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.

FIRAZYR (NDA-022150)

(ICATIBANT ACETATE)

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

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01/19/2024 (SUPPL-16)

Approved Drug Label (PDF)

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

PATIENT INFORMATION FIRAZYR (FIR-a-zeer) (icatibant) Injection, for subcutaneous use

(Additions and/or revisions underlined)

Please read this Patient Information before you use FIRAZYR and each time you get a refill. There may be new information. This information does not take the place of talking with your healthcare provider about your medical condition or your treatment.

What is FIRAZYR?

FIRAZYR is a medicine used to treat acute attacks of hereditary angioedema (HAE) in adults 18 years and older.
It is not known if FIRAZYR is safe or effective for children under 18 years of age.
What should I tell my healthcare provider before using FIRAZYR?
Before you use FIRAZYR, tell your healthcare provider about all your medical conditions including if you:

are pregnant or plan to become pregnant. It is not known if FIRAZYR will harm your unborn baby. You and your healthcare provider will decide if FIRAZYR is right for you.
are breastfeeding or plan to breastfeed. It is not known if FIRAZYR passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby if you use FIRAZYR.

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

How should I use FIRAZYR?

Read the Instructions for Use at the end of this Patient Information leaflet for detailed instructions about the right way to use FIRAZYR…

04/16/2020 (SUPPL-12)

Approved Drug Label (PDF)

8 Use in Specific Populations

8.1 Pregnancy

(PLLR conversion)

Risk Summary

Available data from published literature and the pharmacovigilance database with Firazyr (icatibant) use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. In animal reproduction studies, icatibant, administered by the subcutaneous route during the period of organogenesis, did not cause structural abnormalities in rats or rabbits; however, premature birth and abortion were observed in rabbits at doses approximately 0.025 times the maximum recommended human dose (MRHD) and higher. Decreased embryofetal survival was observed in rabbits at a subcutaneous dose that was 13 times the MRHD. In a pre- and post-natal development study in rats, delayed parturition was observed at subcutaneous doses 0.5 times the MRHD and higher, which resulted in deaths of dams at doses 2 times the MRHD and higher. Fetal death and early pup deaths were observed with doses 2 times the MRHD.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the

U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Data

Animal Data

In an embryo-fetal development study with rats that received icatibant from gestation days 7 to 18, there was no evidence of any treatment-related structural abnormalities or effects on embryo-fetal survival with maternal doses up to 2.7 times the MRHD (on a mg/m2 basis with maternal subcutaneous doses up to 25 mg/kg/day). In a fertility and early embryonic development study with rats, icatibant increased pre- implantation loss at a dose that was 7 times the MRHD (on an AUC basis at a maternal dose of 10 mg/kg/day).

In an embryo-fetal development study with rabbits that received icatibant from gestation days 7 to 18, premature birth and abortion rates increased at doses approximately 0.025 times the MRHD and higher (on a mg/m2 basis at maternal subcutaneous doses of 0.1 mg/kg and higher). Icatibant treatment resulted in dose-related decreases of total implantations and total number of live fetuses as well as dose-related increases of percent pre-implantation loss at a dose that was 13 times the MRHD (on an AUC basis with a maternal subcutaneous dose of 10 mg/kg/day). There was no evidence of any treatment-related structural abnormalities with maternal doses up to 13 times the MRHD (on an AUC basis with maternal subcutaneous doses up to 10 mg/kg/day).

In a pre- and post-natal development study in the rat, dams received icatibant by the subcutaneous route at doses of 1, 3, and 10 mg/kg/day from gestation day 6 to post-partum (PPD) day 20. Delayed parturition was observed at doses 0.5 times the MRHD and higher (on an AUC basis with maternal subcutaneous doses of 1 mg/kg/day and higher), which resulted in deaths of dams at doses 2 times the MRHD and higher (on an AUC basis with maternal subcutaneous doses of 3 mg/kg/day and higher). Fetal death and increased pup deaths through PPD 4 were observed with doses 2 times the MRHD (on an AUC with a maternal subcutaneous dose of 3 mg/kg/day and higher). Impairment of pup righting reflex and decreased pup hair growth were also observed at 7 times the MRHD (on an AUC basis with a maternal dose of 10 mg/kg). Icatibant and the M2 metabolite were found in maternal milk following subcutaneous administration of icatibant. The no effect dose for F1 pups was identified at a dose 0.5 times the MRHD (on an AUC basis with a maternal subcutaneous dose of 1 mg/kg/day). A no effect dose was not identified for F0 maternal toxicity.

8.2 Lactation

(PLLR conversion)

Risk Summary

There are no data on the presence of icatibant in human milk, the effects on the breastfed infant, or the effects on milk production. Icatibant and the M2 metabolite were found in rat milk following subcutaneous administration of icatibant. When a drug is present in animal milk, it is likely that the drug will be present in human milk. However, systemic absorption of icatibant in infants is not expected after oral exposure through breast milk. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for FIRAZYR and any potential adverse effects on the breastfed child from FIRAZYR or from the underlying maternal condition.

Data

Animal Data

Icatibant is excreted into the milk of lactating rats at concentrations that sometimes slightly exceeded those measured in the maternal plasma.

04/16/2020 (SUPPL-13)

Approved Drug Label (PDF)

6 Adverse Reactions

6.3 Postmarketing Experience

(Additions and/or revisions underlined)

The following adverse reactions have been identified during post approval use of FIRAZYR: urticaria. Because these events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.