Drug Safety-related Labeling Changes (SrLC)

Get Email Alerts | Guide

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.

LETAIRIS (NDA-022081)

(AMBRISENTAN)

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

Download Data

Expand all

04/04/2025 (SUPPL-45)

Approved Drug Label (PDF)

Boxed Warning

Additions and/or revisions underlined:

WARNING: EMBRYO-FETAL TOXICITY

Letairis is contraindicated for use during pregnancy because it may cause major birth defects if used by pregnant patients, based on studies in animals [see Contraindications (4.1), Warnings and Precautions (5.1), and Use in Specific Populations (8.1)].

Therefore, for females of reproductive potential, exclude pregnancy before the initiation of treatment with Letairis. Advise use of effective contraception before initiation, during treatment, and for one month after treatment with Letairis [see Dosage and Administration (2.2) Contraindications (4.1), Warnings and Precautions (5.1), and Use in Specific Populations (8.1, 8.3)].

When pregnancy is detected, discontinue Letairis as soon as possible (5.1).

5 Warnings and Precautions

5.1 Embryo-fetal Toxicity

Additions and/or revisions underlined:

Based on data from animal reproduction studies, Letairis may cause fetal harm when administered during pregnancy and is contraindicated during pregnancy. The available human data for endothelin receptor antagonists do not establish the presence or absence of major birth defects related to the use of Letairis. Advise patients who can become pregnant of the potential risk to a fetus. Obtain a pregnancy test prior to initiation of treatment with Letairis. Advise patients who can become pregnant to use effective contraception prior to initiation of treatment, during treatment, and for one month after discontinuation of treatment with Letairis. When pregnancy is detected, discontinue use as soon as possible [see Dosage and Administration (2.2), and Use in Specific Populations (8.1, 8.3)].

8 Use in Specific Populations

8.1 Pregnancy

Additions and/or revisions underlined:

Risk Summary

Based on data from animal reproduction studies, Letairis may cause fetal harm, including birth defects and fetal death, when administered to a pregnant woman and is contraindicated during pregnancy. There are limited data on Letairis use in pregnant women. Available data from post- marketing reports and published literature over decades of use with endothelin receptor antagonists in the same class as Letairis have not identified an increased risk of major birth defects; however, these data are limited. Methodological limitations of these postmarketing reports and published literature include lack of a control group; limited information regarding dose, duration, and timing of drug exposure; and missing data. These limitations preclude establishing a reliable estimate of the risk of adverse fetal and neonatal outcomes with maternal endothelin receptor antagonist use. In animal reproduction studies, Letairis was teratogenic in rats and rabbits at doses which resulted in exposures of 3.5 and 1.7 times, respectively, the human dose of 10 mg per day [see Animal Data]. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, advise the patient of the potential hazard to a fetus [see Contraindications (4.1), Warnings and Precautions (5.1)].

…

8.3 Females and Males of Reproductive Potential

Additions and/or revisions underlined:

Based on data from animal reproductive toxicity studies, ambrisentan may cause fetal harm, including birth defects and fetal death, when administered to a pregnant patient and is contraindicated during pregnancy [see Contraindications (4.1), Use in Specific Populations (8.1)].

Pregnancy Testing

Verify that patients who can become pregnant are not pregnant prior to initiating ambrisentan. The patient should contact their physician immediately for pregnancy testing if onset of menses is delayed or pregnancy is suspected . If the pregnancy test is positive, the physician and patient should discuss the risks to the pregnancy and the fetus.

Contraception

Patients who can become pregnant who are using ambrisentan should use effective contraception prior to initiation of treatment, during treatment, and for one month after discontinuation of treatment with ambrisentan to prevent pregnancy [see Warnings and Precautions (5.1)].

…

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

PATIENT COUNSELING INFORMATION

Additions and/or revisions underlined:

…

Embryo-fetal Toxicity

Instruct patients on the risk of fetal harm when Letairis is used in pregnancy [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1)]. Instruct females of reproductive potential to immediately contact their physician if they suspect they may be pregnant.Educate and counsel patients who can become pregnant about the need to use effective contraception prior to treatment with Letairis, during treatment, and for one month after treatment discontinuation [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1, 8.3)]. Patients who can become pregnant should have a negative pregnancy test prior to treatment with Letairis [see Dosage and Administration (2.2), Contraindications (4.1), Warnings and Precautions (5.1), Use in Specific Populations (8.1, 8.3)].

Counsel patients who can become pregnant about pregnancy planning and prevention, including emergency contraception, or designate counseling by another healthcare provider trained in contraceptive counseling [see Boxed Warning].

…

Medication Guide

Additions and/or revisions underlined:

…

What is the most important information I should know about Letairis?

…

Females who are able to get pregnant should use effective contraception before beginning Letairis, during treatment with Letairis, and for one month after stopping Letairis because the medicine may still be in the body.

…

08/23/2019 (SUPPL-41)

Approved Drug Label (PDF)

Boxed Warning

‘Ambrisentan REMS’ replaces ‘Letairis REMS’

5 Warnings and Precautions

5.2 Ambrisentan Risk Evaluation and Mitigation Strategy (REMS)

Additions and/or revisions underlined:

For all females, Letairis is available only through a restricted program under a REMS called the Ambrisentan REMS …

Further information is available at www.ambrisentanrems.us.com or 1-888-417-3172.

In this subsection, all instances of ‘Letairis REMS’ and ‘the program’ are replaced by ‘Ambrisentan REMS’.

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

PATIENT COUNSELING INFORMATION

Additions and/or revisions underlined:

Ambrisentan Risk Evaluation and Mitigation Strategy (REMS)

In this section, all instances of ‘Letairis REMS’ and ‘the program’ are replaced by ‘Ambrisentan REMS’.

Letairis is available only from certified pharmacies participating in the program. Therefore, provide patients with the telephone number …

11/30/2018 (SUPPL-40)

Approved Drug Label (PDF)

8 Use in Specific Populations

8.1 Pregnancy

(PLLR conversion, please refer to label for complete information)

8.2 Lactation

(PLLR conversion, please refer to label for complete information)

8.4 Pediatric Use

(additions underlined)

Safety and effectiveness of Letairis in pediatric patients have not been established.

Juvenile Animal Data

In juvenile rats administered ambrisentan orally once daily during postnatal day 7 to 26, 36, or 62, a decrease in brain weight (-3% to -8%) with no morphologic or neurobehavioral changes occurred after breathing sounds, apnea, and hypoxia were observed, at exposures approximately 1.8 to 7.0 times human pediatric exposures at 10 mg, based on AUC.