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  • CLASSES

    Emergency Contraceptives and Abortifacients

    DEA CLASS

    Rx

    DESCRIPTION

    Oral progesterone agonist/antagonist; available by prescription only
    1-dose emergency contraceptive that may be given up to 5 days following unprotected intercourse or suspected routine contraceptive failure
    Contraindicated during pregnancy; does not terminate existing pregnancy

    COMMON BRAND NAMES

    ella

    HOW SUPPLIED

    ella/Ulipristal/Ulipristal Acetate Oral Tab: 30mg

    DOSAGE & INDICATIONS

    For postcoital contraception after unprotected intercourse or a known or suspected contraceptive failure.
    Oral dosage
    Adult and Adolescent females

    30 mg (1 tablet) PO as soon as possible within 120 hours (5 days) of unprotected intercourse or a known or suspected contraceptive failure. If vomiting occurs within 3 hours of taking the tablet, consider repeating the dose. May administer at any time during the menstrual cycle. Safety and efficacy of repeat use within the same cycle has not been evaluated. Ulipristal is not intended for routine contraception and does not replace the need for routine contraception. After ulipristal use, initiate or resume hormonal contraception no sooner than 5 days after the intake of ulipristal and use a reliable barrier method until the next menstrual period. For known or suspected failure of hormonal contraception, refer to the hormonal contraceptive's prescribing information.

    For the treatment of uterine leiomyomata† (uterine fibroids†).
    Oral dosage
    Adult females

    5 or 10 mg PO once daily for up to 3 months has been studied in a double blind noninferiority trial. In the PEARL II trial, patients eligible for fibroid surgery were randomly assigned to 5 or 10 mg ulipristal PO once daily or 3.75 mg leuprolide IM once monthly. Following 13 weeks of treatment, both 5 and 10 mg daily doses of ulipristal were non-inferior to leuprolide (within a prespecified -20% margin) in controlling uterine bleeding. In addition, ulipristal was less likely to cause hot flashes than leuprolide. Surgical rates and types of surgery were similar across the treatment groups. Ulipristal 5 mg PO once daily is approved in Europe for the pre-operative treatment of moderate to severe symptoms of uterine fibroids in adult women of reproductive age. Therapy should be initiated during the first week of a menstrual cycle and should not exceed 3 months; no data are available on treatment beyond 3 months or on repeat courses of treatment.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    30 mg PO single dose for emergency postcoital contraception. If the patient vomits within 3 hours of first dose, a second 30 mg dose may be given; limit use to 1 course of treatment during any given menstrual cycle.

    Geriatric

    Safety and efficacy have not been established.

    Adolescents

    30 mg PO single dose for emergency postcoital contraception. If the patient vomits within 3 hours of first dose, a second 30 mg dose may be given; limit use to 1 course of treatment during any given menstrual cycle.

    Children

    Use before menarche is not indicated.

    Infants

    Not indicated.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    No dose adjustment is recommended when ulipristal is used as a single dose for post-coital emergency contraception. Guidelines note that the limited duration of use for emergency contraception would be expected to have less clinical impact in patients with liver dysfunction than with use of routine hormonal contraception. No dosage adjustments are needed with the chronic use of ulipristal for other indications in patients with mild hepatic impairment. In the absence of specific studies, the chronic use of ulipristal acetate is not recommended in patients with moderate or severe hepatic impairment unless the patient is closely monitored.

    Renal Impairment

    No dose adjustment is recommended in patients with renal impairment when ulipristal is used as a single dose for post-coital contraception. With chronic use for other indications, no dosage adjustment is recommended for patients with mild or moderate renal impairment. In the absence of specific studies, chronic use is not recommended in patients with severe renal impairment unless the patient is closely monitored.

    ADMINISTRATION

    Oral Administration
    Oral Solid Formulations

    Take with or without food.

    STORAGE

    ella:
    - Protect from light
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    - Store in outer carton when not in use

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Ulipristal should not replace a regular method of contraception. Repeated use of ulipristal within the same menstrual cycle is not recommended, as safety and efficacy of repeat use within the same cycle has not been evaluated.

    Ectopic pregnancy, pregnancy

    Ulipristal is contraindicated for use during an existing or suspected pregnancy. Ulipristal is not indicated for termination of an existing pregnancy. A history of ectopic pregnancy is not a contraindication for use; however, healthcare providers should consider the possibility of ectopic pregnancy in women who complain of lower abdominal pain or who become pregnant after taking ulipristal. A follow-up physical or pelvic examination is recommended if there is any doubt regarding the general health or pregnancy status of a woman taking ulipristal. During postmarketing studies with ulipristal, there was no signal of concern regarding pregnancy complications or outcomes. Known pregnancy outcomes were available for 462 of 784 pregnancies in which women received ulipristal at doses of 30 mg or greater during the conception cycle or during pregnancy. Data of pregnancies with known outcome were analyzed prospectively for 272 cases and retrospectively for 190 cases. Pregnancy outcomes included 302 elective abortions (2 for fetal anomalies including 1 with trisomy 21), 63 spontaneous abortions, and 13 ectopic pregnancies. No maternal or fetal deaths were reported. 84 pregnancies continued until birth, with congenital anomalies reported in 5 infants, including 4 major malformations (2/4 with genetic syndromes). These isolated cases of major malformations in ulipristal-exposed pregnancies do not provide sufficient data to determine a risk for birth defects with inadvertent use of ulipristal during pregnancy. However, the data show that ulipristal-exposed pregnancies were not associated with a pattern of increased risk of adverse outcomes. Miscarriage was reported in 14% of the known pregnancy outcomes; a rate that is similar to the U.S. background rate for miscarriage. In animal studies, embryofetal loss occurred in all rats and half of the rabbits receiving daily doses during organogenesis that were one-third and one-half the human exposure, respectively.

    Contraception requirements, menstrual irregularity

    A rapid return of fertility is likely following intake of ulipristal. Suggested contraception requirements are outlined in the manufacturer label. After use of ulipristal, a reliable barrier method of contraception should be used with subsequent acts of intercourse until the next menstrual period. After using ulipristal, if a woman wishes to initiate or resume hormonal routine contraception, she can do so no sooner than 5 days after ulipristal treatment; the patient should use a reliable barrier method until the next menstrual period. Progestin-containing contraceptives may impair the ability of ulipristal to delay ovulation. Advise women to follow the instructions on the initiation or resumption of hormonal contraceptives after ulipristal intake. Minor menstrual irregularity may occur in the next menses following treatment with ulipristal; the patient's menses may occur a few days earlier or later than expected. In clinical trials, cycle length was increased by a mean of 2.5 days but returned to normal in the subsequent cycle. Some women studied reported intermenstrual bleeding after use of ulipristal. If there is a delay in the onset of expected menstruation beyond 1 week, testing should be conducted to ensure the woman is not pregnant.

