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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.
JEMPERLI (BLA-761174)
(DOSTARLIMAB-GXLY)
Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)
08/01/2024 (SUPPL-9)
6 Adverse Reactions
6.1 Clinical Trials ExperienceExtensive additions and/or revisions; please refer to label for complete information.
8 Use in Specific Populations
8.5 Geriatric UseAdditions and/or revisions underlined:
In Combination with Carboplatin and Paclitaxel
Of the 241 patients treated with JEMPERLI in RUBY, 52.3% were younger than 65 years, 36.5% were aged 65 through 74 years, and 11.2% were 75 years or older. No overall differences in safety or effectiveness were observed between these patients and younger patients.
…
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION GUIDEAdditions and/or revisions underlined:
…
What are the possible side effects of JEMPERLI? JEMPERLI can cause serious side effects.
See “What is the most important information I should know about JEMPERLI?”
The most common side effects of JEMPERLI when given with carboplatin and paclitaxel in people with EC include:
nerve problems in your arms, hands, legs, and feet
joint pain
shortness of breath
rash
decreased appetite
tiredness
constipation
urinary tract infections
nausea
diarrhea
vomiting
hair loss
stomach-area (abdomen) pain
…
03/06/2024 (SUPPL-10)
5 Warnings and Precautions
5.1 Severe and Fatal Immune-Mediated Adverse ReactionsAdditions and revisions underlined:
Other (Hematologic/Immune): Hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenic purpura, solid organ transplant rejection, other transplant (including corneal graft) rejection.
07/31/2023 (SUPPL-6)
5 Warnings and Precautions
5.1 Severe and Fatal Immune-Mediated Adverse ReactionsAdditions and/or revisions underlined:
…
JEMPERLI in Combination with Carboplatin and Paclitaxel: Hypophysitis (Grade 3) occurred in 0.4% (1/241) of patients receiving JEMPERLI in combination with carboplatin and paclitaxel. Systemic corticosteroids were required and the event resolved. JEMPERLI was withheld and the patient reinitiated treatment.
JEMPERLI as a Single Agent: Hypophysitis (Grade 2) occurred in 0.2% (1/605) of patients receiving JEMPERLI as a single agent. Systemic corticosteroids were required and the event did not resolve. JEMPERLI was withheld and the patient reinitiated treatment.
…
Hypothyroidism: JEMPERLI in Combination with Carboplatin and Paclitaxel: Hypothyroidism occurred in 12% (28/241) of patients receiving JEMPERLI in combination with carboplatin and paclitaxel, all of which were Grade 2. Hypothyroidism led to discontinuation of JEMPERLI in 1 patient and resolved in 18% (5/28) of patients. JEMPERLI was withheld for 5 patients and all reinitiated treatment with JEMPERLI. Thyroid hormone replacement was required for 26 of the 28 patients with hypothyroidism.
JEMPERLI as a Single Agent: Hypothyroidism occurred in 8% (46/605) of patients receiving JEMPERLI as a single agent, all of which were Grade 2. Hypothyroidism did not lead to discontinuation of JEMPERLI and resolved in 37% (17/46) of patients. JEMPERLI was withheld for 2 patients and both reinitiated treatment. Thyroid hormone replacement therapy was required for 45 of the 46 patients with hypothyroidism.
Hyperthyroidism: JEMPERLI in Combination with Carboplatin and Paclitaxel: Hyperthyroidism occurred in 3.3% (8/241) of patients receiving JEMPERLI in combination with carboplatin and paclitaxel, including Grade 2 (2.9%) and Grade 3 (0.4%). Hyperthyroidism did not lead to discontinuation of JEMPERLI and resolved in 63% (5/8) of patients. JEMPERLI was withheld for 1 patient and the patient reinitiated treatment. Anti-thyroid therapy was required for 2 of the 8 patients while systemic corticosteroids were required for 1 of the 8 patients with hyperthyroidism.
