Ropeginterferon alfa-2b-njft consists of interferon alfa-2b (recombinant DNA origin) covalently bound to methoxy polyethylene glycol (mPEG); ropeginterferon alfa-2b exerts cellular effects in bone marrow in the management of polycythemia vera.1, 2
Ropeginterferon alfa-2b-njft is used for the treatment of adults with polycythemia vera.1, 2 Ropeginterferon alfa-2b-njft has been designated an orphan drug by FDA for this use.7 The drug has been evaluated in treatment-naive patients as well as patients transitioning from hydroxyurea treatment.1
Safety and efficacy of ropeginterferon alfa-2b for the treatment of polycythemia are based principally on the results of a prospective, multicenter, single-arm, open-label phase 1/2 study of 7.5 years' duration (PEGINVERA; NCT01193699).1, 2, 3 Ropeginterferon alfa-2b-njft was also evaluated in a phase 3 randomized, open-label, multicenter study (PROUD-PV) and its extension (CONTINUATION-PV).2 Due to statistical issues with the design and analysis of these studies, results were considered exploratory and used for confirmatory evidence of the drug's effectiveness.2
The PEGINVERA study included 51 adults with polycythemia vera and the JAK2V617F mutation.1, 2, 3 The mean age of patients at baseline was 56 years (range 35-82 years); 61% were men, 16% were newly diagnosed, and 84% had known disease with a median duration of 2.2 years.1 The study was conducted in 2 stages.1 The first stage was designed to establish the maximum tolerated dose, which was determined to be 540 mcg.1 In the second stage, the dose of ropeginterferon alfa-2b-njft was escalated from 100 to 450 mcg based on patient tolerance and hematological parameters.1, 2 For patients receiving hydroxyurea, dosage of hydroxyurea was reduced until full discontinuance over the first 12 weeks of treatment to avoid toxicity.1 The primary efficacy outcome of the study was complete hematological response, defined as hematocrit <45% without phlebotomy in the preceding 2 months, platelets ≤400,000/mm3 and leukocytes ≤10,000/mm3, normal spleen size, and absence of thromboembolic events.1 A complete hematological response was achieved in 61% of patients and the median duration of response was 14.3 months.1 The median time to response was 7.8 months.1 Approximately 1.2 years of treatment was required for 50% of the patients who were hydroxyurea-naive to achieve a response and 1.4 years of treatment was required for 50% of the patients who received prior treatment with hydroxyurea to achieve a response.1 Hematological response based on laboratory parameters only (hematocrit, platelets, and leukocytes) was achieved in 80% of patients, and the median duration of this response was 20.8 months.1
Polycythemia vera is a myeloproliferative neoplasm characterized by uncontrolled malignant proliferation of hematopoietic cells resulting in erythrocytosis, leukocytosis, and thrombocytosis.2, 4 Almost all patients harbor a JAK mutation.9 Without treatment, the disease continues to progress with no remission, and patients are at increased risk of thrombosis and cardiovascular events.2 All patients with polycythemia vera require phlebotomy to maintain hematocrit concentrations below 45%; aspirin (given in a dosage of 81 mg once or twice daily) is also in the treatment regimen of these patients, unless contraindicated.4 In high-risk patients, cytoreductive therapy is also recommended, with hydroxyurea given as first-line therapy followed by interferon alfa and busulfan.9 Ropeginterferon alfa-2b-njft may provide an additional treatment option in these patients.4 Compared to other pegylated interferon alfa products, ropeginterferon alfa-2b consists of a single positional isomer, resulting in an extended elimination half-life and less frequent dosing (every other week or monthly during maintenance therapy).4
Ropeginterferon alfa-2b-njft is administered by subcutaneous injection every 2 weeks.1 The drug is commercially available as a 500-mcg/mL solution in a single-dose prefilled syringe for subcutaneous administration.1
Several peginterferon alfa subtypes (alfa-2a, alfa-2b), dosage forms, and strengths are commercially available.1 Verify that the correct preparation is used.1
Ropeginterferon alfa-2b-njft may be self-administered if the clinician determines that the patient and/or their caregiver is competent to prepare and safely administer the drug after appropriate training is provided.1
