Besremi

— THERAPEUTIC CATEGORIES —
  • Leukemias, lymphomas, and other hematologic cancers
PAGE CONTENTS
  • Jump to Section
  • Generic Name & Formulations
  • Indications
  • Dosage and Administration
  • Contraindications
  • Boxed Warnings
  • Warnings/Precautions
  • Pharmacokinetics
  • Interactions
  • Adverse Reactions
  • Clinical Trials
  • Note
  • Patient Counseling

    • Besremi Generic Name & Formulations

    Legal Class

    Rx

    General Description

    Ropeginterferon alfa-2b-njft 500mcg/mL; soln for SC inj; preservative-free.

    Pharmacological Class

    Interferon.

    How Supplied

    Single-dose prefilled syringe—1 (w. safety needle)

    How Supplied

    BESREMi injection is a sterile, preservative-free, clear and colorless to slightly yellowish solution for subcutaneous administration in a single-dose prefilled syringe. Each carton contains one 500mcg/mL prefilled syringe with a 30 gauge, ½ inch safety hypodermic needle.

    Storage

    Store in a refrigerator at 36°F to 46 °F (2°C to 8°C) in the original carton to protect from light.  Do not freeze.

    Manufacturer

    PharmaEssentia USA Corporation

    Generic Availability

    NO

    Besremi Indications

    Indications

    Polycythemia vera.

    Besremi Dosage and Administration

    Prior to Treatment Evaluations

    Pregnancy testing is recommended prior to BESREMi treatment in females of reproductive potential.

    Adult

    Not already on hydroxyurea: Initially 100mcg by SC inj every 2 weeks. Transitioning from hydroxyurea: Initially 50mcg by SC inj every 2 weeks in combination with hydroxyurea; gradually taper off hydroxyurea by reducing the total biweekly dose by 20–40% every 2 weeks during weeks 3–12 and discontinue hydroxyurea by week 13. Both: Increase Besremi dose by 50mcg every 2 weeks (up to max 500mcg) until hematological parameters are stabilized (hematocrit <45%, platelets <400×109/L, and leukocytes <10×109/L). Dosing interval may be expanded to every 4 weeks after achieving hematological stability for at least 1 year on a stable Besremi dose. Dose modifications for adverse reactions: see full labeling.

    Adult

    Patients not already on hydroxyurea:

    • Initially 100mcg by SC inj every 2 weeks. 

    • Increase Besremi dose by 50mcg every 2 weeks (up to max 500mcg) until hematological parameters are stabilized (hematocrit <45%, platelets <400×109/L, and leukocytes <10×109/L). 

    Patients transitioning from hydroxyurea: 

    • Initially 50mcg by SC inj every 2 weeks in combination with hydroxyurea.

    • Gradually taper off hydroxyurea by reducing the total biweekly dose by 20–40% every 2 weeks during weeks 3–12 and discontinue hydroxyurea by week 13. 

    • Increase Besremi dose by 50mcg every 2 weeks (up to max 500mcg) until hematological parameters are stabilized (hematocrit <45%, platelets <400×109/L, and leukocytes <10×109/L). 

    Dosing interval may be expanded to every 4 weeks after achieving hematological stability for at least 1 year on a stable Besremi dose. Monitor patients closely during the titration phase. 

    Perform CBCs regularly, every 2 weeks during the titration phase and every 3–6 months during the maintenance phase. Monitor CBCs more frequently if indicated. Phlebotomy as rescue treatment to normalize blood hyperviscosity may be necessary during the titration phase.

    Dose modifications for adverse reactions: see full labeling.

     

    Children

    Not established.

    Besremi Contraindications

    Contraindications

    Existence of, or history of severe psychiatric disorders, particularly severe depression, suicidal ideation or suicide attempt. Moderate or severe hepatic impairment (Child-Pugh B or C). History or presence of active serious or untreated autoimmune disease. Immunosuppressed transplant recipients.

    Besremi Boxed Warnings

    Boxed Warning

    Risk of serious disorders.

    Boxed Warning

    Risk of Serious Disorders

    • Interferon alfa products may cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders. 

    • Patients should be monitored closely with periodic clinical and laboratory evaluations. 

