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.

OPSYNVI (NDA-218490)

(MACITENTAN; TADALAFIL)

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

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04/02/2025 (SUPPL-2)

Approved Drug Label (PDF)

Boxed Warning

Additions and/or revisions underlined:

WARNING: EMBRYO-FETAL TOXICITY

OPSYNVI is contraindicated for use during pregnancy because it may cause fetal harm based on animal data [see Contraindications (4.1), Warnings and Precautions (5.1), Use in Specific Populations (8.1)].

Therefore, for females of reproductive potential, exclude pregnancy before the start of treatment with OPSYNVI. Advise use of effective contraception before the initiation of treatment, during treatment, and for one month after stopping treatment with OPSYNVI [see Dosage and Administration (2.2), Use in Specific Populations (8.3)]. When pregnancy is detected, discontinue OPSYNVI as soon as possible [see Warnings and Precautions (5.1)].

5 Warnings and Precautions

5.1 Embryo-fetal Toxicity

Additions and/or revisions underlined:

Based on data from animal reproduction studies, OPSYNVI may cause fetal harm when administered to a pregnant patient and is contraindicated during pregnancy. The available human data for ERAs do not establish the presence or absence of major birth defects related to the use of OPSYNVI. Advise patients who can become pregnant of the potential risk to a fetus. Obtain a pregnancy test prior to initiation of therapy with OPSYNVI. Advise patients who can become pregnant to use effective contraceptive methods prior to initiation of treatment, during treatment, and for one month after discontinuation of treatment with OPSYNVI. When pregnancy is detected, discontinue use as soon as possible [see Dosage and Administration (2.2), Contraindications (4.1), and Use in Specific Populations (8.1, 8.3)].

8 Use in Specific Populations

8.1 Pregnancy

Additions and/or revisions underlined:

…

Available data from postmarketing reports and published literature over decades of use with ERAs in the same class as OPSYNVI 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 ERA use. Macitentan was teratogenic in rabbits and rats at all doses tested.

…

8.3 Females and Males of Reproductive Potential

Additions and/or revisions underlined:

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

Pregnancy Testing

Verify that patients who can become pregnant are not pregnant prior to initiating OPSYNVI. 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 OPSYNVI should use an effective method of contraception prior to initiation of treatment, during treatment, and for one month after discontinuation of treatment with OPSYNVI 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 female patients of reproductive potential about the need to use effective methods of contraception prior to initiation of treatment with OPSYNVI, during treatment, and for one month after treatment discontinuation. Females of reproductive potential should have a negative pregnancy test prior to treatment with OPSYNVI [see Contraindications (4.1), 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 OPSYNVI?

…

Females who are able to get pregnant should use effective birth control before starting treatment with OPSYNVI, during treatment, and for 1 month after stopping OPSYNVI because the medicine may still be in the body.

…

Tell your healthcare provider right away if you miss a menstrual period or think you may be pregnant.
If you are the parent or caregiver of a female child who started taking OPSYNVI before reaching puberty, you should check your child regularly to see if she is developing signs of puberty. Tell your healthcare provider right away if you notice that she is developing breast buds or any pubic hair. Your healthcare provider should decide if your child has reached puberty. Your child may reach puberty before having her first menstrual period.
If you are a female who can get pregnant, you should talk to your healthcare provider to understand the benefits and risks of OPSYNVI.
See “What are the possible side effects of OPSYNVI?” for more information about side effects.
…