Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral, as acetate:
Ella: 30 mg
Pharmacology
Mechanism of Action
Prevents progestin from binding to the progesterone receptor. Ulipristal postpones follicular rupture when administered prior to ovulation, thereby inhibiting or delaying ovulation. May also alter the normal endometrium, impairing implantation. When used for the treatment of signs and symptoms of uterine fibroids, ulipristal reduces the size of uterine fibroids by inhibiting cellular proliferation and inducing apoptosis.
Pharmacokinetics/Pharmacodynamics
Absorption
Rapid
Metabolism
Hepatic via CYP3A4; forms monodemethylated metabolite (active) and inactive metabolites
Excretion
Feces (primary route of elimination); urine (<10%)
Time to Peak
Serum: 1 hour (ulipristal and monodemethylated metabolite)
Half-Life Elimination
Ulipristal: ~32 to 38 hours; Monodemethylated metabolite: ~27 hours
Protein Binding
Ulipristal: >98% to plasma proteins including albumin, alpha1-acid glycoprotein, high-density lipoprotein, and low-density lipoprotein
Use in Specific Populations
Special Populations: Race
Exposure in South Asian patients may exceed that in white and black patients. However, no difference in efficacy and safety was observed.
Use: Labeled Indications
Emergency contraception (ella): Prevention of pregnancy following unprotected intercourse or a known or suspected contraceptive failure. Ulipristal is not intended for routine use as a contraceptive.
Uterine fibroids (Fibristal [Canadian product]): Treatment of moderate to severe signs/symptoms of uterine fibroids in adult women of reproductive age who are eligible for surgery; intermittent treatment of moderate to severe signs/symptoms of uterine fibroids in adult women of reproductive age
Contraindications
ella: Pregnancy (known or suspected)
Canadian labeling: Additional contraindications (not in US labeling):Hypersensitivity to ulipristal or any component of the formulation
Fibristal [Canadian product]: Hypersensitivity to ulipristal or any component of the formulation; pregnancy; breastfeeding; genital bleeding of unknown etiology or for reasons other than uterine fibroids; cancer of the breast, cervix, uterus, or ovaries; hepatic disease (current or history of)
Dosage and Administration
Dosing: Adult
Emergency contraception (ella): Oral: 30 mg as soon as possible, but within 120 hours (5 days) of unprotected intercourse or contraceptive failure.
Uterine fibroids (Fibristal [Canadian product]): Females (premenopausal): Oral: 5 mg once daily for 3 consecutive months (each course of therapy is limited to 3 months). Initiate the first treatment course within the first 7 days of menstruation; initiate subsequent treatment courses, at the earliest, the first week of the second menstruation following completion of the prior treatment course. The recommended treatment-free interval between treatment courses is 2 menstrual cycles. Repeated intermittent treatment has been studied up to 4 intermittent courses.
Dosing: Geriatric
Not indicated for use in postmenopausal women.
Dosing: Pediatric
Emergency contraception (ella): Oral:
Children and Adolescents (prepubertal): Not indicated for use prior to menarche.
Adolescents (postpubertal): Refer to adult dosing.
Administration
Oral:
ella: Administer with or without food at any time during menstrual cycle. If vomiting occurs within 3 hours of administration, consider repeating dose.
Fibristal [Canadian product]: Administer with water and with or without food; initiate during the first 7 days of menstrual cycle.
Storage
ella: Store at 20°C to 25°C (68°F to 77°F). Protect from light.
Fibristal [Canadian product]: Store at 15°C to 30°C (59°F to 86°F). Protect from light.
