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.
REVUFORJ (NDA-218944)
(REVUMENIB CITRATE)
Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)
10/24/2025 (SUPPL-3)
5 Warnings and Precautions
5.1 Differentiation Syndrome
Additions and/or revisions underlined:
REVUFORJ can cause fatal or life-threatening differentiation syndrome (DS). Symptoms of differentiation syndrome, including those seen in patients treated with REVUFORJ, include fever, dyspnea, hypoxia, peripheral edema, pleuropericardial effusion, acute renal failure, rash, and/or hypotension.
In clinical trials, DS occurred in 60 (25%) of 241 patients treated with REVUFORJ at the recommended dosage for relapsed or refractory acute leukemia [see Adverse Reactions (6.1)]. Among those with a KMT2A translocation, DS occurred in 33% of patients with acute myeloid leukemia (AML), 33% of patients with mixed-phenotype acute leukemia (MPAL), and 9% of patients with acute lymphoblastic leukemia (ALL); DS occurred in 18% of patients with NPM1 mutated AML. DS was Grade 3 or 4 in 12% of patients and fatal in two patients. The median time to initial onset was 9 days (range 3-41 days). Some patients experienced more than 1 DS event. Treatment interruption was required for 7% of patients, and treatment was withdrawn for 1%.
. . .
5.2 QTc Interval Prolongation and Torsades de Pointes
Subsection title revised
Additions and/or revisions underlined:
REVUFORJ can cause QT (QTc) interval prolongation and Torsades de Pointes [see Clinical Pharmacology (12.2)].
Of the 241 patients treated with REVUFORJ at the recommended dosage for relapsed or refractory acute leukemia in clinical trials, QTc interval prolongation was reported as an adverse reaction in 86 (36%) of patients. QTc interval prolongation was Grade 3 in 15% and Grade 4 in 2%. The heart-rate corrected QT interval (using Fridericia’s method) (QTcF) was greater than 500 msec in 10%, and the increase from baseline QTcF was greater than 60 msec in 24%. REVUFORJ dose reduction was required for 7% due to QTc interval prolongation [see Adverse Reactions (6.1)]. QTc prolongation occurred in 21% of the 34 patients less than 17 years old, 35% of the 146 patients 17 years to less than 65 years old, and in 46% of the 61 patients 65 years or older. One patient had a fatal outcome of cardiac arrest, and one patient had nonsustained Torsades de Pointes.
Correct electrolyte abnormalities, including hypokalemia and hypomagnesemia, prior to and throughout treatment with REVUFORJ. Perform an ECG prior to initiation of treatment with
REVUFORJ, and do not initiate REVUFORJ in patients with QTcF greater than 450 msec. Perform an ECG at least once a week for the first 4 weeks on treatment, and at least monthly thereafter [see Dosage and Administration (2.3)]. In patients with congenital long QTc syndrome, congestive heart failure, electrolyte abnormalities, or those who are taking medications known to prolong the QTc interval, more frequent ECG monitoring may be necessary. Concomitant use of REVUFORJ with drugs known to prolong the QTc interval may increase the risk of QTc interval prolongation. [see Drug Interactions (7.1), Clinical Pharmacology (12.2)].
6 Adverse Reactions
Additions and/or revisions underlined:
The following clinically significant adverse reactions are described elsewhere in the labeling:
Differentiation Syndrome [see Warnings and Precautions (5.1)]
QTc Interval Prolongation and Torsades de Pointes [see Warnings and Precautions (5.2)]
6.1 Clinical Trials Experience
Extensive changes; please refer to label for complete information
8 Use in Specific Populations
8.4 Pediatric Use
Additions and/or revisions underlined:
The safety and
efficacy of REVUFORJ have been established in pediatric patients 1 year and
older with relapsed or refractory acute leukemia with a KMT2A translocation or an NPM1
mutation. Use of REVUFORJ for this indication is supported by evidence
from adequate and well-controlled trials in adults and pediatric patients [see Clinical Studies (14)] and
additional pharmacokinetic and safety data in pediatric patients [see Adverse Reactions (6.1) and Clinical
Pharmacology (12.3)]. The patients included 25 infants (age less
than 2 years), 78 children (age 2 to less than 12 years) and 29
adolescents (age 12 to less than 17 years). The recommended dosage in patients
weighing less than 40 kg is BSA-based.
. . .
8.5 Geriatric Use
Additions and/or revisions underlined:
Of the 241 patients with relapsed or refractory acute leukemia with a KMT2A translocation or an NPM1 mutation in clinical studies of REVUFORJ, 61 (25%) patients were 65 years of age and older and 25 (10%) patients were 75 years of age and older [see Clinical Studies (14)].
. . .
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING INFORMATION
Additions and/or revisions underlined:
. . .
Differentiation Syndrome
Advise patients of the risks of developing differentiation syndrome as early as 3 days after the start of therapy and during treatment. Ask patients to immediately report any symptoms suggestive of differentiation syndrome, such as fever, cough or difficulty breathing, rash, low blood pressure, rapid weight gain, swelling of their arms or legs, or decreased urinary output, to their healthcare provider for further evaluation [see Boxed Warning and Warnings and Precautions (5.1)].
Prolonged QT Interval and Torsades de Pointes
. . .
MEDICATION GUIDE
Additions and/or revisions underlined:
. . .
REVUFORJ is a prescription medicine used to treat adults and children 1 year and older with:
. . .
acute myeloid leukemia with a nucleophosmin 1 (NPM1) mutation whose disease has come back or has not improved after previous treatment(s) and who have no other satisfactory treatment options
. . .
Take REVUFORJ fasted (on an empty stomach) or with a low-fat meal (400 calories, 25% or less fat). Talk to your healthcare provider about examples of low-fat meals that you can eat.
. . .
Your healthcare provider may change your dose, temporarily stop, or permanently stop treatment with REVUFORJ if you develop certain side effects.
REVUFORJ may cause fertility problems in females and males, which may affect your ability to have children. Talk to your healthcare provider if this is a concern for you.
. . .