    Breast-feeding

    Use of ulipristal is not recommended during breast-feeding. Ulipristal is excreted in human milk. The breast milk of 12 lactating women following ulipristal administration was collected in 24-hour increments (0 to 120 hours) to measure the concentrations of ulipristal acetate and monodemethyl-ulipristal acetate in breast milk. The mean daily concentrations of ulipristal acetate in breast milk, at their highest and lowest, were 22.7 ng/mL (0 to 24 hours) and 0.69 ng/mL (96 to 120 hours); concentrations of monodemethyl-ulipristal acetate, at their highest and lowest, were 4.49 ng/mL (0 to 24 hours) and 0.10 ng/mL (96 to 120 hours). The effect of this exposure on a nursing infant has not been studied; therefore, risk to the breast-fed infant cannot be excluded. Recommendations have been made for when ulipristal is necessary for emergency contraception in lactating women. Breast-feeding is not recommended for 24 hours after taking ulipristal because the highest concentrations in milk occur in the first 24 hours, and maximum maternal serum levels are attained 1 to 3 hours after administration. Mean ulipristal concentrations in breast milk decrease markedly from 0 to 24 to 48 hours and then slowly decline over 5 days. Breast milk should be expressed and discarded for at least 24 hours after taking ulipristal. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    Hepatic disease

    Ulipristal has not been studied in patients with hepatic disease. Guidelines recommend caution when used in this population as emergency contraception, but note that the limited duration of use for emergency contraception would be expected to have less clinical impact in these patients than with use of routine hormonal contraception. While ulipristal has not been systematically studied in patients with renal impairment, there are no particular cautions for use as an emergency contraception in guidelines for use.

    Acquired immunodeficiency syndrome (AIDS), human immunodeficiency virus (HIV) infection, sexually transmitted disease

    Like other hormonal contraceptives, patients should be reminded that ulipristal does not protect against the transmission of human immunodeficiency virus (HIV) infection, the acquired immunodeficiency syndrome (AIDS), or other sexually transmitted disease or infections.

    Children

    There is no relevant use of ulipristal for children of prepubertal age as emergency contraception. The safety and efficacy of ulipristal have been established in women of reproductive age. During clinical and postmarketing evaluation studies of ulipristal, the safety and efficacy profile observed in postmenarchal adolescent females aged 17 and younger was similar to that in adults.

    ADVERSE REACTIONS

    Severe

    angioedema / Rapid / Incidence not known

    Mild

    headache / Early / 18.0-19.0
    menstrual irregularity / Delayed / 7.0-19.0
    abdominal pain / Early / 8.0-15.0
    nausea / Early / 12.0-13.0
    dysmenorrhea / Delayed / 7.0-13.0
    breakthrough bleeding / Delayed / 9.0-9.0
    fatigue / Early / 6.0-6.0
    dizziness / Early / 5.0-5.0
    urticaria / Rapid / Incidence not known
    pruritus / Rapid / Incidence not known
    acne vulgaris / Delayed / Incidence not known
    rash / Early / Incidence not known

