REBLOZYL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for REBLOZYL (REBLOZYL).
Reblozyl (luspatercept-aamt) is a recombinant fusion protein that acts as an erythroid maturation agent. It binds to select transforming growth factor-beta (TGF-β) superfamily ligands, such as GDF11 and activin B, to inhibit Smad2/3 signaling, thereby promoting late-stage erythroid differentiation and maturation.
| Metabolism | Catabolized into small peptides and amino acids via general protein degradation pathways. |
| Excretion | Primarily eliminated via proteolytic catabolism; minimal renal elimination (less than 3% as intact drug in urine). Fecal excretion negligible. |
| Half-life | Terminal half-life approximately 11.3 ± 1.5 days, supporting once-every-3-week subcutaneous dosing. |
| Protein binding | Approximately 97% bound to plasma proteins, primarily to albumin. |
| Volume of Distribution | Mean Vd approximately 0.45 L/kg, indicating distribution primarily within plasma and interstitial fluid. |
| Bioavailability | Subcutaneous: absolute bioavailability approximately 85%. |
| Onset of Action | Subcutaneous: initial hemoglobin increase observed within 1-2 weeks after first dose. |
| Duration of Action | Duration of effect persists for approximately 6-8 weeks after last dose; repeated dosing required to maintain hemoglobin response. |
1.0 mg/kg subcutaneously every 3 weeks. Dose may be titrated up to a maximum of 1.33 mg/kg every 3 weeks based on hemoglobin response.
| Dosage form | POWDER |
| Renal impairment | No dose adjustment recommended for mild to moderate renal impairment. Data insufficient for severe renal impairment or dialysis. |
| Liver impairment | No specific dose adjustment provided; use caution in moderate to severe hepatic impairment (Child-Pugh B or C) due to limited data. |
| Pediatric use | Safety and efficacy not established in pediatric patients; no approved pediatric dosing. |
| Geriatric use | No specific dose adjustment required based on age; consider renal and hepatic function as per adult recommendations. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for REBLOZYL (REBLOZYL).
| Breastfeeding | No data on presence in human milk, effects on breastfed infant, or milk production. M/P ratio unknown. Due to potential for serious adverse reactions, breastfeeding is not recommended during treatment and for at least 4 months after the last dose. |
| Teratogenic Risk | Animal studies show no evidence of fetal harm. No adequate human data in pregnant women. First trimester: unknown risk. Second and third trimesters: unknown risk. Use only if clearly needed. |
| Fetal Monitoring |
■ FDA Black Box Warning
REBLOZYL has a boxed warning for thrombosis/thromboembolism. In patients with beta-thalassemia, thrombotic events have occurred. Monitor for signs and symptoms. Manage according to standard of care.
| Serious Effects |
None known. However, REBLOZYL should not be used in patients with history of hypersensitivity to luspatercept-aamt or any components of the formulation.
| Precautions | Increased risk of thromboembolic events (especially in beta-thalassemia), hypertension, progressive multifocal leukoencephalopathy (if switching from an erythropoiesis stimulating agent), potential for fetal harm, and albuminuria (observed in animal studies). Monitor blood pressure, hemoglobin, and for signs of thrombosis. |
Loading safety data…
| Monitor for hypertension (including hypertensive crisis) and preeclampsia. Monitor renal function and proteinuria. Perform periodic blood counts for early detection of cytopenias. Monitor for excessive erythropoiesis leading to increased blood viscosity and thrombotic events. |
| Fertility Effects | No human fertility data. In animal studies, no adverse effects on male or female fertility were observed at exposures up to 12 times the human exposure. |