    • Therapy should be withdrawn in patients with persistently severe or worsening signs or symptoms of these conditions. In many, but not all cases, these disorders resolve after stopping therapy

    Besremi Warnings/Precautions

    Warnings/Precautions

    May cause or exacerbate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, or infectious disorders: monitor closely, discontinue if they worsen. Avoid use in active serious or untreated endocrine disorders associated with autoimmune disease, severe or unstable cardiovascular disease (eg, uncontrolled hypertension, CHF [≥ NYHA class 2], serious cardiac arrhythmia, significant coronary artery stenosis, unstable angina), recent stroke or MI, or eGFR <30mL/min. Uncontrolled thyroid abnormalities. Diabetes. History of cardiovascular disorders; monitor closely. Pulmonary disease. Interrupt treatment if pancreatitis is suspected; consider discontinuing if confirmed. Discontinue if colitis, pulmonary infiltrates/dysfunction, new or worsening eye disorders, evidence of hepatic decompensation (eg, jaundice, ascites, hepatic encephalopathy, hepatorenal syndrome, variceal hemorrhage), or severe renal impairment develops. Consider discontinuing if significant dermatologic toxicity occurs. Obtain eye exams before and during therapy, especially in those with retinopathy-associated disease (eg, diabetes, hypertension). Monitor CBCs at baseline, every 2 weeks during titration phase, then every 3–6 months during maintenance phase, and as clinically indicated. Monitor for infection or bleeding. Monitor serum triglycerides, creatinine, thyroid, visual, and liver function at baseline and during therapy. Dental and periodontal disorders. Have regular dental exams. Elderly. Embryo-fetal toxicity. Advise females of reproductive potential to use effective contraception during and for at least 8 weeks after the last dose. Pregnancy: exclude status prior to initiation. Nursing mothers: not recommended (during and for 8 weeks after the last dose).

    Warnings/Precautions

    Depression and Suicide

    • Life-threatening or fatal neuropsychiatric reactions have occurred in patients receiving interferon alfa products, including BESREMi. 

    • Closely monitor for any symptoms of psychiatric disorders and consider psychiatric consultation and treatment if such symptoms emerge. 

    • Discontinue If psychiatric symptoms worsen.

    Endocrine Toxicity

    • May include worsening hypothyroidism and hyperthyroidism, autoimmune thyroiditis and hyperglycemia, including new onset type 1 diabetes.

    • Do not use BESREMi in patients with active serious or untreated endocrine disorders associated with autoimmune disease. Evaluate thyroid function in patients who develop symptoms suggestive of thyroid disease during therapy. 

    • Discontinue in patients who develop endocrine disorders that cannot be adequately managed during treatment with BESREMi. 

    Cardiovascular Toxicity

    • May include cardiomyopathy, myocardial infarction, atrial fibrillation and coronary artery ischemia. 

    • Monitor closely in patients with a history of cardiovascular disorders during therapy.

    • Avoid use 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. 

    Decreased Peripheral Blood Counts 

    • May include thrombocytopenia (increasing the risk of bleeding), anemia, and leukopenia (increasing the risk of infection). 

    • 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.

    Hypersensitivity Reactions

    • May include serious, acute hypersensitivity reactions (e.g., urticaria, angioedema, bronchoconstriction, anaphylaxis). 

    • Discontinue and institute appropriate medical therapy immediately if hypersensitivity reactions occur. Transient rashes may not necessitate interruption of treatment.

    Pancreatitis

    • May experience elevated lipase, amylase, white blood cell count, or altered renal/hepatic function. 

    • Interrupt treatment in patients with possible pancreatitis and evaluate promptly. Consider discontinuation in patients with confirmed pancreatitis.

    Colitis

    • Fatal and serious 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. 

    • Discontinue in patients who develop these signs or symptoms. Colitis may resolve within 1 to 3 weeks of stopping treatment.

    Pulmonary Toxicity

    • Pulmonary toxicity may manifest as dyspnea, pulmonary infiltrates, pneumonia, bronchiolitis obliterans, interstitial pneumonitis, pulmonary hypertension, and sarcoidosis. Some events have resulted in respiratory failure or death. 

    • Discontinue in patients who develop pulmonary infiltrates or pulmonary function impairment.

    Ophthalmologic Toxicity

    • 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. 

    • Advise patients to have eye examinations before and during therapy, specifically in those patients with a retinopathy-associated disease such as diabetes mellitus or hypertension. Evaluate eye symptoms promptly. 

    • Discontinue in patients who develop new or worsening eye disorders. 

    Hyperlipidemia

    • Monitor serum triglycerides before and intermittently during therapy and manage when elevated. 

    • Consider discontinuing in patients with persistently, markedly elevated triglycerides.