    DRUG INTERACTIONS

    Aldesleukin, IL-2: (Minor) Ulipristal is a substrate of CYP3A4 and Aldesleukin (IL-2) is a CYP3A4 inhibitor. Concomitant use may increase the plasma concentration of ulipristal resulting in an increased risk for adverse events. When used for emergency contraception, be alert for ulipristal-related side effects. Ulipristal is not recommended to be administered with moderate or potent CYP3A4 inhibitors when given chronically (e.g., daily for female hormonal conditions).
    Amobarbital: (Major) Avoid administration of ulipristal with drugs that induce CYP3A4. Ulipristal is a substrate of CYP3A4 and barbiturates (such as phenobarbital or primidone) are CYP3A4 inducers. Concomitant use may decrease the plasma concentration and effectiveness of ulipristal.
    Amoxicillin; Clarithromycin; Omeprazole: (Minor) Ulipristal is a substrate of CYP3A4 and clarithromycin is a CYP3A4 inhibitor. Concomitant use may increase the plasma concentration of ulipristal resulting in an increased risk for adverse events.
    Amprenavir: (Minor) Ulipristal is a substrate of CYP3A4 and amprenavir is a CYP3A4 inhibitor, and may be a CYP3A4 inducer. Concomitant use may increase the plasma concentration of ulipristal. With single doses of ulipristal for emergency contraception it is not clear this interaction will have clinical consequence. The potential for interaction has not been studied.
    Apalutamide: (Major) Avoid administration of ulipristal with drugs that induce CYP3A4. Ulipristal is a substrate of CYP3A4 and apalutamide is a CYP3A4 inducer. Concomitant use may decrease the plasma concentration and effectiveness of ulipristal.
    Armodafinil: (Major) Avoid administration of ulipristal with drugs that induce CYP3A4. Ulipristal is a substrate of CYP3A4 and armodafinil is a CYP3A4 inducer. Concomitant use may decrease the plasma concentration and effectiveness of ulipristal.
    Aspirin, ASA; Butalbital; Caffeine: (Major) Avoid administration of ulipristal with drugs that induce CYP3A4. Ulipristal is a substrate of CYP3A4 and barbiturates (such as phenobarbital or primidone) are CYP3A4 inducers. Concomitant use may decrease the plasma concentration and effectiveness of ulipristal.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Major) Avoid administration of ulipristal with drugs that induce CYP3A4. Ulipristal is a substrate of CYP3A4 and barbiturates (such as phenobarbital or primidone) are CYP3A4 inducers. Concomitant use may decrease the plasma concentration and effectiveness of ulipristal.
    Atazanavir: (Minor) Ulipristal is a substrate of CYP3A4 and atazanavir is a CYP3A4 inhibitor. Concomitant use may increase the plasma concentration of ulipristal resulting in an increased risk for adverse events.
    Atazanavir; Cobicistat: (Minor) Concomitant use of ulipristal and cobicistat may increase the plasma concentration of ulipristal resulting in an increased risk for ulipristal-related adverse events; however, this is not likely to be significant for single-dose emergency contraceptive use. Ulipristal is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased ulipristal overall exposure by 5.9-fold and increased the overall exposure if ulipristal's active metabolite, monodemethyl-ulipristal acetate, by 2.4-fold. (Minor) Ulipristal is a substrate of CYP3A4 and atazanavir is a CYP3A4 inhibitor. Concomitant use may increase the plasma concentration of ulipristal resulting in an increased risk for adverse events.
    Barbiturates: (Major) Avoid administration of ulipristal with drugs that induce CYP3A4. Ulipristal is a substrate of CYP3A4 and barbiturates (such as phenobarbital or primidone) are CYP3A4 inducers. Concomitant use may decrease the plasma concentration and effectiveness of ulipristal.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (Major) Avoid administration of ulipristal with drugs that induce CYP3A4. Ulipristal is a substrate of CYP3A4 and barbiturates (such as phenobarbital or primidone) are CYP3A4 inducers. Concomitant use may decrease the plasma concentration and effectiveness of ulipristal.
    Bexarotene: (Major) Avoid administration of ulipristal with drugs that induce CYP3A4. Ulipristal is a substrate of CYP3A4 and bexarotene is a CYP3A4 inducer. Concomitant use may decrease the plasma concentration and effectiveness of ulipristal.
    Bosentan: (Major) Avoid administration of ulipristal with drugs that induce CYP3A4. Ulipristal is a substrate of CYP3A4 and bosentan is a CYP3A4 inducer. Concomitant use may decrease the plasma concentration and effectiveness of ulipristal.
    Butabarbital: (Major) Avoid administration of ulipristal with drugs that induce CYP3A4. Ulipristal is a substrate of CYP3A4 and barbiturates (such as phenobarbital or primidone) are CYP3A4 inducers. Concomitant use may decrease the plasma concentration and effectiveness of ulipristal.
    Butalbital; Acetaminophen: (Major) Avoid administration of ulipristal with drugs that induce CYP3A4. Ulipristal is a substrate of CYP3A4 and barbiturates (such as phenobarbital or primidone) are CYP3A4 inducers. Concomitant use may decrease the plasma concentration and effectiveness of ulipristal.
    Butalbital; Acetaminophen; Caffeine: (Major) Avoid administration of ulipristal with drugs that induce CYP3A4. Ulipristal is a substrate of CYP3A4 and barbiturates (such as phenobarbital or primidone) are CYP3A4 inducers. Concomitant use may decrease the plasma concentration and effectiveness of ulipristal.
    Butalbital; Acetaminophen; Caffeine; Codeine: (Major) Avoid administration of ulipristal with drugs that induce CYP3A4. Ulipristal is a substrate of CYP3A4 and barbiturates (such as phenobarbital or primidone) are CYP3A4 inducers. Concomitant use may decrease the plasma concentration and effectiveness of ulipristal.
    Carbamazepine: (Major) Avoid administration of ulipristal with drugs that induce CYP3A4. Ulipristal is a substrate of CYP3A4 and carbamazepine is a CYP3A4 inducer. Concomitant use may decrease the plasma concentration and effectiveness of ulipristal.
    Cenobamate: (Major) Avoid administration of ulipristal with drugs that induce CYP3A4. Ulipristal is a substrate of CYP3A4 and cenobamate is a moderate CYP3A4 inducer. Concomitant use may decrease the plasma concentration and effectiveness of ulipristal.
    Ceritinib: (Minor) Concomitant use of ulipristal and ceritinib may increase the plasma concentration of ulipristal resulting in an increased risk for ulipristal-related adverse events; however, this is not likely to be significant for single-dose emergency contraceptive use. Ulipristal is a CYP3A substrate and ceritinib is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased ulipristal overall exposure by 5.9-fold and increased the overall exposure if ulipristal's active metabolite, monodemethyl-ulipristal acetate, by 2.4-fold.
    Chloramphenicol: (Minor) Ulipristal is a substrate of CYP3A4 and chloramphenicol is a CYP3A4 inhibitor. Concomitant use may increase the plasma concentration of ulipristal resulting in an increased risk for adverse events.
    Clarithromycin: (Minor) Ulipristal is a substrate of CYP3A4 and clarithromycin is a CYP3A4 inhibitor. Concomitant use may increase the plasma concentration of ulipristal resulting in an increased risk for adverse events.
