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.

IZBA (NDA-204822)

(TRAVOPROST)

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

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06/09/2021 (SUPPL-2)

Approved Drug Label (PDF)

6 Adverse Reactions

6.1 Clinical Trials Experience

(Subsection title revised; Additions and/or revisions underlined)

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

…

8 Use in Specific Populations

8.1 Pregnancy

(PLLR conversion)

Risk Summary

There are no adequate and well-controlled studies of IZBA administration in pregnant women to inform a drug associated risk.

In animal reproduction studies, subcutaneous (SC) administration of travoprost to pregnant mice and rats throughout the period of organogenesis produced embryo-fetal lethality, spontaneous abortion, and premature delivery at potentially clinically relevant doses.

Advise pregnant women of a potential risk to a fetus. Because animal reproductive studies are not always predictive of human response, IZBA® should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

The background risk of major birth defects and miscarriage for the indicated population is unknown; however, in the U.S. general population, the estimated background risk of major birth defects is 2%-4% and of miscarriage is 15%-20% of clinically recognized pregnancies.

Data

Animal Data

An embryo-fetal study was conducted in pregnant rats administered travoprost once daily by SC injection from gestation Day 6 to 17 to target the period of organogenesis. At 10 mcg/kg [81 times the maximum recommended human ocular dose (MRHOD), based on plasma Cmax)], travoprost was teratogenic in rats, evidenced by an increase in the incidence of skeletal malformations as well as external and visceral malformations, including fused sternebrae, domed head, and hydrocephaly. Travoprost caused post- implantation loss at 10 mcg/kg. The no observed adverse effect level (NOAEL) for post-implantation loss was 3 mcg/kg (24 times the MRHOD, based on estimated plasma Cmax). The maternal NOAEL was 10 mcg/kg.

An embryo-fetal study was conducted in pregnant mice administered travoprost once daily by SC injection from gestation Day 6 to 11, to target the period of organogenesis. At 1 mcg/kg (8.1 times the MRHOD, based on plasma Cmax), travoprost caused post-implantation loss and decreased fetal weight. The NOAEL for embryo- fetal toxicity was 0.3 mcg/kg (2.4 times the MRHOD, based on estimated plasma Cmax). The maternal NOAEL was 1 mcg/kg.

Pre/postnatal studies were conducted in rats administered travoprost once daily by SC injection from gestation Day 7 (early embryonic period) to postnatal Day 21 (end of lactation period). At doses of greater than or equal to 0.12 mcg/kg/day (0.97 times the MRHOD, based on estimated plasma Cmax), adverse pregnancy outcomes (embryo-fetal lethality, abortion, early delivery), low birth weight, and developmental delays were observed. The NOAEL for adverse pregnancy outcomes, low birth weight, and developmental delay was 0.1 mcg/kg (0.81 times the MRHOD, based on estimated plasma Cmax). The NOAEL for maternal toxicity was 0.72 mcg/kg (5.8 times the MRHOD, based on estimated plasma C max).

8.2 Lactation

(PLLR conversion)

Risk Summary

There are no data on the effects of travoprost on the breastfed child or milk production. It is not known if travoprost is present in human milk following ophthalmic administration. A study in lactating rats demonstrated that radiolabeled travoprost and/or its metabolites were transferred into milk following SC administration.

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for use IZBA and any potential adverse effects on the breast-fed child from use of IZBA.