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.

TEGSEDI (NDA-211172)

(INOTERSEN SODIUM)

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

Download Data

Expand all

01/12/2024 (SUPPL-14)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.1 Thrombocytopenia

Additions and/or revisions underlined:

TEGSEDI causes reductions in platelet count at any time during treatment that may result in sudden and unpredictable thrombocytopenia that can be life-threatening.

5.6 Liver Injury

Additions and/or revisions underlined:

Monitor alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin at baseline and monthly during treatment with TEGSEDI.

…

If a patient is suspected to have developed liver injury induced by TEGSEDI treatment, TEGSEDI should be discontinued.

6 Adverse Reactions

Addition of the following to the bulleted line listing:

Reduced Serum Vitamin A Levels and Recommended Supplementation [see Warnings and Precautions (5.9)]

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

PATIENT COUNSELING INFORMATION

Additions and/or revisions underlined:

Thrombocytopenia

Inform patients that TEGSEDI can cause reductions in platelet count at any time during treatment that may result in thrombocytopenia.

…

Liver Injury

Instruct patients to inform a healthcare professional of symptoms suggestive of hepatic dysfunction that occur after administration of TEGSEDI [see Warnings and Precautions (5.6)]. Advise patients of the importance of monitoring during treatment with TEGSEDI.

MEDICATION GUIDE

Additions and/or revisions underlined:

TEGSEDI can cause serious side effects, including:

low platelet counts (thrombocytopenia). TEGSEDI may cause the number of platelets in your blood to be reduced at any time during treatment.

…

07/30/2020 (SUPPL-8)

Approved Drug Label (PDF)

8 Use in Specific Populations

8.1 Pregnancy

Newly added information:

Pregnancy Exposure Registry

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to TEGSEDI during pregnancy. Health care providers are encouraged to register patients and pregnant women are encouraged to register themselves by calling: 1-877-465-7510 , emailing: tegsedipregnancy@ubc.com, or visiting online at: www.tegsedipregnancystudy.com.

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

MEDICATION GUIDE

Before you start using TEGSEDI, tell your healthcare provider about all your medical conditions, including if you:

Additions and/or revisions underlined:

are pregnant or plan to become pregnant. It is not known if TEGSEDI can harm your unborn baby.

There is a registry for women who become pregnant during treatment with TEGSEDI. If you become pregnant while taking TEGSEDI, talk to your healthcare provider about registering with the TEGSEDI Pregnancy Exposure Registry. The purpose of this registry is to collect information about your health and your baby’s health. You can get more information about this registry by calling: 1-877-465-7510, emailing: tegsedipregnancy@ubc.com, or visiting online at: www.tegsedipregnancystudy.com.

PATIENT COUNSELING INFORMATION

Additions and/or revisions underlined:

TEGSEDI they should inform their healthcare provider. Advise female patients of childbearing potential of the potential risk to the fetus. Encourage patients to enroll in the TEGSEDI Pregnancy Registry if they become pregnant while taking TEGSEDI [see Use in Specific Populations (8.1)].

For more information about TEGSEDI, go to www.TEGSEDIREMS.com or call 1-844-483- 4736.

10/25/2019 (SUPPL-4)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.6 Liver Injury

(subsection title renamed; additions and/or revisions are underlined)

The liver is a site of accumulation of antisense oligonucleotides. In clinical studies, 8% of TEGSEDI-treated patients had an increased alanine aminotransferase (ALT) at least 3 times the upper limit of normal (ULN), compared to 3% of patients on placebo; 3% of TEGSEDI-treated patients had an ALT at least 8 times the ULN, compared to no patient on placebo. One clinical study patient experienced an increased ALT more than 30 times the ULN. After a course of corticosteroids and discontinuation of TEGSEDI, the patient’s ALT returned to normal levels. Some patients had resolution of the liver laboratory abnormalities with continued use of TEGSEDI.

In clinical studies, demonstrated or possible cases of immune-mediated biliary disease occurred in TEGSEDI-treated patients. There was a single case of autoimmune hepatitis with primary biliary cirrhosis in a patient with a family history of primary biliary cirrhosis, as well as a single case of biliary obstruction of unclear etiology.

