Reblozyl

REBLOZYL is an erythroid maturation agent indicated for the treatment of:

• •Anemia in adult patients with beta thalassemia who require regular red blood cell (RBC) transfusions (
  1.1 Beta Thalassemia

  REBLOZYL is indicated for the treatment of anemia in adult patients with beta thalassemia who require regular red blood cell (RBC) transfusions.
  ).
• •Anemia without previous erythropoiesis stimulating agent use (ESA-naïve) in adult patients with very low- to intermediate-risk myelodysplastic syndromes (MDS) who may require regular red blood cell (RBC) transfusions (
  1.2 Myelodysplastic Syndromes Associated Anemia

  REBLOZYL is indicated for the treatment of anemia without previous erythropoiesis stimulating agent use (ESA-naïve) in adult patients with very low- to intermediate-risk myelodysplastic syndromes (MDS) who may require regular red blood cell (RBC) transfusions.
  ).
• •Anemia failing an erythropoiesis stimulating agent and requiring 2 or more RBC units over 8 weeks in adult patients with very low- to intermediate-risk myelodysplastic syndromes with ring sideroblasts (MDS-RS) or with myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T) (
  1.3 Myelodysplastic Syndromes with Ring Sideroblasts or Myelodysplastic/ Myeloproliferative Neoplasm with Ring Sideroblasts and Thrombocytosis Associated Anemia

  REBLOZYL is indicated for the treatment of anemia failing an erythropoiesis stimulating agent and requiring 2 or more red blood cell units over 8 weeks in adult patients with very low- to intermediate-risk myelodysplastic syndromes with ring sideroblasts (MDS-RS) or with myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T).
  ).
• •Limitations of Use: REBLOZYL is not indicated for use as a substitute for RBC transfusions in patients who require immediate correction of anemia (
  1.4 Limitations of Use

  REBLOZYL is not indicated for use as a substitute for RBC transfusions in patients who require immediate correction of anemia.
  ).

• •The recommended starting dose is 1 mg/kg once every 3 weeks by subcutaneous injection (
  2.1 Recommended Dosage for Beta Thalassemia

  The recommended starting dose of REBLOZYL is 1 mg/kg once every 3 weeks by subcutaneous injection for patients with beta thalassemia. Prior to each REBLOZYL dose, review the patient’s hemoglobin and transfusion record. Titrate the dose based on responses according to Table 1. Interrupt treatment for adverse reactions as described in Table 2. Discontinue REBLOZYL if a patient does not experience a decrease in transfusion burden after 9 weeks of treatment (administration of 3 doses) at the maximum dose level or if unacceptable toxicity occurs at any time.

  If a planned administration of REBLOZYL is delayed or missed, administer REBLOZYL as soon as possible and continue dosing as prescribed, with at least 3 weeks between doses.

  Dose Modifications for Response

  Assess and review hemoglobin results prior to each administration of REBLOZYL. If an RBC transfusion occurred prior to dosing, use the pretransfusion hemoglobin for dose evaluation.

  If a patient does not achieve a reduction in RBC transfusion burden after at least 2 consecutive doses (6 weeks) at the 1 mg/kg starting dose, increase the REBLOZYL dose to 1.25 mg/kg. Do not increase the dose beyond the maximum dose of 1.25 mg/kg. In the absence of transfusions, if hemoglobin increase is greater than 2 g/dL within 3 weeks or the predose hemoglobin is greater than or equal to 11.5 g/dL, reduce the dose or interrupt treatment with REBLOZYL as described in Table 1.

  Dose level modifications for response are provided in Table 1.

  1 mg/kg every 3 weeksIncrease the dose to 1.25 mg/kg every 3 weeksDiscontinue treatmentInterrupt treatment

  Restart when the hemoglobin is no more than 11 g/dLcurrent dose is 1.25 mg/kg

  current dose is 1 mg/kg

  current dose is 0.8 mg/kg

  current dose is 0.6 mg/kgReduce dose to 1 mg/kg

  Reduce dose to 0.8 mg/kg

  Reduce dose to 0.6 mg/kg

  Discontinue treatment

  Table 1: Beta Thalassemia - REBLOZYL Dose Titration for Response

  •

  •

  •

  •

  •

  •

  •

  •

  •

  •

  •

  •

  •

  * Do not increase the dose if the patient is experiencing an adverse reaction as described in Table 2.
  	REBLOZYL Dosing Recommendation*
  Starting Dose
  Dose Increases for Insufficient Response at Initiation of Treatment
  No reduction in RBC transfusion burden after at least 2 consecutive doses (6 weeks) at the 1 mg/kg starting dose
  No reduction in RBC transfusion burden after 3 consecutive doses (9 weeks) at 1.25 mg/kg
  Dose Modifications for Predose Hemoglobin Levels or Rapid Hemoglobin Rise
  Predose hemoglobin is greater than or equal to 11.5 g/dL in the absence of transfusions
  Increase in hemoglobin greater than 2 g/dL within 3 weeks in the absence of transfusions and

  Dose Modifications for Toxicity

  For patients experiencing Grade 3 or higher adverse reactions, modify treatment as described in Table 2.

