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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.
RETEVMO (NDA-218160)
(SELPERCATINIB)
Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)
07/14/2026 (SUPPL-7)
5 Warnings and Precautions
5.1 Hepatotoxicity
Additions and/or revisions underlined:
Serious hepatic adverse reactions occurred in 4.6% of patients treated with RETEVMO. Increased AST occurred in 62% of patients, including Grade 3 or 4 events in 11% and increased ALT occurred in 58% of patients, including Grade 3 or 4 events in 13% [see Adverse Reactions (6.1)]. The median time to first onset for increased AST was 5 weeks (range: 4.9 days to 6 years) and increased ALT was 4.9 weeks (range: 6 days to 5 years).
. . .
5.2 Interstitial Lung Disease/Pneumonitis
Additions and/or revisions underlined:
Severe, life-threatening, and fatal interstitial lung disease (ILD)/pneumonitis can occur in patients treated with RETEVMO. ILD/pneumonitis occurred in 3% of patients who received RETEVMO, including 0.3% with Grade 3 or 4 events, and 0.2% with fatal reactions.
. . .
5.3 Hypertension
Additions and/or revisions underlined:
Hypertension occurred in 43% of patients, including Grade 3 hypertension in 20% and Grade 4 in one (0.1%) patient [see Adverse Reactions (6.1)]. Overall, 6.4% had their dose interrupted, 1.5% had their dose reduced, and 0.2% discontinued RETEVMO for hypertension.
. . .
5.4 QT Interval Prolongation
Additions and/or revisions underlined:
RETEVMO can cause concentration-dependent QT interval prolongation [see Clinical Pharmacology (12.2)]. An increase in QTcF interval to >500 ms was measured in 8% of patients and an increase in the QTcF interval of at least 60 ms over baseline was measured in 22% of patients [see Adverse Reactions (6.1)]. RETEVMO has not been studied in patients with clinically significant active cardiovascular disease or recent myocardial infarction.
. . .
5.5 Hemorrhagic Events
Additions and/or revisions underlined:
Serious including fatal hemorrhagic events can occur with RETEVMO. Grade greater than or equal to 3 hemorrhagic events occurred in 4.3% of patients treated with RETEVMO, including 4 (0.5%) patients with fatal hemorrhagic events, including cerebral hemorrhage (n = 2), tracheostomy site hemorrhage, and hemoptysis (1 each).
Permanently discontinue RETEVMO in patients with severe or life-threatening hemorrhage [see Dosage and Administration (2.5)].
5.6 Hypersensitivity
Additions and/or revisions underlined:
RETEVMO can cause hypersensitivity, including severe skin reactions such as Stevens-Johnson Syndrome. All grade hypersensitivity occurred in 6% of patients receiving RETEVMO, including Grade 3 in 2%. The median time to onset was 1.9 weeks (range: 5 days to 6.5 years).
. . .
5.7 Tumor Lysis Syndrome
Additions and/or revisions underlined:
Tumor lysis syndrome (TLS) occurred in 0.9% of patients with medullary thyroid carcinoma and 0.3% of patients with non-small cell lung cancer receiving RETEVMO [see Adverse Reactions (6.1)]. Patients may be at risk of TLS if they have rapidly growing tumors, a high tumor burden, renal dysfunction, or dehydration. Closely monitor patients at risk, consider appropriate prophylaxis including hydration, and treat as clinically indicated.
5.9 Hypothyroidism
Additions and/or revisions underlined:
RETEVMO can cause hypothyroidism. Hypothyroidism occurred in 15% of patients treated with RETEVMO; all reactions were Grade 1 or 2. Hypothyroidism occurred in 15% of patients (59/390) with thyroid cancer and 14% of patients (65/467) with other solid tumors including NSCLC [see Adverse Reactions (6.1)].
. . .
6 Adverse Reactions
6.1 Clinical Trials Experience
Additions and/or revisions underlined:
. . .
