptor that is activated by binding of either of the androgenic hormones testosterone or dihydrotestosterone in the cytoplasm and then translocating into the nucleus...
and mineralocorticoid receptor
Mineralocorticoid receptor
The mineralocorticoid receptor , also known as the aldosterone receptor or nuclear receptor subfamily 3, group C, member 2, is a protein that in humans is encoded by the NR3C2 gene that is located on chromosome 4q31.1-31.2.MR is a receptor with high affinity for mineralocorticoids...
s. Phase II clinical trial
Clinical trial
Clinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...
s suggest that the mechanism might consist of blocking or delaying ovulation
Ovulation
Ovulation is the process in a female's menstrual cycle by which a mature ovarian follicle ruptures and discharges an ovum . Ovulation also occurs in the estrous cycle of other female mammals, which differs in many fundamental ways from the menstrual cycle...
and of delaying the maturation of the endometrium
Endometrium
-Function:The endometrium is the innermost glandular layer and functions as a lining for the uterus, preventing adhesions between the opposed walls of the myometrium, thereby maintaining the patency of the uterine cavity. During the menstrual cycle or estrous cycle, the endometrium grows to a...
.
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.Pregnancy
Unlike levonorgestrel, and like mifepristoneMifepristone
Mifepristone is a synthetic steroid compound used as a pharmaceutical. It is a progesterone receptor antagonist used as an abortifacient in the first months of pregnancy, and in smaller doses as an emergency contraceptive. During early trials, it was known as RU-38486 or simply RU-486, its...
, 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
Abortifacient
An abortifacient is a substance that induces abortion. Abortifacients for animals that have mated undesirably are known as mismating shots....
in the package insert to avert off-label use
Off-label use
Off-label use is the practice of prescribing pharmaceuticals for an unapproved indication or in an unapproved age group, unapproved dose or unapproved form of administration...
. It is unlikely that Ellaone 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
Prostaglandin
A prostaglandin is any member of a group of lipid compounds that are derived enzymatically from fatty acids and have important functions in the animal body. Every prostaglandin contains 20 carbon atoms, including a 5-carbon ring....
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".
Lactation
It is not recommended to breast feed within 36 hours of taking the drug since it is not known whether ulipristal acetate or its metabolites are excreted into the breast milk.Side effects
Common side effects include abdominal painAbdominal pain
Abdominal pain can be one of the symptoms associated with transient disorders or serious disease. Making a definitive diagnosis of the cause of abdominal pain can be difficult, because many diseases can result in this symptom. Abdominal pain is a common problem...
and temporary menstrual disorder
Menstrual disorder
-Disorders of ovulation:Infrequent or irregular ovulation -Disorders of ovulation:Infrequent or irregular ovulation -Disorders of ovulation:Infrequent or irregular ovulation (usually defined as cycles of ≥36 days or -Disorders of ovulation:Infrequent or irregular ovulation (usually defined as...
. Headache and nausea were observed under long-term administration (12 weeks), but not after a single dose.
Interactions
No interaction studies have been conducted. Ulipristal acetate is likely to interact with substrates of CYP3A4, like St John's wortSt John's wort
St John's wort is the plant species Hypericum perforatum, and is also known as Tipton's Weed, Chase-devil, or Klamath weed....
or carbamazepine
Carbamazepine
Carbamazepine is an anticonvulsant and mood-stabilizing drug used primarily in the treatment of epilepsy and bipolar disorder, as well as trigeminal neuralgia...
, but this might not be clinically relevant because only a single dose of the drug is taken. It might also interact with levonorgestrel and other substrates of the progesterone receptor, as well as with glucocorticoids.