Ulipristal

Introduction Overview

Generic Name

ulipristal

Brand Name

Ella

Dosage Form

oral tablet (30 mg)

Drug Class

Progesterone receptor modulators

Pharmacokinetics

Absorption:
Ulipristal acetate is rapidly absorbed following oral administration. Peak plasma concentrations are usually achieved within 0.5 to 3 hours post-dose. Absolute bioavailability is moderate due to first-pass metabolism, but the drug is efficiently absorbed across the gastrointestinal tract. Food intake does not significantly affect the extent of absorption, allowing ulipristal to be administered with or without food without compromising efficacy.

Distribution:
After absorption, ulipristal demonstrates extensive tissue distribution. It has a high plasma protein binding rate, predominantly to albumin, estimated at over 98%, which influences its distribution volume and half-life. The drug distributes rapidly into reproductive tissues, critical for its mechanism of action. The apparent volume of distribution ranges from moderate to large, reflecting penetration into peripheral compartments.

Metabolism:
Ulipristal is extensively metabolized by the cytochrome P450 enzyme system, mainly CYP3A4, to pharmacologically active and inactive metabolites. The primary metabolic pathways involve oxidative transformations including demethylation and hydroxylation. These metabolites contribute to the drug’s overall pharmacodynamic profile. Concomitant use of CYP3A4 inducers or inhibitors can significantly impact ulipristal plasma levels, affecting both efficacy and safety.

Elimination:
Elimination of ulipristal occurs predominantly via hepatic metabolism followed by biliary and renal excretion. The terminal elimination half-life is approximately 32 hours, permitting sustained pharmacological activity after a single oral dose. Less than 20% of the drug and its metabolites are recovered unchanged in the urine. Fecal excretion of metabolites constitutes a significant proportion of elimination. The prolonged half-life supports its use within 120 hours after unprotected intercourse.

Dosage Forms

Available Dosage Forms:
- Oral tablet (30 mg): single-dose tablets formulated specifically for emergency contraception.

Dosages for Adults and Adolescents:
- Standard adult dose for emergency contraception: a single 30 mg oral tablet taken as soon as possible within 120 hours (5 days) after unprotected sexual intercourse or contraceptive failure.
- No standard repeated dosing; not intended or approved for regular contraceptive use.

Specific Patient Populations:
- Adolescents older than menarche can use the same 30 mg single-dose tablet.
- Not indicated in pregnancy or for individuals who are premenarcheal or postmenopausal.
- No dose adjustment established for hepatic or renal impairment; clinical use generally contraindicated in pregnancy.

Clinical Guidelines:
- If vomiting occurs within 3 hours post-dose, consider re-administration to ensure efficacy.
- Administration timing is critical; efficacy is higher the sooner the tablet is taken after unprotected sex.
- It is advised to avoid initiating hormonal contraceptives within 5 days following ulipristal use to prevent reduced efficacy.

Mechanism Of Action

Ulipristal is a selective progesterone receptor modulator (SPRM) that exerts its contraceptive effects primarily by modulating progesterone receptor activity in reproductive tissues. By binding to these receptors, ulipristal inhibits progesterone-induced processes essential for ovulation and implantation. Specifically, it blocks or delays the luteinizing hormone (LH) surge necessary for follicular rupture in the ovary, thereby preventing or postponing ovulation. This action is crucial since fertilization cannot occur without the release of the ovum.

On a cellular level, ulipristal binds with high affinity to progesterone receptors located in the hypothalamus and pituitary, leading to altered feedback regulation of gonadotropins and downstream suppression of ovulatory events. Additionally, ulipristal induces changes in the endometrial lining, decreasing receptivity and making it less suitable for implantation of a fertilized egg. These dual effects on ovulation and endometrial function underscore its utility as both an ovulation inhibitor and a post-fertilization contraceptive agent.

Biochemically, ulipristal competes with endogenous progesterone, attenuating its regulatory influence over gene expression related to follicular development and endometrial maturation. Unlike pure progesterone antagonists, ulipristal has mixed agonist/antagonist effects depending on tissue context and dosing, providing a tailored contraceptive mechanism with reduced systemic side effects.

Clinical studies have demonstrated that ulipristal significantly delays ovulation even when administered shortly before the LH surge, a window where other emergency contraceptives such as levonorgestrel are less effective. Comparative research indicates that ulipristal maintains contraceptive efficacy up to 120 hours post-unprotected intercourse, outperforming levonorgestrel-based emergency contraception in this regard. This mechanism confers a broader window for effective use and improved pregnancy prevention in clinical practice.

Pharmacological Actions

Selective modulation of progesterone receptors to inhibit ovulation.
Delay or blockage of the luteinizing hormone surge required for follicular rupture.
Alteration of endometrial receptivity to reduce implantation potential.
Mixed agonist and antagonist activity on progesterone-responsive tissues.
Rapid absorption and sustained systemic presence facilitating single-dose efficacy.
Reduction of progesterone-dependent gene expression in reproductive tissues.
No estrogen receptor interaction, minimizing estrogen-related adverse effects.
Emergency contraceptive action effective up to five days post-unprotected intercourse.
Does not interrupt established pregnancy; acts prior to implantation.
Metabolized through CYP3A4 pathway affecting duration and interactions.

