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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.
BESREMI (BLA-761166)
(ROPEGINTERFERON ALFA-2B-NJFT)
Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)
08/28/2026 (SUPPL-13)
5 Warnings and Precautions
5.1 Depression and Suicide
Additions and/or revisions underlined:
Life-threatening or fatal neuropsychiatric reactions have occurred in patients receiving interferon alfa products, including BESREMi. These reactions may occur in patients with and without previous psychiatric illness. Psychiatric reactions have been observed in 10% of BESREMi-treated patients with essential thrombocythemia including depression, adjustment disorder with depressed mood, and depressed mood. Serious neuropsychiatric reactions have been observed in 3% of BESREMi-treated patients with polycythemia vera, including depression, depressive symptoms, depressed mood, and listlessness. Of these cases, 3.4% of the patients recovered with temporary drug interruption and 2.8% stopped BESREMi treatment.
…
5.2 Endocrine Toxicity
Additions and/or revisions underlined:
Endocrine toxicity has occurred in patients receiving interferon alfa products, including BESREMi. These toxicities may include worsening hypothyroidism and hyperthyroidism. Autoimmune thyroiditis and hyperglycemia, including new onset type 1 diabetes, have been reported in patients receiving interferon alfa-2b products. Endocrine toxicities included hyperthyroidism (1.1%), hypothyroidism (1.1%), autoimmune thyroiditis (0.5%), and thyroiditis (0.5%) in BESREMi-treated patients with essential thrombocythemia. Endocrine toxicities included hyperthyroidism (4.5%), hypothyroidism (3.9%), and autoimmune thyroiditis/thyroiditis (2.8%) in BESREMi-treated patients with polycythemia vera.
Do not use BESREMi in patients with active serious or untreated endocrine disorders associated with autoimmune disease [see Contraindications (4)]. Evaluate thyroid function in patients who develop symptoms suggestive of thyroid disease during BESREMi therapy. Discontinue BESREMi in patients who develop endocrine disorders that cannot be adequately managed during treatment with BESREMi.
5.3 Cardiovascular Toxicity
Additions and/or revisions underlined:
Cardiovascular toxicity has occurred in patients receiving interferon alfa products, including BESREMi. Toxicities may include cardiomyopathy, myocardial infarction, atrial fibrillation, coronary artery ischemia, and acute coronary syndrome [see Adverse Reactions (6.1)]. Three thrombotic events of transient ischemic attack (grade 2, 1 patient), pulmonary embolism (grade 3, 1 patient), and peripheral vein thrombosis (grade 2, 1 patient) occurred in the essential thrombocythemia Phase 3 SURPASS ET study. Patients with a history of cardiovascular disorders and/or thrombotic events should be closely monitored for cardiovascular toxicity and/or thrombotic events during BESREMi therapy. Avoid use of BESREMi in patients with severe or unstable cardiovascular disease (e.g., uncontrolled hypertension, congestive heart failure (? NYHA class 2), serious cardiac arrhythmia, significant coronary artery stenosis, unstable angina) or recent stroke or myocardial infarction.
5.4 Hematologic and Hemorrhagic Disorders
Subsection title revised
Additions and/or revisions underlined:
Decreased peripheral blood counts have occurred in patients receiving interferon alfa products, including BESREMi. These toxicities may include thrombocytopenia (increasing the risk of bleeding), anemia, and leukopenia (increasing the risk of infection). In BESREMi-treated patients with essential thrombocythemia, anemia of grade 3 or greater occurred in 1% of patients. Leukopenia of grade 3 or greater occurred in 2% of patients. Infection occurred in 45% of patients, while serious infections occurred in 4% of patients. Essential thrombocythemia-related hemorrhagic cases occurred in 6% of patients and included gingival bleeding, tongue hemorrhage, epistaxis, purpura, and retinal hemorrhage. In BESREMi-treated patients with polycythemia vera, thrombocytopenia of grade 3 (platelet counts <50,000 – 25,000/mm3) or greater occurred in 2% of patients. Anemia of grade 3 (Hgb <8 g/dL) or greater occurred in 1% of patients. Leukopenia of grade 3 (WBC counts <2,000 – 1,000/mm3) or greater occurred in 2% of patients. Infection occurred in 48% of patients, while serious infections occurred in 8% of patients. Monitor complete blood counts at baseline, during titration and every 3-6 months during the maintenance phase. Monitor patients for signs and symptoms of infection or bleeding.
