Ropeginterferon alfa 2b

Ropeginterferon alfa 2b is a prescription medication used for the treatment of polycythemia vera.

• Ropeginterferon alfa 2b is available under the following different brand names: Besremi, ropeginterferon alfa-2b-njft.

Common side effects of Ropeginterferon alfa 2b include:

• influenza-like illness 
• joint pain
• fatigue
• itching
• runny or stuffy nose 
• musculoskeletal pain
• headache
• diarrhea
• increased sweating
• nausea
• upper respiratory tract infection
• local administration site reactions
• dizziness
• abdominal pain
• depression
• sleep problems (insomnia, abnormal dreams) 
• low white blood cell count (leukopenia, neutropenia)
• decreased appetite
• hair loss
• fluid retention (edema)
• high blood pressure (hypertension)
• muscle spasms
• rash
• transaminase elevations
• urinary tract infection (UTI) 
• low blood platelets (thrombocytopenia)
• spinning sensation (vertigo)

Serious side effects of Ropeginterferon alfa 2b include:

• hives
• rash 
• itching 
• difficulty breathing or swallowing 
• swelling of the eyes, face, mouth, lips, tongue, or throat 
• hoarseness
• lightheadedness 
• fainting; or chest pain
• decreased urination
• swelling of the feet, ankles, or lower legs
• blood in the urine
• lower back pain
• fast heartbeat
• shortness of breath
• ongoing pain that begins in the stomach area but may spread to the back nausea, vomiting, or loss of appetite
• yellowing of the skin or eyes, 
• light-colored bowel movements, 
• dark-colored urine, or pain in the upper right part of the stomach
• pale skin, 
• weakness, or excessive tiredness
• unusual bleeding or bruising
• bloody diarrhea or bowel movements
• stomach pain, tenderness, or swelling

Rare side effects of Ropeginterferon alfa 2b include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, coordination loss, unsteady, very stiff muscles, high fever, profuse sweating, or tremors.
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

Injectable solution

• 500 mcg/mL (single-dose prefilled syringe)

Polycythemia vera

Adult dosage

• Not currently on hydroxyurea
• Initial dose: 100 mcg SC every 2 weeks
• Increase dose by 50 mcg every 2 weeks (not to exceed 500 mcg/dose) until hematological parameters are stabilized (hematocrit [Hct] less than 45%, platelets [Plt] less than 400× 109/L, leukocytes less than 10× 109/L)
• Transitioning from hydroxyurea
• Initial dose: 50 mcg SC every 2 weeks in combination with hydroxyurea
• Increase dose by 50 mcg every 2 weeks (not to exceed 500 mcg/dose) until hematological parameters are stabilized (HCT less than 45%, Plt less than 400 x 109/L, leukocytes less than 10 × 109/L)
• Weeks 3-12: Gradually taper off hydroxyurea by reducing the total biweekly dose by 20-40% every 2 weeks
• Week 13: Discontinue hydroxyurea

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Ropeginterferon alfa 2b has severe interactions with no other drugs
• Ropeginterferon alfa 2b has serious interactions with at least 181 other drugs
• Ropeginterferon alfa 2b has moderate interactions with at least 30 other drugs
• Ropeginterferon alfa 2b has minor interactions with no other drugs

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• Presence or history of severe psychiatric disorders, particularly severe depression, suicidal ideation, or suicide attempt
• Hypersensitivity to interferons including interferon alfa-2b or any inactive ingredients
• Moderate or severe (Child-Pugh B or C) hepatic impairment
• History or presence of active serious or untreated autoimmune disease
• Immunosuppressed transplant recipients

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Ropeginterferon alfa 2b?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Ropeginterferon alfa 2b?”