Drug Interactions
Barbiturates: May decrease the serum concentration of Ulipristal. Avoid combination
Bosentan: May decrease the serum concentration of Ulipristal. Avoid combination
CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
CYP3A4 Inducers (Strong): May decrease the serum concentration of Ulipristal. Avoid combination
CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Ulipristal. Management: This is specific for when ulipristal is being used for signs/symptoms of uterine fibroids (Canadian indication). When ulipristal is used as an emergency contraceptive, patients receiving this combination should be monitored for ulipristal toxicity. Avoid combination
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Ulipristal. Management: This is specific for when ulipristal is being used for signs/symptoms of uterine fibroids (Canadian indication). When ulipristal is used as an emergency contraceptive, patients receiving this combo should be monitored for ulipristal toxicity. Avoid combination
Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
Efavirenz: May decrease the serum concentration of Ulipristal. Avoid combination
Erdafitinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
Felbamate: May decrease the serum concentration of Ulipristal. Avoid combination
Griseofulvin: May decrease the serum concentration of Ulipristal. Avoid combination
Ivosidenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
Lorlatinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Avoid concurrent use of lorlatinib with any CYP3A4 substrates for which a minimal decrease in serum concentrations of the CYP3A4 substrate could lead to therapeutic failure and serious clinical consequences. Consider therapy modification
OXcarbazepine: May decrease the serum concentration of Ulipristal. Avoid combination
Progestins: May diminish the therapeutic effect of Ulipristal. Ulipristal may diminish the therapeutic effect of Progestins. Management: Ulipristal for uterine fibroids (Canadian indication): avoid progestins within 12 days of stopping ulipristal; as emergency contraceptive (U.S. indication): avoid progestins within 5 days of stopping ulipristal. Avoid combination
Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
St John's Wort: May decrease the serum concentration of Ulipristal. Avoid combination
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
Topiramate: May decrease the serum concentration of Ulipristal. Avoid combination
Adverse Reactions
Emergency contraception (ella):
>10%:
Central nervous system: Headache (18% to 19%)
Endocrine & metabolic: Suppressed menstruation (≥7 days later than expected: 19%)
Gastrointestinal: Abdominal pain (8% to 15%), nausea (12% to 13%)
Genitourinary: Dysmenorrhea (7% to 13%)
1% to 10%:
Central nervous system: Fatigue (6%), dizziness (5%)
Endocrine & metabolic: Intermenstrual bleeding (9%)
Genitourinary: Early menses (≥7 days earlier than expected: 7%)
Postmarketing and/or case reports: Acne vulgaris
Treatment of moderate-to-severe signs/symptoms of uterine fibroids (Fibristal [Canadian product]):
>10%:
Central nervous system: Headache (1% to 16%)
Endocrine & metabolic: Hot flash (1% to 25%)
1% to 10%:
Cardiovascular: Edema (≤1%), hypotension (≤1%), sinus bradycardia (≤1%)
Central nervous system: Fatigue (≤4%), vertigo (≤4%), insomnia (≤2%), dizziness (1%), aggressive behavior (≤1%), drowsiness (≤1%), emotional lability (≤1%), migraine (≤1%), sleep disorder (≤1%)
Dermatologic: Night sweats (≤2%), acne vulgaris (≤1%), alopecia (≤1%), seborrhea (≤1%), xeroderma (≤1%)
Endocrine & metabolic: Hypercholesterolemia (3%), hypertriglyceridemia (≤3%), hypothyroidism (≤2%), obesity (1%), amenorrhea (≤1%), increased gamma-glutamyl transferase (≤1%), ovarian cyst (≤1%), ovarian hyperstimulation (≤1%), thyroid disease (≤1%)
Gastrointestinal: Nausea (3%), constipation (1%), dyspepsia (≤1%), upper abdominal pain (≤1%)
Genitourinary: Mastalgia (2%), pelvic pain (1% to 2%), endometrial hyperplasia (≤2%), genital bleeding (≤2%), breast swelling (≤1%), breast tenderness (≤1%), genital discharge (≤1%), uterine disease (≤1%), uterine hemorrhage (≤1%), vaginal dryness (≤1%), vulvovaginal candidiasis (≤1%)
Infection: Herpes virus infection (≤1%)
Neuromuscular & skeletal: Arthralgia (2%), muscle spasm (≤2%), back pain (≤1%), limb pain (≤1%)
Respiratory: Dyspnea (≤1%), epistaxis (≤1%), pharyngitis (≤1%)
Miscellaneous: Fever (≤1%)
Warnings/Precautions
Concerns related to adverse effects:
- Bleeding irregularities: Menstrual bleeding patterns may be altered (cycle length may be delayed or shortened by a few days), but returns to normal in subsequent cycles. Intermenstrual bleeding (spotting) has also been observed. The possibility of pregnancy should be considered if menstruation is delayed for >7 days of the expected menstrual period. In the treatment of uterine fibroids with Fibristal [Canadian product], a significant reduction in menstrual blood loss or amenorrhea is usually observed within 10 days of initiation; menses generally returns within 4 weeks after discontinuation.
