Daratumumab- Darzalex -@-(Nov 2015)- Anti-cancer
Drug Name:Daratumumab- Darzalex -@-(Nov 2015)- Anti-cancer
List Of Brands:
Indication Type Description:
Drug Interaction
Indication
Adverse Reaction
Contra-Indications
Dosages/ Overdosage Etc
Patient Information
Pharmacology/ Pharmacokinetics
Pregnancy and lactation
Drug Interaction:
No drug interaction studies have been performed.
Effects of Daratumumab on Laboratory Tests-
Interference with Indirect Antiglobulin Tests (Coombs Test)
Daratumumab binds to CD38 on RBCs and interferes with compatibility testing, including
antibody screening and cross matching. Daratumumab interference mitigation
methods include treating reagent RBCs with dithiothreitol (DTT) to disrupt
daratumumab binding1 [seeReferences (15)] or genotyping.
Since the Kell blood group system is also sensitive to DTT treatment, K-negative units
should be supplied after ruling out or identifying alloantibodies using DTT-treated RBCs.
If an emergency transfusion is required, non-cross-matched ABO/RhD-compatible
RBCs can be given per local blood bank practices.
Interference with Serum Protein Electrophoresis and Immunofixation Tests-
Daratumumab may be detected on serum protein electrophoresis (SPE) and
immunofixation (IFE) assays used for monitoring disease monoclonal
immunoglobulins (M protein).
This can lead to false positive SPE and IFE assay results for patients with IgG kappa
myeloma protein impacting initial assessment of complete responses by
International Myeloma Working Group (IMWG) criteria.
In patients with persistent very good partial response, consider other methods
to evaluate the depth of response.
Indication:
DARZALEX (daratumumab) injection, for intravenous use
Initial U.S. Approval 2015
NEW MOLECULAR ENTITY AND NEW THERAPEUTIC BIOLOGICAL
PRODUCTS APPROVED FOR 2015
Certain drugs are classified as New molecular Emtities- NME- for FDA review
Many of these products contain active moieties that have not been approved
by FDA previously, either as a single ingredient or as part of a combination
products; these products frequently provide important new therapies for the
patients.
Some drugs are characterized as NMEs for administrative purposes ,but
nonetheless contain certain active moieties in products that have been
previously approved by FDA. For example, CDER classifies biological
products submitted in an application under section 351(a) of the Public
Service Act as NME for purposes of FDA review, regardless of whether
the agency previously approved a related active moiety in a different
product.
FDAs classification of a drug as an -NME- for review purposes is distinct
from FDAs determination of whether a drug is a - New Chemical Entity or - NCE-
within the meaning of the Federal Food,Drug, and Cosmetic Act
No.37
Drug Name - Daratumumab
Active Ingredient- Darazalex
Date of approval - 11/16/2015
FDA-approved use - To treat people with multiple myeloma who have
received at least three prior treatments
Approved by US FDA on 11/16/2015- (Ref- FDA approved List- 2015)
INDICATIONS AND USAGE
DARZALEX is a human CD38-directed monoclonal antibody indicated for
the treatment of patients with multiple myeloma who have received at least
three prior lines of therapy including a proteasome inhibitor (PI) and an
immunomodulatory agent or who are double-refractory to a PI and an
immunomodulatory agent.
This indication is approved under accelerated approval based on response rate
Continued approval for this indication may be contingent upon verification and
description of clinical benefit in confirmatory trials.
Adverse Reaction:
The most frequently reported (20%) were:
infusion reactions, fatigue, nausea, back pain, pyrexia, cough, and upper
respiratory tract infection.
Contra-Indications:
CONTRAINDICATIONS
None.
WARNINGS AND PRECAUTIONS
Infusion reactions: Interrupt DARZALEX infusion for infusion reactions of any
severity. Permanently discontinue the infusion in case of life-threatening infusion
reactions.
Interference with cross-matching and red blood cell antibody screening:
Type and screen patients prior to starting treatment. Inform blood banks that
a patient has received DARZALEX.
Dosages/ Overdosage Etc:
INDICATIONS AND USAGE
DARZALEX is a human CD38-directed monoclonal antibody indicated for
the treatment of patients with multiple myeloma who have received at least
three prior lines of therapy including a proteasome inhibitor (PI) and an
immunomodulatory agent or who are double-refractory to a PI and an
immunomodulatory agent.