The safety population described in the WARNINGS and PRECAUTIONS and below reflects exposure to RETEVMO as a single agent administered at 160 mg orally twice daily evaluated in 857 patients with advanced solid tumors in LIBRETTO-001 [see Clinical Studies (14)].
RET Gene Fusion or Gene Mutation Positive Solid Tumors LIBRETTO-001
Among the 857 patients who received RETEVMO, 74% were exposed for 12 months or longer and 57% were exposed for 24 months or longer. Among these patients, 97% received at least one dose of RETEVMO at the recommended dosage of 160 mg orally twice daily.
The median age was 59 years (range: 15 to 92 years); 0.2% were pediatric patients 12 to 16 years of age; 51% were male; and 68% were White, 24% were Asian, and 3% were Black or African American; and 5% were Hispanic/Latino. The most common tumors were NSCLC (43%), MTC (39%), and non-medullary thyroid carcinoma (8%).
Serious adverse reactions occurred in 58% of patients who received RETEVMO. The most frequent serious adverse reactions (greater than or equal to 2% of patients) were pneumonia, hemorrhage, abdominal pain, dyspnea, pleural effusion, sepsis, musculoskeletal pain, hyponatremia, vomiting, diarrhea, and increased blood creatinine. Fatal adverse reactions occurred in 3% of patients; fatal adverse reactions included sepsis (n = 6), respiratory failure (n = 5), hemorrhage (n = 4), pneumonia (n = 4), cardiac arrest (n=3), pneumonitis, cardiac failure (n=2 each), sudden death, cerebral infarction and dyspnea (n = 1 each).
Permanent discontinuation due to an adverse reaction occurred in 10% of patients who received RETEVMO. Adverse reactions resulting in permanent discontinuation in greater than or equal to 0.5% of patients included increased ALT (0.7%), fatigue (0.6%), sepsis (0.5%), pneumonia (0.5%), and increased AST (0.5%).
Dosage interruptions due to an adverse reaction occurred in 72% of patients who received RETEVMO. Adverse reactions requiring dosage interruption in greater than or equal to 5% of patients included increased ALT, increased AST, diarrhea, hypertension, and QT prolongation.
Dose reductions due to an adverse reaction occurred in 45% of patients who received RETEVMO. Adverse reactions requiring dosage reductions in greater than or equal to 2% of patients included increased ALT, increased AST, fatigue, QT prolongation, diarrhea, drug hypersensitivity, and ascites.
The most common adverse reactions (greater than or equal to 25%) were musculoskeletal pain, edema, diarrhea, fatigue, dry mouth, hypertension, abdominal pain, rash, nausea, constipation, headache, vomiting, cough, dyspnea, and hemorrhage.
The most common Grade 3 or 4 laboratory abnormalities (greater than or equal to 5%) were decreased lymphocytes, increased alanine aminotransferase (ALT), decreased sodium, increased aspartate aminotransferase (AST), decreased calcium, and decreased phosphate.
Table 6 summarizes the adverse reactions in LIBRETTO-001.
Table 6: Adverse Reactions (greater than or equal to 20%) in Patients Who Received RETEVMO in LIBRETTO-001
Extensive changes to table; please refer to label for complete information.
Clinically relevant adverse reactions in less than or equal to 15% of patients who received RETEVMO include hypothyroidism (15%); pneumonia (14%), hypersensitivity (6%); interstitial lung disease/pneumonitis, chylothorax, chylous ascites or tumor lysis syndrome (all < 3%).
Table 7 summarizes the laboratory abnormalities in LIBRETTO-001.
Table 7: Select Laboratory Abnormalities (greater than or equal to 20%) Worsening from Baseline in Patients Who Received RETEVMO in LIBRETTO-001
Extensive changes to table; please refer to label for complete information.
. . .
8 Use in Specific Populations
8.5 Geriatric Use
Additions and/or revisions underlined:
Of 857 patients who received RETEVMO, 35% (298 patients) were greater than or equal to 65 years of age and 10% (85 patients) were greater than or equal to 75 years of age. No overall differences were observed in the safety or effectiveness of RETEVMO between patients who were greater than or equal to 65 years of age and younger patients.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT INFORMATION
Additions and/or revisions underlined:
. . .