    Clobazam: (Moderate) Clobazam is a weak CYP3A4 inducer. As ulipristal is metabolized by CYP3A4, its effectiveness may be diminished when given with clobazam. Strong CYP3A4 inducers should be avoided with ulipristal. Monitor the patient for the desired clinical effect if ulipristal must be administered to a patient taking clobazam.
    Cobicistat: (Minor) Concomitant use of ulipristal and cobicistat may increase the plasma concentration of ulipristal resulting in an increased risk for ulipristal-related adverse events; however, this is not likely to be significant for single-dose emergency contraceptive use. Ulipristal is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased ulipristal overall exposure by 5.9-fold and increased the overall exposure if ulipristal's active metabolite, monodemethyl-ulipristal acetate, by 2.4-fold.
    Dabrafenib: (Major) Avoid administration of ulipristal with drugs that induce CYP3A4. Ulipristal is a substrate of CYP3A4 and dabrafenib is a CYP3A4 inducer. Concomitant use is expected to decrease the plasma concentration of ulipristal and may decrease its effectiveness.
    Danazol: (Minor) Ulipristal is a substrate of CYP3A4 and danazol is a CYP3A4 inhibitor. Concomitant use may increase the plasma concentration of ulipristal resulting in an increased risk for adverse events.
    Darunavir: (Minor) Ulipristal is a substrate of CYP3A4 and darunavir is a CYP3A4 inhibitor. Concomitant use may increase the plasma concentration of ulipristal resulting in an increased risk for adverse events
    Darunavir; Cobicistat: (Minor) Concomitant use of ulipristal and cobicistat may increase the plasma concentration of ulipristal resulting in an increased risk for ulipristal-related adverse events; however, this is not likely to be significant for single-dose emergency contraceptive use. Ulipristal is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased ulipristal overall exposure by 5.9-fold and increased the overall exposure if ulipristal's active metabolite, monodemethyl-ulipristal acetate, by 2.4-fold. (Minor) Ulipristal is a substrate of CYP3A4 and darunavir is a CYP3A4 inhibitor. Concomitant use may increase the plasma concentration of ulipristal resulting in an increased risk for adverse events
    Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Minor) Concomitant use of ulipristal and cobicistat may increase the plasma concentration of ulipristal resulting in an increased risk for ulipristal-related adverse events; however, this is not likely to be significant for single-dose emergency contraceptive use. Ulipristal is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased ulipristal overall exposure by 5.9-fold and increased the overall exposure if ulipristal's active metabolite, monodemethyl-ulipristal acetate, by 2.4-fold. (Minor) Ulipristal is a substrate of CYP3A4 and darunavir is a CYP3A4 inhibitor. Concomitant use may increase the plasma concentration of ulipristal resulting in an increased risk for adverse events
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Use of ulipristal and ritonavir may increase the plasma concentration of ulipristal but is not likely to be significant for emergency contraceptive use. Avoid ritonavir if ulipristal is given chronically for hormonal conditions. Ulipristal is a substrate of CYP3A4 and ritonavir is a potent CYP3A4 inhibitor and in chronic use, may induce CYP3A4. Use together is likely to increase ulipristal concentrations overall, which may increase the risk for ulipristal-related adverse reactions.
    Deferasirox: (Moderate) Deferasirox is a weak CYP3A4 inducer. As ulipristal is metabolized by CYP3A4, its effectiveness may be diminished when given with deferasirox. Strong CYP3A4 inducers should be avoided with ulipristal. Monitor the patient for the desired clinical effect if ulipristal must be administered to a patient taking deferasirox.
    Delavirdine: (Minor) Ulipristal is a substrate of CYP3A4 and delavirdine is a CYP3A4 inhibitor. Concomitant use may increase the plasma concentration of ulipristal resulting in an increased risk for adverse events.
    Dexamethasone: (Major) Avoid administration of ulipristal with drugs that induce CYP3A4. Ulipristal is a substrate of CYP3A4 and dexamethasone is a CYP3A4 inducer. Concomitant use may decrease the plasma concentration and effectiveness of ulipristal.
    Dronedarone: (Minor) Ulipristal is a substrate of CYP3A4 and dronedarone is a CYP3A4 inhibitor. Concomitant use may increase the plasma concentration of ulipristal resulting in an increased risk for adverse events.
    Efavirenz: (Major) Avoid administration of ulipristal with drugs that induce CYP3A4. Ulipristal is a substrate of CYP3A4 and efavirenz is a CYP3A4 inducer. Concomitant use may decrease the plasma concentration and effectiveness of ulipristal.
    Efavirenz; Emtricitabine; Tenofovir: (Major) Avoid administration of ulipristal with drugs that induce CYP3A4. Ulipristal is a substrate of CYP3A4 and efavirenz is a CYP3A4 inducer. Concomitant use may decrease the plasma concentration and effectiveness of ulipristal.
    Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Avoid administration of ulipristal with drugs that induce CYP3A4. Ulipristal is a substrate of CYP3A4 and efavirenz is a CYP3A4 inducer. Concomitant use may decrease the plasma concentration and effectiveness of ulipristal.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Minor) Concomitant use of ulipristal and cobicistat may increase the plasma concentration of ulipristal resulting in an increased risk for ulipristal-related adverse events; however, this is not likely to be significant for single-dose emergency contraceptive use. Ulipristal is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased ulipristal overall exposure by 5.9-fold and increased the overall exposure if ulipristal's active metabolite, monodemethyl-ulipristal acetate, by 2.4-fold.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Minor) Concomitant use of ulipristal and cobicistat may increase the plasma concentration of ulipristal resulting in an increased risk for ulipristal-related adverse events; however, this is not likely to be significant for single-dose emergency contraceptive use. Ulipristal is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased ulipristal overall exposure by 5.9-fold and increased the overall exposure if ulipristal's active metabolite, monodemethyl-ulipristal acetate, by 2.4-fold.
    Enzalutamide: (Major) Avoid coadministration of ulipristal with enzalutamide due to decreased plasma concentrations of ulipristal. Ulipristal is a CYP3A4 substrate and enzalutamide is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased ulipristal exposure by 93%, while exposure to monodemethyl-ulipristal acetate decreased by 90%.
    Eslicarbazepine: (Major) Avoid administration of ulipristal with drugs that induce CYP3A4. Ulipristal is a substrate of CYP3A4 and eslicarbazepine is a CYP3A4 inducer. Concomitant use may decrease the plasma concentration and effectiveness of ulipristal.
    Etravirine: (Major) Avoid administration of ulipristal with drugs that induce CYP3A4. Ulipristal is a substrate of CYP3A4 and etravirine is a CYP3A4 inducer. Concomitant use may decrease the plasma concentration and effectiveness of ulipristal.
    Felbamate: (Major) Avoid administration of ulipristal with drugs that induce CYP3A4. Ulipristal is a substrate of CYP3A4 and felbamate is a CYP3A4 inducer. Concomitant use may decrease the plasma concentration and effectiveness of ulipristal.
