ella

Generic Name: Ulipristal Acetate
Class: Contraceptives
VA Class: HS200
Chemical Name: 19-Norpregna-4,9-diene-3,20-dione, 17-(acetyloxy)-11-[4-(dimethylamino)phenyl]-, (11β)-
Molecular Formula: C30H37NO4
CAS Number: 126784-99-4

Introduction

Postcoital contraceptive; synthetic selective progesterone receptor modulator.1 2 3 6 13 14

Uses for ella

Postcoital Contraception

Prevention of unintended pregnancy after unprotected intercourse or known or suspected contraceptive failure as an emergency contraceptive.1 2 3 6 13 14 Postcoital (emergency) contraceptive regimens are not as effective as most other methods of long-term contraception;not intended for routine use as a contraceptive.1 5 14

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Levonorgestrel currently is the preferred postcoital contraceptive when the drug is initiated within 72 hours of unprotected intercourse.5 14 15 16 17 Ulipristal is an effective alternative to levonorgestrel for postcoital contraception when used within 120 hours after unprotected intercourse.1 2 3

ella Dosage and Administration

Administration

Administer orally without regard to meals.1

Administer as soon as possible but within 120 hours following unprotected intercourse.1 2 3

May be used at any time during the menstrual cycle.1

If vomiting occurs within 3 hours after administration, consider repeating the dose.1

Dosage

Available as ulipristal acetate; dosage expressed in terms of the salt.1

Adults

Postcoital Contraception
Oral

Single 30-mg dose taken within 120 hours of unprotected intercourse or known or suspected contraceptive failure.1 2 3

Special Populations

No special population dosage recommendations at this time.1

Cautions for ella

Contraindications

  • Known or suspected pregnancy.1

Warnings/Precautions

Warnings

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm; exclude pregnancy before initiating treatment.1 Embryofetal death reported in animals, but no adequate and well-controlled studies to date in pregnant women.1 If inadvertently used during pregnancy, apprise of potential fetal hazard.1

Existing Pregnancy

Not intended for termination of existing pregnancy; exclude possibility of pregnancy prior to administration.1 Perform pregnancy testing if pregnancy cannot be excluded on basis of history and/or physical examination.1

Follow-up physical and/or pelvic examination recommended if there is concern regarding general health or pregnancy status of women receiving the drug.1

Ectopic Pregnancy

Consider possibility of ectopic pregnancy in women who become pregnant or complain of severe lower abdominal pain.1 Manufacturer states that history of ectopic pregnancy is not considered a contraindication to use.1

Repeated Use

Intended for occasional use as emergency contraceptive.1 Postcoital (emergency) contraceptive regimens are not as effective as most other methods of long-term contraception; not intended for routine use as a contraceptive.1 5 14 Repeated use within the same menstrual cycle not recommended; safety and efficacy of such repeated use not evaluated.1

Fertility Following Use

Rapid return of fertility likely following treatment for emergency contraception; continue or initiate routine methods of contraception as soon as possible to prevent pregnancy.1 4

Ulipristal may reduce the efficacy of other hormonal contraceptives.1 (See Drug Interactions.) Reliable barrier contraceptives (e.g., condom with spermicide) recommended in women for subsequent acts of intercourse within the same menstrual cycle after receiving ulipristal.1

Effect on Menstrual Cycle

Onset of menstruation may occur a few days earlier or later than expected.1 2 3 8 If menstruation delayed by >1 week, rule out pregnancy.1 Intermenstrual bleeding also reported.1

HIV and STDs

Does not protect against HIV infection or other sexually transmitted diseases (STDs).1

Specific Populations

Pregnancy

Category X.1 (See Fetal/Neonatal Morbidity and Mortality and also see Contraindications under Cautions.)