  Discontinue treatmentInterrupt treatment

  Restart when the adverse reaction resolves to no more than Grade 1Discontinue treatment

  Table 2: Beta Thalassemia - REBLOZYL Dosing Modifications for Adverse Reactions

  •

  •

  •

  •

  * Grade 1 is mild, Grade 2 is moderate, Grade 3 is severe, and Grade 4 is life-threatening.
  	REBLOZYL Dosing Recommendation*
  Grade 3 or 4 hypersensitivity reactions
  Other Grade 3 or 4 adverse reactions
  Extramedullary hematopoietic (EMH) masses causing serious complications
  ,
  2.2 Recommended Dosage for Myelodysplastic Syndromes Associated Anemia

  The recommended starting dosage of REBLOZYL is 1 mg/kg once every 3 weeks by subcutaneous injection for the treatment of anemia of MDS. Prior to each REBLOZYL dose, review the patient’s hemoglobin and transfusion record. Titrate the dose based on responses according to Table 3. Interrupt treatment for adverse reactions as described in Table 4. Discontinue REBLOZYL if a patient does not experience a decrease in transfusion burden including no increase from baseline hemoglobin after 9 weeks of treatment (administration of 3 doses) at the maximum dose level (1.75 mg/kg), or if unacceptable toxicity occurs at any time.

  If a planned administration of REBLOZYL is delayed or missed, administer REBLOZYL as soon as possible and continue dosing as prescribed, with at least 3 weeks between doses.

  Dose Modifications for Response

  Assess and review hemoglobin results prior to each administration of REBLOZYL. If an RBC transfusion occurred prior to dosing, use the pretransfusion hemoglobin for dose evaluation.

  If a patient is not RBC transfusion-free after at least 2 consecutive doses (6 weeks) at the 1 mg/kg starting dose, increase the REBLOZYL dose to 1.33 mg/kg (Table 3). If a patient is not RBC transfusion-free after at least 2 consecutive doses (6 weeks) at the 1.33 mg /kg dose level, increase the REBLOZYL dose to 1.75 mg/kg. Do not increase the dose more frequently than every 6 weeks (2 doses) or beyond the maximum dose of 1.75 mg/kg.

  In the absence of transfusions, if hemoglobin increase is greater than 2 g/dL within 3 weeks or if the predose hemoglobin is greater than or equal to 11.5 g/dL, reduce the dose or interrupt treatment with REBLOZYL as described in Table 3. If, upon dose reduction, the patient loses response (i.e., requires a transfusion) or hemoglobin concentration drops by 1 g/dL or more in 3 weeks in the absence of transfusion, increase the dose by one dose level. Wait a minimum of 6 weeks between dose increases.

  Dose modifications for response are provided in Table 3.

  1 mg/kg every 3 weeksIncrease the dose to 1.33 mg/kg every 3 weeksIncrease the dose to 1.75 mg/kg every 3 weeksDiscontinue treatmentInterrupt treatment