Before taking RETEVMO, tell your healthcare provider about all your medical conditions, including if you:
. . .
- Males with female partners who are able to become pregnant:
- Use effective birth control during treatment with RETEVMO and for 1 week after your last dose of RETEVMO.
- Tell your healthcare provider right away if your female partner becomes pregnant during your treatment with RETEVMO.
. . .
What are the possible side effects of RETEVMO? RETEVMO can cause serious side effects, including:
. . .
- Allergic reactions. RETEVMO can cause allergic reactions, including severe skin reactions, especially during the first month of treatment. Tell your healthcare provider right away if you get a fever, rash, muscle or joint pain at any time during treatment with RETEVMO.
. . .
The most common side effects of RETEVMO in adults with solid tumors include:
- muscle and bone pain
- nausea
- swelling of your arms, legs, hands, and feet (edema)
- constipation
- diarrhea
- cough
- tiredness
- headache
- dry mouth
- vomiting
- high blood pressure
- shortness of breath
- stomach-area (abdominal) pain
- bleeding
- rash
The most common side effects of RETEVMO in children 2 years and older with solid tumors include:
. . .
- swelling of your arms, legs, hands, and feet (edema)
The most common severe abnormal laboratory test results with RETEVMO in adults with solid tumors include decreased white blood cell count, increased liver enzymes, decreased levels of sodium in the blood, decreased levels of calcium in the blood, and decreased levels of phosphate in the blood.
. . .
11/20/2025 (SUPPL-5)
5 Warnings and Precautions
5.6 Hypersensitivity
Additions and/or revisions underlined:
RETEVMO can cause hypersensitivity, including severe skin reactions such as Stevens Johnson Syndrome. All grade hypersensitivity occurred in 6% of patients receiving RETEVMO, including Grade 3 in 1.9%. The median time to onset was 1.9 weeks (range: 5 days to 2 years). Signs and symptoms of hypersensitivity included fever, rash and arthralgias or myalgias with concurrent decreased platelets or transaminitis. Stevens Johnsons Syndrome has been observed in the post-marketing setting [see Adverse Reactions (6.2)]. Discontinue RETEVMO in patients with Stevens Johnson Syndrome.
If hypersensitivity occurs, withhold RETEVMO and begin corticosteroids at a dose of 1 mg/kg prednisone (or equivalent). Upon resolution of the event, resume RETEVMO at a reduced dose and increase the dose of RETEVMO by 1 dose level each week as tolerated until reaching the dose taken prior to onset of hypersensitivity [see Dosage and Administration (2.5)]. Continue steroids until patient reaches target dose and then taper. Permanently discontinue RETEVMO for recurrent hypersensitivity.
6 Adverse Reactions
6.2 Postmarketing Experience
Newly added subsection:
The following adverse reaction has been identified during post-approval use of RETEVMO. Because such 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.
Skin and subcutaneous tissue disorders: Stevens-Johnson Syndrome
11/20/2025 (SUPPL-6)
5 Warnings and Precautions
5.11 Slipped Capital Femoral Epiphysis/Slipped Upper Femoral Epiphysis in Pediatric Patients
Additions and/or revisions underlined:
Slipped capital femoral epiphysis/slipped upper femoral epiphysis (SCFE/SUFE) occurred in 1 adolescent (2.8% of 36 patients) receiving RETEVMO in LIBRETTO-121 and 1 adolescent (0.5% of 193 patients) receiving RETEVMO in LIBRETTO-531 [see Adverse Reactions (6.1)]. Monitor patients for symptoms indicative of SCFE/SUFE and treat as medically and surgically appropriate [see Adverse Reactions (6.1)].
6 Adverse Reactions
6.1 Clinical Trials Experience
Additions and/or revisions underlined
. . .