5.5 Hypersensitivity Reactions
Additions and/or revisions underlined:
Hypersensitivity reactions have occurred in patients receiving interferon alfa products, including BESREMi. BESREMi is contraindicated in patients with hypersensitivity reactions to interferon products or any of the inactive ingredients in BESREMi [see Contraindications (4)]. Toxicities may include serious, acute hypersensitivity reactions (e.g., urticaria, angioedema, bronchoconstriction, anaphylaxis, drug eruption). If such reactions occur, discontinue BESREMi and institute appropriate medical therapy immediately. Transient rashes may not necessitate interruption of treatment.
5.6 Pancreatitis
Additions and/or revisions underlined:
Pancreatitis has occurred in patients receiving interferon alfa products, including BESREMi. Pancreatitis was reported in 2.2% of patients receiving BESREMi for polycythemia vera. Symptoms may include nausea, vomiting, upper abdominal pain, bloating, and fever. Patients may experience elevated lipase, amylase, white blood cell count, or altered renal/hepatic function. Interrupt BESREMi treatment in patients with possible pancreatitis and evaluate promptly. Consider discontinuation of BESREMi in patients with confirmed pancreatitis.
5.7 Colitis
Additions and/or revisions underlined:
Serious and, in very rare cases potentially life-threatening ulcerative or hemorrhagic/ischemic colitis have occurred in patients receiving interferon alfa products, some cases occurring as early as 12 weeks after start of treatment. Symptoms may include abdominal pain, bloody diarrhea, and fever. Discontinue BESREMi in patients who develop these signs or symptoms. Colitis may resolve within 1 to 3 weeks of stopping treatment.
5.8 Pulmonary Toxicity
Additions and/or revisions underlined:
Pulmonary toxicity has occurred in patients receiving interferon alfa products, including BESREMi. Pulmonary toxicity may manifest as dyspnea, pulmonary infiltrates, pneumonia, bronchiolitis obliterans, interstitial pneumonitis, pulmonary hypertension, pleural effusion, and sarcoidosis. Some events have resulted in respiratory failure or death. Discontinue BESREMi in patients who develop pulmonary infiltrates or pulmonary function impairment.
5.9 Ophthalmologic Toxicity
Additions and/or revisions underlined:
Ophthalmologic toxicity has occurred in patients receiving interferon alfa products, including BESREMi. These toxicities may include severe eye disorders such as retinopathy, retinal hemorrhage, retinal exudates, retinal detachment and retinal artery or vein occlusion which may result in blindness. During BESREMi therapy in patients with essential thrombocythemia, 23% of patients were identified with eye disorders. Eye disorders in ?5% of patients included vision blurred (8%) and dry eye (7%). During BESREMi therapy in patients with polycythemia vera, 23% of patients were identified with an eye disorder. Eyes disorders ?5% included cataract (6%) and dry eye (5%). Advise patients to have eye examinations before and during BESREMi therapy, specifically in those patients with a retinopathy-associated disease such as diabetes mellitus or hypertension. Evaluate eye symptoms promptly. Discontinue BESREMi in patients who develop new or worsening eye disorders.
5.10 Hyperlipidemia
Additions and/or revisions underlined:
Hyperlipidemia has occurred in patients treated with interferon alfa products, including BESREMi. Hypertriglyceridemia occurred in 9% of patients, hyperlipidemia occurred in 2% of patients, and dyslipidemia occurred in 0.5% of patients receiving BESREMi for essential thrombocythemia. Hyperlipidemia, hypertriglyceridemia, or dyslipidemia occurred in 3% of patients receiving BESREMi for polycythemia vera. Elevated triglycerides may result in pancreatitis [see Warnings and Precautions (5.6)]. Monitor serum triglycerides before BESREMi treatment and intermittently during therapy and manage when elevated. Consider discontinuation of BESREMi in patients with persistently, markedly elevated triglycerides.
5.11 Hepatotoxicity
Additions and/or revisions underlined:
Hepatotoxicity has occurred in patients receiving interferon alfa products, including BESREMi. These toxicities may include increases in serum ALT, AST, GGT, and bilirubin. BESREMi is contraindicated in patients with moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment [see Contraindications (4)].