Before each injection, remove the carton that contains the ropeginterferon alfa-2b-njft prefilled syringe from the refrigerator.1 Keep the prefilled syringe in the carton and lay it flat on a clean work surface for 15-30 minutes to allow the syringe to reach room temperature.1
Visually inspect the solution in the prefilled syringe for particulate matter and discoloration before administration.1 The solution should be clear and colorless to slightly yellowish; do not use the drug if the solution is cloudy, discolored, or contains particulate matter, or if the syringe shows any sign of damage.1
Depending on the prescribed dose, the amount of solution in the syringe may need to be adjusted by discarding some of the drug.1 To administer the subcutaneous injection, pinch the skin; insert the needle at a 45- to 90-degree angle into the pinched skin, then release the skin.1 After all of the drug is injected, remove the needle from the skin.1
The recommended starting dosage of ropeginterferon alfa-2b-njft in patients not already receiving hydroxyurea is 100 mcg by subcutaneous injection every 2 weeks.1 Increase the dosage by 50 mcg every 2 weeks (up to a maximum of 500 mcg) until hematologic parameters are stabilized (hematocrit <45%, platelet counts <400,000/mm3, and leukocytes <10,000/mm3).1
In patients transitioning from hydroxyurea, initiate ropeginterferon alfa-2b-njft at a dosage of 50 mcg by subcutaneous injection every 2 weeks in combination with hydroxyurea.1 Gradually taper the dosage of hydroxyurea by reducing the total biweekly dosage by 20-40% every 2 weeks during weeks 3-12.1 Increase the dosage of ropeginterferon alfa-2b-njft by 50 mcg every 2 weeks (up to a maximum of 500 mcg) until hematologic parameters are stabilized (hematocrit <45%, platelets <400,000/mm3, and leukocytes <10,000/mm3).1 Discontinue hydroxyurea by week 13.1
Maintain the 2-week dosing interval at which hematological stability is achieved for at least 1 year.1 After achievement of hematological stability for at least 1 year on a stable dosage of the drug, the dosing interval may be increased to every 4 weeks.1
Dosage Modification for Toxicity
If drug-related toxicities arise during ropeginterferon alfa-2b-njft therapy, reduce the dose to the next lower dose level or interrupt therapy in accordance with Table 1.1 If there is insufficient efficacy at the decreased dose following dose modification, consider attempting a dose increase to the next higher dose level after recovery to grade 1 toxicity.1
Adverse Reaction | Severity | Dosage Modification |
|---|---|---|
Liver enzyme elevation with concomitant bilirubin elevation, or other evidence of hepatic decompensation | Any increase above baseline | Interrupt treatment until recovery, then restart at a dose 50 mcg lower than the interrupted dose. If the interrupted dose is 50 mcg, refrain from treatment until recovery. Consider permanent discontinuation if toxicity persists after four dose modifications. |
Liver enzyme elevation | >5 times the upper limit of normal (ULN) but ≤20 times the ULN | Decrease dose by 50 mcg; if toxicity does not improve, continue decreasing at biweekly intervals until ALT and AST recover to <3 times the ULN if baseline was normal or to 3 times baseline if baseline was abnormal, and γ-glutamyltransferase (GGT) recovers to <2.5 times the ULN if baseline was normal, or to 2.5 times baseline if baseline was abnormal. If the interrupted dose is 50 mcg, refrain from treatment until recovery. |
Liver enzyme elevation | >20 times the ULN | Interrupt treatment until ALT and AST recover to <3 times the ULN if baseline was normal, or to 1.5 times baseline if baseline was abnormal, and GGT recovers to <2.5 times the ULN if baseline was normal, or to 2 times baseline if baseline was abnormal. Consider permanent discontinuation if toxicity persists after four dose modifications. |
Cytopenia | Anemia: hemoglobin (Hgb) <8 g/dL Thrombocytopenia: platelet count <50,000/mm3 but ≥25,000/mm3 Leukopenia: white blood cell count (WBC) <2000/mm3 but ≥1000/mm3 | Decrease dose by 50 mcg; if toxicity does not improve, continue decreasing at biweekly intervals until recovery of Hgb >10 g/dL, platelets >75,000/mm3, and WBC >3,000/mm3 If the interrupted dose is 50 mcg, refrain from treatment until recovery. |