LIBRETTO-121
The safety population described below reflects exposure to RETEVMO as a single agent at 92 mg/m2 orally twice daily evaluated in 36 patients with advanced solid tumors harboring an activating RET alteration in LIBRETTO-121 [see Clinical Studies (14)]. Among the 36 pediatric and adolescent patients who received RETEVMO, 86% were exposed for 6 months or longer and 72% were exposed for greater than one year.
The median age was 13 years (range: 2 to 20 years); 31% were pediatric patients 2 to 12 years of age; 53% were male; and 47% were White, 28% were Asian, and 8% were Black or African American; and 19% were Hispanic/Latino. The most common cancers were MTC (42%), and papillary thyroid cancer (42%).
Serious adverse reactions occurred in 42% of patients who received RETEVMO. Serious adverse reactions occurring in more than 1 patient were vomiting and fracture (2 patients each). Dosage interruptions due to an adverse reaction occurred in 42% of patients who received RETEVMO. Adverse reactions requiring dosage interruption in greater than or equal to 5% of patients included increased ALT, increased AST, ascites, increased bilirubin, decreased neutrophils, and pyrexia.
Dose reductions due to an adverse reaction occurred in 22% of patients who received RETEVMO. Adverse reactions requiring dosage reductions in greater than or equal to 2% of patients included increased ALT, decreased neutrophils, increased weight, and increased bilirubin.
The most common adverse reactions (greater than or equal to 25%) were musculoskeletal pain, diarrhea, nausea, hemorrhage, pyrexia, abdominal pain, headache, vomiting, fatigue, cough, rash, coronavirus infection, upper respiratory tract infection, and edema.
The most common Grade 3 or 4 laboratory abnormalities (greater than or equal to 5%) were decreased lymphocytes, decreased calcium, decreased hemoglobin, decreased neutrophils, increased ALT, decreased magnesium, and decreased potassium.
Table 8 summarizes the adverse reactions in LIBRETTO-121.
Table 8: Adverse Reactions (greater than or equal to 15%) in Patients Who Received RETEVMO in LIBRETTO-121
Extensive changes in table; please refer to label for complete information.
Clinically relevant adverse reactions in <15% of patients who received RETEVMO include dizziness (14%), electrocardiogram QT prolonged (14%), hypersensitivity (11%), stomatitis (14%), proteinuria (11%), hypertension (8%), decreased appetite (8%), erectile dysfunction (6%), chylous ascites (2.8%), dry mouth (2.8%), epiphysiolysis (2.8%), and pneumonia (2.8%).
Table 9 summarizes the laboratory abnormalities in LIBRETTO-121.
Table 9: Select Laboratory Abnormalities (greater than or equal to 15%) Worsening from Baseline in Patients Who Received RETEVMO in LIBRETTO-121
Extensive changes in table; please refer to label for complete information.
. . .
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT INFORMATION
How should I take RETEVMO?
. . .
- Do not take or give RETEVMO capsules or tablets if you or your child are unable to swallow.
- If you or your child are unable to swallow RETEVMO whole or if you or your child has a feeding tube, RETEVMO can be prepared and taken or given as a dispersion using only the RETEVMO 40 mg tablets. See the Instructions for Use that comes with RETEVMO for information about the right way to prepare and take or give a dose of RETEVMO 40 mg tablets.
. . .
The most common side effects of RETEVMO in children 2 years and older with solid tumors include:
- muscle and bone pain
- vomiting
- diarrhea
- tiredness
- nausea
- cough
- bleeding
- rash
- fever
- coronavirus infection
- stomach-area (abdominal) pain
- upper respiratory tract infection
- headache
- swelling
. . .
The most common severe abnormal laboratory test results with RETEVMO in children 2 years and older with solid tumors include decreased white blood cell count, decreased levels of calcium in the blood, decreased red blood cell count, increased liver enzymes, decreased levels of magnesium in the blood, and decreased levels of potassium in the blood.
. . .