JEMPERLI as a Single Agent: Hyperthyroidism occurred in 2.3% (14/605) of patients receiving JEMPERLI as a single agent, including Grade 2 (2.1%) and Grade 3 (0.2%).
Hyperthyroidism did not lead to discontinuation of JEMPERLI and resolved in 71% (10/14) of the 14 patients. JEMPERLI was withheld for 2 patients and both reinitiated treatment. Anti- thyroid therapy was required for 10 of the 14 patients with hyperthyroidism.
…
JEMPERLI in Combination with Carboplatin and Paclitaxel: Type 1 diabetes mellitus (Grade 3) occurred in 0.4% (1/241) of patients receiving JEMPERLI in combination with carboplatin and paclitaxel. Type 1 diabetes mellitus led to withholding JEMPERLI; the patient reinitated treatment and required long-term insulin therapy.
JEMPERLI as a Single Agent: Type 1 diabetes mellitus occurred in 0.2% (1/605) of patients receiving JEMPERLI as a single agent, which was Grade 3. Type 1 diabetes mellitus did not result in treatment discontinuation and did not resolve.
…
6 Adverse Reactions
6.1 Clinical Trials ExperienceAdditions and/or revisions underlined:
…
The safety population described in the Warnings and Precautions for use of JEMPERLI in combination with carboplatin and paclitaxel was evaluated in 241 patients with primary advanced or recurrent endometrial cancer (EC) in the randomized, double-blind, active- controlled RUBY trial.
…
Mismatch Repair Deficient (dMMR) or Microsatellite Instability-High (MSI-H) Primary Advanced or Recurrent EC: JEMPERLI In Combination with Carboplatin and Paclitaxel
The safety of JEMPERLI in patients with primary advanced or recurrent dMMR/MSI-H EC was evaluated in RUBY [see Clinical Studies (14.1)]. Patients received JEMPERLI 500 mg (n = 52) or placebo (n = 65) in combination with carboplatin and paclitaxel every 3 weeks for 6 doses followed by JEMPERLI 1,000 mg or placebo every 6 weeks until disease progression or unacceptable toxicity. Among the 52 patients, 56% were exposed for >1 year and 31% were exposed for >2 years.
Serious adverse reactions occurred in 13% of patients receiving JEMPERLI in combination with carboplatin and paclitaxel; the most common serious adverse reaction was sepsis, including urosepsis (6%). Fatal adverse reactions occurred in 6% of patients receiving JEMPERLI including septic shock (3.8%), and myelosuppression (1.9%).
In patients receiving JEMPERLI in combination with carboplatin and paclitaxel, JEMPERLI was permanently discontinued due to adverse reactions in 8 patients (15%) including 1 case (1.9%) each of rash maculo-papular, fatigue, general physical health deterioration, acute kidney injury, infusion-related reaction, keratitis, muscular weakness, and myelosuppression.
Dosage interruptions due to an adverse reaction occurred in 35% of patients who received JEMPERLI in combination with carboplatin and paclitaxel. Adverse reactions that required dosage interruption in greater than or equal to 5% of patients who received JEMPERLI in combination with carboplatin and paclitaxel were anemia, thrombocytopenia, platelet count decreased, peripheral neuropathy, and rash.
The most common adverse reactions, including laboratory abnormalities (greater than or equal to 20%), were decreased hemoglobin, decreased white blood cell count, decreased platelets, decreased lymphocytes, increased glucose, increased alkaline phosphatase, decreased neutrophils, rash, diarrhea, increased aspartate aminotransferase, increased alanine aminotransferase, decreased sodium, hypothyroidism, and hypertension.
Table 3 summarizes the adverse reactions that occurred in greater than or equal to 10% of patients with primary advanced or recurrent dMMR/MSI-H EC receiving JEMPERLI in combination with carboplatin and paclitaxel in RUBY.
Please refer to label to view Table 3.
Clinically relevant adverse reactions in <10% of patients with primary advanced or recurrent dMMR/MSI-H EC who received JEMPERLI in combination with carboplatin and paclitaxel included:
Endocrine Disorders: Hyperthyroidism, thyroiditis.