Therapeutic Or Clinical Uses

Prevention of pregnancy after unprotected sexual intercourse.
Emergency contraception to be used within 120 hours (5 days) post-intercourse.
Use after known or suspected contraceptive failure, such as condom rupture.
Alternative to levonorgestrel-based emergency contraception, especially later in the 5-day window.
Not intended for routine, repeated, or primary contraception.
Utilized in patients who require non-estrogen emergency contraceptive options.
Recommended when timing of ovulation is uncertain and rapid intervention is needed.
Use in women of reproductive age who are not currently pregnant.
Off-label exploration in management of certain progesterone-related gynecologic disorders (under research).

Side Or Adverse Effects

Headache, commonly mild to moderate in intensity.
Dizziness and general fatigue or tiredness following administration.
Nausea and occasional vomiting; vomiting within 3 hours affects efficacy.
Abdominal or stomach pain, usually transient.
Menstrual irregularities including delayed or altered menstrual bleeding.
Potential for severe lower abdominal pain signaling possible ectopic pregnancy.
Rare hypersensitivity reactions such as urticaria, facial swelling, and respiratory difficulty.
No significant impact on long-term fertility when used for emergency contraception.
Uncommon reports of mood changes or breast tenderness.
No evidence of teratogenicity when not used during established pregnancy.

Precautions

Do not use if pregnancy is confirmed or suspected to avoid fetal harm.
Avoid use in individuals without established menstrual cycles or postmenopausal women.
Use barrier contraceptive methods after intake until next menstrual period to prevent pregnancy due to possible reduced efficacy of hormonal contraceptives.
Delay initiation of hormonal contraceptives by at least 5 days after ulipristal administration.
Consult physician if last menstrual period was over 4 weeks prior or if history of ectopic pregnancy exists.
Not recommended for repeated use as a contraceptive method.
Monitor patients for signs of severe abdominal pain after use to rule out ectopic pregnancy.
Exercise caution in patients with known hypersensitivity to ulipristal or similar agents.
Breastfeeding is not recommended during ulipristal treatment due to lack of safety data.
Advise patients on lack of protection against sexually transmitted infections; condom use remains essential.

Warnings

Should not be used as a regular contraceptive method for daily, weekly, or monthly use.
Potential teratogenic effects if used during pregnancy warrant strict avoidance in pregnant women.
Risk of ectopic pregnancy must be considered if severe unilateral lower abdominal pain occurs after use.
Concomitant use with hormonal contraceptives within 5 days may reduce effectiveness of both drugs.
Patients with delayed menstruation greater than one week post-use should undergo pregnancy testing.
Effectiveness may be impaired if vomiting occurs within 3 hours after dosing.
Drug interactions with CYP3A4 inducers or inhibitors may alter ulipristal plasma concentrations.
Not effective for prevention of sexually transmitted infections; barrier protection remains necessary.
Contraindicated in patients with known hypersensitivity to ulipristal acetate.
May have diminished efficacy in patients concurrently taking enzyme-inducing medications, necessitating alternative approaches.

Contraindication

Known or suspected pregnancy.
Hypersensitivity or allergic reaction to ulipristal or any component of the formulation.
Women who have not yet started menstruating (pre-menarcheal).
Postmenopausal women.
Patients with undiagnosed abnormal uterine bleeding until etiology is determined.
Concurrent use with hormonal contraceptives within 5 days post ulipristal dosing is contraindicated due to interaction risks.
History of ectopic pregnancy without adequate follow-up or monitoring.
Severe hepatic impairment (caution advised due to metabolism reliance on hepatic enzymes).
Use in conjunction with strong CYP3A4 inducers or inhibitors without medical supervision.
Not to be used for pregnancy termination.

Drug Interactions

CYP3A4 inducers (e.g., rifampin, carbamazepine, phenobarbital) reduce ulipristal effectiveness by increasing metabolism.
CYP3A4 inhibitors (e.g., ketoconazole) may increase ulipristal plasma levels, potentially enhancing adverse effects.
Concomitant use with hormonal contraceptives within 5 days may reduce efficacy of both ulipristal and hormonal methods.
Interactions with herbal supplements like St. John's Wort can decrease ulipristal plasma concentration.
Potential reduced efficacy when used with anticonvulsant drugs such as topiramate, oxcarbazepine, felbamate, phenytoin, and phenobarbital.
Bosentan may affect ulipristal metabolism altering its pharmacokinetics.
Drugs altering gastrointestinal motility or pH may potentially affect absorption.
No known interactions with non-steroidal anti-inflammatory drugs or antibiotics generally, but monitoring recommended.
Effects of ulipristal on other drugs not well studied; caution advised when combined with narrow therapeutic index drugs.
Patients should inform providers of all medications, including over-the-counter and herbal products, prior to use.

Preparations Of The Drug

Ella: Ulipristal acetate 30 mg oral tablet, standardized single-dose packaging for emergency contraception.
Available in blister packs designed for single-use administration.
Stored at room temperature, protected from moisture and light to maintain stability.
Manufactured to facilitate rapid dissolution and absorption.
No other common commercial preparations for routine contraceptive use currently approved.
No injectable, transdermal, or intrauterine formulations marketed as of current data.
Prescribed only under specific indications of emergency contraception with appropriate healthcare provider guidance.
Available globally under different brand names but Ella is predominant in United States and European markets.
Dispensed with patient education materials detailing timing, administration, and side effect profile.
Special handling or storage conditions generally not required beyond standard room temperature precautions.