luspatercept

REMS

Anemia in patients with beta thalassemia who require regular red blood cell (RBC) transfusions.
Anemia in patients with very low- to intermediate-risk myelodysplastic syndromes with ring sideroblasts or with myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis who have failed an erythropoiesis stimulating agent and require ≥2 RBC units over 8 wk.
Anemia in patients who have not previously used erythropoiesis-stimulating agents, have very low- to intermediate-risk myelodysplastic syndromes, and may require regular RBC transfusions.

Action ⬆ ⬇

A fusion protein that binds several endogenous transforming growth factor-beta (TGF-β) superfamily ligands. Inhibition of TGF-β superfamily results in increased differentiation and proliferation of erythroid precursors.

Therapeutic effects:

Reduction in RBC transfusions.
Increase in hemoglobin.

Pharmacokinetics ⬆ ⬇

Absorption: Unknown.

Distribution: Not significantly distributed to tissues.

Metabolism/Excretion: Broken down into amino acids.

Half-Life: 11–13 days.

Time/Action Profile ⬆ ⬇

(↑ in hemoglobin levels)

ROUTE	ONSET	PEAK	DURATION
SUBQ	Within 7 days	Unknown	8 wk

Contraind./Precautions ⬆ ⬇

Contraindicated in:

OB: Pregnancy;
Lactation: Lactation;
Pedi: Not recommended for use in children (may ↑ risk of hematologic malignancies).

Use Cautiously in:

Risk factors for thromboembolism;
Hypertension;
History of extramedullary hematopoietic masses, splenectomy, hepatomegaly, or low baseline hemoglobin (<8.5 g/dL) (↑ risk of extramedullary hematopoietic masses);
Rep: Women of reproductive potential.

Adv. Reactions/Side Effects ⬆ ⬇

CV: hypertension, DEEP VEIN THROMBOSIS, syncope

EENT: vertigo

GI: ↑liver enzymes, abdominal pain, diarrhea, nausea

GU: ↓fertility (females)

Hemat: extramedullary hematopoietic masses

Local: injection site reactions

Metab: hyperuricemia

MS: arthralgia, bone pain

Neuro: dizziness, fatigue, headache, STROKE

Resp: cough, PULMONARY EMBOLISM, upper respiratory tract infection

Misc: hypersensitivity reactions

Interactions ⬆ ⬇

Drug-drug:

None reported.

Route/Dosage ⬆ ⬇

Anemia in Beta Thalassemia

SC (Adults ): 1 mg/kg every 3 wk. If no reduction in RBC transfusion burden occurs after 2 consecutive doses (6 wk), ↑ dose to 1.25 mg/kg every 3 wk. Discontinue therapy if no reduction in RBC transfusion burden occurs after 3 consecutive doses (9 wk) at maximum dose (1.25 mg/kg) or if unacceptable toxicity occurs.

Anemia in Myelodysplastic Syndromes

SC (Adults ): 1 mg/kg every 3 wk. If patient is not RBC transfusion-free after ≥2 consecutive doses (6 wk), ↑ dose to 1.33 mg/kg every 3 wk. Then, if patient is not RBC transfusion-free after ≥2 consecutive doses (6 wk) at 1.33 mg/kg dose, ↑ dose to 1.75 mg/kg every 3 wk. Discontinue therapy if no reduction in RBC transfusion burden occurs after 3 consecutive doses (9 wk) at maximum dose (1.75 mg/kg) or if unacceptable toxicity occurs.

Availability ⬆ ⬇

Lyophilized powder for injection: 25 mg/vial; 75 mg/vial

Assessment ⬆ ⬇

Monitor patient for signs and symptoms of thromboembolic events during therapy.
Monitor BP before each administration. Manage hypertension or exacerbations.

Lab Test Considerations:

