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.

TRYVIO (NDA-217686)

(APROCITENTAN)

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

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04/02/2025 (SUPPL-4)

Approved Drug Label (PDF)

Boxed Warning

Additions and/or revisions underlined:

WARNING: EMBRYO–FETAL TOXICITY

TRYVIO is contraindicated for use during pregnancy because it may cause fetal harm if used by pregnant patients. Therefore in patients who can become pregnant, exclude pregnancy prior to initiation of TRYVIO.
Advise use of effective contraception before the start of TRYVIO, during treatment and for one month after stopping treatment.
When pregnancy is detected, discontinue TRYVIO as soon as possible [see Dosage and Administration (2.2), Contraindications (4.1), Warnings and Precautions (5.1), Use in Specific Populations (8.1)].

5 Warnings and Precautions

5.1 Embryo-Fetal Toxicity

Additions and/or revisions underlined:

Based on data from animal reproduction studies with endothelin receptor antagonists (ERAs), TRYVIO may cause fetal harm when administered during pregnancy and is contraindicated for use in patients who are pregnant. The available human data for endothelin receptor antagonists do not establish the presence or absence of fetal harm related to the use of TRYVIO. Counsel patients who can become pregnant about thepotential risk to a fetus. Obtain a pregnancy test prior to initiation of treatment with TRYVIO. Advise patients who can become pregnant to use effective contraception prior to initiation of treatment with TRYVIO, during treatment, and for one month after the final dose of TRYVIO. When pregnancy is detected, discontinue TRYVIO as soon as possible [see Dosage and Administration (2.2), Contraindications (4.1), 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 animal reproduction studies with other ERAs, TRYVIO can cause embryo-fetal toxicity, including birth defects and fetal death when administered to a pregnant patient and is contraindicated during pregnancy [see Contraindications (4.1)]. Available data from post-marketing reports and published literature over decades of use with endothelin receptor antagonists in the same class as TRYVIO have not identified an increased risk of fetal harm; however, these data are limited. Methodological limitations of these post- marketing 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.

…

8.3 Females and Males of Reproductive Potential

Additions and/or revisions underlined:

…

Pregnancy Testing

Verify that patients who can become pregnant, are not pregnant prior to initiating TRYVIO. The patient should contact their physician immediately 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 patient, the pregnancy, and the fetus [see Warnings and Precautions (5.1), Dosage and Administration (2.2), Contraindications (4.1)].

Contraception

Patients using TRYVIO who can become pregnant should use effective contraception prior to initiation of treatment, during treatment, and for one month after discontinuation of treatment with TRYVIO 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

Counsel patients who can become pregnant to use effective methods of contraception before treatment with TRYVIO, during treatment with TRYVIO, and for one month after treatment discontinuation. Patients who can become pregnant should have a negative pregnancy test prior to initiation of TRYVIO, [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1, 8.3)].

…

MEDICATION GUIDE

Additions and/or revisions underlined:

…

What is the most important information I should know about TRYVIO? TRYVIO may cause serious side effects, including:

Serious birth defects.

…

Females who can become pregnant should use effective birth control before starting treatment with TRYVIO, during treatment with TRYVIO, and for 1 month after stopping TRYVIO because the medicine may still be in your body.
- Talk with your healthcare provider or gynecologist (a healthcare provider who specializes in female reproduction) to find out about options for effective birth control that you may use to prevent pregnancy during treatment with TRYVIO.
- If you decide that you want to change the form of birth control that you use, talk with your healthcare provider or gynecologist to be sure that you choose another acceptable form of birth control.
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