Increases in serum ALT greater than or equal to 3 × the upper limit of normal (ULN), AST greater than or equal to 3 × the ULN, GGT greater than or equal to 3 × ULN, and bilirubin >2 × ULN have been observed in patients treated with BESREMi.
In BESREMi-treated patients with essential thrombocythemia, 4% of patients experienced Grade greater than or equal to 3 liver enzyme elevations including alanine aminotransferase increased in 2.7% of patients, aspartate aminotransferase increased in 1.1% of patients, and blood bilirubin increased in 0.5% of patients. There were 20% of patients with alanine aminotransferase levels greater than or equal to 3 × ULN and 9% of patients with aspartate aminotransferase levels greater than or equal to 3 × ULN. A single Grade 4 adverse reaction of hepatitis was reported in an open-label single arm study of BESREMi in patients with essential thrombocythemia, with a time to recovery of 11 days.
In BESREMi-treated patients with polycythemia vera, 36 patients (20%) experienced liver enzyme elevations, 33 of whom had elevations of 1.25-5 × ULN. Patients were able to resume BESREMi upon resolution of liver enzyme elevations. Liver enzyme elevations have also been reported in patients after long-term BESREMi therapy.
Monitor liver enzymes and hepatic function at baseline and during BESREMi treatment. For dose modifications see Table 1 for patients with essential thrombocythemia and see Table 3 for patients with polycythemia vera [see Dosage and Administration (2.3)].
Discontinue BESREMi in patients who develop evidence of hepatic decompensation (characterized by jaundice, ascites, hepatic encephalopathy, hepatorenal syndrome or variceal hemorrhage) during treatment [see Use in Specific Populations (8.7)].
5.12 Renal Toxicity
Additions and/or revisions underlined:
Renal toxicity has occurred in patients receiving interferon alfa products, including BESREMi. During BESREMi therapy in patients with polycythemia vera, <1% of patients were reported to develop renal impairment and <1% of patients were reported to have toxic nephropathy. Monitor serum creatinine at baseline and during therapy. Avoid use of BESREMi in patients with eGFR <30 mL/min. Discontinue BESREMi if severe renal impairment develops during treatment [see Use in Specific Populations (8.6)].
6 Adverse Reactions
Addition of the following to the bulleted line listing:
Hematologic and Hemorrhagic Disorders [see Warnings and Precautions (5.4)]
Embryo-Fetal Toxicity [see Warning and Precautions (5.16)]
6.1 Clinical Trials Experience
Extensive changes; please refer to label for complete information
8 Use in Specific Populations
8.1 Pregnancy
Additions and/or revisions underlined:
Risk Summary
Available human data with BESREMi use in pregnant women are insufficient to identify a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. An abortifacient effect was reported in cynomolgus monkeys receiving ropeginterferon alfa-2b (see Data). Based on mechanism of action and the role of interferon alfa in pregnancy and fetal development, BESREMi can cause fetal harm and should be assumed to have abortifacient potential when administered to a pregnant woman. There are adverse effects on maternal and fetal outcomes associated with polycythemia vera in pregnancy (see Clinical Considerations). Advise pregnant women of the potential risk to a fetus.
…
8.3 Females and Males of Reproductive Potential
Additions and/or revisions underlined:
BESREMi can cause embryo-fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)].
8.5 Geriatric Use
Additions and/or revisions underlined:
Of the total number of BESREMi-treated patients in the essential thrombocythemia studies, 65 (36%) were 65 years of age and older, while 15 (8%) were 75 years of age and older [see Clinical Studies (14)]. Of the total number of BESREMi-treated patients in the polycythemia studies, 17 (33%) were 65 years of age and older, while 5 (10%) were 75 years of age and older.Clinical studies of BESREMi did not include sufficient numbers of subjects aged 65 years and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION GUIDEExtensive changes; please refer to label for complete information
Additions and/or revisions underlined:
…
Hematologic and Hemorrhagic Disorders
Advise patients to seek prompt medical attention if they experience weakness/fatigue, fever, easy bruising, or frequent nose bleeds [see Warnings and Precautions (5.4)].
