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.
LUMIZYME (BLA-125291)
(ALGLUCOSIDASE ALFA)
Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)
12/30/2024 (SUPPL-161)
Boxed Warning
Additions and/or revisions underlined:
…
Hypersensitivity Reactions Including Anaphylaxis
Patients treated with enzyme replacement therapies have experienced life-threatening hypersensitivity reactions, including anaphylaxis. Anaphylaxis has occurred during the early course of enzyme replacement therapy and after extended duration of therapy.
Initiate LUMIZYME in a healthcare setting with appropriate medical monitoring and support measures, including access to cardiopulmonary resuscitation equipment. If a severe hypersensitivity reaction (e.g., anaphylaxis) occurs, discontinue LUMIZYME and immediately initiate appropriate medical treatment, including use of epinephrine. Inform patients of the symptoms of life-threatening hypersensitivity reactions, including anaphylaxis and to seek immediate medical care should symptoms occur [see Warnings and Precautions (5.1)].
5 Warnings and Precautions
5.1 Hypersensitivity Reactions Including AnaphylaxisAdditions and/or revisions underlined:
…
In clinical trials, hypersensitivity reactions including anaphylaxis were managed with infusion interruption; decreased infusion rate; and administration of antihistamines, corticosteroids, intravenous fluids, and/or oxygen. In some cases of anaphylaxis, epinephrine was administered. Some LUMIZYME-treated patients who experienced a hypersensitivity reaction and who tested positive for alglucosidase alfa-specific IgE antibodies were successfully rechallenged with a slower infusion rate at a lower dosage of LUMIZYME and continued to receive LUMIZYME under close clinical supervision. Because LUMIZYME-treated patients who develop anti-IgE alglucosidase alfa antibodies appear to be at a higher risk for developing hypersensitivity reactions including anaphylaxis, these patients should be monitored more closely during LUMIZYME administration.
Recommendations to Prevent, Mitigate, and Monitor for Hypersensitivity Reactions
Prior to LUMIZYME administration, consider pretreating with antihistamines, antipyretics, and/or corticosteroids. Administration of LUMIZYME should be supervised by a healthcare provider knowledgeable in the management of hypersensitivity reactions including anaphylaxis. Anaphylaxis has occurred during the early course of enzyme replacement therapy and after extended duration of therapy. Initiate LUMIZYME in a healthcare setting with appropriate medical monitoring and support measures, including access to cardiopulmonary resuscitation equipment.
If a severehypersensitivity reaction (e.g., anaphylaxis) occurs, discontinue LUMIZYME and immediately initiate appropriate medical treatment, including use of epinephrine.
If a mild or moderate hypersensitivity reaction occurs, consider temporarily holding the LUMIZYME infusion or slowing the infusion rate.
Consider the risks and benefits of readministering LUMIZYME following a hypersensitivity reaction including anaphylaxis. Patients may be rechallenged using slower infusion rates at a lower dosage than the recommended dosage [see Adverse Reactions (6.2)]. Inform patients of the symptoms of life-threatening hypersensitivity reactions, including anaphylaxis and recommend they seek immediate medical care should these symptoms occur.
Additions and/or revisions underlined:
As shown from clinical trials and published literature, individualized immune tolerance induction regimen administered prior to and with initiation of LUMIZYME has been reported to aid tolerability of LUMIZYME and reduce the development of high ADA titers in CRIM-negative IOPD patients. Furthermore, CRIM status has been shown to be associated with immunogenicity and patients’ responses to LUMIZYME. LUMIZYME-treated infants with IOPD who are CRIM-negative (indicating no endogenous enzyme is detected) have shown poorer clinical response (loss of motor function, ventilator dependence, or death) in the presence of high sustained IgG ADA titers and positive inhibitory antibodies compared to CRIM-positive infants [see Adverse Reactions (6.2)]. However, high and sustained ADA titers has also occurred in a limited number of CRIM-positive patients, generally with very low endogenous enzyme [see Clinical Pharmacology (12.6)]. Therefore, these patients must be managed by a clinical specialist knowledgeable in immune tolerance induction in Pompe disease.
Some alglucosidase alfa-treated patients who developed high sustained IgG ADA titers had reduced efficacy. Some alglucosidase alfa-treated patients with high IgG ADA titers had a higher incidence of IARs.
Patients with IOPD should have a cross-reactive immunologic material (CRIM) assessment early in their disease course.
Anti-alglucosidase alfa antibody (referred to as ADA) titers should be obtained during LUMIZYME treatment. Contact Genzyme Corporation at 1-800-745-4447 for information on ADA testing.
Recommend the following ADA testing:
Baseline serum ADA sample collection prior to the first LUMIZYME infusion is strongly encouraged.
For patients with:
IOPD, suggest regular ADA monitoring during first year of treatment (example: every 3 months).
LOPD, suggest ADA be monitored within six months of LUMIZYME initiation with subsequent monitoring as clinically warranted based on safety and efficacy considerations.
If patients [see Adverse Reactions (6.2) and Clinical Pharmacology (12.6)]:
Develop hypersensitivity reactions, consider testing for IgG ADA, IgE ADA and other mediators.
Develop immune-mediated reactions that are not hypersensitivity reactions, consider testing for IgG ADA.
Lose or have a reduced clinical response, consider testing for IgG ADA and for inhibitory antibody activity.
Additions and/or revisions underlined:
The following serious adverse reactions are described below and elsewhere in the labeling:
Hypersensitivity Reactions Including Anaphylaxis [see Warnings and Precautions (5.1)]
8 Use in Specific Populations
8.1 PregnancyAdditions and/or revisions underlined:
Pregnancy Exposure Registry
There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to LUMIZYME during pregnancy.
…
Additions and/or revisions underlined:
…
The use of LUMIZYME for this pediatric indication is supported by evidence from an adequate and well-controlled trial in 57 treatment- naive pediatric patients with IOPD treated with alglucosidase alfa, aged 0.2 month to 3.5 years at first infusion, (Trials 1, 2, and 3) [see Clinical Studies (14.1 )] and 90 adult and pediatric patients with LOPD in a randomized, double-blind, placebo-controlled trial including 2 patients 16 years of age or less [see Clinical Studies (14.2)]
.…
Additions and/or revisions underlined:
The randomized, double-blind, placebo-controlled study of alglucosidase alfa did not include sufficient numbers (n=4) of patients aged 65 years and over to determine whether they respond differently from younger adult patients [see Clinical Studies (14.1)].
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING INFORMATIONAdditions and/or revisions underlined:
…
Advise the patient and caregiver that anaphylaxis and immune-mediated reactions may occur during the early course of enzyme replacement therapy and after extended duration of therapy.
Inform the patient and caregiver of the symptoms of life-threatening hypersensitivity reactions including anaphylaxis, IARs, and immune-mediated reactions and have them seek immediate medical care should these symptoms occur [see Warning and Precautions (5.1, 5.2, 5.3)].
…