luspatercept

Action and Spectrum

Actions and Spectrum: 

luspatercept works by increasing the production of red blood cells and improving their ability to carry oxygen. 

luspatercept belongs to a class of medications called erythroid maturation agents. These drugs bind to a protein called transforming growth factor-beta (TGF-beta) in the blood and help to block its activity. TGF-beta is a molecule that usually suppresses the production of red blood cells. By blocking its activity, luspatercept helps to increase the production of red blood cells and improve their maturation. 

The spectrum of luspatercept’s actions includes the stimulation of erythroid differentiation, which increases red blood cell production. It also reduces the level of a protein called growth differentiation factor-11 (GDF11), which can interfere with red blood cell production. By reducing the level of GDF11, luspatercept further enhances the production of red blood cells. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

Headache 

Bone Pain 

Fatigue 

Arthralgia 

Cough  

Abdominal Pain 

Diarrhea 

Dizziness 

Nausea 

Dyspnea 

Musculoskeletal Pain 

Elevated total bilirubin 

Hypertension 

Hyperuricemia 

1-10% 

Tachycardia 

Renal impairment 

Elevated ALT 

Upper respiratory infection 

Influenza-like infections 

Reaction at the injection site 

Hypersensitivity reactions 

<1% 

Headache 

Diarrhea 

Black Box Warning

Contraindication / Caution

Contraindication/Caution: 

Contraindications: 

• luspatercept is contraindicated in patients with a history of severe hypersensitivity reaction to luspatercept or its components. 

Precautions: 

• Patients with a history of thrombosis (blood clotting) or underlying conditions that increase the risk of thrombosis should be monitored closely during treatment with luspatercept. 
• luspatercept may increase the risk of bleeding, so caution should be exercised in patients with a history of bleeding or taking medications that increase the risk. 
• luspatercept should be used cautiously in patients with hepatic (liver) impairment as it can lead to increased drug exposure. 
• luspatercept should also be used cautiously in pregnant and breastfeeding women as there is limited information on its safety in these populations. 

Pregnancy / Lactation

Pregnancy consideration:  

No data is available regarding the usage during pregnancy  

Breastfeeding warnings:  

Lactation is advised 3 months after the last dose 

Pregnancy category: 

• Category A: Satisfactory and well-controlled studies show no risk to the fetus in the first or later trimester. 
• <b>Category B: No evidence of risk to the fetus is found in animal reproduction studies, and there are not enough studies on pregnant women. 
• Category C: Adverse effects on the fetus found with evidence in animal reproduction studies and no adequate evidence for a human product; Pregnant women must take care of the potential risks. 
• Category D: There is adequate data with sufficient evidence of human fetal risk from various platforms. However, despite potential dangers may be used only in emergencies for potential benefits. 
• Category X: Drugs listed in this category outweigh the risks over benefits. The drug is not for pregnant women. 
• Category N: No data for the drug under this category is available. 

Pharmacology

Pharmacology: 

luspatercept is a recombinant fusion protein that binds to specific molecules in the blood, including transforming growth factor beta (TGF-β) superfamily ligands, to regulate red blood cell production. It works by inhibiting the TGF-β signaling pathway, which plays a critical role in the maturation and differentiation of red blood cells. 

luspatercept comprises a modified human IgG1 antibody fragment and a portion of the TGF-β receptor that binds to TGF-β ligands. The antibody fragment helps to extend the drug’s half-life in the blood, while the receptor portion blocks the activity of TGF-β ligands, which would typically suppress red blood cell production. 

By inhibiting TGF-β signaling, luspatercept stimulates erythroid differentiation and maturation, increasing the production of red blood cells. This leads to improved hemoglobin levels and a reduction in the need for blood transfusions in patients with certain blood disorders, such as beta-thalassemia and myelodysplastic syndromes. 

Pharmacodynamics: 

The pharmacodynamics of luspatercept involve its interactions with various components of the TGF-β signaling pathway, which plays a crucial role in erythroid cell maturation and differentiation.  

In addition to its effects on ligand-receptor interactions, luspatercept also regulates the expression of genes involved in erythropoiesis, such as GATA1 and KLF1, which are critical for erythroid cell differentiation and maturation. By upregulating the expression of these genes, luspatercept promotes erythropoiesis and enhances red blood cell production. 

Pharmacokinetics: 

Absorption 

The area under the curve in patients with beta-thalassemia is 126 days ·mcg/mL (for 1 mg/kg); 157 days ·mcg/mL (for 1.25 mg/kg) 

The peak plasma concentration at steady-state in patients with beta-thalassemia is 8.17 mcg/mL (for 1 mg/kg) and 10.2 mcg/mL (for 1.25 mg/kg) 

Peak plasma concentration is achieved in 7 days after the dose in healthy patients and patients with beta-thalassemia 

Distribution 

The volume of distribution is 7.1 L 

Metabolism 

With the help of general protein degradation processes, the drug is catabolized into amino acids in multiple tissues. 

Elimination and Excretion 

The half-life is 11 days 

The rate of clearance is 0.44 L/day 

Adminstartion

Administration: 

luspatercept is administered as a subcutaneous injection, injected into the fatty tissue below the skin. A healthcare professional can give the injection or self-administered by the patient after proper training and instruction. 

The recommended dose of luspatercept is based on the patient’s body weight and is administered every three weeks. The medication is supplied as a single-use vial, and the injection should be prepared according to the instructions provided with the medication. 

Before administration, the injection site should be cleaned with an alcohol swab, and the medication should be allowed to reach room temperature. The medication should be inspected visually for any particles or discoloration before use. It should not be used if the medication appears cloudy or contains particles. 

The injection should be administered into the upper arm, thigh, or abdomen, rotating the injection site with each injection to avoid causing irritation or inflammation. After injection, the site should be covered with a sterile bandage if necessary. 

Patient Information Leaflet

Patient information leaflet 

Generic Name:  luspatercept 

Pronounced: lus-PAT-er-sept 

Why do we use luspatercept? 

luspatercept treats anemia in two specific patient populations: beta-thalassemia and myelodysplastic syndromes (MDS). 

Beta-thalassemia is an inherited blood disorder that affects the production of hemoglobin. In beta-thalassemia, the body produces less hemoglobin than usual, which can lead to anemia and other complications. 

Patients with MDS may develop anemia due to a lack of red blood cells. luspatercept is used in patients with MDS who have anemia and require regular blood transfusions. 

luspatercept is a type of erythropoiesis-stimulating agent (ESA) that stimulates the production of red blood cells, thereby reducing the need for blood transfusions in patients with beta-thalassemia and MDS. It works by inhibiting the TGF-β signaling pathway, which plays a critical role in the maturation and differentiation of red blood cells.