    Flutamide: (Moderate) Ulipristal is a substrate of CYP3A4 and flutamide is a CYP3A4 inducer. Concomitant use may decrease the plasma concentration and effectiveness of ulipristal.
    Fluvoxamine: (Minor) Ulipristal is a substrate of CYP3A4 and fluvoxamine is a CYP3A4 inhibitor. Concomitant use may increase the plasma concentration of ulipristal resulting in an increased risk for adverse events.
    Fosamprenavir: (Minor) Ulipristal is a substrate of CYP3A4 and fosamprenavir is a CYP3A4 inhibitor, and may be a CYP3A4 inducer. Concomitant use may increase the plasma concentration of ulipristal. With single doses of ulipristal for emergency contraception it is not clear this interaction will have clinical consequence. The potential for interaction has not been studied.
    Fosphenytoin: (Major) Avoid coadministration of ulipristal with fosphenytoin. Concomitant use may decrease the plasma concentration and effectiveness of ulipristal. Ulipristal is a substrate of CYP3A4 and fosphenytoin is a CYP3A4 inducer.
    Grapefruit juice: (Moderate) Use of ulipristal and grapefruit juice may increase the plasma concentration of ulipristal but is not likely to be significant for single-dose emergency contraceptive use. Avoid grapefruit juice if ulipristal is given chronically for hormonal conditions. Concomitant use of ulipristal, a CYP3A4 substrate and grapefruit juice, a potent CYP3A4 inhibitor may increase the plasma concentration of ulipristal resulting in an increased risk for ulipristal-related adverse events.
    Griseofulvin: (Major) Avoid administration of ulipristal with drugs that induce CYP3A4. Ulipristal is a substrate of CYP3A4 and griseofulvin is a CYP3A4 inducer. Concomitant use may decrease the plasma concentration and effectiveness of ulipristal.
    Idelalisib: (Moderate) Use of ulipristal and idelalisib may increase the plasma concentration of ulipristal but is not likely to be significant for single-dose emergency contraceptive use. Avoid idelalisib if ulipristal is given chronically for hormonal conditions. Concomitant use of ulipristal, a CYP3A4 substrate and idelalisib, a potent CYP3A4 inhibitor may increase the plasma concentration of ulipristal resulting in an increased risk for ulipristal-related adverse events.
    Imatinib: (Minor) Ulipristal is a substrate of CYP3A4 and imatinib, STI-571 is a CYP3A4 inhibitor. Concomitant use may increase the plasma concentration of ulipristal resulting in an increased risk for adverse events.
    Indinavir: (Minor) Ulipristal is a substrate of CYP3A4 and indinavir is a CYP3A4 inhibitor. Concomitant use may increase the plasma concentration of ulipristal resulting in an increased risk for adverse events.
    Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Avoid use of rifampin with ulipristal. Ulipristal is a substrate of CYP3A4 and rifampin is a strong CYP3A4 inducer. Concomitant use decreases the plasma concentration of ulipristal significantly and may decrease its effectiveness. When a single 30-mg dose of ulipristal acetate was administered following administration of rifampin 600 mg/day for 9 days, the Cmax and AUC of ulipristal acetate decreased by 90% and 93% respectively. The Cmax and AUC of monodemethyl-ulipristal acetate decreased by 84% and 90% respectively.
    Isoniazid, INH; Rifampin: (Major) Avoid use of rifampin with ulipristal. Ulipristal is a substrate of CYP3A4 and rifampin is a strong CYP3A4 inducer. Concomitant use decreases the plasma concentration of ulipristal significantly and may decrease its effectiveness. When a single 30-mg dose of ulipristal acetate was administered following administration of rifampin 600 mg/day for 9 days, the Cmax and AUC of ulipristal acetate decreased by 90% and 93% respectively. The Cmax and AUC of monodemethyl-ulipristal acetate decreased by 84% and 90% respectively.
    Itraconazole: (Minor) Ulipristal is a substrate of CYP3A4 and itraconazole is a CYP3A4 inhibitor. Concomitant use may increase the plasma concentration of ulipristal resulting in an increased risk for adverse events.
    Ivosidenib: (Major) Consider alternative methods of contraception in patients receiving ivosidenib. Coadministration may decrease the concentrations of hormonal contraceptives.
    Ketoconazole: (Minor) Ulipristal is a substrate of CYP3A4 and ketoconazole is a CYP3A4 inhibitor. Concomitant use may increase the plasma concentration of ulipristal resulting in an increased risk for adverse events.
    Lansoprazole; Amoxicillin; Clarithromycin: (Minor) Ulipristal is a substrate of CYP3A4 and clarithromycin is a CYP3A4 inhibitor. Concomitant use may increase the plasma concentration of ulipristal resulting in an increased risk for adverse events.
    Lesinurad: (Moderate) Lesinurad is a weak CYP3A4 inducer. As ulipristal is metabolized by CYP3A4, its effectiveness may be diminished when given with lesinurad. Strong CYP3A4 inducers should be avoided with ulipristal. Monitor the patient for the desired clinical effect if ulipristal must be administered to a patient taking lesinurad.
    Lesinurad; Allopurinol: (Moderate) Lesinurad is a weak CYP3A4 inducer. As ulipristal is metabolized by CYP3A4, its effectiveness may be diminished when given with lesinurad. Strong CYP3A4 inducers should be avoided with ulipristal. Monitor the patient for the desired clinical effect if ulipristal must be administered to a patient taking lesinurad.
    Letermovir: (Moderate) An increase in the plasma concentration of ulipristal may occur if given with letermovir. In patients who are also receiving treatment with cyclosporine, the magnitude of this interaction may be amplified. Ulipristal is predominately metabolized by CYP3A4. Letermovir is a moderate CYP3A4 inhibitor; however, when given with cyclosporine, the combined effect on CYP3A4 substrates may be similar to a strong CYP3A4 inhibitor. In a drug interaction study, concurrent administration with another strong CYP3A4 inhibitor increased the maximum plasma concentration (Cmax) and exposure (AUC) of ulipristal by 2- and 5.9-fold, respectively; while the AUC of monodemethyl-ulipristal acetate increased by 2.4-fold and the Cmax decreased by 47%.
    Levoketoconazole: (Minor) Ulipristal is a substrate of CYP3A4 and ketoconazole is a CYP3A4 inhibitor. Concomitant use may increase the plasma concentration of ulipristal resulting in an increased risk for adverse events.
    Lonafarnib: (Minor) Concomitant use of ulipristal and lonafarnib may increase the plasma concentration of ulipristal resulting in an increased risk for ulipristal-related adverse events; however, this is not likely to be significant for single-dose emergency contraceptive use. Ulipristal is a CYP3A substrate and lonafarnib is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased ulipristal overall exposure by 5.9-fold and increased the overall exposure if ulipristal's active metabolite, monodemethyl-ulipristal acetate, by 2.4-fold.
    Lopinavir; Ritonavir: (Moderate) Use of ulipristal and ritonavir may increase the plasma concentration of ulipristal but is not likely to be significant for emergency contraceptive use. Avoid ritonavir if ulipristal is given chronically for hormonal conditions. Ulipristal is a substrate of CYP3A4 and ritonavir is a potent CYP3A4 inhibitor and in chronic use, may induce CYP3A4. Use together is likely to increase ulipristal concentrations overall, which may increase the risk for ulipristal-related adverse reactions.