  Restart when the hemoglobin is no more than 11 g/dLcurrent dose is 1.75 mg/kg

  current dose is 1.33 mg/kg

  current dose is 1 mg/kg

  current dose is 0.8 mg/kg

  current dose is 0.6 mg/kgReduce dose to 1.33 mg/kg

  Reduce dose to 1 mg/kg

  Reduce dose to 0.8 mg/kg

  Reduce dose to 0.6 mg/kg

  Discontinue treatment

  Table 3: MDS Associated Anemia - REBLOZYL Dose Titration for Response

  •

  •

  •

  •

  •

  •

  •

  •

  •

  •

  •

  •

  •

  •

  •

  •

  * Do not increase the dose if the patient is experiencing an adverse reaction as described in Table 4.
  	REBLOZYL Dosing Recommendation*
  Starting Dose
  Dose Increases for Insufficient Response at Initiation of Treatment
  Not RBC transfusion-free after at least 2 consecutive doses (6 weeks) at the 1 mg/kg starting dose
  Not RBC transfusion-free after at least 2 consecutive doses (6 weeks) at 1.33 mg/kg
  No reduction in RBC transfusion burden including no increase from baseline hemoglobin after at least 3 consecutive doses (9 weeks) at 1.75 mg/kg
  Dose Modifications for Predose Hemoglobin Levels or Rapid Hemoglobin Rise
  Predose hemoglobin is greater than or equal to 11.5 g/dL in the absence of transfusions
  Increase in hemoglobin greater than 2 g/dL within 3 weeks in the absence of transfusions and

  Dose Modifications for Toxicity

  For patients experiencing Grade 3 or higher adverse reactions, modify treatment as described in Table 4.

  Discontinue treatmentInterrupt treatment

  When the adverse reaction resolves to no more than Grade 1, restart treatment at the next lower dose level**

  If the dose delay is > 12 consecutive weeks, discontinue treatment

  Table 4: MDS Associated Anemia - REBLOZYL Dosing Modifications for Adverse Reactions

  •

  •

  •

  •

  * Grade 1 is mild, Grade 2 is moderate, Grade 3 is severe, and Grade 4 is life-threatening. **Per Table 3 dose reductions above.
  	REBLOZYL Dosing Recommendation*
  Grade 3 or 4 hypersensitivity reactions
  Other Grade 3 or 4 adverse reactions
  ).
• •Review hemoglobin (Hgb) results prior to each administration (
  2.1 Recommended Dosage for Beta Thalassemia

  The recommended starting dose of REBLOZYL is 1 mg/kg once every 3 weeks by subcutaneous injection for patients with beta thalassemia. Prior to each REBLOZYL dose, review the patient’s hemoglobin and transfusion record. Titrate the dose based on responses according to Table 1. Interrupt treatment for adverse reactions as described in Table 2. Discontinue REBLOZYL if a patient does not experience a decrease in transfusion burden after 9 weeks of treatment (administration of 3 doses) at the maximum dose level or if unacceptable toxicity occurs at any time.

  If a planned administration of REBLOZYL is delayed or missed, administer REBLOZYL as soon as possible and continue dosing as prescribed, with at least 3 weeks between doses.

  Dose Modifications for Response

  Assess and review hemoglobin results prior to each administration of REBLOZYL. If an RBC transfusion occurred prior to dosing, use the pretransfusion hemoglobin for dose evaluation.

  If a patient does not achieve a reduction in RBC transfusion burden after at least 2 consecutive doses (6 weeks) at the 1 mg/kg starting dose, increase the REBLOZYL dose to 1.25 mg/kg. Do not increase the dose beyond the maximum dose of 1.25 mg/kg. In the absence of transfusions, if hemoglobin increase is greater than 2 g/dL within 3 weeks or the predose hemoglobin is greater than or equal to 11.5 g/dL, reduce the dose or interrupt treatment with REBLOZYL as described in Table 1.

  Dose level modifications for response are provided in Table 1.

  1 mg/kg every 3 weeksIncrease the dose to 1.25 mg/kg every 3 weeksDiscontinue treatmentInterrupt treatment

  Restart when the hemoglobin is no more than 11 g/dLcurrent dose is 1.25 mg/kg

  current dose is 1 mg/kg

  current dose is 0.8 mg/kg

  current dose is 0.6 mg/kgReduce dose to 1 mg/kg

  Reduce dose to 0.8 mg/kg

  Reduce dose to 0.6 mg/kg

  Discontinue treatment

  Table 1: Beta Thalassemia - REBLOZYL Dose Titration for Response

  •

  •

  •

  •

  •

  •

  •

  •

  •

  •

  •

  •

  •

  * Do not increase the dose if the patient is experiencing an adverse reaction as described in Table 2.
  	REBLOZYL Dosing Recommendation*
  Starting Dose
  Dose Increases for Insufficient Response at Initiation of Treatment
  No reduction in RBC transfusion burden after at least 2 consecutive doses (6 weeks) at the 1 mg/kg starting dose
  No reduction in RBC transfusion burden after 3 consecutive doses (9 weeks) at 1.25 mg/kg
  Dose Modifications for Predose Hemoglobin Levels or Rapid Hemoglobin Rise
  Predose hemoglobin is greater than or equal to 11.5 g/dL in the absence of transfusions
  Increase in hemoglobin greater than 2 g/dL within 3 weeks in the absence of transfusions and

  Dose Modifications for Toxicity

  For patients experiencing Grade 3 or higher adverse reactions, modify treatment as described in Table 2.

