Daratumumab/hyaluronidase
| Daratumumab/hyaluronidase | |
|---|---|
| INN | |
| Drug class | Monoclonal antibody + Enzyme |
| Routes of administration | Subcutaneous injection |
| Pregnancy category | |
| Bioavailability | |
| Metabolism | |
| Elimination half-life | |
| Excretion | |
| Legal status | Rx-only |
| CAS Number | 1909107-80-7 |
| PubChem | |
| DrugBank | DB15181 |
| ChemSpider | |
| KEGG | D11930 |
Daratumumab/hyaluronidase (brand name Darzalex Faspro) is a combination medication used for the treatment of multiple myeloma. It consists of daratumumab, a monoclonal antibody, and hyaluronidase, an enzyme that enhances drug absorption when administered subcutaneously.
Mechanism of Action[edit]
Daratumumab[edit]
Daratumumab is a CD38-targeting monoclonal antibody that works by binding to the CD38 protein found on the surface of multiple myeloma cells. This leads to:
- Complement-dependent cytotoxicity (CDC)
- Antibody-dependent cell-mediated cytotoxicity (ADCC)
- Apoptosis (programmed cell death)
Hyaluronidase[edit]
Hyaluronidase-fihj is an enzyme that breaks down hyaluronic acid, a component of the extracellular matrix. This:
- Increases permeability of subcutaneous tissues, allowing better absorption of daratumumab.
- Reduces infusion time, making administration more convenient compared to intravenous daratumumab.
Indications[edit]
Daratumumab/hyaluronidase is approved for the treatment of:
- Multiple myeloma, in combination with:
Lenalidomide and Dexamethasone Bortezomib and Dexamethasone Carfilzomib and Dexamethasone
- Light chain amyloidosis (AL amyloidosis) – as a first-line treatment.
Administration[edit]
- Route: Subcutaneous injection (SC) in the abdominal region.
- Advantages over IV daratumumab:
Faster administration (5 minutes vs. several hours for IV infusion). Lower risk of infusion-related reactions.
Side Effects[edit]
Common adverse effects include:
- Infusion-related reactions (less frequent than IV formulation)
- Fatigue
- Nausea
- Back pain
- Cytopenias (low blood cell counts)
Neutropenia (risk of infection) Thrombocytopenia (risk of bleeding) Anemia
- Respiratory infections
- Peripheral edema (fluid retention)
Contraindications and Precautions[edit]
- Hypersensitivity to daratumumab or hyaluronidase.
- Increased risk of respiratory infections requires monitoring.
- Interference with blood typing – Daratumumab binds to CD38 on red blood cells, which can interfere with compatibility testing.
- Pregnancy and lactation – Limited data; use with caution.
Drug Interactions[edit]
- Immunomodulatory agents (e.g., Lenalidomide) – Used in combination for synergistic effect.
- Corticosteroids (e.g., Dexamethasone) – Used to reduce infusion reactions.
- Live vaccines – Avoid due to potential immunosuppression.
Comparison with IV Daratumumab[edit]
| Feature | IV Daratumumab | SC Daratumumab/Hyaluronidase |
|---|---|---|
| Route | Intravenous (IV) | Subcutaneous (SC) |
| Administration Time | 3–7 hours | 5 minutes |
| Infusion-related Reactions | More common | Less frequent |
| Convenience | Requires IV access | No IV required |
| Hospital Visits | More frequent | Less frequent |
Regulatory Approval[edit]
- Approved by the U.S. Food and Drug Administration (FDA) in 2020.
- Approved by the European Medicines Agency (EMA) and other regulatory bodies.
- Included in National Comprehensive Cancer Network (NCCN) guidelines for multiple myeloma.