Monitor alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin at baseline and every four months during treatment with TEGSEDI. If a patient develops clinical signs or symptoms suggestive of hepatic dysfunction (e.g., unexplained nausea, vomiting, abdominal pain, fatigue, anorexia, or jaundice and/or dark urine), promptly measure serum transaminases and total bilirubin and interrupt or discontinue treatment with TEGSEDI, as appropriate.

Liver Transplant Rejection

In a clinical study, cases of liver transplant rejection were reported 2-4 months after starting TEGSEDI in patients whose liver allografts had previously been clinically stable (for over 10 years) prior to starting TEGSEDI. In these cases, the patients clinically improved and transaminase levels normalized after glucocorticoid administration and cessation of TEGSEDI.

In patients with a history of liver transplant, monitor ALT, AST, and total bilirubin monthly. Discontinue TEGSEDI in patients who develop signs of liver transplant rejection.

6 Adverse Reactions

(additions and/or revisions are underlined)

The following serious adverse reactions are discussed in greater detail in other sections of the labeling:

Thrombocytopenia
Glomerulonephritis and Renal Toxicity
Stroke and Cervicocephalic Arterial Dissection
Inflammatory and Immune Effects
Liver Injury
Hypersensitivity
Reduced Serum Vitamin A Levels and Recommended Supplementation

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

MEDICATION GUIDE

(additions and/or revisions are underlined)

…

Before you start using TEGSEDI, tell your healthcare provider about all your medical conditions, including if you:

have or had bleeding problems
have or had kidney problems
have received a liver transplant
are pregnant or plan to become pregnant. It is not known if TEGSEDI can harm your unborn baby.
are breastfeeding or plan to breastfeed. It is not known if TEGSEDI can pass into your breast milk or harm your baby. Talk with your healthcare provider about the best way to feed your baby while you are using TEGSEDI.

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

Especially tell your healthcare provider if you take:

Vitamin A or beta-carotene supplements. Your healthcare provider should tell you to take vitamin A, but only take the amount they tell you to take.
blood thinners (anticoagulants) or medicines that affect blood clotting.

Ask your healthcare provider or pharmacist if you are not sure if you take any of these medicines. Know the medicines you take. Keep a list of them to show your healthcare provider or pharmacist when you get a new medicine.

…

PATIENT COUNSELING INFORMATION

(additions and/or revisions are underlined)

Advise the patient and caregiver to read the FDA-approved patient labeling (Medication Guide and Instructions for Use).

Thrombocytopenia

Inform patients that TEGSEDI can cause reductions in platelet count that may result in thrombocytopenia. Instruct patients to notify a healthcare provider immediately if they show symptoms of thrombocytopenia (e.g., unusual or prolonged bleeding, neck stiffness, or atypical severe headache). Advise patients of the importance of monitoring during treatment with TEGSEDI. Also instruct patients to notify their healthcare provider of all medications, including over-the-counter, that they are taking.

Glomerulonephritis and Renal Toxicity

Inform patients that glomerulonephritis has occurred in patients treated with TEGSEDI. Advise patients of the importance of monitoring of urine protein to creatinine ratio (UPCR during treatment with TEGSEDI).

TEGSEDI REMS Program

TEGSEDI is available only through a restricted program called the TEGSEDI

REMS Program. Inform the patient of the following notable requirements:

Patients must enroll in the program and comply with ongoing monitoring requirements.

TEGSEDI is available only from certified pharmacies participating in the program. Therefore, provide patients with the telephone number and website for information on how to obtain the product.

Stroke and Cervicocephalic Arterial Dissection

Educate patient on symptoms of stroke and central nervous system arterial dissection and instruct them to seek help as soon as possible if symptoms of these or other serious neurologic adverse reactions occur [see Warnings and Precautions (5.4)].

Liver Injury

Instruct patients to inform a healthcare professional of symptoms suggestive of hepatic dysfunction that occur after administration of TEGSEDI

…