  Discontinue treatmentInterrupt treatment

  Restart when the adverse reaction resolves to no more than Grade 1Discontinue treatment

  Table 2: Beta Thalassemia - REBLOZYL Dosing Modifications for Adverse Reactions

  •

  •

  •

  •

  * Grade 1 is mild, Grade 2 is moderate, Grade 3 is severe, and Grade 4 is life-threatening.
  	REBLOZYL Dosing Recommendation*
  Grade 3 or 4 hypersensitivity reactions
  Other Grade 3 or 4 adverse reactions
  Extramedullary hematopoietic (EMH) masses causing serious complications
  ,
  2.2 Recommended Dosage for Myelodysplastic Syndromes Associated Anemia

  The recommended starting dosage of REBLOZYL is 1 mg/kg once every 3 weeks by subcutaneous injection for the treatment of anemia of MDS. Prior to each REBLOZYL dose, review the patient’s hemoglobin and transfusion record. Titrate the dose based on responses according to Table 3. Interrupt treatment for adverse reactions as described in Table 4. Discontinue REBLOZYL if a patient does not experience a decrease in transfusion burden including no increase from baseline hemoglobin after 9 weeks of treatment (administration of 3 doses) at the maximum dose level (1.75 mg/kg), or if unacceptable toxicity occurs at any time.

  If a planned administration of REBLOZYL is delayed or missed, administer REBLOZYL as soon as possible and continue dosing as prescribed, with at least 3 weeks between doses.

  Dose Modifications for Response

  Assess and review hemoglobin results prior to each administration of REBLOZYL. If an RBC transfusion occurred prior to dosing, use the pretransfusion hemoglobin for dose evaluation.

  If a patient is not RBC transfusion-free after at least 2 consecutive doses (6 weeks) at the 1 mg/kg starting dose, increase the REBLOZYL dose to 1.33 mg/kg (Table 3). If a patient is not RBC transfusion-free after at least 2 consecutive doses (6 weeks) at the 1.33 mg /kg dose level, increase the REBLOZYL dose to 1.75 mg/kg. Do not increase the dose more frequently than every 6 weeks (2 doses) or beyond the maximum dose of 1.75 mg/kg.

  In the absence of transfusions, if hemoglobin increase is greater than 2 g/dL within 3 weeks or if the predose hemoglobin is greater than or equal to 11.5 g/dL, reduce the dose or interrupt treatment with REBLOZYL as described in Table 3. If, upon dose reduction, the patient loses response (i.e., requires a transfusion) or hemoglobin concentration drops by 1 g/dL or more in 3 weeks in the absence of transfusion, increase the dose by one dose level. Wait a minimum of 6 weeks between dose increases.

  Dose modifications for response are provided in Table 3.

  1 mg/kg every 3 weeksIncrease the dose to 1.33 mg/kg every 3 weeksIncrease the dose to 1.75 mg/kg every 3 weeksDiscontinue treatmentInterrupt treatment

  Restart when the hemoglobin is no more than 11 g/dLcurrent dose is 1.75 mg/kg

  current dose is 1.33 mg/kg

  current dose is 1 mg/kg

  current dose is 0.8 mg/kg

  current dose is 0.6 mg/kgReduce dose to 1.33 mg/kg

  Reduce dose to 1 mg/kg

  Reduce dose to 0.8 mg/kg

  Reduce dose to 0.6 mg/kg

  Discontinue treatment

  Table 3: MDS Associated Anemia - REBLOZYL Dose Titration for Response

  •

  •

  •

  •

  •

  •

  •

  •

  •

  •

  •

  •

  •

  •

  •

  •

  * Do not increase the dose if the patient is experiencing an adverse reaction as described in Table 4.
  	REBLOZYL Dosing Recommendation*
  Starting Dose
  Dose Increases for Insufficient Response at Initiation of Treatment
  Not RBC transfusion-free after at least 2 consecutive doses (6 weeks) at the 1 mg/kg starting dose
  Not RBC transfusion-free after at least 2 consecutive doses (6 weeks) at 1.33 mg/kg
  No reduction in RBC transfusion burden including no increase from baseline hemoglobin after at least 3 consecutive doses (9 weeks) at 1.75 mg/kg
  Dose Modifications for Predose Hemoglobin Levels or Rapid Hemoglobin Rise
  Predose hemoglobin is greater than or equal to 11.5 g/dL in the absence of transfusions
  Increase in hemoglobin greater than 2 g/dL within 3 weeks in the absence of transfusions and

  Dose Modifications for Toxicity

  For patients experiencing Grade 3 or higher adverse reactions, modify treatment as described in Table 4.