    Hepatotoxicity

    • For dosage modifications: See Hepatic Impairment.

    • Monitor liver enzymes and hepatic function at baseline and during treatment. 

    • Discontinue in patients who develop evidence of hepatic decompensation (characterized by jaundice, ascites, hepatic encephalopathy, hepatorenal syndrome or variceal hemorrhage) during treatment.

    Renal Toxicity 

    • Monitor serum creatinine at baseline and during therapy. 

    • Avoid use in patients with eGFR <30mL/min. Discontinue BESREMi if severe renal impairment develops during treatment.

    Dental and Periodontal Toxicity

    • May include dental and periodontal disorders, which may lead to loss of teeth. 

    • In addition, dry mouth could have a damaging effect on teeth and oral mucous membranes during long-term treatment with BESREMi. 

    • Patients should have good oral hygiene and regular dental examinations. 

    Dermatologic Toxicity

    • These toxicities have included skin rash, pruritus, alopecia, erythema, psoriasis, xeroderma, dermatitis acneiform, hyperkeratosis, and hyperhidrosis. 

    • Consider discontinuation of BESREMi if clinically significant dermatologic toxicity occurs. 

    Driving and Operating Machinery 

    • Avoid driving or operating heavy machinery until patients know how BESREMi affects their abilities.

    Embryo-Fetal Toxicity

    • Pregnancy testing is recommended in females of reproductive potential prior to initiation. 

    • Advise females of reproductive potential to use an effective method of contraception during treatment and for at least 8 weeks after the final dose. 

    Pregnancy Considerations

    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.

    • 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. Advise pregnant women of the potential risk to a fetus.

    Clinical Considerations

    • Disease-Associated Maternal and/or Embryo-Fetal Risk: Untreated polycythemia vera during pregnancy is associated with adverse maternal outcomes such as thrombosis and hemorrhage. Adverse pregnancy outcomes associated with polycythemia vera include increased risk for miscarriage.

    Nursing Mother Considerations

    • There is no data on the presence of BESREMi in human or animal milk, the effects on the breastfed child, or the effects on milk production. 

    • Advise women not to breastfeed during treatment and for 8 weeks after the final dose because of the potential for serious adverse reactions in breastfed children from BESREMi.

    Pediatric Considerations

    Safety and effectiveness in pediatric patients have not been established.

    Geriatric Considerations

    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. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other therapy.

    Renal Impairment Considerations

    No dose adjustment is necessary in patients with estimated glomerular filtration rate (eGFR) ≥30mL/min. Avoid use of BESREMi in patients with eGFR <30mL/min.

    Hepatic Impairment Considerations

    BESREMi is contraindicated in patients with hepatic impairment (Child-Pugh B or C). When the increase in liver enzyme levels is progressive and persistent, reduce the dose of BESREMi. If the increase in liver enzymes is progressive and clinically significant despite dose-reduction, or if there is evidence of hepatic impairment (Child-Pugh B or C), discontinue BESREMi.

    Other Considerations for Specific Populations

    Females and Males of Reproductive Potential

    • BESREMi may cause embryo-fetal harm when administered to a pregnant woman. Pregnancy testing prior to initiation is recommended.

    • Advise female patients of reproductive potential to use effective contraception during treatment with BESREMi and for at least 8 weeks after the final dose. 

    • Based on its mechanism of action, BESREMi can cause disruption of the menstrual cycle. No animal fertility studies have been conducted with BESREMi.

    Besremi Pharmacokinetics

    Absorption

    The estimated geometric mean (CV%) of the absorption rate constant of BESREMi is 0.12 day-1 (27%) in patients with polycythemia vera. 

    Distribution

    The estimated geometric mean (CV%) of apparent volume of distribution of BESREMi is 4.8 L (21%) in patients with polycythemia vera.

    Elimination

    Half-life: ~7 days.

    Besremi Interactions

    Interactions

    Avoid concomitant myelosuppressive agents, narcotics, hypnotics, or sedatives; if unavoidable, monitor for excessive effects. Concomitant drugs that are CYP450 substrates with a narrow therapeutic index; monitor.

    Besremi Adverse Reactions

    Adverse Reactions

    Influenza-like illness, arthralgia, fatigue, pruritus, nasopharyngitis, musculoskeletal pain, headache, diarrhea, hyperhidrosis, nausea, upper RTI, liver enzyme elevations, leukopenia, neutropenia, thrombocytopenia; depression, suicide, hypersensitivity reactions (discontinue if occurs), pancreatitis, colitis, hyperlipidemia, cardiovascular toxicity, endocrine toxicity, ophthalmologic toxicity, pulmonary toxicity, renal toxicity, hepatotoxicity.