12/18/2024 (SUPPL-4)
7 Drug Interactions
7.2 Effects of RETEVMO on Other Drugs
Additions and/or revisions underlined:
…
Certain P-gp and BCRP Substrates
RETEVMO is a P-gp and BCRP inhibitor. Concomitant use of RETEVMO with P-gp or BCRP substrates increases their plasma concentrations [see Clinical Pharmacology (12.3)], which may increase the risk of adverse reactions related to these substrates. Avoid coadministration of RETEVMO with P-gp or BCRP substrates where minimal concentration changes may lead to increased adverse reactions. If coadministration cannot be avoided, follow recommendations for P- gp and BCRP substrates provided in their approved product labeling.
09/27/2024 (SUPPL-3)
5 Warnings and Precautions
WARNINGS AND PRECAUTIONS
5.11 Slipped Capital Femoral Epiphysis/Slipped Upper Femoral Epiphysis in Pediatric Patients
Additions and/or revisions underlined:
Slipped capital femoral epiphysis/slipped upper femoral epiphysis (SCFE/SUFE) occurred in 1 adolescent (3.7% of 27 patients) receiving RETEVMO in LIBRETTO-121 and 1 adolescent (0.5% of 193 patients) receiving RETEVMO in LIBRETTO-531 [see Adverse Reactions (6.1)]. Monitor patients for symptoms indicative of SCFE/SUFE and treat as medically and surgically appropriate [see Adverse Reactions (6.1)].
6 Adverse Reactions
6.1 Clinical Trials Experience
Extensive changes; please refer to label
06/12/2024 (SUPPL-1)
5 Warnings and Precautions
5.11 Slipped Capital Femoral Epiphysis/Slipped Upper Femoral Epiphysis in Pediatric PatientsSlipped capital femoral epiphysis/slipped upper femoral epiphysis (SCFE/SUFE) occurred in 1 adolescent (3.7% of 27 patients) receiving RETEVMO in LIBRETTO-121 [see Adverse Reactions (6.1)]. Monitor patients for symptoms indicative of SCFE/SUFE and treat as medically and surgically appropriate [see Adverse Reactions (6.1)].
6 Adverse Reactions
The following clinically significant adverse reactions are described elsewhere in the labeling:
. . .
Slipped Capital Femoral Epiphysis/Slipped Upper Femoral Epiphysis in Adolescent Patients [see Warnings and Precautions (5.11)
Extensive changes; please refer to label
8 Use in Specific Populations
8.4 Pediatric UseAdditions and revisions underlined:
The safety and effectiveness of RETEVMO have been established in pediatric patients 2 years of age and older for the treatment of:
advanced or metastatic medullary thyroid cancer (MTC) with a RET mutation who require systemic therapy
advanced or metastatic thyroid cancer with a RET gene fusion who require systemic therapy and are radioactive iodine-refractory (if radioactive iodine is appropriate)
locally advanced or metastatic solid tumors with a RET gene fusion that have progressed on or following prior systemic treatment or who have no satisfactory alternative treatment options.
Use of RETEVMO for these indications is supported by evidence from adequate and well-controlled studies in adult and pediatric patients with additional pharmacokinetic and safety data in pediatric patients 2 years of age and older [see Adverse Reactions (6.1), Clinical Pharmacology (12.3), Clinical Studies (14.2, 14.3, 14.4)]. The predicted exposures of selpercatinib in pediatric patients at the recommended dosages were within the range of values predicted in patients ? 12 years and ? 50 kg in body weight receiving the approved recommended dosage of 160 mg twice daily [see Clinical Pharmacology (12.3)].
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING INFORMATIONNewly added information:
Slipped Capital Femoral Epiphysis/Slipped Upper Femoral Epiphysis
Advise pediatric patients and caregivers to contact their healthcare provider promptly to report any signs and symptoms indicative of slipped capital femoral epiphysis/slipped upper femoral epiphysis [see Warnings and Precautions (5.11)].
Extensive changes; please refer to label