Lactation

Distributed into milk in rats; not known whether distributed into human milk.1 Use not recommended.1

Pediatric Use

Safety and efficacy established in women of reproductive age.1 Safety and efficacy expected to be identical for postpubertal adolescents <18 years of age and women ≥18 years of age.1 Not intended for use before menarche.1

Geriatric Use

Not evaluated in women ≥65 years of age and not intended for use in postmenopausal women.1

Hepatic Impairment

Not studied in patients with hepatic impairment.1

Renal Impairment

Not studied in patients with renal impairment.1

Common Adverse Effects

Headache,1 2 3 6 abdominal pain,1 2 3 6 nausea,1 2 3 6 dysmenorrhea,1 2 3 fatigue,1 2 3 6 dizziness.1 2 3 6

Interactions for ella

Appears to be principally metabolized by CYP3A4.1 10 No evidence of induction or inhibition of CYP isoenzymes from in vitro studies.1

Specific Drugs

Drug

Interaction

Comments

Anticonvulsants (carbamazepine, felbamate, oxcarbazepine, phenytoin, topiramate)

Possible decrease in plasma concentrations and efficacy of ulipristal1

Antifungal agents, azole (itraconazole, ketoconazole)

Possible increase in plasma concentrations of ulipristal1

Barbiturates (e.g., phenobarbital)

Possible decrease in plasma concentrations and efficacy of ulipristal1

Bosentan

Possible decrease in plasma concentrations and efficacy of ulipristal1

Griseofulvin

Possible decrease in plasma concentrations and efficacy of ulipristal1

Hormonal contraceptives

May reduce efficacy of other hormonal contraceptives as a result of high-affinity binding to progesterone receptors1

Recommend reliable barrier contraceptives (e.g., condom with spermicide) for subsequent acts of intercourse within the same menstrual cycle1

Rifampin

Possible decrease in plasma concentrations and efficacy of ulipristal1

St. John's wort (Hypericum perforatum)

Possible decrease in plasma concentrations and efficacy of ulipristal1

ella Pharmacokinetics

Absorption

Bioavailability

Rapidly absorbed following oral administration with peak plasma concentrations attained within 60–90 minutes.1 8

Food

High-fat meal reduces peak plasma concentrations by 40–45% and delays time to peak plasma concentrations from median of 0.75 to 3 hours.1 However, food not expected to result in clinically important effects on efficacy or safety.1

Distribution

Plasma Protein Binding

>94% (mainly HDL-cholesterol, alpha-1-acid glycoprotein, albumin).1 10

Elimination

Metabolism

In vitro data indicate metabolism is predominantly mediated by CYP3A4 in the liver to mono-demethylated (active) and di-demethylated (inactive) metabolites.1 8

Half-life

About 32 hours.1 14

Stability

Storage

Oral

Tablets

20–25°C.1 Protect from light.1

Actions

  • Exhibits antagonist activity at progesterone receptors and inhibits progesterone from binding to its receptors; also possesses partial agonist activity at progesterone receptors.1 7 9 11 14

  • Contraceptive effects may involve inhibition or delay of ovulation, inhibition of follicular growth or rupture, and/or alteration of the endometrium possibly affecting implantation.1 4 10 11 12 13 At recommended doses for postcoital contraception, no clinically important effects on the endometrium.2 14

Advice to Patients

  • Importance of reading the patient information (medication guide) provided by the manufacturer before initiating therapy.1

  • Importance of administering as soon as possible and not >120 hours after unprotected intercourse or known or suspected contraceptive failure.1

  • Importance of women informing a clinician if pregnancy is known or suspected.1 Do not use for termination of existing pregnancy.1

  • Importance of women informing a clinician if vomiting occurs within 3 hours of administration and to discuss the need for a repeat dose.1

  • Importance of advising women to seek medical attention if severe lower abdominal pain occurs 3–5 weeks after administration to rule out possibility of ectopic pregnancy.1

  • Importance of women contacting a clinician if menstruation delayed >1 week beyond the expected date to rule out possibility of pregnancy.1

  • Importance of advising women not to use the drug routinely for contraception and not to repeat use within the same menstrual cycle.1

  • Importance of informing women that ulipristal may reduce the efficacy of other hormonal contraceptives and to use reliable barrier contraceptives (e.g., condom with spermicide) for subsequent acts of intercourse within the same menstrual cycle.1 5

  • Importance of advising women not to use the drug while breast-feeding.1

  • Importance of advising women that ulipristal is not effective in all cases; drug may be less effective in women with body mass index >30 kg/m2.1

  • Importance of informing women that ulipristal does not protect against HIV-infection (AIDS) or other STDs.1

  • Importance of women informing a clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and herbal supplements, as well as any concomitant illnesses.1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Ulipristal Acetate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

30 mg

ella

Watson

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Ella 30MG Tablets (WATSON LABS): 1/$45.99 or 3/$125.97

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions June 21, 2011. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Watson Pharma. ella (ulipristal acetate) tablets prescribing information. Morristown, NJ; 2010 Aug.

