Ropeginterferon alfa-2b
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From MedlinePlus, U.S. National Library of Medicine
Boxed warning
WARNING: RISK OF SERIOUS DISORDERS 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 Therapy should be withdrawn in patients with persistently severe or worsening signs or symptoms of these conditions.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 [see Warnings and Precautions ( 5.1 , 5,2 , 5.3 , 5.4 ) and Adverse Reactions ( 6.1 )] . WARNING: RISK OF SERIOUS DISORDERS See full prescribing information for complete boxed warning.
Risk of Serious Disorders: Interferon alfa products may cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders. Monitor closely and withdraw therapy with persistently severe or worsening signs or symptoms of the above disorders. ( 5.1 , 5.2 , 5.3 , 5.4 )
Interferon alfa-2b
Dosing in kidney impairment
Renal Impairment No dose adjustment is necessary in patients with estimated glomerular filtration rate (eGFR) ≥30 mL/min [see Clinical Pharmacology]. Avoid use of BESREMi in patients with eGFR <30 mL/min [see Warnings and Precautions].
Dosing in liver impairment
Hepatic Impairment BESREMi is contraindicated in patients with hepatic impairment (Child-Pugh B or C) [see Contraindications] . Increased liver enzyme levels have been observed in patients treated with BESREMi. 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 [see Dosage and Administration and Warnings and Precautions] .
| aNational Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 3.0 | ||
| Adverse Reactiona | Severity | Dosage Modification |
| Liver enzyme elevation with concomitant bilirubin elevation, or other evidence of hepatic decompensation | Any increase above baseline | Interrupt treatment until recovery, restart at 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 reductions. |
| Liver enzyme elevation | >5 × the upper limit of normal (ULN) but ≤20 × ULN | Decrease dose by 50 mcg; if toxicity does not improve, continue decreasing by 50 mcg at biweekly intervals until alanine aminotransferase (ALT) and aspartate aminotransferase (AST) recover <3 × ULN if baseline was normal; 3 × baseline if baseline was abnormal, and gamma-glutamyltransferase (GGT) recovers to <2.5 × ULN if baseline was normal; 2.5 × baseline if baseline was abnormal.If the interrupted dose is 50 mcg, refrain from treatment until recovery. |
| >20 × ULN | Interrupt treatment until ALT and AST recover to <3 × ULN if baseline was normal; 1.5 × baseline if baseline was abnormal, and gamma-glutamyltransferase (GGT) recovers to <2.5 × ULN if baseline was normal; 2 × baseline if baseline was abnormal. Continued monitoring of the patient is advised; re-escalation to the previous dose level may be considered. Re-escalate the dose to the previous dose level if recovered to Grade ≤1, and if patient is a non-responder (hematological parameters).Consider permanent discontinuation if toxicity persists after four dose reductions. | |
| Cytopenia | Anemia: Hemoglobin (Hgb) <8 g/dL Thrombocytopenia: platelet count <50,000/mm3 but ≥25,000/mm3 Leukopenia: white blood cell count (WBC) <2,000/mm3 but≥1,000/mm3 | Decrease dose by 50 mcg; if toxicity does not improve, continue decreasing by 50 mcg at bi-weekly intervals until recovery of Hgb >10.0 g/dL, platelets >75,000/mm3, and WBC >3,000/mm3. If the interrupted dose is 50 mcg, refrain from treatment until recovery. Continued monitoring of the patient is advised; re-escalation to the previous dose level may be considered. Re-escalate the dose to the previous dose level if recovered to Grade ≤1, and if patient is a non-responder (hematological parameters). |
| Anemia: Hemoglobin levels are life threatening, or urgent intervention needed Thrombocytopenia: platelet count<25,000/mm3 Leukopenia: WBC <1,000/mm3 | Interrupt treatment until recovery of Hgb >10.0 g/dL, platelets >75,000/mm3, and WBC >3,000/mm3. Re-escalate the dose to the previous dose level if recovered to Grade ≤1, and if patient is a non-responder (hematological parameters). Consider permanent discontinuation if toxicity persists after four dose reductions. | |
| Depression | Mild, without suicidal ideation | Consider psychiatric consultation if persistent (>8 weeks). |
| Moderate, without suicidal ideation | Consider dose reduction to 50 mcg and psychiatric consultation is recommended. | |
| Severe, or any severity with suicidal ideation | Discontinue therapy, recommend psychiatric consultation. | |
Preparation and administration
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Preparation and Administration Read the INSTRUCTIONS FOR USE before administering the single-dose BESREMi prefilled syringe or prefilled pen injector. BESREMi is for subcutaneous injection only and may be administered by either a healthcare professional, a patient or a caregiver. Before a decision is made to allow BESREMi to be administered by a patient or caregiver, ensure that the patient is an appropriate candidate for self-administration or administration by a caregiver.
Proper training on storage, preparation and administration technique should be provided. If a patient or caregiver is not an appropriate candidate for any reason, then BESREMi should be administered by a healthcare professional. Before each injection, remove the carton that contains the BESREMi prefilled syringe or prefilled pen injector from the refrigerator.
Keep the prefilled syringe or prefilled pen injector in the carton and lay it flat on a clean work surface for 15-30 minutes to allow the prefilled syringe or prefilled pen injector to reach room temperature [59˚F to 77˚F (15˚C to 25˚C)]. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit (do not use if the solution in the syringe or pen injector is cloudy, discolored, contains particulate matter or if the syringe or pen injector shows any sign of damage).
Prefilled Syringe Preparation
Remove the prefilled syringe cap by unscrewing it counterclockwise.
Attach the covered needle to the prefilled syringe by firmly pushing it onto the collar of the syringe and then screwing (turn clockwise) it on until it feels securely attached.