Cytopenia | Anemia: Hemoglobin levels are life threatening, or urgent intervention needed Thrombocytopenia: platelet count <25,000/mm3 Leukopenia: WBC <1000/mm3 | Interrupt treatment until recovery of Hgb >10 g/dL, platelets >75,000/mm3, and WBC >3,000/mm3 Consider permanent discontinuation if toxicity persists after four dose modifications. |
Depression | Mild, without suicidal ideation | Consider psychiatric consultation if persistent (>8 weeks) |
Depression | Moderate, without suicidal ideation | Consider dose reduction and psychiatric consultation |
Depression | Severe, or any severity with suicidal ideation | Discontinue therapy, recommend psychiatric consultation |
Ropeginterferon is contraindicated in patients with moderate (Child-Pugh class B) or severe (Child-Pugh class C) hepatic impairment.1
No dosage adjustment is necessary in patients with mild to moderate renal impairment (estimated glomerular filtration rate [eGFR] ≥30 mL/minute).1 Avoid use in patients with an eGFR <30 mL/minute.1
In general, dosage selection for geriatric patients 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.1
Interferon alfa products may cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders.1 A boxed warning about these risks are included in the prescribing information for ropeginterferon alfa-2b-njft.1 Patients should be monitored closely with periodic clinical and laboratory evaluations.1 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.1
Life-threatening or fatal neuropsychiatric reactions have occurred in patients receiving interferon alfa products, including ropeginterferon alfa-2b-njft.1 These reactions may occur in patients with and without previous psychiatric illness.1 Serious neuropsychiatric reactions were observed in 3% of patients treated with ropeginterferon alfa-2b-njft during the clinical development program.1 Among the 178 patients evaluated, 17 cases of depression, depressive symptoms, depressed mood, and listlessness occurred.1 Of these cases, 3.4% of the patients recovered with temporary drug interruption and 2.8% stopped ropeginterferon alfa-2b-njft treatment.1
Other CNS effects, including suicidal ideation, attempted suicide, aggression, bipolar disorder, mania, and confusion, have been observed with other interferon alfa products.1 Ropeginterferon alfa-2b-njft is contraindicated in patients with a history of severe psychiatric disorders, particularly severe depression, suicidal ideation, or suicide attempt.1
Closely monitor patients for any symptoms of psychiatric disorders; consider psychiatric consultation and treatment if such symptoms emerge.1 If psychiatric symptoms worsen, discontinuance of ropeginterferon alfa-2b therapy is recommended.1
Endocrine toxicity has occurred in patients receiving interferon alfa products, including ropeginterferon alfa-2b.1 These toxicities may include worsening hypothyroidism and hyperthyroidism.1 Autoimmune thyroiditis and hyperglycemia, including new onset type 1 diabetes, have been reported in patients receiving interferon alfa-2b products.1 In the development program of ropeginterferon alfa-2b-njft, 8 cases of hyperthyroidism (4.5%), 7 cases of hypothyroidism (3.9%), and 5 cases (2.8%) of autoimmune thyroiditis/thyroiditis were reported.1
Do not use ropeginterferon alfa-2b in patients with active serious or untreated endocrine disorders associated with autoimmune disease.1 Evaluate thyroid function in patients who develop symptoms suggestive of thyroid disease during therapy.1 Discontinue ropeginterferon alfa-2b in patients who develop endocrine disorders that cannot be adequately managed.1
Cardiovascular toxicity has occurred in patients receiving interferon alfa products, including ropeginterferon alfa-2b-njft.1 Toxicities may include cardiomyopathy, myocardial infarction (MI), atrial fibrillation, and coronary artery ischemia.1 Patients with a history of cardiovascular disorders should be closely monitored for cardiovascular toxicity during ropeginterferon alfa-2b therapy.1 Avoid use of the drug in patients with severe or unstable cardiovascular disease (e.g., uncontrolled hypertension, congestive heart failure [≥ New York Heart Association (NYHA) class 2], serious cardiac arrhythmia, significant coronary artery stenosis, unstable angina) or recent stroke or MI.1
Decreased Peripheral Blood Counts