2. Glasier AF, Cameron ST, Fine PM et al. Ulipristal acetate versus levonorgestrel for emergency contraception: a randomised non-inferiority trial and meta-analysis. Lancet. 2010; 375:555-62. [PubMed 20116841]

3. Fine P, Mathé H, Ginde S et al. Ulipristal acetate taken 48-120 hours after intercourse for emergency contraception. Obstet Gynecol. 2010; 115:257-63. [PubMed 20093897]

4. Brache V, Cochon L, Jesam C et al. Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture. Hum Reprod. 2010; 25:2256-63. [PubMed 20634186]

5. American Academy of Pediatrics Committee on Adolescence. Emergency contraception. Pediatrics. 2005; 116:1026-35. [PubMed 16147972]

6. Creinin MD, Schlaff W, Archer DF et al. Progesterone receptor modulator for emergency contraception: a randomized controlled trial. Obstet Gynecol. 2006; 108:1089-97. [PubMed 17077229]

7. Attardi BJ, Burgenson J, Hild SA et al. In vitro antiprogestational/antiglucocorticoid activity and progestin and glucocorticoid receptor binding of the putative metabolites and synthetic derivatives of CDB-2914, CDB-4124, and mifepristone. J Steroid Biochem Mol Biol. 2004; 88:277-88. [PubMed 15120421]

8. Blithe DL, Nieman LK, Blye RP et al. Development of the selective progesterone receptor modulator CDB-2914 for clinical indications. Steroids. 2003; 68:1013-7. [PubMed 14667994]

9. Chabbert-Buffet N, Meduri G, Bouchard P et al. Selective progesterone receptor modulators and progesterone antagonists: mechanisms of action and clinical applications. Hum Reprod Update. 2005 May-Jun; 11:293-307.

10. Gainer EE, Ulmann A. Pharmacologic properties of CDB(VA)-2914. Steroids. 2003; 68:1005-11. [PubMed 14667993]

11. Passaro MD, Piquion J, Mullen N et al. Luteal phase dose-response relationships of the antiprogestin CDB-2914 in normally cycling women. Hum Reprod. 2003; 18:1820-7. [PubMed 12923133]

12. Stratton P, Hartog B, Hajizadeh N et al. A single mid-follicular dose of CDB-2914, a new antiprogestin, inhibits folliculogenesis and endometrial differentiation in normally cycling women. Hum Reprod. 2000; 15:1092-9. [PubMed 10783359]

13. Stratton P, Levens ED, Hartog B et al. Endometrial effects of a single early luteal dose of the selective progesterone receptor modulator CDB-2914. Fertil Steril. 2010; 93:2035-41. [PubMed 19200989]

14. Gemzell-Danielsson K, Rabe T. Emergency contraception. J Reproduktionsmed Endokrinol. 2010; 7 (Sonderheft 1): 73-77.

15. Glasier A. Emergency postcoital contraception. N Engl J Med. 1997; 337:1058-64. [IDIS 393096] [PubMed 9321535]

16. . Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception. Task Force on Postovulatory Methods of Fertility Regulation. Lancet. 1998; 352:428-33. [IDIS 415081] [PubMed 9708750]

17. von Hertzen H, Piaggio G, Ding J et al. Low dose mifepristone and two regimens of levonorgestrel for emergency contraception: a WHO multicentre randomised trial. Lancet. 2002; 360:1803-10. [PubMed 12480356]

18. Hild SA, Reel JR, Hoffman LH et al. CDB-2914: anti-progestational/anti-glucocorticoid profile and post-coital anti-fertility activity in rats and rabbits. Hum Reprod. 2000; 15:822-9. [PubMed 10739827]

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