    Lorlatinib: (Major) Do not administer ulipristal with lorlatinib due to decreased plasma concentrations of ulipristal. Ulipristal is a CYP3A4 substrate and lorlatinib is a moderate CYP3A4 inducer. Concomitant use may significantly decrease ulipristal exposure.
    Lumacaftor; Ivacaftor: (Major) Avoid administration of ulipristal with drugs that induce CYP3A4. Concomitant use of ulipristal, a CYP3A4 substrate and lumacaftor, a potent CYP3A4 inducer, may decrease the plasma concentration and effectiveness of ulipristal.,
    Lumacaftor; Ivacaftor: (Major) Avoid administration of ulipristal with drugs that induce CYP3A4. Concomitant use of ulipristal, a CYP3A4 substrate and lumacaftor, a potent CYP3A4 inducer, may decrease the plasma concentration and effectiveness of ulipristal.,
    Mephobarbital: (Major) Avoid administration of ulipristal with drugs that induce CYP3A4. Ulipristal is a substrate of CYP3A4 and barbiturates (such as phenobarbital or primidone) are CYP3A4 inducers. Concomitant use may decrease the plasma concentration and effectiveness of ulipristal.
    Methohexital: (Major) Avoid administration of ulipristal with drugs that induce CYP3A4. Ulipristal is a substrate of CYP3A4 and barbiturates (such as phenobarbital or primidone) are CYP3A4 inducers. Concomitant use may decrease the plasma concentration and effectiveness of ulipristal.
    Mitapivat: (Major) Avoid coadministration of ulipristal with mitapivat. Concomitant use may decrease the plasma concentration and effectiveness of ulipristal. Ulipristal is a substrate of CYP3A and mitapivat is a weak CYP3A inducer.
    Mitotane: (Major) Avoid administration of ulipristal with drugs that induce CYP3A4. Ulipristal is a substrate of CYP3A4 and mitotane is a CYP3A4 inducer. Concomitant use may decrease the plasma concentration and effectiveness of ulipristal.
    Modafinil: (Major) Avoid administration of ulipristal with drugs that induce CYP3A4. Ulipristal is a substrate of CYP3A4 and modafinil is a CYP3A4 inducer. Concomitant use may decrease the plasma concentration and effectiveness of ulipristal.
    Nefazodone: (Minor) Ulipristal is a substrate of CYP3A4 and nefazodone is a CYP3A4 inhibitor. Concomitant use may increase the plasma concentration of ulipristal resulting in an increased risk for adverse events.
    Nelfinavir: (Minor) Ulipristal is a substrate of CYP3A4 and nelfinavir is a CYP3A4 inhibitor. Concomitant use may increase the plasma concentration of ulipristal resulting in an increased risk for adverse events.
    Nevirapine: (Major) Avoid administration of ulipristal with drugs that induce CYP3A4. Ulipristal is a substrate of CYP3A4 and nevirapine is a CYP3A4 inducer. Concomitant use may decrease the plasma concentration and effectiveness of ulipristal.
    Nicardipine: (Minor) Ulipristal is a substrate of CYP3A4 and nicardipine is a CYP3A4 inhibitor. Concomitant use may increase the plasma concentration of ulipristal resulting in an increased risk for adverse events.
    Nirmatrelvir; Ritonavir: (Moderate) Use of ulipristal and ritonavir may increase the plasma concentration of ulipristal but is not likely to be significant for emergency contraceptive use. Avoid ritonavir if ulipristal is given chronically for hormonal conditions. Ulipristal is a substrate of CYP3A4 and ritonavir is a potent CYP3A4 inhibitor and in chronic use, may induce CYP3A4. Use together is likely to increase ulipristal concentrations overall, which may increase the risk for ulipristal-related adverse reactions.
    Octreotide: (Minor) Ulipristal is a substrate of CYP3A4 and octreotide is a CYP3A4 inhibitor. Concomitant use may increase the plasma concentration of ulipristal resulting in an increased risk for adverse events.
    Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Use of ulipristal and ritonavir may increase the plasma concentration of ulipristal but is not likely to be significant for emergency contraceptive use. Avoid ritonavir if ulipristal is given chronically for hormonal conditions. Ulipristal is a substrate of CYP3A4 and ritonavir is a potent CYP3A4 inhibitor and in chronic use, may induce CYP3A4. Use together is likely to increase ulipristal concentrations overall, which may increase the risk for ulipristal-related adverse reactions.
    Omeprazole; Amoxicillin; Rifabutin: (Major) Avoid administration of ulipristal with drugs that induce CYP3A4. Ulipristal is a substrate of CYP3A4 and rifabutin is a CYP3A4 inducer. Concomitant use is expected to decrease the plasma concentration of ulipristal and may decrease its effectiveness.
    Oxcarbazepine: (Major) Avoid administration of ulipristal with drugs that induce CYP3A4. Ulipristal is a substrate of CYP3A4 and oxcarbazepine is a CYP3A4 inducer. Concomitant use may decrease the plasma concentration and effectiveness of ulipristal.
    Pentobarbital: (Major) Avoid administration of ulipristal with drugs that induce CYP3A4. Ulipristal is a substrate of CYP3A4 and barbiturates (such as phenobarbital or primidone) are CYP3A4 inducers. Concomitant use may decrease the plasma concentration and effectiveness of ulipristal.
    Phenobarbital: (Major) Avoid administration of ulipristal with drugs that induce CYP3A4. Ulipristal is a substrate of CYP3A4 and barbiturates (such as phenobarbital or primidone) are CYP3A4 inducers. Concomitant use may decrease the plasma concentration and effectiveness of ulipristal.
    Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Avoid administration of ulipristal with drugs that induce CYP3A4. Ulipristal is a substrate of CYP3A4 and barbiturates (such as phenobarbital or primidone) are CYP3A4 inducers. Concomitant use may decrease the plasma concentration and effectiveness of ulipristal.
    Phentermine; Topiramate: (Major) Avoid administration of ulipristal with drugs that induce CYP3A4. Ulipristal is a substrate of CYP3A4 and topiramate is a mild CYP3A4 inducer. Concomitant use may decrease the plasma concentration and effectiveness of ulipristal.
    Phenytoin: (Major) Avoid administration of ulipristal with drugs that induce CYP3A4. Ulipristal is a substrate of CYP3A4 and phenytoin is a CYP3A4 inducer. Concomitant use may decrease the plasma concentration and effectiveness of ulipristal.
    Posaconazole: (Minor) Concomitant use of ulipristal and posaconazole may increase the plasma concentration of ulipristal resulting in an increased risk for ulipristal-related adverse events; however, this is not likely to be significant for single-dose emergency contraceptive use. Ulipristal is a CYP3A substrate and posaconazole is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased ulipristal overall exposure by 5.9-fold and increased the overall exposure if ulipristal's active metabolite, monodemethyl-ulipristal acetate, by 2.4-fold.
    Primidone: (Major) Avoid administration of ulipristal with drugs that induce CYP3A4. Ulipristal is a substrate of CYP3A4 and barbiturates (such as phenobarbital or primidone) are CYP3A4 inducers. Concomitant use may decrease the plasma concentration and effectiveness of ulipristal.