Decreased peripheral blood counts have occurred in patients receiving interferon alfa products, including ropeginterferon alfa-2b-njft.1 These toxicities may include thrombocytopenia (increasing the risk of bleeding), anemia, and leukopenia (increasing the risk of infection).1 Thrombocytopenia of grade 3 (platelet counts <50,000-25,000/mm3) or greater occurred in 2% of ropeginterferon alfa-2b-njft-treated patients in clinical studies.1 Grade ≥3 anemia (Hgb <8 g/dL) occurred in 1% of ropeginterferon alfa-2b-njft-treated patients.1 Leukopenia of grade 3 (WBC counts <2000-1000/mm3) or greater occurred in 2% of ropeginterferon alfa-2b-njft-treated patients.1 Infections occurred in 48% of ropeginterferon alfa-2b-njft treated patients, while serious infections were reported in 8% of these patients.1
Monitor CBCs at baseline, during dosage titration, and then every 3-6 months during the maintenance phase.1 Monitor patients for signs and symptoms of infection or bleeding.1
Hypersensitivity reactions have occurred in patients receiving interferon alfa products, including ropeginterferon alfa-2b-njft.1 Ropeginterferon alfa-2b-njft is contraindicated in patients with hypersensitivity reactions to interferon products or any of the inactive ingredients in the ropeginterferon alfa-2b-njft formulation.1 Toxicities may include serious, acute hypersensitivity reactions (e.g., urticaria, angioedema, bronchoconstriction, anaphylaxis).1 If such reactions occur, discontinue ropeginterferon alfa-2b-njft and institute appropriate medical therapy immediately.1 Transient rashes may not necessitate interruption of treatment.1
Pancreatitis has occurred in patients receiving interferon alfa products, including ropeginterferon alfa-2b-njft.1 Pancreatitis was reported in 2.2% of patients receiving ropeginterferon alfa-2b-njft in clinical studies.1 Symptoms may include nausea, vomiting, upper abdominal pain, bloating, and fever.1 Patients may experience elevated lipase, amylase, WBC count, or altered renal/hepatic function.1
Interrupt ropeginterferon alfa-2b treatment in patients with possible pancreatitis and evaluate promptly.1 Consider discontinuation of ropeginterferon alfa-2b-njft in patients with confirmed pancreatitis.1
Fatal and serious ulcerative or hemorrhagic/ischemic colitis have occurred in patients receiving interferon alfa products; some cases occurred as early as 12 weeks after initiating therapy.1 Symptoms may include abdominal pain, bloody diarrhea, and fever.1
Discontinue ropeginterferon alfa-2b in patients who develop these signs or symptoms.1 Colitis may resolve within 1 to 3 weeks of stopping treatment.1
Pulmonary toxicity has occurred in patients receiving interferon alfa products, including ropeginterferon alfa-2b-njft.1 Pulmonary toxicity may manifest as dyspnea, pulmonary infiltrates, pneumonia, bronchiolitis obliterans, interstitial pneumonitis, pulmonary hypertension, and sarcoidosis.1 Some cases have resulted in respiratory failure or death.1
Discontinue ropeginterferon alfa-2b in patients who develop pulmonary infiltrates or pulmonary function impairment.1
Ophthalmologic toxicity has occurred in patients receiving interferon alfa products, including ropeginterferon alfa-2b-njft.1 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.1 In clinical studies with ropeginterferon alfa-2b-njft, 23% of patients were identified with an eye disorder.1 Eye disorders included cataract (6%) and dry eye (5%).1
Advise patients to have eye examinations before and during ropeginterferon alfa-2b therapy, especially in those patients with a retinopathy-associated disease such as diabetes mellitus or hypertension.1 If any eye symptoms occur during treatment, evaluate the patient promptly.1 Discontinue ropeginterferon alfa-2b in patients who develop new or worsening eye disorders.1
Hyperlipidemia has occurred in patients treated with interferon alfa products, including ropeginterferon alfa-2b-njft.1 Hyperlipidemia, hypertriglyceridemia, or dyslipidemia occurred in 3% of patients receiving ropeginterferon alfa-2b-njft in clinical studies.1 Elevated triglycerides may result in pancreatitis.1
Monitor serum triglycerides prior to initiating ropeginterferon alfa-2b treatment and intermittently during therapy; manage any abnormalities.1 Consider discontinuation of ropeginterferon alfa-2b in patients with persistently, markedly elevated triglycerides.1
