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.

ELITEK (BLA-103946)

(RASBURICASE)

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

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12/12/2019 (SUPPL-5103)

Approved Drug Label (PDF)

8 Use in Specific Populations

8.1 Pregnancy

(PLLR conversion)

Risk Summary

Based on findings in animals, Elitek may cause fetal harm when administered to pregnant women. In animal reproduction studies, intravenous administration of rasburicase to pregnant rabbits during organogenesis at 5-times the human exposure (based on AUC) at the recommended human dose of 0.2 mg/kg resulted in adverse developmental outcomes, including structural abnormalities, embryo-fetal mortality, and alterations to growth (see Data). The limited available data with Elitek use in pregnant women are insufficient to inform a drug- associated risk of major birth defects, miscarriage, or adverse maternal fetal outcomes. Consider the benefits and risks of Elitek and possible risks to the fetus when prescribing Elitek to a pregnant woman.

The estimated background risk of major birth defects and miscarriage in the indicated population is unknown. All pregnancies have a background risk of birth defect, miscarriage, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriages in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Data Animal data

Intravenous administration of rasburicase at doses of 10, 20, or 50 mg/kg/day (approximately 14, 34, and 100 times the exposure at the recommended human dose of 0.2 mg/kg) to pregnant rats from gestation days (GD) 6 to 17 produced multiple heart and great vessel malformations at

50 mg/kg/day (approximately 100 times the exposure at the recommended human dose). Intravenous administration of rasburicase from GD 6 to 19 at doses of 2, 10, or 20 mg/kg/day (approximately 5, 26, and 54 times the exposure at the recommended human dose) to pregnant rabbits produced increased pre and postimplantation loss, abortion, decreased uterine weight, decreased fetal body weights, and heart and great vessel malformations at all dose levels.

8.2 Lactation

(PLLR conversion)

Risk Summary

There are no available data on the presence of rasburicase in human breast milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in the breastfed child, advise patients that breastfeeding is not recommended during treatment with Elitek, and for 2 weeks after the last dose.

8.4 Pediatric Use

(additions and or revisions underlined)

The safety and effectiveness of Elitek have been established in pediatric patients ages 1 month to 17 years for initial management of plasma uric acid levels in patients with leukemia, lymphoma, and solid tumor malignancies who are receiving anticancer therapy expected to result in tumor lysis and subsequent elevation of plasma uric acid. Elitek was studied in 246 pediatric patients.

…

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

PATIENT COUNSELING INFORMATION

(additions underlined)

…

Lactation

Advise females not to breastfeed during treatment with Elitek and for at least 2 weeks after the last dose.

06/13/2016 (SUPPL-5097)

Approved Drug Label (PDF)

Boxed Warning

Anaphylaxis

Change 1st section of Anaphylaxis to read:

Hypersensitivity Reactions: Elitek can cause serious and fatal hypersensitivity reactions including anaphylaxis. Immediately and permanently discontinue Elitek if a serious hypersensitivity reaction occurs.

5 Warnings and Precautions

Hypersensitivity Reactions replaces Anapylaxis section

(addition) Elitek can cause serious and fatal hypersensitivity reactions including anaphylaxis. In clinical studies, anaphylaxis was reported in <1% patients receiving Elitek. This can occur at any time during treatment including the first dose. Signs and symptoms of these reactions include bronchospasm, chest pain and tightness, dyspnea, hypoxia, hypotension, shock, and urticaria. Immediately and permanently discontinue Elitek administration in any patient developing clinical evidence of a serious hypersensitivity reaction.

Replace subheading of Laboratory Sample Handling Procedure with Laboratory Test Interference

6 Adverse Reactions

Post-marketing Experience

Immune system disorders: Cases of anaphylaxis with potential fatal outcome have been reported. (addition)

7 Drug Interactions

Laboratory Test Interference (new subsection)

At room temperature, Elitek causes enzymatic degradation of the uric acid in blood/plasma/serum samples potentially resulting in spuriously low plasma uric acid assay readings. The following special sample handling procedure must be followed to avoid ex vivo uric acid degradation. Uric acid must be analyzed in plasma. Blood must be collected into pre-chilled tubes containing heparin anticoagulant. Immediately immerse plasma samples for uric acid measurement in an ice water bath. Plasma samples must be prepared by centrifugation in a pre-cooled centrifuge (4°C). Finally, the plasma must be maintained in an ice water bath and analyzed for uric acid within four hours of collection.

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

PCI - Hypersensitivity Reactions (new subsection)

Instruct patients to notify their physician immediately if any of the following occur: allergic reaction, bronchospasm, chest pain or tightness, dyspnea, hypoxia, hypotension, shock or urticarial.