Reblozyl

Last reviewed on RxList: 6/15/2020
Reblozyl Side Effects Center

Medical Editor: John P. Cunha, DO, FACOEP

What Is Reblozyl?

Reblozyl (luspatercept-aamt) 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.

What Are Side Effects of Reblozyl?

Side effects of Reblozyl include:

Dosage for Reblozyl

The recommended starting dose of Reblozyl is 1 mg/kg once every 3 weeks by subcutaneous injection.

Reblozyl In Children

Safety and effectiveness in pediatric patients have not been established. Based on findings in juvenile animals, Reblozyl is not recommended for use in pediatric patients.

What Drugs, Substances, or Supplements Interact with Reblozyl?

Reblozyl may interact with other medicines.

Tell your doctor all medications and supplements you use.

Reblozyl During Pregnancy and Breastfeeding

Reblozyl is not recommended for use during pregnancy; it may harm a fetus. Pregnancy testing is recommended for females of reproductive potential before starting Reblozyl treatment. Female patients of reproductive potential are advised to use effective contraception during treatment with Reblozyl and for at least 3 months after the last dose. Because of the potential for serious adverse reactions in the breastfed child, breastfeeding is not recommended during treatment with Reblozyl, and for 3 months after the last dose.

Additional Information

Our Reblozyl (luspatercept-aamt) for Injection, For Subcutaneous Use Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

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Reblozyl Consumer Information

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Tell your caregivers right away if you have:

  • severe headache, blurred vision, pounding in your neck or ears;
  • signs of a stroke--sudden numbness or weakness (especially on one side of the body), severe headache, slurred speech, balance problems;
  • signs of a blood clot in the lung--chest pain, sudden cough, wheezing, rapid breathing, coughing up blood; or
  • signs of a blood clot deep in the body--swelling, warmth, or redness in an arm or leg.

Your luspatercept injections may be delayed or permanently discontinued if you have certain side effects.

Common side effects may include:

  • stomach pain, diarrhea;
  • headache, dizziness;
  • feeling tired;
  • cough; or
  • bone pain, joint pain.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Reblozyl (Luspatercept-aamt for Injection )

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Reblozyl Professional Information

SIDE EFFECTS

The following clinically significant adverse reactions are described elsewhere in the labeling:

  • Thrombosis/Thromboembolism [see WARNINGS AND PRECAUTIONS]
  • Hypertension [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The data in the WARNINGS AND PRECAUTIONS reflect exposure to REBLOZYL as a single agent administered across a range of doses (0.125 mg/kg to 1.75 mg/kg) in 571 patients in 4 trials.

Beta Thalassemia

The safety of REBLOZYL in patients with beta thalassemia was evaluated in the BELIEVE trial [see Clinical Studies]. Key eligibility criteria included adult patients with beta thalassemia (with the exception of patients with hemoglobin S or alpha-thalassemia disease) without major organ damage or recent DVT stroke and platelet counts less than or equal to 1000 x 109/L.

Patients received a starting dose of REBLOZYL 1 mg/kg subcutaneous injection every 3 weeks. Overall, 53% of patients had their dose increased to 1.25 mg/kg (46% REBLOZYL, n = 223) or placebo (66%, n = 109). The median duration of treatment was similar between the REBLOZYL and placebo arms (63.3 weeks vs. 62.1 weeks, respectively). Per protocol, patients in the REBLOZYL and placebo arms were to remain on therapy for at least 48 weeks in the doubleblind phase of the trial.

Among patients receiving REBLOZYL, 94% were exposed for 6 months or longer and 72% were exposed for greater than one year.

The median age of patients who received REBLOZYL was 30 years (range: 18, 66); 59% female; 54% White and 36% Asian.

Serious adverse reactions occurred in 3.6% of patients on REBLOZYL. Serious adverse reactions reported in 1% of patients were cerebrovascular accident and deep vein thrombosis. A fatal adverse reaction occurred in one patient treated with REBLOZYL who died due to an unconfirmed case of AML (M6).

Permanent discontinuation due to an adverse reaction (Grades 1-4) occurred in 5.4% of patients who received REBLOZYL. Most frequent adverse reactions requiring permanent discontinuation in patients who received REBLOZYL included arthralgia (1%), back pain (1%), bone pain (<1%), and headache (<1%).

Dosage reductions due to an adverse reaction occurred in 2.7% of patients who received REBLOZYL. Most frequent adverse reactions requiring dosage reduction in >0.5% of patients who received REBLOZYL included hypertension and headache.