Hepatotoxicity has occurred in patients receiving interferon alfa products, including ropeginterferon alfa-2b-njft.1 These toxicities may include increases in serum ALT, AST, γ-glutamyltransferase (GGT), and bilirubin.1 Ropeginterferon alfa-2b is contraindicated in patients with moderate (Child-Pugh class B) or severe (Child-Pugh class C) hepatic impairment.1
Increases in serum ALT to ≥3 times the upper limit of normal (ULN), AST to ≥3 times the ULN, GGT to ≥3 times the ULN, and bilirubin to >2 times the ULN have been observed in patients treated with ropeginterferon alfa-2b-njft.1
In the clinical development program for the drug, 36 patients (20%) experienced liver enzyme elevations, 33 of whom had elevations of 1.25-5 times the ULN.1 Patients were able to resume ropeginterferon alfa-2b therapy upon resolution of liver enzyme elevations.1 Liver enzyme elevations have also been reported in patients after long-term ropeginterferon alfa-2b therapy.1
Monitor liver enzymes and hepatic function at baseline and during ropeginterferon alfa-2b treatment.1 Reduce dose of ropeginterferon alfa-2b-njft by 50 mcg in patients with increased AST/ALT/GGT, then monitor these liver enzymes weekly until values return to baseline or grade 1 (ALT and AST <3 times the ULN if baseline values were normal; ALT and AST 1.5-3 times baseline if baseline values were abnormal and GGT <2.5 times the ULN if baseline values were normal; or GGT 2-2.5 times baseline values if baseline values were abnormal).1 If toxicity does not improve, continue decreasing the ropeginterferon alfa-2b-njft dose at biweekly intervals until recovery to grade 1.1 Withhold therapy if AST/ALT/GGT >20 times the ULN and consider permanent discontinuation if increased liver enzyme levels persist after four dose reductions.1 Discontinue ropeginterferon alfa-2b in patients who develop evidence of hepatic decompensation (characterized by jaundice, ascites, hepatic encephalopathy, hepatorenal syndrome, or variceal hemorrhage) during treatment.1
Renal toxicity has occurred in patients receiving interferon alfa products, including ropeginterferon alfa-2b-njft.1 In clinical studies of ropeginterferon alfa-2b-njft, <1% of patients developed renal impairment and <1% of patients reported toxic nephropathy.1
Monitor serum creatinine at baseline and during therapy.1 Avoid use of ropeginterferon alfa-2b in patients with eGFR <30 mL/minute.1 Discontinue therapy if severe renal impairment develops during treatment.1
Dental and Periodontal Toxicity
Dental and periodontal toxicities may occur in patients receiving interferon alfa products, including ropeginterferon alfa-2b-njft.1 These toxicities may include dental and periodontal disorders, which may lead to loss of teeth.1 In addition, dry mouth could have a damaging effect on teeth and oral mucous membranes during long-term treatment with ropeginterferon alfa-2b-njft.1 Patients should have good oral hygiene and regular dental examinations.1
Dermatologic toxicity has occurred in patients receiving interferon alfa products, including ropeginterferon alfa-2b-njft.1 These toxicities have included skin rash, pruritus, alopecia, erythema, psoriasis, xeroderma, dermatitis acneiform, hyperkeratosis, and hyperhidrosis.1 Consider discontinuation of ropeginterferon alfa-2b-njft if clinically significant dermatologic toxicity occurs.1
Effects on Driving and Operating Machinery
Ropeginterferon alfa-2b may impact the ability to drive and use machinery.1 Patients should not drive or use heavy machinery until they know how the drug affects their abilities.1 Patients who experience dizziness, somnolence, or hallucination during ropeginterferon alfa-2b therapy should avoid driving or using machinery.1
Fetal/Neonatal Morbidity and Mortality
Based on its mechanism of action, ropeginterferon alfa-2b can cause fetal harm when administered to a pregnant woman.1
As with all therapeutic proteins, there is potential for immunogenicity with ropeginterferon alfa-2b-njft.1 Binding antibodies to ropeginterferon alfa-2b-njft were detected in 1.4% (2/146) of patients and were observed as early as 8 weeks post-dosing.1 Among the patients who tested positive for binding antibodies, none developed neutralizing antibodies.1