    Progestins: (Major) Avoid concurrent use of ulipristal and progestin-containing hormonal contraceptives or other progestins. Hormonal contraceptives may be started or resumed no sooner than 5 days after ulipristal treatment. Also, a reliable barrier method of contraception should be used during the same menstrual cycle in which ulipristal was administered (until the next menstrual period). Progestin-containing contraceptives may impair the ability of ulipristal to delay ovulation. Ulipristal may reduce the effectiveness of progestin-containing hormonal contraceptives by competitively binding at the progesterone receptor.
    Ribociclib: (Minor) Concomitant use of ulipristal and ribociclib may increase the plasma concentration of ulipristal resulting in an increased risk for ulipristal-related adverse events; however, this is not likely to be significant for single-dose emergency contraceptive use. Ulipristal is a CYP3A substrate and ribociclib is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased ulipristal overall exposure by 5.9-fold and increased the overall exposure if ulipristal's active metabolite, monodemethyl-ulipristal acetate, by 2.4-fold.
    Ribociclib; Letrozole: (Minor) Concomitant use of ulipristal and ribociclib may increase the plasma concentration of ulipristal resulting in an increased risk for ulipristal-related adverse events; however, this is not likely to be significant for single-dose emergency contraceptive use. Ulipristal is a CYP3A substrate and ribociclib is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased ulipristal overall exposure by 5.9-fold and increased the overall exposure if ulipristal's active metabolite, monodemethyl-ulipristal acetate, by 2.4-fold.
    Rifabutin: (Major) Avoid administration of ulipristal with drugs that induce CYP3A4. Ulipristal is a substrate of CYP3A4 and rifabutin is a CYP3A4 inducer. Concomitant use is expected to decrease the plasma concentration of ulipristal and may decrease its effectiveness.
    Rifampin: (Major) Avoid use of rifampin with ulipristal. Ulipristal is a substrate of CYP3A4 and rifampin is a strong CYP3A4 inducer. Concomitant use decreases the plasma concentration of ulipristal significantly and may decrease its effectiveness. When a single 30-mg dose of ulipristal acetate was administered following administration of rifampin 600 mg/day for 9 days, the Cmax and AUC of ulipristal acetate decreased by 90% and 93% respectively. The Cmax and AUC of monodemethyl-ulipristal acetate decreased by 84% and 90% respectively.
    Rifapentine: (Major) Avoid concurrent use of ulipristal and rifapentine. Concomitant use may decrease the plasma concentration and effectiveness of ulipristal. Ulipristal is a substrate of CYP3A4 and rifapentine is a strong CYP3A4 inducer. Another strong CYP3A4 inducer reduced ulipristal exposure by 93% and exposure of its active metabolite by 90%.
    Ritonavir: (Moderate) Use of ulipristal and ritonavir may increase the plasma concentration of ulipristal but is not likely to be significant for emergency contraceptive use. Avoid ritonavir if ulipristal is given chronically for hormonal conditions. Ulipristal is a substrate of CYP3A4 and ritonavir is a potent CYP3A4 inhibitor and in chronic use, may induce CYP3A4. Use together is likely to increase ulipristal concentrations overall, which may increase the risk for ulipristal-related adverse reactions.
    Saquinavir: (Minor) Concomitant use of ulipristal and saquinavir may increase the plasma concentration of ulipristal resulting in an increased risk for ulipristal-related adverse events; however, this is not likely to be significant for single-dose emergency contraceptive use. Ulipristal is a CYP3A substrate and saquinavir is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased ulipristal overall exposure by 5.9-fold and increased the overall exposure if ulipristal's active metabolite, monodemethyl-ulipristal acetate, by 2.4-fold.
    Secobarbital: (Major) Avoid administration of ulipristal with drugs that induce CYP3A4. Ulipristal is a substrate of CYP3A4 and barbiturates (such as phenobarbital or primidone) are CYP3A4 inducers. Concomitant use may decrease the plasma concentration and effectiveness of ulipristal.
    St. John's Wort, Hypericum perforatum: (Major) Avoid administration of ulipristal with drugs or herbal/dietary supplements that induce CYP3A4. Ulipristal is a substrate of CYP3A4 and St. John's Wort is a CYP3A4 inducer. Concomitant use may decrease the plasma concentration and effectiveness of ulipristal.
    Telithromycin: (Minor) Concomitant use of ulipristal and telithromycin may increase the plasma concentration of ulipristal resulting in an increased risk for ulipristal-related adverse events; however, this is not likely to be significant for single-dose emergency contraceptive use. Ulipristal is a CYP3A substrate and telithromycin is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased ulipristal overall exposure by 5.9-fold and increased the overall exposure if ulipristal's active metabolite, monodemethyl-ulipristal acetate, by 2.4-fold.
    Thiopental: (Major) Avoid administration of ulipristal with drugs that induce CYP3A4. Ulipristal is a substrate of CYP3A4 and barbiturates (such as phenobarbital or primidone) are CYP3A4 inducers. Concomitant use may decrease the plasma concentration and effectiveness of ulipristal.
    Tipranavir: (Minor) Concomitant use of ulipristal and tipranavir may increase the plasma concentration of ulipristal resulting in an increased risk for ulipristal-related adverse events; however, this is not likely to be significant for single-dose emergency contraceptive use. Ulipristal is a CYP3A substrate and tipranavir is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased ulipristal overall exposure by 5.9-fold and increased the overall exposure if ulipristal's active metabolite, monodemethyl-ulipristal acetate, by 2.4-fold.
    Topiramate: (Major) Avoid administration of ulipristal with drugs that induce CYP3A4. Ulipristal is a substrate of CYP3A4 and topiramate is a mild CYP3A4 inducer. Concomitant use may decrease the plasma concentration and effectiveness of ulipristal.
    Tucatinib: (Minor) Concomitant use of ulipristal and tucatinib may increase the plasma concentration of ulipristal resulting in an increased risk for ulipristal-related adverse events; however, this is not likely to be significant for single-dose emergency contraceptive use. Ulipristal is a CYP3A substrate and tucatinib is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased ulipristal overall exposure by 5.9-fold and increased the overall exposure if ulipristal's active metabolite, monodemethyl-ulipristal acetate, by 2.4-fold.
    Voriconazole: (Minor) Concomitant use of ulipristal and voriconazole may increase the plasma concentration of ulipristal resulting in an increased risk for ulipristal-related adverse events; however, this is not likely to be significant for single-dose emergency contraceptive use. Ulipristal is a CYP3A substrate and voriconazole is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased ulipristal overall exposure by 5.9-fold and increased the overall exposure if ulipristal's active metabolite, monodemethyl-ulipristal acetate, by 2.4-fold.
    Zafirlukast: (Minor) Ulipristal is a substrate of CYP3A4 and zafirlukast is a CYP3A4 inhibitor. Concomitant use may increase the plasma concentration of ulipristal resulting in an increased risk for adverse events.