Dosage interruptions due to an adverse reaction occurred in 15.2% of patients who received REBLOZYL. Most frequent adverse reactions requiring dosage interruption in >1% of patients who received REBLOZYL included upper respiratory tract infection, ALT increase, and cough.

The most common adverse reactions (at least 10% for REBLOZYL and 1% more than placebo) were headache (26%), bone pain (20%), arthralgia (19%), fatigue (14%), cough (14%), abdominal pain (14%), diarrhea (12%), and dizziness (11%).

Table 6 summarizes the adverse reactions in BELIEVE.

Table 6: Adverse Drug Reactions (>5%) in Patients with Beta Thalassemia Receiving REBLOZYL with a Difference Between Arms of 1% in BELIEVE Trial

Body System
  Adverse Reaction
REBLOZYL
(N=223)
Placebo
(N=109)
All Grades
n (%)
Grades ≥3a
n (%)
All Grades
n (%)
Grades ≥3
n (%)
Musculoskeletal and connective tissue disorders
  Bone Pain44 (20)3 (1)9 (8)0 (0)
  Arthralgia43 (19)0 (0)13 (12)0 (0)
Infections and infestation
  Influenza19 (9)0 (0)6 (6)0 (0)
  Viral Upper Respiratory Infection14 (6)1 (0.4)2 (2)0 (0)
Nervous system disorders
  Headache58 (26)1 (<1)26 (24)1 (1)
  Dizziness25 (11)0 (0)5 (5)0 (0)
General disorders and administration site conditions
  Fatigue30 (14)0 (0)14 (13)0 (0)
Gastrointestinal disorders
  Abdominal Pain b31 (14)0 (0)13 (12)0 (0)
  Diarrhea27 (12)1 (<1)11 (10)0 (0)
  Nausea20 (9)0 (0)6 (6)0 (0)
Vascular disorders
  Hypertension c18 (8)4 (2)3 (3)0 (0)
Metabolism and nutrition disorders
  Hyperuricemia16 (7)6 (3)0 (0)0 (0)
Respiratory, thoracic and mediastinal disorders
  Cough32 (14)0 (0)12 (11)0 (0)
a Limited to Grade 3 reactions with the exception of 4 events of Grade 4 hyperuricemia.
b Grouped term includes abdominal pain and abdominal pain upper.
c Grouped term includes essential hypertension, hypertension, and hypertensive crisis.

Clinically relevant adverse reactions in <5% of patients include vertigo/vertigo positional, syncope/presyncope, injection site reactions and hypersensitivity.

Liver function abnormalities in the BELIEVE trial are shown in Table 7.

Table 7: Liver Function Laboratory Abnormalities in Patients with Beta Thalassemia in the BELIEVE Trial

REBLOZYL
N = 223
n (%)
Placebo
N = 109
n (%)
ALT ≥ 3 × ULN26 (12)13 (12)
AST ≥ 3 × ULN25 (11)5 (5)
ALP ≥ 2 × ULN17 (8)1 (<1)
Total bilirubin ≥ 2 × ULN143 (64)51 (47)
Direct bilirubin ≥ 2 × ULN13 (6)4 (4)
ALP = alkaline phosphatase; ALT = alanine aminotransferase;
AST = aspartate aminotransferase; ULN = upper limit of normal.

Myelodysplastic Syndromes With Ring Sideroblasts Or Myelodysplastic / Myeloproliferative Neoplasm With Ring Sideroblasts And Thrombocytosis Associated Anemia

The safety of REBLOZYL at the recommended dose and schedule was evaluated in 242 patients with MDS with ring sideroblasts (n=192) or other myeloid neoplasms (n=50). The safety population included 63% males and 37% females of median age 72 years (range, 30 – 95 years); of these patients, 81% were White, 0.4% Black, 0.4% Other, and race was not reported in 18.2% of patients. The median time on treatment with REBLOZYL was 50.4 weeks (range, 3 – 221 weeks); 67% of patients were exposed for 6 months or longer and 49% were exposed for greater than one year.

Among the 242 patients treated with REBLOZYL, 5 (2.1%) had a fatal adverse reaction, 11 (4.5%) discontinued due to an adverse reaction, and 7 (2.9%) had a dose reduction due to an adverse reaction. The most common (≥10%) all-grade adverse reactions included fatigue, musculoskeletal pain, dizziness, diarrhea, nausea, hypersensitivity reactions, hypertension, headache, upper respiratory tract infection, bronchitis, and urinary tract infection. The most common (≥2%) Grade ≥ 3 adverse reactions included fatigue, hypertension, syncope and musculoskeletal pain. Selected laboratory abnormalities that changed from Grade 0-1 at baseline to Grade ≥ 2 at any time during the studies in at least 10% of patients included creatinine clearance decreased, total bilirubin increased, and alanine aminotransferase increased.