- Endometrial thickening: Endometrial thickening has been observed with use of Fibristal [Canadian product] in the treatment of uterine fibroids; effects are reversible following discontinuation of therapy. Persistent endometrial thickening (>3 months after discontinuation of therapy and return of menses) should be further evaluated. Changes in endometrial tissue observed with use are referred to as progesterone receptor modulator-associated endometrial changes; may be mistaken for endometrial hyperplasia. Pathologists should be informed of ulipristal therapy when submitting endometrial tissue for histologic evaluation.
- Hepatic impairment: Fibristal [Canadian product]: May cause liver injury, including serious cases requiring liver transplantation; onset may vary. Use is contraindicated in patients with a history of or current hepatic disease (including baseline ALT or AST >2 times ULN). Monitor LFTs within 4 weeks of treatment initiation, monthly during treatment, 2 to 4 weeks after stopping treatment, and as clinically indicated during and after treatment. Discontinue treatment if ALT or AST >3 times ULN and further evaluate for liver injury.
Disease related concerns:
- Asthma: Fibristal [Canadian product] is not recommended in patients with severe uncontrolled asthma.
Special populations:
- Pediatric: Not for use prior to menarche.
- Postmenopausal women: Not indicated for use in postmenopausal women.
Concurrent drug therapy issues:
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
Other warnings/precautions:
- Appropriate use: Not intended for routine contraception. Repeated use within the same menstrual cycle is not recommended.
- Ectopic pregnancy: A history of ectopic pregnancy is not a contraindication to use in emergency contraception. The possibility of ectopic pregnancy should be considered in patients if pregnancy occurs after treatment or in patients with lower abdominal pain after administration of ulipristal.
- Fertility: A return of fertility is likely to be rapid following treatment of ulipristal for emergency contraception. Efficacy of hormonal contraception may be decreased; hormonal contraception should not be initiated until ≥5 days after emergency contraception and barrier contraception is recommended immediately following use of ulipristal; barrier contraception should be continued throughout the same menstrual cycle. Any nonhormonal contraceptive may be started immediately after ulipristal (Curtis 2016a). A nonhormonal method of contraception is recommended for women receiving Fibristal [Canadian product] for the treatment of uterine fibroids.
- HIV infection protection: Does not protect against HIV infection or other sexually-transmitted diseases.
Monitoring Parameters
Evaluate for pregnancy or ectopic pregnancy if expected menses is delayed for ≥1 week following emergency contraception, or if lower abdominal pain (3 to 5 weeks after administration) or persistent irregular bleeding develops. A pregnancy test is recommended if withdrawal bleeding does not occur within 3 weeks following use as an emergency contraceptive (Curtis 2015a).
Fibristal [Canadian product]: Rule out pregnancy prior to treatment initiation; periodic monitoring of the endometrium; unexpected or persistent irregular bleeding; LFTs at baseline, within 4 weeks of treatment initiation, monthly during treatment, 2 to 4 weeks after stopping treatment, and as clinically indicated during and after treatment.
Pregnancy
Pregnancy Considerations
Use is contraindicated during a known or suspected pregnancy.
Isolated cases of major malformations have been reported following inadvertent use during pregnancy; however, data are not sufficient to determine a causal relationship and no pattern of adverse outcomes has been identified.
When used for emergency contraception, exclude pregnancy prior to therapy; ulipristal is not indicated for terminating an existing pregnancy. A rapid return of fertility is expected following use for emergency contraception; routine contraceptive measures should be initiated or continued following use to ensure ongoing prevention of pregnancy. Barrier contraception is recommended immediately following emergency contraception and throughout the same menstrual cycle; efficacy of hormonal contraceptives may be decreased. The manufacturer recommends waiting ≥5 days after taking ulipristal before resuming oral contraceptives. The CDC notes any contraceptive method may be started immediately after taking ulipristal; however, a barrier method should also be used for 14 days following the dose (or until menses occurs, whichever occurs first) (Curtis 2016a). The manufacturer labeling suggests that ulipristal may be less effective in females with BSA >30 kg/m2.
When ulipristal is used for treatment of uterine fibroids (Canadian labeling; not in US labeling) a nonhormonal method of contraception is recommended.
Patient Education
What is this drug used for?
- It is used to prevent pregnancy.
- It is used to treat fibroids of the uterus.
- It may be given to you for other reasons. Talk with the doctor.
Frequently reported side effects of this drug
- Headache
- Dizziness
- Nausea
- Abdominal pain
- Loss of strength and energy
- Menstrual pain
- Menstrual changes
- Hot flashes
Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:
- Abnormal vaginal bleeding
- Groin or pelvic pain or swelling
- Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.
Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.
Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.