Eye Disorders: Keratitis.
Gastrointestinal Disorders: Colitis, pancreatitis.
Metabolism and Nutrition Disorders: Type 1 diabetes mellitus.
Nervous System Disorders: Encephalopathy.
Table 4 summarizes the laboratory abnormalities in patients with primary advanced or recurrent dMMR/MSI-H EC receiving JEMPERLI in combination with carboplatin and paclitaxel in RUBY.
Please refer to label to view Table 4.
…
The most common adverse reactions (greater than or equal to 20%) were fatigue/asthenia, anemia, nausea, diarrhea, constipation, vomiting, and rash.
…
8 Use in Specific Populations
8.5 Geriatric UseAdditions and/or revisions underlined:
In Combination with Carboplatin and Paclitaxel
Of the 241 patients treated with JEMPERLI in RUBY, 52.3% were younger than 65 years, 36.5% were aged 65 through 75 years, and 11.2% were 75 years or older. No overall differences in safety or effectiveness were observed between these patients and younger patients.
As a Single Agent
Of the 605 patients treated with JEMPERLI in GARNET, 51.6% were younger than 65 years, 36.9% were aged 65 through 75 years, and 11.5% were 75 years or older. No overall differences in safety or effectiveness were observed between these patients and younger patients.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION GUIDEAdditions and/or revisions underlined
…
What is JEMPERLI?
JEMPERLI is a prescription medicine used to treat adults with:
a kind of uterine cancer called endometrial cancer (EC)
JEMPERLI may be used in combination with the chemotherapy medicines, carboplatin and paclitaxel, and then after that JEMPERLI may be used alone:
when a laboratory test shows that your tumor is mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H), and
your cancer has spread outside your uterus (advanced) or,
your cancer has returned.
JEMPERLI may be used alone:
when a laboratory test shows that your tumor is mismatch repair deficient (dMMR), and
your cancer has returned, or it has spread (advanced EC), and
you have received chemotherapy that contains platinum and it did not work or is no longer working, and
your cancer cannot be treated by surgery or radiation.
a kind of cancer that is shown by laboratory test to be mismatch repair deficient (dMMR) solid tumor. JEMPERLI may be used to treat:
cancer that has returned or has spread (advanced cancer) and,
has progressed during treatment or after treatment, and you have no satisfactory treatment options.
…
What are the possible side effects of JEMPERLI?
JEMPERLI can cause serious side effects.
See “What is the most important information I should know about JEMPERLI?”
The most common side effects of JEMPERLI when given with carboplatin and paclitaxel in people with dMMR/MSI-H endometrial cancer include:
rash
decreased thyroid function
diarrhea
blood pressure
02/09/2023 (SUPPL-3)
5 Warnings and Precautions
5.1 Severe and Fatal Immune-Mediated Adverse Reactions
Extensive changes; please refer to label for complete information
6 Adverse Reactions
6.1 Clinical Trials Experience
Extensive changes; please refer to label for complete information
8 Use in Specific Populations
8.2 Lactation
Additions and/or revisions underlined:
Risk Summary
There is no information regarding the presence of dostarlimab-gxly in human milk or its effects on the breastfed child or on milk production. Maternal IgG is known to be present in human milk. The effects of local gastrointestinal exposure and limited systemic exposure in the breastfed child to JEMPERLI are unknown. Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment and for 4 months after the last dose of JEMPERLI.
8.5 Geriatric Use
Additions and/or revisions underlined:
Of the 605 patients treated with JEMPERLI, 51.6% were younger than 65 years, 36.9% were aged 65 through 75 years, and 11.5% were 75 years or older. No overall differences in safety or effectiveness were observed between these patients and younger patients.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION GUIDE
Additions and/or revisions underlined:
…
What is JEMPERLI?
