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.

GIVLAARI (NDA-212194)

(GIVOSIRAN SODIUM)

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

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04/29/2024 (SUPPL-7)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.6 Pancreatitis

Newly added subsection:

Cases of acute pancreatitis, some severe, have been reported in GIVLAARI-treated patients. Consider acute pancreatitis as a potential diagnosis in GIVLAARI-treated patients with signs/symptoms of acute pancreatitis including acute upper abdominal pain, clinically significant elevation of pancreatic enzymes, and/or imaging findings of acute pancreatitis, to ensure appropriate management. Consider interruption and/or discontinuation of GIVLAARI treatment for severe cases.

6 Adverse Reactions

Addition of the following to the bulleted line listing:

Pancreatitis [see Warnings and Precautions (5.6)]

6.3 Postmarketing Experience

Newly added subsection:

The following additional adverse reactions have been reported during post-approval use. Because these events are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Gastrointestinal Disorders: Acute pancreatitis

10/28/2021 (SUPPL-4)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.5 Blood Homocysteine Increased

(Newly added subsection)

Increases in blood homocysteine levels have occurred in patients receiving GIVLAARI [see Adverse Reactions (6.1)]. In the ENVISION study, during the open label extension, adverse reactions of blood homocysteine increased were reported in 15 of 93 (16%) patients treated with GIVLAARI. The clinical relevance of the elevations in blood homocysteine during treatment with GIVLAARI is unknown. Measure blood homocysteine levels prior to initiating treatment and monitor for changes during treatment with GIVLAARI. In patients with elevated blood homocysteine levels, assess folate, vitamins B12 and B6. Consider treatment with a supplement containing vitamin B6 (as monotherapy or a multivitamin preparation).

6 Adverse Reactions

(Addition of the following to the bulleted line listing)

Blood Homocysteine Increased [see Warnings and Precautions (5.5)]

6.1 Clinical Trial Experience

(Additions and/or revisions underlined)

…

In the ENVISION study, during the open label extension, adverse reactions of blood homocysteine increased were reported in 15 of 93 (16%) patients treated with GIVLAARI [see Warnings and Precautions (5.5)].

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

PATIENT COUNSELING INFORMATION

(Additions and/or revisions underlined)

Advise patients of the potential risks of GIVLAARI treatment:

Anaphylactic Reaction: Inform patients about the risk and possible symptoms of severe hypersensitivity reactions that could occur [see Warnings and Precautions (5.1)].
Hepatic Toxicity: Inform patients that transaminase elevations may occur, and that laboratory testing will be conducted in the first 6 months of treatment and as clinically indicated thereafter [see Warnings and Precautions (5.2)].
Renal Toxicity: Inform patients that increases in serum creatinine and decreases in eGFR have been reported and that laboratory testing will be conducted as clinically indicated [see Warnings and Precautions (5.3)].
Injection Site Reactions: Inform patients of the signs and symptoms of injection site reactions (examples include redness, pain, itching, rash, discoloration, or localized swelling) [see Warnings and Precautions (5.4)].
Blood Homocysteine Increased: Inform patients that increases in blood homocysteine levels have been reported when using GIVLAARI, and that laboratory testing will be conducted prior to and during treatment with GIVLAARI. Vitamin supplementation may be considered for elevated blood homocysteine levels [see Warnings and Precautions (5.5)].