Hypersensitivity Reactions
Advise patients to seek immediate medical attention if they experience any symptoms of serious hypersensitivity reactions [see Warnings and Precautions (5.5)].
…
06/26/2026 (SUPPL-10)
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION GUIDE
Additions and/or revisions underlined:
How should I use BESREMi?
Read the Instructions for Use that comes with BESREMi for detailed instructions on how to prepare and inject a dose of BESREMi.
Use BESREMi exactly as your healthcare provider tells you to use it. Your healthcare provider will tell you how much BESREMi to inject and when to inject it. Do not inject more than your prescribed dose.
BESREMi comes in a single-dose prefilled syringe and in a single-dose prefilled pen injector.
BESREMi is given as an injection under your skin (subcutaneous injection).
BESREMi can be given by yourself, a caregiver, or healthcare provider. If your healthcare provider decides that you or a caregiver may give your injections of BESREMi at home, you should receive training on the right way to prepare and inject BESREMi. Do not try to inject BESREMi yourself until your healthcare provider has shown you how to give BESREMi the right way.
Do not reuse the BESREMi single-dose prefilled syringe or the single-dose prefilled pen injector. They are for one time use only.
If you inject too much BESREMi, call your healthcare provider or the Poison Help Line at 1-800-222-1222 right away.
04/29/2024 (SUPPL-7)
4 Contraindications
(Additions and/or revisions underlined)
BESREMi is contraindicated in patients with:
• Existence of, or history of severe psychiatric disorders, particularly severe depression, suicidal ideation, or suicide attempt.
• Hypersensitivity to interferons including interferon alfa-2b or any of the inactive ingredients of BESREMi.
• Moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment.
• History or presence of active serious or untreated autoimmune disease.
• History of transplantation and receiving immunosuppressant agents.
5 Warnings and Precautions
5.16 Embryo-Fetal Toxicity
(Additions and/or revisions underlined)
Based on the mechanism of action, BESREMi can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1) and Clinical Pharmacology (12.1) ]. Obtain a pregnancy test in females of reproductive potential prior to initiating treatment with BESREMi. Advise females of reproductive potential to use an effective method of contraception during treatment with BESREMi and for at least 8 weeks after the final dose [see Dosage and Administration (2.1) and Use in Specific Populations (8.1, 8.3)].
8 Use in Specific Populations
8.1 Pregnancy
(Additions and/or revisions underlined)
Risk Summary
Available human data with BESREMi use in pregnant women are insufficient to identify a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. An abortifacient effect was reported in cynomolgus monkeys receiving ropeginterferon alfa-2b (see Data). Based on mechanism of action and the role of interferon alfa in pregnancy and fetal development, BESREMi may cause fetal harm and should be assumed to have abortifacient potential when administered to a pregnant woman. There are adverse effects on maternal and fetal outcomes associated with polycythemia vera in pregnancy (see Clinical Considerations). Advise pregnant women of the potential risk to a fetus.
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage is 2-4% and 15-20%, respectively.
Animal Data
In an embryo-fetal development study, pregnant cynomolgus monkeys received subcutaneous injection of ropeginterferon alfa-2b twice weekly during the period of organogenesis (Gestation Days 20-48). Maternal toxicity, characterized by a significant decline in food consumption and transient body weight loss, occurred at all dose levels and ropeginterferon alfa-2b was abortifacient and caused embryonic death at exposures 275-times (Cmax) and 64-times (AUC) the human exposure at the maximum recommended human dose of 500 µg. There were no effects on fetal developmental parameters or abnormalities in the surviving fetuses (GD 100) where the ropeginterferon alfa-2b exposures achieved in pregnant cynomolgus monkeys during the first trimester were 961-times (Cmax) and 224-times (AUC) the human exposure at the maximum recommended human dose of 500 µg.
…
8.5 Geriatric Use
(Additions and/or revisions underlined)
There were 17 patients 65 years of age and older in the clinical study in polycythemia vera [see Clinical Studies (14)]. Of the total number of BESREMi-treated patients in this study, 17 (33%) were 65 years of age and older, while 5 (9.8%) were 75 years of age and older. Clinical studies of BESREMi did not include sufficient numbers of subjects aged 65 years and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.