Daratumumab/hyaluronidase

Daratumumab/hyaluronidase
Trade names	Darzalex Faspro
Synonyms	Daratumumab and hyaluronidase-fihj
Pharmacology
Drug class	Monoclonal antibody + Enzyme
Routes	Subcutaneous injection
Legal status	Rx-only
Identifiers
CAS Number	1909107-80-7
DrugBank	DB15181
UNII	9N02H7KZ4D
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

Daratumumab

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

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

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

• 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

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

• 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

• 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

Comparison of IV vs. Subcutaneous Daratumumab

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

• 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.

See Also

• Multiple myeloma
• Monoclonal antibodies
• Cancer immunotherapy
• CD38 inhibitors

• Dailymed label info on Daratumumab/hyaluronidase
• FDA Daratumumab/hyaluronidase