ELLA

Indications

• Emergency contraception
• Postcoital contraceptive

Dosage

Children: Refer to the BNF for Children for appropriate paediatric dosing guidelines.

Adults: For emergency contraception, a single dose of 30 mg should be taken as soon as possible, ideally within 120 hours after unprotected intercourse or contraceptive failure.

Mechanism of action

The mechanism of action of ulipristal is primarily centered on its ability to inhibit or delay ovulation by suppressing luteinizing hormone (LH) surges, which are essential for follicular rupture. Additionally, ulipristal may prevent embryo implantation by altering endometrial tissue, making it inhospitable for a fertilized egg.

Pharmacodynamics

Ulipristal acts as a selective, reversible progestin receptor modulator, influencing various tissues such as the uterus, cervix, ovaries, and hypothalamus. Its effects can be tissue-specific, functioning as an agonist or antagonist depending on the presence of progesterone. It delays follicular development and reduces estradiol levels when administered in the mid-follicular phase. During the LH peak, it can delay follicular rupture, and in the early luteal phase, it reduces endometrial thickness.

Pharmacokinetics

Ulipristal has a molecular formula of C28H35NO3. It is absorbed rapidly after oral administration, with peak plasma concentrations occurring within a few hours. The drug is extensively metabolized in the liver, primarily through the cytochrome P450 system, and excreted mainly via the feces, with a smaller portion eliminated in urine. Its half-life is approximately 30 hours, allowing for effective dosing in emergency contraception scenarios.

Adverse effects

• Headache
• Nausea
• Abdominal pain
• Dizziness
• Fatigue
• Menstrual changes

Interactions

• etonogestrel: Severe (decreases efficacy)
• levonorgestrel: Severe (decreases efficacy)
• norethisterone: Severe (decreases efficacy)
• antacids: Unknown (decreases efficacy)
• apalutamide: Unknown (decreases efficacy)
• enzalutamide: Unknown (decreases efficacy)
• dronedarone: Unknown (increases exposure)
• antifungals, azoles: Unknown (increases exposure)
• cobicistat: Unknown (increases exposure)
• crizotinib: Unknown (increases exposure)

Precautions

• Use with caution in patients with liver impairment
• Monitor for potential interactions with hormonal contraceptives
• Assess for other medications that may alter the effectiveness

Pregnancy

Ulipristal is contraindicated in pregnancy as it may disrupt implantation and is not intended for use as a regular contraceptive method.

Breast-feeding

It is recommended to avoid breastfeeding for at least 24 hours after taking ulipristal to minimize exposure to the infant.

Storage

Store at room temperature (15-30°C). Protect from light and moisture.

Formulations

• Tablets: 30 mg

Indications

• Emergency contraception
• Uterine fibroids

Dosage

Children: Refer to BNF for Children for pediatric dosing guidance as specific dosing for children is not provided.

Adults: For emergency contraception, the recommended dose is 30 mg taken as soon as possible after coitus, but no later than 120 hours after. For the treatment of uterine fibroids, dosing is determined by expert supervision and may involve multiple treatment courses, with a maximum of 4 courses recommended.

Mechanism of action

Ulipristal acetate acts as a selective progesterone receptor modulator, primarily exerting its effects by binding to the progesterone receptor. This binding leads to a partial agonistic effect on the receptor, resulting in the modulation of progesterone-responsive pathways. Consequently, ulipristal acetate can inhibit ovulation by preventing the LH surge necessary for ovulation and altering the endometrial lining to prevent implantation.

Pharmacodynamics

The pharmacodynamics of ulipristal acetate involve its role as a selective modulator of the progesterone receptor, which helps in regulating reproductive processes. Its partial antagonist effect allows it to interfere with the action of endogenous progesterone, thereby affecting follicular development and maturation, and influencing the menstrual cycle. The timing of administration post-coitus is crucial for its effectiveness in emergency contraception.

Pharmacokinetics

Ulipristal acetate is rapidly absorbed after oral administration, with peak plasma concentrations occurring within 1-2 hours. It has a high bioavailability and is primarily metabolized in the liver. The elimination half-life is approximately 30 hours, allowing for sustained action. It is excreted mainly in the feces and urine. The pharmacokinetics can be affected by hepatic and renal impairment, necessitating caution in patients with such conditions.

Contra-indications

• Severe hepatic impairment
• Severe renal impairment
• Underlying liver disorders

Adverse effects

• Drowsiness
• Dry mouth
• Fever
• Flatulence
• Genital pain
• Dysmenorrhea
• Altered taste
• Thirst
• Angioedema
• Epistaxis
• Eye erythema
• Painful sexual intercourse
• Syncope

Precautions

• Monitor liver function tests before, during, and after treatment courses
• Avoid use in patients with severe hepatic impairment
• Discuss risks and benefits with patients before prescribing
• Use non-hormonal contraceptive methods during treatment for uterine fibroids

Pregnancy

Ulipristal acetate is not recommended during pregnancy. It is classified as a Category X drug due to potential risks to the fetus.

Breast-feeding

Avoid use while breastfeeding as it is present in milk.

Storage

Store at room temperature, away from moisture and heat. Keep out of reach of children.

Formulations

• Tablets: 30 mg

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.

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.