Available human data with ropeginterferon alfa-2b-njft use in pregnant women are insufficient to identify a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.1 Animal reproductive studies have not been conducted.1 Based on its mechanism of action and the role of interferon alfa in pregnancy and fetal development, ropeginterferon alfa-2b may cause fetal harm and should be assumed to have abortifacient potential when administered to a pregnant woman.1 Advise pregnant women of the potential risk to a fetus.1 Adverse maternal and fetal outcomes such as thrombosis and hemorrhage, including a risk of miscarriage, have been associated with polycythemia vera in pregnant women.1
It is not known whether ropeginterferon alfa-2b-njft distributes into human or animal milk, or if the drug has any effects on the breast-fed child or on milk production.1 Because of the potential for serious adverse reactions in breast-fed infants from ropeginterferon alfa-2b, breastfeeding is not recommended during treatment and for 8 weeks after the final dose.1
Females and Males of Reproductive Potential
Pregnancy testing prior to ropeginterferon alfa-2b treatment is recommended for females of reproductive potential.1 Advise such females to use effective contraception during treatment with the drug and for at least 8 weeks after the final dose.1
Based on its mechanism of action, ropeginterferon alfa-2b-njft can cause disruption of the menstrual cycle.1 No animal fertility studies have been conducted with the drug.1
Safety and effectiveness of ropeginterferon alfa-2b-njft have not been established in pediatric patients.1
Clinical studies of ropeginterferon alfa-2b-njft did not include sufficient numbers of patients ≥ 65 years of age to determine whether they respond differently than younger patients.1 Other reported clinical experience has not identified differences in responses between the elderly and younger patients.1 In general, dose selection for geriatric patients 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.1
Ropeginterferon alfa-2b-njft is contraindicated in patients with moderate to severe hepatic impairment (Child-Pugh class B or C).1
Increased liver enzyme levels have been observed in patients treated with ropeginterferon alfa-2b-njft in clinical studies.1 If progressive and persistent liver enzyme elevations occur during treatment, reduce the dosage of ropeginterferon alfa-2b-njft.1 If progressive and clinically significant increases occur despite dosage reduction or there is evidence of hepatic impairment (Child-Pugh class B or C), discontinue ropeginterferon alfa-2b therapy.1
No dosage adjustment is necessary in patients with estimated glomerular filtration rate (eGFR) ≥30 mL/minute.1 Avoid use of ropeginterferon alfa-2b-njft in patients with eGFR <30 mL/minute 1
The most common adverse reactions reported in >40% of patients receiving ropeginterferon alfa-2b-njft in clinical studies include influenza-like illness, arthralgia, fatigue, pruritus, nasopharyngitis, and musculoskeletal pain.1
No clinical studies evaluating the drug interaction potential of ropeginterferon alfa-2b have been conducted.1 In vitro studies indicate that the drug can inhibit cytochrome P-450 (CYP) 2A6, but does not appear to inhibit CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, or CYP3A4.1 Ropeginterferon alfa-2b is not expected to induce CYP enzymes.1
Drugs Metabolized by Hepatic Microsomal Enzymes
Certain proinflammatory cytokines, including interferons, can suppress cytochrome P-450 (CYP) isoenzymes, resulting in increased exposures of some CYP substrates.1 Monitor patients taking CYP substrates with a narrow therapeutic index for adverse reactions; adjust dosage of the concomitant CYP substrate drug as necessary when used with ropeginterferon alfa-2b.1
Concomitant use of ropeginterferon alfa-2b and myelosuppressive agents can produce additive myelosuppression.1 Avoid such concomitant therapy; if concomitant use is necessary, monitor patients for effects of excessive myelosuppression.1
Narcotics, Hypnotics, or Sedatives
Concomitant use of ropeginterferon alfa-2b and narcotics, hypnotics, or sedatives can produce additive neuropsychiatric effects.1 Avoid concomitant use with these drugs.1 If concomitant use is necessary, monitor patients for excessive CNS toxicity.1
