Product Information
Registration Status: ActiveSIN15111P
DARZALEX CONCENTRATE FOR SOLUTION FOR INFUSION 400MG/20ML is approved to be sold in Singapore with effective from 2016-10-26. It is marketed by JOHNSON & JOHNSON PTE LTD, with the registration number of SIN15111P.
This product contains Daratumumab 20mg/mL in the form of INTRAVENOUS INFUSION, SOLUTION CONCENTRATE. It is approved for INTRAVENOUS use.
This product is manufactured by Vetter Pharma-Fertigung GmbH & Co. KG in SWITZERLAND, andCilag A.G. in GERMANY.
It is a Prescription Only Medicine that can only be obtained from a doctor or a dentist, or a pharmacist with a prescription from a Singapore-registered doctor or dentist.
Product Reference
Important Note: For generic product, the SPC/PIL provided may not be brand specific.
{{/items}} {{^items}}Description
Daratumumab is an anti-cancer drug indicated for multiple myeloma in patients who have received at least 3 prior treatments. It was granted accelerated approval by the FDA in November 2016. Marketed under the brand name Darzalex by Janssen Biotech, daratumumab is the first monoclonal antibody injection approved for this indication and provides another options for patients with multiple myeloma resistant to other therapies. Daratumumab induces apoptosis of cancer cells by targeting the CD38 epitope, which is highly expressed on haematological malignancies.
Indication
For the treatment of patients with multiple myeloma who have received at least three prior lines of therapy (a proteasome inhibitor (PI) and an immunomodulatory agent) or who are double-refractory to a PI and an immunomodulatory agent. This indication was approved by accelerated approval based on response rate.
Mechanism of Action
Daratumumab is an immunoglobulin G1 kappa monoclonal antibody against CD38 antigen. CD38 is a transmembrane glycoprotein of many functions, including receptor mediated adhesion, signaling, and modulation of cyclase and hydrolase activity. CD38 is expressed on many cell types and tissues, and highly expressed in haematological malignancies including multiple myeloma tumor cells. By binding CD38, daratumumab causes inhibition of tumor cell growth and induces broad-spectrum apoptosis in multiple ways: by Fc-mediated cross linking, by immune-mediate tumor cell lysis through complement dependent cytotoxicity, antibody dependent cell cytotoxicity, and antibody dependent cellular phagocytosis.
Pharmacokinetics
- Absorption
- Following the recommended schedule and dose of 16 mg/kg, the mean serum Cmax value was 915 μg/mL at the end of weekly dosing, approximately 2.9-fold higher than following the first infusion. The mean predose serum concentration at the end of weekly dosing was 573 μg/mL.
- Distribution
- 4.7 L
- Metabolism
- Elimination
Clearance
171.4 mL/day. Clearance decreased with increasing dose and repeated dosing, indicating target-mediated pharmacokinetics.
Toxicity
Immunoglobulin G1 (IgG1) monoclonal antibodies are transferred across the placenta. Due to its mechanism of action, daratumumab may cause fetal myeloid or lymphoid-cell depletion and decreased bone density. The FDA label recommends to defer administering live vaccines to neonates and infants exposed to daratumumab in utero until a hematology evaluation is completed. Women of reproductive potential should also should use effective contraception methods during treatment and 3 months post-treatment to avoid pregnancy and exposure to the fetus while on daratumumab.
Active Ingredient/Synonyms
HuMax-CD38 | Daratumumab |
Source of information: Drugbank (External Link). Last updated on: 3rd July 18. *Trade Name used in the content below may not be the same as the HSA-registered product.