JEMPERLI is a prescription medicine used to treat adults with certain cancers that have been shown by a laboratory test to be mismatch repair deficient (dMMR), and your cancer has returned, or it has spread (advanced cancer). JEMPERLI may be used when:
- you have a kind of uterine cancer called endometrial cancer, and you have received chemotherapy that contains platinum and it did not work or is no longer working and your cancer cannot be treated by surgery or radiation.
- you have a solid tumor that progressed during treatment or after treatment, and you have no satisfactory treatment options.
…
02/09/2023 (SUPPL-4)
5 Warnings and Precautions
5.1 Severe and Fatal Immune-Mediated Adverse Reactions
Extensive changes; please refer to label for complete information
6 Adverse Reactions
6.1 Clinical Trials Experience
Extensive changes; please refer to label for complete information
8 Use in Specific Populations
8.2 Lactation
Additions and/or revisions underlined:
Risk Summary
There is no information regarding the presence of dostarlimab-gxly in human milk or its effects on the breastfed child or on milk production. Maternal IgG is known to be present in human milk. The effects of local gastrointestinal exposure and limited systemic exposure in the breastfed child to JEMPERLI are unknown. Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment and for 4 months after the last dose of JEMPERLI.
8.5 Geriatric Use
Additions and/or revisions underlined:
Of the 605 patients treated with JEMPERLI, 51.6% were younger than 65 years, 36.9% were aged 65 through 75 years, and 11.5% were 75 years or older. No overall differences in safety or effectiveness were observed between these patients and younger patients.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION GUIDE
Additions and/or revisions underlined:
…
What is JEMPERLI?
JEMPERLI is a prescription medicine used to treat adults with certain cancers that have been shown by a laboratory test to be mismatch repair deficient (dMMR), and your cancer has returned, or it has spread (advanced cancer). JEMPERLI may be used when:
you have a kind of uterine cancer called endometrial cancer, and you have received chemotherapy that contains platinum and it did not work or is no longer working and your cancer cannot be treated by surgery or radiation.
- you have a solid tumor that progressed during treatment or after treatment, and you have no satisfactory treatment options.
…
04/28/2022 (SUPPL-2)
5 Warnings and Precautions
5.1 Severe and Fatal Immune-Mediated Adverse ReactionsExtensive revisions, please refer to label for complete information.
Revisions underlined
Severe or life-threatening infusion-related reactions have been reported with PD-1/PD-L1– blocking antibodies. Severe infusion-related reactions (Grade 3) occurred in 0.2% (1/515) of patients receiving JEMPERLI. All patients recovered from the infusion-related reactions.
…
6 Adverse Reactions
Additions and/or revisions under
…
Severe and fatal immune-mediated adverse reactions [see Warnings and Precautions (5.1)]
…
6.1 Clinical Trials Experience
Extensive additions and/or revisions, please refer to label for complete information
6.2 Immunogenicity
Additions and/or revisions underlined
…
The immunogenicity of dostarlimab was evaluated in GARNET. Treatment-emergent anti-drug antibodies (ADAs) against dostarlimab-gxly were detected in 2.1% of 384 patients who received dostarlimab-gxly at the recommended dosage. Neutralizing antibodies were detected in 1% of patients. Because of the small number of patients who developed ADAs, the effect of immunogenicity on the efficacy and safety of dostarlimab-gxly is inconclusive.
8 Use in Specific Populations
8.5 Geriatric UseRevisions underlined
Of the 515 patients treated with JEMPERLI, 51% were younger than 65 years, 37% were aged 65 through 75 years, and 12% were 75 years or older. No overall differences in safety or effectiveness were observed between these patients and younger patients.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING INFORMATION
Additions underlined
…
Other immune-mediated adverse reactions:
…
Advise patients of the risk of solid organ transplant rejection and to contact their healthcare provider immediately for signs or symptoms of organ transplant rejection [see Warnings and Precautions (5.1)].
…
Complications of Allogeneic HSCT
Advise patients of the risk of post-allogeneic hematopoietic stem cell transplantation complications [see Warnings and Precautions (5.3)].
…
MEDICATION GUIDE
Additions and/or revisions, please refer to label for complete information.