  Discontinue treatmentInterrupt treatment

  When the adverse reaction resolves to no more than Grade 1, restart treatment at the next lower dose level**

  If the dose delay is > 12 consecutive weeks, discontinue treatment

  Table 4: MDS Associated Anemia - REBLOZYL Dosing Modifications for Adverse Reactions

  •

  •

  •

  •

  * Grade 1 is mild, Grade 2 is moderate, Grade 3 is severe, and Grade 4 is life-threatening. **Per Table 3 dose reductions above.
  	REBLOZYL Dosing Recommendation*
  Grade 3 or 4 hypersensitivity reactions
  Other Grade 3 or 4 adverse reactions
  ).
• •See full prescribing information for preparation and administration instructions (
  2.3 Preparation and Administration

  REBLOZYL should be reconstituted and administered by a healthcare professional.

  Reconstitute REBLOZYL with Sterile Water for Injection, USP only.

  Table 5: Reconstitution Volumes

  Vial Size	Amount of Sterile Water for Injection, USP required for reconstitution	Final Concentration	Deliverable Volume
  25 mg vial	0.68 mL	25 mg/0.5 mL (50 mg/mL)	0.5 mL
  75 mg vial	1.6 mL	75 mg/1.5 mL	1.5 mL
  		(50 mg/mL)

  Reconstitute the number of REBLOZYL vials to achieve the appropriate dose based on the patient’s weight. Use a syringe with suitable graduations for reconstitution to ensure accurate dosage.

  Reconstitution Instructions

  • 1.000000000000000e+00Reconstitute with Sterile Water for Injection, USP using volumes described in Table 5 (Reconstitution Volumes) with the stream directed onto the lyophilized powder. Allow to stand for one minute.
  • 2.000000000000000e+00Discard the needle and syringe used for reconstitution. The needle and syringe used for reconstitution should not be used for subcutaneous injections.
  • 3.000000000000000e+00Gently swirl the vial in a circular motion for 30 seconds. Stop swirling and let the vial sit in an upright position for 30 seconds.
  • 4.000000000000000e+00Inspect the vial for undissolved particles in the solution. If undissolved powder is observed, repeat step 3 until the powder is completely dissolved.
  • 5.000000000000000e+00Invert the vial and gently swirl in an inverted position for 30 seconds. Bring the vial back to the upright position, and let it sit for 30 seconds.
  • 6.000000000000000e+00Repeat step 5 seven more times to ensure complete reconstitution of material on the sides of the vial.
  • 7.000000000000000e+00Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. REBLOZYL is a colorless to slightly yellow, clear to slightly opalescent solution which is free of foreign particulate matter. Do not use if undissolved product or foreign particulate matter are observed.
  • 8.000000000000000e+00If the reconstituted solution is not used immediately:
    • •Store at room temperature at 20°C to 25°C (68°F to 77°F) in the original vial for up to 8 hours. Discard if not used within 8 hours of reconstitution.
    • •Alternatively, store refrigerated at 2°C to 8°C (36°F to 46°F) for up to 24 hours in the original vial. Remove from refrigerated condition 15-30 minutes prior to injection to allow solution to reach room temperature for a more comfortable injection. Discard if not used within 24 hours of reconstitution.
    • •Do not freeze the reconstituted solution.

  Discard any unused portion. Do not pool unused portions from the vials. Do not administer more than 1 dose from a vial. Do not mix with other medications.

  Instructions for Subcutaneous Administration

  Calculate the exact total dosing volume of 50 mg/mL solution required for the patient.

  Slowly withdraw the dosing volume of the reconstituted REBLOZYL solution from the single-dose vial(s) into a syringe. Divide doses requiring larger reconstituted volumes (i.e., greater than 1.2 mL) into separate similar volume injections and inject into separate sites. If multiple injections are required, use a new syringe and needle for each subcutaneous injection.

  Administer the injection subcutaneously into the upper arm, thigh, and/or abdomen.
  ).

• •For injection: 25 mg white to off-white lyophilized powder in a single-dose vial for reconstitution.
• •For injection: 75 mg white to off-white lyophilized powder in a single-dose vial for reconstitution.

Lactation: Advise not to breastfeed (