This indication is approved under accelerated approval based on response rate
Continued approval for this indication may be contingent upon verification and
description of clinical benefit in confirmatory trials.
DOSAGE AND ADMINISTRATION
Pre-medicate with corticosteroids, antipyretics and antihistamines.
Dilute and administer as an intravenous infusion.
Recommended dose is 16 mg/kg body weight:
Weekly Weeks 1 to 8
Every two weeks Weeks 9 to 24
Every four weeks Week 25 onwards until disease progression
Administer post-infusion medications.
DOSAGE FORMS AND STRENGTHS
Injection: x 100 mg/5 mL solution in a single-dose vial
x 400 mg/20 mL solution in a single-dose vial
Patient Information:
PATIENT COUNSELING INFORMATION
Advise the patient to read the FDA-approved patient labeling (Patient Information).
Infusion Reactions
Advise patients to seek immediate medical attention for any of the following signs
and symptoms of infusion reactions:
itchy, runny or blocked nose; chills, nausea, throat irritation, cough, headache,
shortness of breath or difficulty breathing
Interference with Laboratory Tests
Advise patients to inform healthcare providers including blood transfusion
centers/personnel that they are taking DARZALEX, in the event of a planned transfusion.
Advise patients that DARZALEX can affect the results of some tests used to determine
complete response in some patients and additional tests may be needed to evaluate response.
Manufactured by: Janssen Biotech, Inc. Horsham, PA 19044
U.S. License Number 1864
© Janssen Biotech, Inc., 2015
Pharmacology/ Pharmacokinetics:
CLINICAL PHARMACOLOGY
1. Mechanism of Action
CD38 is a transmembrane glycoprotein (48 kDa) expressed on the surface of
hematopoietic cells, including multiple myeloma and other cell types and tissues
and has multiple functions, such as receptor mediated adhesion, signaling,
and modulation of cyclase and hydrolase activity.
2. Pharmacokinetics
The pharmacokinetics (PK) of daratumumab following intravenous administration
were evaluated in patients with relapsed and refractory multiple myeloma at dose levels
from 0.1 mg/kg to 24 mg/kg, and included the recommended 16 mg/kg dose and regimen.
The population PK analysis included 223 patients with multiple myeloma receiving
DARZALEX in two clinical trials (150 subjects received 16 mg/kg).
Over the dose range from 1 to 24 mg/kg, increases in area under the
concentration-time curve (AUC) were more than dose-proportional. Clearance
decreased with increasing dose and repeated dosing, indicating target-mediated
pharmacokinetics.
Following the recommended schedule and dose of 16 mg/kg, the mean
[standard deviation (SD)] serum Cmax value was 915 (410) µg/mL at the end of weekly
dosing, approximately 2.9-fold higher than following the first infusion.
The mean (SD) predose (trough) serum concentration at the end of weekly dosing
was 573 (332) µg/mL.
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
1 Pregnancy
Risk Summary
There are no human data to inform a risk with use of DARZALEX during pregnancy.
Animal studies have not been conducted. However, there are clinical
considerations [see Clinical Considerations].
The estimated background risk of major birth defects and miscarriage for the
indicated population is unknown. In the U.S. general population, the estimated
background risk of major birth defects and miscarriage in clinically recognized
pregnancies is 2-4% and 15-20%, respectively
2 Lactation
Risk Summary
There is no information regarding the presence of daratumumab in human milk,
the effects on the breastfed infant, or the effects on milk production.
Human IgG is known to be present in human milk. Published data suggest that
antibodies in breast milk do not enter the neonatal and infant circulations
in substantial amounts.
The developmental and health benefits of breast-feeding should be considered
along with the mother’s clinical need for DARZALEX and any potential adverse
effects on the breast-fed child from DARZALEX or from the underlying maternal condition.
3. Females and Males of Reproductive Potential
Contraception
To avoid exposure to the fetus, women of reproductive potential should use effective
contraception during treatment and for 3 months after cessation of DARZALEX treatment.
4. Pediatric Use
Safety and effectiveness of DARZALEX in pediatric patients have not been established.
5. Geriatric Use
Of the 156 patients on the recommended dose, 45% were 65 years of age or older,
and 10% were 75 years of age or older. No overall differences in safety or effectiveness
were observed between these patients and younger patients
