Introduction
Ulipristal is a selective progesterone receptor modulator used for the purposes of emergency contraception (Ella) and for the treatment of uterine fibroids (Fibristal). It is a derivative of 19-norprogesterone and has both antagonistic and partial agonist activity at the progesterone receptor. It also binds to glucocorticoid receptor, however compared to mifepristone (a progesterone receptor antagonist), ulipristal is more tolerable and has lower glucocorticoid activity and better binding affinity.
Ulipristal is currently recommended as first line therapy for emergency contraception, due to improved efficacy and similar side effect profile as compared to the traditional use of levonorgestrel or the Yuzpe regimen. The exact mechanism of action for ulipristal is still currently debated, though there is evidence that it functions by inhibiting ovulation. A recent systematic review proclaimed that the majority of available evidence demonstrates an inhibitory effect on ovulation rather than a post-fertilization effect on the endometrium, which has been heavily debated due to ethical concerns related to abortion (Rosato et al, 2016). Nevertheless, current and ongoing research into the agent's mechanism of action as an emergency contraceptive continue to provide potentially plausible evidence that ulipristal may, in fact, elicit activity on the endometrium that prevents embryo implantation .
Uses
Ulipristal is a selective progesterone receptor modulator used for emergency contraception after unprotected intercourse or in a situation where a planned method of contraception has failed.
As the product Ella (available in Canada and the US), ulipristal is indicated for use as emergency contraception after unprotected intercourse or possible contraceptive failure when administered within 120 hours (5 days) after unprotected intercourse or a known or suspected contraceptive failure. As the product Fibristal (available in Canada), ulipristal is indicated for treatment of the signs and symptoms of uterine fibroids in adult women.
Associated Conditions
Pharmacodynamics
Ulipristal is a selective, reversible progestin receptor modulator and its tissue targets include the uterus, cervix, ovaries, and hypothalamus. Ulipristal may act as an agonist or antagonist in the presence or absence of progesterone based on the tissue target. If given mid-follicular phase, development of the follicle growth is delayed and estradiol concentrations decrease. If given at the time when luteinizing hormone peaks, follicular rapture is delayed by several days. If given early-luteal phase, a decrease in endometrial thickness can be observed.
Mechanism of Action
The exact mechanism of action of ulipristal has been heavily debated . On one hand, the majority of official prescribing information labels, monographs, and prior research studies for ulipristal indicated as an emergency contraceptive suggest that its primary mechanism of action revolves around inhibiting or delaying ovulation by suppressing surges in LH that result in the postponement of follicular rupture .
Conversely, some of the latest investigations pertaining to ulipristal's mechanism of action as an emergency contraceptive propose that it principally elicits its action by preventing embryo implantation, as opposed to preventing ovulation . Although previous investigations have shown that ulipristal essentially has the ability to prevent ovulation equivalent to placebo (ie. null effect or ability) when administered during LH peaks one to two days before ovulation, the agent still demonstrates a stable and consistently high contraceptive effect of approximately >=80% when used at this time . Subsequently, current studies attempt to investigate how ulipristal could elicit emergency contraception via ovulation prevention under circumstances where ovulation had already clearly been observed . Endometrial biopsy samples studied from such circumstances in such investigations subsequently show that the administered ulipristal causes endometrial tissue to become inhospitable and unsuitable for embryo implantation where a variety of genes characteristic of receptive, pro-gestational endometrium are downregulated .
Nevertheless, most if not all proposed mechanisms commonly agree that ulipristal ultimately demonstrates its pharmacological effects by binding to human progesterone receptors and prevents natural, endogenous progesterone from occupying such receptors . Regardless, however, considering current and on-going research into ulipristal's ability to prevent embryo implantation, the notion that the medication can elicit post-fertilization effects potentially raises alerts and/or ethical debates over the use of ulipristal owing to potential abortifacient activity , which is considered to be on par or equipotent to that of mifepristone . Attention should be drawn to the fact that some prescribing information, however, such as the US FDA label for ulipristal indicated for emergency contraception, has included new supplementary commentary since 2018 that directly warns about ulipristal not being indicated for termination of existing pregnancies and suggesting that ulipristal use may confer alterations to the endometrium that may affect implantation and contribute to efficacy .
In the treatment of fibroids, ulipristal has been shown to exert direct actions on fibroids reducing their size through inhibition of cell proliferation and induction of apoptosis.
Absorption
Tmax, healthy subjects, single oral dose = 60-90 minutes; Cmax, healthy subjects, single oral dose = 176 ± 89 ng/mL; AUC(0-∞), healthy subjects, single oral dose = 556 ± 260 ng·h/mL;
Protein Binding
>94% bound to plasma proteins such as albumin, alpha1-acid glycoprotein, lipoproteins (VLDL, LDL, and HDL- due to its lipophillic nature)
Half Life
Mean elimination half-life, single oral dose, healthy subject = 32.4 ± 6.3 hours
Clearance
Mean oral clearance, single oral dose, healthy subject (CL/F) = 76.8 ± 64.0L/h
Food Interactions
- Take with or without food. High-fat food increases drug absorption, but not to a clinically significant extent.