Choose one of the following injection sites: Lower stomach (abdomen) area, at least 2 inches away from the belly button, or top of thighs. Rotate (change) the injection site for each injection. Do not inject into skin that is irritated, red, bruised, infected, or scarred; clean the chosen injection site with an alcohol swab and let air dry.
Uncap needle and move air bubbles to top. Pull the pink needle shield back and hold the syringe from the syringe body. Remove the clear needle cap by pulling it straight off. Throw away the needle cap into the trash. Hold the prefilled syringe with the needle pointing up. Tap on the body of the prefilled syringe to move any air bubbles to the top.
Set Injection Dose
The dose markings on the prefilled syringe are in 50 mcg increments.
Depending on the prescribed dose, the amount of dose in the syringe may need to be adjusted by discarding some of the medication.
Hold the prefilled syringe at eye level with the needle pointing straight up over a paper towel, sink, or trash can. Check that you can see the dose lines and number markings on the prefilled syringe.
Pinch the end of the plunger and slowly push up to remove liquid medicine until the top edge of the gray stopper lines up with the marking for the prescribed dose. Inject BESREMi
Pinch the chosen injection site. While pinching the skin, insert needle at a 45- to 90-degree angle into the pinched skin, then release the pinched skin.
Inject BESREMi by slowly pressing on the plunger all the way until it stops. After all the liquid medicine is injected, remove the needle from the skin. Dispose of Used Prefilled Syringe
Carefully push the pink needle shield over the needle until it snaps into place and covers the needle. Do not recap the needle using the needle cap; only use the pink needle shield to cover the needle.
Throw away the used prefilled syringe with the needle still attached, into an FDA-cleared sharps disposal container. Prefilled Pen Injector Preparation
The prefilled pen injector delivers BESREMi in 50 mcg increments.
Remove the prefilled pen injector cap by pulling it straight off.
Choose one of the following injection sites: Lower stomach (abdomen) area, at least 2 inches away from the belly button, or top of thighs. Rotate (change) the injection site for each injection. Do not inject into skin that is irritated, red, bruised, infected, or scarred; clean the chosen injection site with an alcohol swab and let air dry.
Clean the rubber stopper on the tip of the prefilled pen injector with an alcohol swab. Peel off the protective seal from the needle. Attach the capped needle by pushing it straight onto the prefilled pen injector until you feel or hear it snap into place. Turn or rotate the needle until it “clicks” into place. The needle is attached when it no longer turns or rotates freely.
Remove the needle cover by pulling off the needle cover and throw it away. Remove Air/Flow Check
Turn the dose selector knob until the drop symbol is centered in the dose window. Hold the prefilled pen injector with the needle pointing up and press the injection button all the way in until it stops and the dose window returns to “0”. Repeat these steps 3 more times for a total of 4 cycles.
Look for liquid medicine at the tip of the needle. If you do not see liquid at the tip of the needle, repeat these steps up to 3 more times for a total of 7 cycles or until you see liquid medicine at the tip of the needle. Inject BESREMi
Set your dose by turning the dose selector clockwise until the prescribed dose is centered in the dose window. Check the number in the dose window to make sure you have dialed the correct prescribed dose before giving the injection.
Drug interactions
Check ropeginterferon alfa-2b against a medication listLabel text (4 paragraphs)
7 DRUG INTERACTIONS • Monitor patients taking CYP450 substrates with a narrow therapeutic index for adverse reactions to inform the need for dose adjustment of the concomitant drug ( 7.1 ) • Avoid use with myelosuppressive agents and monitor patients receiving the combination for effects of excessive myelosuppression ( 7.2 ) • Avoid use with narcotics, hypnotics or sedatives. Monitor patients receiving the combination for excessive central nervous system toxicity ( 7.3 )
7.1 Drugs Metabolized by Cytochrome P450 Certain proinflammatory cytokines, including interferons, can suppress CYP450 enzymes resulting in increased exposures of some CYP substrates [see Clinical Pharmacology ( 12.3 )] . Therefore, patients on BESREMi who are receiving concomitant drugs that are CYP450 substrates with a narrow therapeutic index should be monitored to inform the need for dosage modification for these concomitant drugs.
7.2 Myelosuppressive Agents Concomitant use of BESREMi and myelosuppressive agents can produce additive myelosuppression. Avoid use and monitor patients receiving the combination for effects of excessive myelosuppression [see Warnings and Precautions ( 5.4 )] .
7.3 Narcotics, Hypnotics or Sedatives Concomitant use of BESREMi and narcotics, hypnotics or sedatives can produce additive neuropsychiatric side effects. Avoid use and monitor patients receiving the combination for effects of excessive CNS toxicity [see Warnings and Precautions ( 5.1 )] .
Contraindications
4 CONTRAINDICATIONS 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. • Immunosuppressed transplant recipients.
BESREMi is contraindicated in patients with: • Existence of, or history of severe psychiatric disorders, particularly severe depression, suicidal ideation or suicide attempt ( 4 ) • Hypersensitivity to interferons or to any of the inactive ingredients in BESREMi ( 4 ) • Hepatic impairment (Child-Pugh B or C) ( 4 ) • History or presence of active serious or untreated autoimmune disease ( 4 ) • Immunosuppressed transplant recipients ( 4 )
Pregnancy and lactation
Pregnancy
8.1 Pregnancy 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. 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. Data 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 (C max ) and 64-times (AUC) the human exposure at the maximum recommended human dose of 500 mcg. 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 (C max ) and 224-times (AUC) the human exposure at the maximum recommended human dose of 500 mcg.
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.
For breastfeeding, also see LactMed (National Library of Medicine), which summarizes milk levels and infant effects.
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