    PREGNANCY AND LACTATION

    Pregnancy

    Use of ulipristal is not recommended during breast-feeding. Ulipristal is excreted in human milk. The breast milk of 12 lactating women following ulipristal administration was collected in 24-hour increments (0 to 120 hours) to measure the concentrations of ulipristal acetate and monodemethyl-ulipristal acetate in breast milk. The mean daily concentrations of ulipristal acetate in breast milk, at their highest and lowest, were 22.7 ng/mL (0 to 24 hours) and 0.69 ng/mL (96 to 120 hours); concentrations of monodemethyl-ulipristal acetate, at their highest and lowest, were 4.49 ng/mL (0 to 24 hours) and 0.10 ng/mL (96 to 120 hours). The effect of this exposure on a nursing infant has not been studied; therefore, risk to the breast-fed infant cannot be excluded. Recommendations have been made for when ulipristal is necessary for emergency contraception in lactating women. Breast-feeding is not recommended for 24 hours after taking ulipristal because the highest concentrations in milk occur in the first 24 hours, and maximum maternal serum levels are attained 1 to 3 hours after administration. Mean ulipristal concentrations in breast milk decrease markedly from 0 to 24 to 48 hours and then slowly decline over 5 days. Breast milk should be expressed and discarded for at least 24 hours after taking ulipristal. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    MECHANISM OF ACTION

    Ulipristal is a progesterone receptor modulator with antagonistic and partial agonist effects (a progesterone agonist/antagonist) that binds to the progesterone receptor and prevents progesterone from occupying the receptor. Ulipristal postpones follicular rupture when taken immediately prior to ovulation. The primary mechanism of action of ulipristal for emergency contraception is likely the inhibition or delay of ovulation. In addition, alterations to the endometrium may affect implantation and may also contribute to efficacy for emergency contraception.
     
    The pharmacodynamic effects of ulipristal depend on the phase of the menstrual cycle in which it was administered. Administration in the mid-follicular phase results in inhibition of folliculogenesis and a reduction in estradiol concentrations. If administered during the time of peak luteinizing hormone, follicular rupture is delayed by 5 to 9 days. Dosing in the early luteal phase does not significantly delay endometrial maturation but does decrease endometrial thickness by 0.6 +/- 2.2 mm.

    PHARMACOKINETICS

    Uliprisal is administered orally. It is highly bound (more than 94%) to plasma proteins, and is excreted into breast milk. Ulipristal acetate is readily converted to its mono-N-demethylated and subsequently to its di-N-demethylated metabolites. In vitro data indicate that this is predominantly mediated by CYP3A4. The main route of elimination is through faeces and less than 10% is excreted in the urine. The terminal half-life after a single 30-mg dose is 32.4 +/- 6.3 hours.
     
    Affected cytochrome P450 (CYP450) isoenzymes and drug transporters: CYP3A4, P-glycoprotein (P-gp)
    Ulipristal is a CYP3A4 substrate. In vitro data indicate ulipristal does not inhibit or induce the activity of CYP450 enzymes. Ulipristal should not be given with drugs or herbal products that potently induce CYP3A4, as effectiveness is likely to be reduced. When a single 30-mg dose of ulipristal acetate was administered following administration of the strong CYP3A4 inducer (rifampin), the Cmax and AUC of ulipristal acetate decreased by 90% and 93% respectively. The Cmax and AUC of monodemethyl-ulipristal acetate decreased by 84% and 90% respectively.
     
    CYP3A4 inhibitors increase the plasma concentrations of ulipristal; the drug is not recommended to be administered with moderate or potent CYP3A4 inhibitors when given chronically (daily for hormonal conditions). When used single-dose for emergency contraception, use with caution and be alert for increased common side effects, like nausea/vomiting, dizziness, and headache. When a single 10-mg dose of ulipristal acetate was administered following administration of the strong CYP3A4 inhibitor, the Cmax and AUC of ulipristal acetate increased by 2- and 5.9- fold, respectively. While the AUC of monodemethyl-ulipristal acetate increased by 2.4-fold, Cmax of monodemethyl-ulipristal acetate decreased by 47%. In vitro data indicate that ulipristal is an inhibitor of P-glycoprotein (P-gp) and breast-cancer resistance protein (BCRP) at the intestinal level, during the time of ulipristal absorption. The effects of ulipristal on P-gp and/or BCRP transport are unlikely to have any clinical consequences when considering a single dose treatment regimen for emergency contraception, although there was no in vivo drug interaction study. It is recommended that coadministration of ulipristal acetate and orally-administered narrow-therapeutic index P-gp substrates be separated in administration time by at least 1.5 hours, particularly with chronic daily administration of ulipristal. This separation time has been shown to negate the potential for interaction when fexofenadine (a sensitive P-gp substrate) was studied with ulipristal.

    Oral Route

    Following oral administration, peak plasma concentrations of ulipristal and its active metabolite are reached in approximately 1 hour. Although administration with a high-fat meal results in a lower maximum concentration and delays time to reach a maximum concentration when compared to administration in the fasting state, these differences are not expected to result in significant changes in efficacy or safety. Therefore, ulipristal may be taken with or without food.