Verify negative pregnancy test before starting therapy.
- Review hemoglobin level and transfusion record before each dose. If an RBC transfusion occurred before dosing, use pretransfusion hemoglobin for dose evaluation. Dose modification for predose hemoglobin levels or rapid hemoglobin rise in beta thalassemia: If predose hemoglobin ≥11.5 g/dL in the absence of transfusions, interrupt therapy and restart when hemoglobin is ≤11 g/dL. If increase in hemoglobin >2 g/dL within 3 wk in the absence of transfusion and current dose is 1.25 mg/kg, reduce dose to 1 mg/kg. If current dose is 1 mg/kg, reduce dose to 0.8 mg/kg. If current dose is 0.8 mg/kg, reduce dose to 0.6 mg/kg. If current dose is 0.6 mg/kg, discontinue therapy. Dose modification for predose hemoglobin levels or rapid hemoglobin rise in myelodysplastic syndromes with ring sideroblasts or with myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosisIf predose hemoglobin ≥11.5 g/dL in the absence of transfusions, interrupt therapy and restart when hemoglobin is ≤11 g/dL. If increase in hemoglobin >2 g/dL within 3 wk in the absence of transfusion and current dose is 1.75 mg/kg, reduce dose to 1.33 mg/kg. If current dose is 1.33 mg/kg, reduce dose to 1 mg/kg. If current dose is 1 mg/kg, reduce dose to 0.8 mg/kg. If current dose is 0.8 mg/kg, reduce dose to 0.6 mg/kg. If current dose is 0.6 mg/kg, discontinue therapy.
- May cause ↑ AST, ALT, alkaline phosphatase, total and direct bilirubin.

Implementation ⬆ ⬇

Luspatercept should be reconstituted and administered by a health care professional.
If a dose is missed administer as soon as possible and continue dosing with at least 3 wk between doses.
Reconstitution: Reconstitute 25 mg vial with 0.68 mL and 75 mg vial with 1.6 mL Sterile Water for Injection, directing stream onto powder.Concentration: 25 mg/0.5 mL and 75 mg/1.5 mL, respectively. Allow to stand for 1 min. Discard needle and syringe; do not use for injection. Swirl gently for 30 sec, then allow vial to sit upright for 30 sec. If undissolved powder is observed, repeat step 3 until the powder is completely dissolved. Invert vial and swirl gently in inverted position for 30 sec. Return vial to upright position and let sit for 30 sec. Repeat procedure in italics 7 more times to ensure complete reconstitution of material on sides of vial. Solution is colorless to slightly yellow, clear to slightly opalescent; do not inject solutions that are cloudy, discolored, or contain particulate matter. Store reconstituted solution in original vial at room temperature for up to 8 hr; discard if not used in 8 hr. May be stored in refrigerator for up to 24 hr in original vial; do not freeze. Remove from refrigerator 15–30 min before injection to allow to reach room temperature. Discard if not used in 24 hr. Vials are for single dose only.
SC: Withdraw dose into syringe; divide doses >1.2 mL into 2 syringes and inject into 2 different sites. Administer into upper arm, thigh, or abdomen.

Patient/Family Teaching ⬆ ⬇

Explain purpose of luspatercept to patient. Advise patient to read Patient Information before starting and periodically during therapy in case of changes.
Advise patient to notify health care professional immediately if signs and symptoms of blood clots (chest pain; trouble breathing or shortness of breath; pain in leg, with or without swelling; a cold or pale arm or leg; sudden numbness or weakness that are both short-term or continue to happen over a long period of time, especially on one side of the body; severe headache or confusion; sudden problems with vision, speech, or balance) occur.
Inform patient that BP will be monitored before each dose. May require antihypertensive medication to treat elevated BP.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
Rep: May cause fetal harm. Advise females of reproductive potential to use effective contraception and avoid breastfeeding during and for at least 3 mo after last dose. May impair female fertility.

Evaluation/Desired Outcomes ⬆ ⬇

Reduction in RBC transfusions.
Increase in hemoglobin.

US Brand Names ⬆ ⬇

Code ⬆

NDC Code

59572- Celgene Corporation
- 59572-711- Reblozyl
  - 59572-711-01- 1 VIAL, GLASS in 1 CARTON (59572-711-01) / 1 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION in 1 VIAL, GLASS

59572- Celgene Corporation
- 59572-775- Reblozyl
  - 59572-775-01- 1 VIAL, GLASS in 1 CARTON (59572-775-01) / 1 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION in 1 VIAL, GLASS

64406- Biogen Inc.
- 64406-550-
  - 64406-550-01- 2 kg in 1 BOTTLE (64406-550-01)

68225- Patheon Italia S.p.A.
- 68225-118-
  - 68225-118-00- 988 VIAL in 1 CASE (68225-118-00) / 2 mL in 1 VIAL

68225- Patheon Italia S.p.A.
- 68225-119-
  - 68225-119-00- 988 VIAL in 1 CASE (68225-119-00) / 2 mL in 1 VIAL

69438- Lonza Biologics Tuas Pte. Ltd.
- 69438-0006-
  69438-0006-1- 2 L in 1 BOTTLE (69438-0006-1)

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