Drug Safety-related Labeling Changes (SrLC)

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Drug Safety-related Labeling Changes (SrLC) Database

ANDA	Abbreviated New Drug Application
BLA	Biologics License Application
CDER	Center for Drug Evaluation and Research
MG	Medication Guide
NDA	New Drug Application
PCI	Patient Counseling Information
PI	Patient Information
PLR	Physician Labeling Rule
PLLR	Pregnancy and Lactation Labeling Rule
Italics	For the most part, italics indicate an FDA comment such as: Additions and/or revisions underlined These italics usually appear at the beginning of the section. In some cases, italics may be an inherent part of the label, and will most often appear in the body of the section.
Underlines	Any text that is underlined indicates text that has been added or revised. There are exceptions where underlining occurs in a section subtitle or heading. This is the case when there is just one word underlined in the body of the text.

Sections

BW	Box Warning
WP	Warnings and Precautions all in one section (PLR-format) Warnings as one section (pre-PLR format) Precautions as one section (pre-PLR format)
AR	Adverse Reactions (in pre-PLR format, this may be a subheading under precautions).
DI	Drug Interactions (in pre-PLR format, this may be a subheading under precautions).
USP	Use in Specific Populations (Inclusive on one or more of the following: Pregnancy; Lactation (PLLR- format); Nursing Mothers (pre-PLLR format); Females and Males of Reproductive Potential (PLLR format only); Pediatric Use, Geriatric Use, Renal Impairment, Hepatic Impairment, Sex, Race (these last six may be a subheading of precautions if label in pre-PLLR format.
PCI/PI/MG	Patient Counseling Information (PLR format only) - summarizes the information that a health care provider should convey to a patient (or caregiver when applicable) when a counseling discussion is taking place (e.g., a physician prescribing a drug during an office visit, a nurse providing discharge instructions at a hospital, or a pharmacist conveying information at a pharmacy). Patient Information - FDA approved patient labeling. Medication Guide - paper handouts that come with many prescription medicines. The guides address issues that are specific to particular drugs and drug classes, and they contain FDA-approved information that can help patients avoid serious adverse events.

Only NDAs and CDER regulated BLAs are included in this database. ANDAs are not included.

Applications that remain active, even if the product has been discontinued, undergo safety-related labeling changes.

ELLA (NDA-022474)

(ULIPRISTAL ACETATE)

Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)

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06/24/2021 (SUPPL-11)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.5 Fertility Following Use

Additions and/or revisions underlined

A rapid return of fertility is likely following treatment with ella for emergency contraception.

After use of ella, a reliable barrier method of contraception should be used with subsequent acts of intercourse until the next menstrual period.

After using ella, if a woman wishes to initiate hormonal contraception as a regular method, she can do so, no sooner than 5 days after the intake of ella and she should use a relia ble barrier method until the next menstrual period [see Dosageand Administration (2.2), Drug Interactions (7.1 and 7.3) and Clinical Pharmacology (12.2)].

Progestin-containing contraceptives may impair the ability of ella to delay ovulation. Advise women to follow the instructions on the initiation or resumption of hormonal contraceptives after ella intake [see Dosageand Administration (2.2)].

6 Adverse Reactions

6.2 Postmarketing Experience

Additions underlined

…

Hypersensitivity reactions, including rash, urticaria, pruritis, and angioedema

…

7 Drug Interactions

7.1 Changes in Emergency Contraceptive Effectiveness Associated with Co-Administration of Other Products

Additions underlined

…

contraceptives
Progestin-containing contraceptives may impair the ability of ella to delay ovulation. After using ella, if a woman wishes to initiate or resume hormonal contraception, she can do so, no sooner than 5 days after the intake of ella and she should use a relia ble barrier method until the next menstrual period. If a woman used ella due to a known or suspected failure of her hormonal contraception refer to the hormonal contraceptive’s prescribing information for instructions on what to do
[see Dosageand Administration (2.2), Warnings and Precautions (5.5) and Clinical Pharmacology (12.2)].

8 Use in Specific Populations

8.3 Females and Males of Reproductive Potential

Additions underlined

Contraception

Progestin-containing contraceptives may impair the ability of ella to delay ovulation. Advise females to use a reliable barrier method for subsequent acts of intercourse until her next menstrual period.

After using ella, if a woman wishes to initiate or resume hormonal contraception, she can do so, no sooner than 5 days after the intake of ella and she should use a relia ble barrier methodof contraception until the next menstrual period. If a woma nused ella due to a known or suspected failure of her hormonal contraception refer to the hormonal contraceptive’s prescribing information for instructions on what to do [see Dosageand Administration (2.2), Warnings and Precautions

(5.5), Drug Interactions (7), and Clinical Pharmacology (12.2, 12.3)].

8.4 Pediatric Use

Additions underlined

There is no relevant use of ulipristal acetate for children of prepubertal age in the indication emergency contraception.