Cautions

• Endocrine toxicity has occurred; do not use 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
• Cardiovascular toxicity (eg, cardiomyopathy, myocardial infarction, atrial fibrillation, coronary artery ischemia) reported; closely monitor for cardiovascular toxicity during therapy; avoid use with severe or unstable cardiovascular disease, (eg, uncontrolled hypertension, congestive heart failure (NYHA class of 2 and above), serious cardiac arrhythmia, significant coronary artery stenosis, unstable angina) or recent stroke or myocardial infarction
• Decreased peripheral blood counts have occurred; these toxicities may include thrombocytopenia (increasing the risk of bleeding), anemia, and leukopenia (increasing the risk of infection)
• Hypersensitivity reactions may occur; may include serious, acute hypersensitivity reactions          (eg, urticaria, angioedema, bronchoconstriction, anaphylaxis); if such reactions occur, discontinue therapy and institute appropriate medical therapy immediately
• Pancreatitis reported; symptoms may include nausea, vomiting, upper abdominal pain, bloating, and fever; may experience elevated lipase, amylase, WBC, or altered renal/hepatic function; interrupt treatment in patients with possible pancreatitis and evaluate promptly; consider discontinuation with confirmed pancreatitis
• Fatal and serious ulcerative or hemorrhagic/ischemic colitis have occurred; symptoms may include abdominal pain, bloody diarrhea, and fever; discontinue if signs or symptoms develop; colitis may resolve within 1-3 weeks of stopping treatment
• Pulmonary toxicities may occur; toxicity may manifest as dyspnea, pulmonary infiltrates, pneumonia, bronchiolitis obliterans, interstitial pneumonitis, pulmonary hypertension, and sarcoidosis; discontinue if pulmonary infiltrates or pulmonary function impairment
• Ophthalmologic toxicity reported; advise patients to have eye examinations before and during treatment; evaluate eye symptoms promptly and discontinue if new or worsening eye disorders, specifically in those patients with a retinopathy-associated disease such as diabetes mellitus or hypertension
• Hyperlipidemia, hypertriglyceridemia, or dyslipidemia occurred; monitor serum triglycerides before treatment and intermittently during therapy and manage when elevated
• Hepatotoxicity may occur; these toxicities may include increases in serum ALT, AST, GGT, and bilirubin; monitor liver enzymes and hepatic function at baseline and during treatment. Reduce dose or discontinue depending on severity; discontinue in patients who develop evidence of hepatic decompensation (eg, jaundice, ascites, hepatic encephalopathy, hepatorenal syndrome, variceal hemorrhage) during treatment
• Renal toxicity reported; monitor serum creatinine at baseline and during therapy; avoid use in patients with eGFR less than 30 mL/min; discontinue if severe renal impairment develops
• Dental and periodontal toxicity may occur; these toxicities may include dental and periodontal disorders; advise patients on good oral hygiene and to have regular dental examinations
• Dermatologic toxicities (eg, skin rash, pruritus, alopecia, erythema, psoriasis, xeroderma, dermatitis, acneiform hyperkeratosis, hyperhidrosis) reported; consider discontinuing if clinically significant dermatologic toxicity
• Advise patients to avoid driving or using machinery if they experience dizziness, somnolence, or hallucination
• May cause fetal harm when administered to pregnant women
  • Depression and suicide
  • Life-threatening or fatal neuropsychiatric reactions have occurred
  • These reactions may occur in patients with and without previous psychiatric illness
  • Other CNS effects, including suicidal ideation, attempted suicide, aggression, bipolar disorder, mania, and confusion have been observed with other interferon alfa products
  • Contraindicated with a history of severe psychiatric disorders, particularly severe depression, suicidal ideation, or suicide attempt
  • Closely monitor for any symptoms of psychiatric disorders and consider psychiatric consultation and treatment if such symptoms emerge
  • If psychiatric symptoms worsen, discontinue therapy
• Drug interaction overview
  • Drugs metabolized by CYP450
  • Certain proinflammatory cytokines, including interferons, can suppress CYP450 enzymes resulting in increased exposures of some CYP substrates
  • Monitor patients on ropeginterferon alfa who are receiving concomitant drugs that are CYP450 substrates with a narrow therapeutic index to inform if dosage modification for these concomitant drugs is necessary
  • Myelosuppressive agents
  • Avoid use and monitor patients receiving the combination for effects of excessive myelosuppression
  • Myelosuppressive agents can produce additive myelosuppression
  • Narcotics, hypnotics, or sedatives
  • Avoid use and monitor patients receiving the combination for effects of excessive CNS toxicity
  • Narcotics, hypnotics, or sedatives can produce additive neuropsychiatric side effects

Pregnancy and Lactation

• Insufficient human data are available on use in pregnant women to identify a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes
• Animal studies assessing reproductive toxicity have not been conducted
• Based on the mechanism of action and the role of interferon alfa in pregnancy and fetal development, fetal harm may occur and should be assumed to have abortifacient potential when administered to pregnant women
• Verify pregnancy in women of reproductive potential before initiating
• 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
• Contraception
  • Females of reproductive potential: Use effective contraception during treatment and for at least 8 weeks after the final dose
• Infertility
  • Based on its mechanism of action, therapy can disrupt the menstrual cycle
  • No animal fertility studies have been conducted
• Lactation
  • There are no data on the presence of human or animal milk, its effects on breastfed children, or its effects on milk production
  • Advise women not to breastfeed during treatment and for 8 weeks after the final dose