Ropeginterferon alfa-2b is a recombinant DNA-derived human interferon alfa-2b covalently bound to methoxy polyethylene glycol (mPEG).1 Ropeginterferon alfa-2b belongs to the class of type I interferons, which exhibit their cellular effects in polycythemia vera in the bone marrow by binding to a transmembrane receptor termed interferon alfa receptor (IFNAR).1 Binding to IFNAR initiates a downstream signaling cascade through the activation of kinases, in particular Janus kinase 1 (JAK1) and tyrosine kinase 2 (TYK2) and activator of transcription (STAT) proteins.1 Nuclear translocation of STAT proteins controls distinct gene-expression programs and exhibits various cellular effects.1 The therapeutic effects of interferon alfa in polycythemia vera are not fully elucidated.1 Compared to conventional peginterferon alfa-2b, ropeginterferon alfa-2b exhibited a longer half-life and increased tolerability in preclinical studies.3
Pharmacokinetic and pharmacodynamic analyses have demonstrated that the effects of ropeginterferon alfa-2b on hematological parameters is dependent on its concentrations, with response increasing with increasing concentrations over time.1 Exposure-response analysis indicate that the maximum probability of a complete hematological response in patients with polycythemia vera is reached after 2 years of continuous treatment.1
Ropeginterferon alfa-2b is eliminated via receptor independent degradation/excretion and receptor binding followed by subsequent degradation of the drug-receptor complex.1 There is evidence that pegylated proteins are susceptible to hydrolysis with the release of interferon and PEG moieties.10 The PEG moiety may undergo uptake by macrophages and Kupffer cells by pinocytosis; however, biliary excretion only plays a minor role in the clearance of PEG, whereas urinary clearance predominates.10 The half-life of the drug is approximately 7 days in patients with polycythemia vera.1 No clinically important differences in the pharmacokinetics of ropeginterferon alfa-2b have been observed based on age, sex, body surface area, and JAK2V617F mutation.1
Additional Information
For further information on the handling of antineoplastic agents, see the ASHP Guidelines on Handling Hazardous Drugs at [Web]. The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Ropeginterferon alfa-2b-njft is available only from designated specialty pharmacies.8 Contact the manufacturer for additional information.8
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Parenteral | Injection, for subcutaneous use | 500 mcg/mL | Besremi® (available as single-dose prefilled syringe) | PharmaEssentia |
AHFS® Drug Information. © Copyright, 1959-2026, Selected Revisions December 10, 2025. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
1. PharmaEssentia USA. BESREMi® (ROPEGINTERFERON ALFA-2B) SUBCUTANEOUS prescribing information. 2021 Nov. [Web]
2. US Food and Drug Administration, Center for Drug Evaluation and Research. Medical review(s) NDA application number 761166. From FDA website. [Web]
3. Gisslinger H, Zagrijtschuk O, Buxhofer-Ausch V, et al. Ropeginterferon alfa-2b, a novel IFNα-2b, induces high response rates with low toxicity in patients with polycythemia vera. Blood. 2015;126(15):1762-1769.
4. Gisslinger H, Klade C, Georgiev P, et al. Ropeginterferon alfa-2B versus standard therapy for polycythemia vera (PROUD-PV and CONTINUATION-PV): a randomized, non-inferiority, phrase 3 trials and its extension study. Lancet Haemetol. 202;7:e196-208.
5. Kiladjian JJ, Klade C, Georgiev P, et al. Long-term outcomes of polcytemia vera patients treated with ropeginterferon Alfa-2b. Leukemia. 2022;36:1408-11.
6. Them N, Bagienski K, Berg, T et al. Molecular responses and chromosomal aberrations int patients with polcythemia vera treated with peg-proline-interferon alpha-2b. AJH. 2015; 90:288-94.
7. Food and Drug Administration. Orphan designations pursuant to Section 526 of the Federal Food and Cosmetic Act as amended by the Orphan Drug Act (P.L. 97 414). Rockville, MD. From FDA web site. Accessed 2013 Sept 25. [Web]
8. PharmaEssentia. Besremi® ordering information. Accessed 2022 Oct 6. From Besremi® website. [Web]
9. Tefferi A, Barbui T. Polycythemia vera and essential thrombocythemia: 2021 update on diagnosis, risk-stratification and management. Am J Hematol. 2020 Dec;95(12):1599-1613. Epub 2020 Oct 23. [PubMed 32974939]
10. US Food and Drug Administration, Center for Drug Evaluation and Research. Clinical pharmacology review(s) NDA application number 761166. From FDA website. [Web]