Table 8 shows the most common adverse reactions for patients treated with REBLOZYL or placebo through the first 8 cycles in the MEDALIST trial [see Clinical Studies].

Table 8: Adverse Reactions (≥5%) in Patients Receiving REBLOZYL with a Difference Between Arms of >2% in MEDALIST Trial Through Cycle 8

Body System /Adverse ReactionREBLOZYL
(N=153)
Placebo
(N=76)
All Grades
n (%)
Grade 3
n (%)
All Grades
n (%)
Grade 3
n (%)
General disorders and administration site conditions
Fatigue a, b63 (41)11 (7)17 (22)2 (3)
Musculoskeletal and connective tissue disorders
Musculoskeletal pain b30 (20)3 (2)11 (14)0 (0)
Nervous system disorders
Dizziness/vertigo28 (18)1 (<1)5 (7)1 (1)
Headache b21 (14)0 (0)5 (7)0 (0)
Syncope / presyncope8 (5)5 (3)0 (0)0 (0)
Gastrointestinal disorders
Nausea b25 (16)1 (<1)8 (11)0 (0)
Diarrhea b25 (16)0 (0)7 (9)0 (0)
Respiratory, thoracic and mediastinal disorders
Dyspnea b20 (13)2 (1)4 (5)1 (1)
Immune system disorders
Hypersensitivity reactions b15 (10)1 (<1)5 (7)0 (0)
Renal and urinary disorders
Renal impairment b12 (8)3 (2)3 (4)0 (0)
Cardiac disorders
Tachycardia b12 (8)0 (0)1 (1)0 (0)
Injury poisoning and procedural complications
Injection site reactions10 (7)0 (0)3 (4)0 (0)
Infections and infestations
Upper respiratory tract infection10 (7)1 (<1)2 (3)0 (0)
Influenza / influenza like illness9 (6)0 (0)2 (3)0 (0)
a Includes asthenic conditions.
b Reaction includes similar/grouped terms.

Other clinically relevant adverse reactions reported in <5% of patients include bronchitis, urinary tract infection, and hypertension [see WARNINGS AND PRECAUTIONS].

Shifts from Grades 0-1 to Grades 2-4 abnormalities for selected laboratory tests during the first 8 cycles in the MEDALIST trial are shown in Table 9.

Table 9: Selected Grades 2-4 Treatment-Emergent Laboratory Abnormalities Through Cycle 8 in the MEDALIST Trial

ParameterREBLOZYLPlacebo
Nan (%)Nan (%)
ALT elevated15113 (9)745 (7)
AST elevated1526 (4)760 (0)
Total bilirubin elevated14017 (12)663 (5)
Creatinine clearance reduced11330 (27)6213 (21)
a Number of patients at Grades 0-1 at baseline.
ALT = alanine aminotransferase; AST = aspartate aminotransferase.

Immunogenicity

As with all therapeutic proteins, there is potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to luspatercept in the studies described below with the incidence of antibodies in other studies or to other products may be misleading.

Of 284 patients with beta thalassemia who were treated with REBLOZYL and evaluable for the presence of anti-luspatercept-aamt antibodies, 4 patients (1.4%) tested positive for treatmentemergent anti-luspatercept-aamt antibodies, including 2 patients (0.7%) who had neutralizing antibodies.

Of 260 patients with MDS who were treated with REBLOZYL and evaluable for the presence of anti-luspatercept-aamt antibodies, 23 patients (8.9%) tested positive for treatment-emergent antiluspatercept- aamt antibodies, including 9 patients (3.5%) who had neutralizing antibodies.

Luspatercept-aamt serum concentration tended to decrease in the presence of neutralizing antibodies. There were no severe acute systemic hypersensitivity reactions reported for patients with anti-luspatercept-aamt antibodies in REBLOZYL clinical trials, and there was no association between hypersensitivity type reaction or injection site reaction and presence of antiluspatercept- aamt antibodies.

Read the entire FDA prescribing information for Reblozyl (Luspatercept-aamt for Injection )

© Reblozyl Patient Information is supplied by Cerner Multum, Inc. and Reblozyl Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

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