    Besremi Clinical Trials

    Clinical Trials

    The efficacy and safety of ropeginterferon alfa-2b-njft were evaluated in the prospective, multicenter, single-arm PEGINVERA trial in 51 adults with polycythemia vera for a duration of 7.5 years. All patients had the JAK2V617F mutation with 16% of subjects being newly diagnosed; 84% had known disease with a median duration of 2.2 years.

    Findings showed that 61% (n=31/51; 95% CI, 46-74) of patients treated with ropeginterferon alfa-2b-njft achieved complete hematological response (CHR; defined as hematocrit less than 45% and no phlebotomy in the preceding 2 months, platelets 400 x 109/L or greater, leukocytes 10 x 109/L or greater, and normal spleen size). The median duration of response was 14.3 months (95% CI, 5.5-30.1).

    Among patients who achieved CHR, the median time to response was 7.8 months of treatment with ropeginterferon alfa-2b-njft. It required 1.2 years of treatment with ropeginterferon alfa-2b-njft for 50% of patients (hydroxyurea-naïve) to achieve a CHR and 1.4 years for 50% of patients with prior hydroxyurea use to achieve a CHR. 

    A hematological response based only on hematocrit, platelets, and leukocytes was achieved among 80% of patients treated with ropeginterferon alfa-2b-njft (n=41/51) (95% CI, 67-90). The median duration of this response was 20.8 months (95% CI, 13.0-43.8). 

    Besremi Note

    Not Applicable

    Besremi Patient Counseling

    Patient Counseling

    Depression and Suicide

    • Advise patients, their caregivers, and family members to be aware of any unusual changes in mood or behavior, new onset or worsening of depression, or the emergence of suicidal thoughts or behavior. Discontinue immediately and seek immediate medical attention if suicidal ideation or attempts occur.

    Endocrine Toxicity 

    • Report any signs or symptoms of diabetes or thyroid dysfunction.

    Cardiovascular Toxicity

    • Report signs or symptoms of cardiovascular toxicity to their healthcare provider.

    Decreased Peripheral Blood Counts

    • Seek prompt medical attention if patients experience weakness/fatigue, fever, easy bruising, or frequent nose bleeds.

    Hypersensitivity

    • Seek immediate medical attention if patients experience any symptoms of serious hypersensitivity reactions.

    Pancreatitis

    • Report signs or symptoms of pancreatitis.

    Colitis

    • Report signs or symptoms of colitis.

    Pulmonary Toxicity  

    • Report signs or symptoms of pulmonary toxicity.

    Ophthalmologic Toxicity

    • Report visual changes and to have eye examinations before and during treatment.

    Hyperlipidemia

    • May increase blood triglycerides and that patients will need blood testing to monitor for this toxicity.

    Hepatotoxicity

    • Report signs or symptoms of hepatic toxicity to their healthcare provider. 

    Renal Toxicity 

    • Report signs or symptoms of kidney disease. 

    Dental and Periodontal Toxicity 

    • Maintain good oral hygiene and to have regular dental examinations.

    Dermatologic Toxicity

    • Seek medical attention if significant pruritus, alopecia, rash and/or other dermatological toxicities occur.

    Hazardous Occupations/Operating Machinery

    • Refrain from engaging in operating heavy or potentially dangerous machinery until patients know how BESREMi will affect their abilities. Advise patients who experience dizziness, somnolence and hallucinations not to drive or use heavy machinery.

    Pregnancy and Contraception

    • Advise women about the need to use an effective method of contraception while taking BESREMi and for at least 8 weeks after the final dose.

    Lactation

    • Advise women not to breastfeed during treatment and for 8 weeks after the final dose.

    Instruction on Injection Technique 

    • Instruct patients on proper storage, preparation and administration techniques for BESREMi. Instruct patients who are self-administering to inject the prescribed dose of BESREMi.

    Cost Savings Program

    BESREMi Patient Support & Education: https://www.pharmaessentiasource.com/getting-started/index.html#treatment_supports

    Images

    • Latest News Your top articles for Wednesday

    • Haymarket Medical NetworkTop Picks

    • Loading...

      Continuing Medical Education (CME/CE) Courses

      Show More