Drug Safety-related Labeling Changes (SrLC)
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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.
MAYZENT (NDA-209884)
(SIPONIMOD FUMARIC ACID)
Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)
08/21/2025 (SUPPL-20)
06/05/2024 (SUPPL-19)
08/10/2023 (SUPPL-16)
5 Warnings and Precautions
5.12 Severe Increase in Disability After Stopping MAYZENTAdditions and/or revisions underlined:
…
After stopping MAYZENT in the setting of PML, monitor for development of immune reconstitution inflammatory syndrome (PML-IRIS) [see Warnings and Precautions (5.1)].
New subsection created:
Cases of progressive multifocal leukoencephalopathy (PML) have occurred in patients with MS treated with S1P receptor modulators, including MAYZENT. PML is an opportunistic viral infection of the brain caused by the JC virus (JCV) that typically only occurs in patients who are immunocompromised, and that usually leads to death or severe disability. PML has occurred in MAYZENT-treated patients who had not been treated previously with natalizumab (which has a known association with PML), were not taking any other immunosuppressive or immunomodulatory medications concomitantly, and did not have any ongoing systemic medical conditions resulting in compromised immune system function. The majority of cases of PML associated with S1P receptor modulators, including MAYZENT, have occurred in patients treated for at least 2 years. The relationship between the risk of PML and the duration of treatment is unknown.
At the first sign or symptom suggestive of PML, withhold MAYZENT and perform an appropriate diagnostic evaluation. Typical symptoms associated with PML are diverse, progress over days to weeks and include progressive weakness on one side of the body or clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes. MRI findings may be apparent before clinical signs or symptoms. Cases of PML, diagnosed based on MRI findings and the detection of JCV DNA in the cerebrospinal fluid in the absence of clinical signs or symptoms specific to PML, have been reported in patients treated with MS medications associated with PML, including S1P receptor modulators. Many of these patients subsequently became symptomatic with PML.
Therefore,
monitoring with MRI for signs that may be consistent with PML may be useful,
and any suspicious findings should lead to further investigation to allow for
an early diagnosis of PML, if present. Lower PML-related mortality and
morbidity have been reported following discontinuation of another MS medication
associated with PML in patients with PML who were initially asymptomatic
compared to patients with PML who had characteristic clinical signs and
symptoms at diagnosis. It is not known whether these differences are due to
early detection and discontinuation of MS treatment or due to differences in
disease in these patients.
If PML is confirmed, treatment with MAYZENT should be discontinued. Immune reconstitution inflammatory syndrome (IRIS) has been reported in patients treated with S1P receptor modulators, including MAYZENT, who developed PML and subsequently discontinued treatment. IRIS presents as a clinical decline in the patient’s condition that may be rapid, can lead to serious neurological complications or death, and is often associated with characteristic changes on MRI. The time to onset of IRIS in patients with PML was generally within a few months after S1P receptor modulator discontinuation. Monitoring for development of IRIS and appropriate treatment of the associated inflammation should be undertaken.
6 Adverse Reactions
Addition of the following to the bulleted line listing:
Progressive Multifocal Leukoencephalopathy [see Warnings and Precautions (5.2)]
6.2 Postmarketing Experience
New subsection added:
The following adverse reactions have been identified during postapproval use of MAYZENT. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Infections and Infestations: Progressive multifocal leukoencephalopathy [see Warnings and Precautions (5.2)].
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING INFORMATION
Additions and/or revisions underlined:
…
Progressive Multifocal Leukoencephalopathy
Inform patients that cases of progressive multifocal leukoencephalopathy (PML) have occurred in patients who received MAYZENT. Inform the patient that PML is characterized by a progression of deficits and usually leads to death or severe disability over weeks or months. Instruct the patient of the importance of contacting their doctor if they develop any symptoms suggestive of PML. Inform the patient that typical symptoms associated with PML are diverse, progress over days to weeks, and include progressive weakness on one side of the body or clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes [see Warnings and Precautions (5.2)].
…
MEDICATION GUIDE
Additions and/or revisions underlined:
What is the most important information I should know about MAYZENT?
…
3. Progressive multifocal leukoencephalopathy (PML). MAYZENT can increase your risk for PML, which is a rare brain infection that usually leads to death or severe disability. If PML happens, it usually happens in people with weakened immune systems but has happened in people who do not have weakened immune systems. Symptoms of PML get worse over days to weeks. Call your doctor right away if you have any new or worsening neurologic symptoms that have lasted several days, including:
weakness on 1 side of your body
changes in your vision
loss of coordination in your arms and legs
changes in your thinking or memory
decreased strength
confusion
problems with balance
changes in your personality
…