…

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

PATIENT COUNSELING INFORMATION

Additions underlined

…

Administration Instructions

Instruct patients to take ella as soon as possible and not more than 120 hours after unprotected intercourse or a known or suspected contraceptive failure.
Advise patients to contact their healthcare provider immediately in case of vomiting within 3 hours of taking the tablet, to discuss whether to take another tablet.
Advise patients that after using ella, a relia ble barrier method of contraception should be used for all subsequent acts of intercourse until the next menstrual period.
Advise patients that after using ella, additional levonorgestrel emergency contraceptive pills should not be used within 5 days of ella intake.
Advise patients that a fter using ella, hormonal contraception should be initia ted or resumed no sooner than 5 days after the intake of ella and to use a relia ble contraceptive barrier method until the next menstrual period.
Advise patients with known or suspectedfailure of a hormonal contraceptive to refer to the hormonal contraceptive’s prescribing information for instructions on what to do.

…

Effect on Menstrual Cycle

Advise women that after ella intake, menses may occur earlier or later than expected, by a few days. Advise patients to contact their healthcare provider and consider the possibility of pregnancy if their period is delayed after taking ella by more than 1 week beyond the date it was expected [see Warnings and Precautions (5.6)].

…

PATIENT INFORMATION

Section revised to reflect all of the changes in the PI and to reduce redundancy, please refer to label for complete information.

05/01/2018 (SUPPL-10)

Approved Drug Label (PDF)

8 Use in Specific Populations

8.1 Pregnancy

(Pregnancy and Lactation Labeling Rule (PLLR) Conversion; additions and/or revisions are underlined)

ella is contraindicated for use during an existing or suspected pregnancy. No signal of concern regarding pregnancy complications was found in postmarketing studies. Isolated cases of major malformations in ella-exposed pregnancies were identified; however, the data are not sufficient to determine a risk for birth defects with inadvertent use of ella during pregnancy. Miscarriage was reported in 14% of the known pregnancy outcomes; a rate that is similar to the U.S background rate for miscarriage. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

In animal reproduction studies, no malformations were observed during repeated administration of ulipristal acetate to pregnant rats, rabbits and monkeys at daily drug exposures ?, ½, and 3 times respectively, the human exposure at a dose of 30 mg

Data

Human Data

ella pregnancy exposure data was collected in the U.S. and Europe from 1999 to 2015 and analyzed post-marketing using data from interventional clinical trials, observational studies and pharmacovigilance reports. Known pregnancy outcomes were available for 462/784 pregnancies in which wome received ella 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). Although these data do not allow estimation of the prevalence rate of congenital anomalies associated with inadvertent use of ella in pregnancy or determination of a causal relationship between reported anomalies and ella, they show that ella-exposed pregnancies were not associated with a pattern of increased risk of adverse outcomes.

Animal Data

8.2 Lactation

Risk Summary

Ulipristal acetate and its active metabolite, monodemethyl-ulipristal acetate, are present in human milk in small amounts. Based on the levels of drug and active metabolite measured in breastmilk, a fully breastfed child would receive a weight-adjusted dosage of approximately 0.8% of ulipristal acetate and monodemethyl-ulipristal acetate on Day 1 of drug administration and an approximate total of 1% of the maternal dose over a 5-day period after drug administration. There is no information on the effects on the breastfed child or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ella and any potential adverse effects on the breastfed child from ella or from the underlying maternal condition

Data

The breast milk of 12 lactating women following administration of ella was collected in 24-hour increments to measure the concentrations of ulipristal acetate and the active metabolite monodemethyl-ulipristal acetate in breast milk. The mean daily concentrations of ulipristal acetate in breast milk were 22.7 ng/mL [0-24 hours], 2.96 ng/mL [24-48 hours], 1.56 ng/mL [48-72 hours], 1.04 ng/mL [72-96 hours], and 0.69 ng/mL [96-120 hours]. The mean daily concentrations of monodemethyl-ulipristal acetate in breast milk were 4.49 ng/mL [0-24 hours], 0.62 ng/mL [24-48 hours], 0.28 ng/mL [48- 72 hours], 0.17 ng/mL [72-96 hours], and 0.10 ng/mL [96-120 hours]. Using these data, a fully breastfed infant would receive approximately 4.1 mcg/kg of ulipristal acetate and monodemethyl-ulipristal acetate on Day 1 following drug administration and approximately 5.2 mcg/kg over a five day period following drug administration.

8.3 Females and Males of Reproductive Potential

(Pregnancy and Lactation Labeling Rule (PLLR) Conversion; additions and/or revisions are underlined)

Contraception

ella and progestin-containing contaceptives may interact and decrease the effectivess of both products. Advise females to use a a reliable barrier method for subsequent acts of intercourse until her next menstrual period and to wait at least 5 days after taking ella to resume oral contraceptives.

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

Patient Information

(Additions and/or revisions are underlined)

What should I tell my healthcare provider before taking ella?

See “Who should not take ella?”

Tell your healthcare provider about all the medicines you take, including prescription and nonprescription medicines, vitamins, and herbal supplements.

Using some other medicines may make ella less effective. These include St. John’s Wort, bosentan, griseofulvin, phenytoin, topiramate, oxcarbazepine, carbamazepine, barbitarates, rifampin, and felbamate. Talk to your healthcare provider about whether ella is right for you if you are currently using these medications. Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.