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DARZALEX FASPRO™ (daratumumab and hyaluronidase-fihj) injection
If an emergency transfusion is required, administer non-cross-matched ABO/RhD-compatible RBCs 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). False positive SPE and IFE assay
results may occur for patients with IgG kappa myeloma protein impacting initial assessment of complete
responses by International Myeloma Working Group (IMWG) criteria. In DARZALEX FASPRO-treated
patients with persistent very good partial response, where daratumumab interference is suspected,
consider using a FDA-approved daratumumab-specific IFE assay to distinguish daratumumab from any
remaining endogenous M protein in the patient’s serum, to facilitate determination of a complete response.
USE IN SPECIFIC POPULATIONS
Pregnancy
Risk Summary
DARZALEX FASPRO can cause fetal harm when administered to a pregnant woman. The assessment of
associated risks with daratumumab products is based on the mechanism of action and data from target
antigen CD38 knockout animal models (see Data). There are no available data on the use of DARZALEX
FASPRO in pregnant women to evaluate drug-associated risk of major birth defects, miscarriage or adverse
maternal or fetal outcomes. Animal reproduction studies have not been conducted.
The estimated background risk of major birth defects and miscarriage for the indicated population is
unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the
U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically
recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
The combination of DARZALEX FASPRO and lenalidomide is contraindicated in pregnant women, because
lenalidomide may cause birth defects and death of the unborn child. Lenalidomide is only available through
a REMS program. Refer to the lenalidomide prescribing information on use during pregnancy.
Clinical Considerations
Fetal/Neonatal Adverse Reactions
Immunoglobulin G1 (IgG1) monoclonal antibodies are transferred across the placenta. Based on its
mechanism of action, DARZALEX FASPRO may cause depletion of fetal CD38 positive immune cells
and decreased bone density. Defer administering live vaccines to neonates and infants exposed to
daratumumab in utero until a hematology evaluation is completed.
Data
Animal Data
DARZALEX FASPRO for subcutaneous injection contains daratumumab and hyaluronidase. Mice that were
genetically modified to eliminate all CD38 expression (CD38 knockout mice) had reduced bone density at
birth that recovered by 5 months of age. Data from studies using CD38 knockout animal models also suggest
the involvement of CD38 in the regulation of humoral immune responses (mice), feto-maternal immune
tolerance (mice), and early embryonic development (frogs).
No systemic exposure of hyaluronidase was detected in monkeys given 22,000 U/kg subcutaneously
(12 times higher than the human dose) and there were no effects on embryo-fetal development in pregnant
mice given 330,000 U/kg hyaluronidase subcutaneously daily during organogenesis, which is 45 times
higher than the human dose.
There were no effects on pre- and post-natal development through sexual maturity in offspring of mice
treated daily from implantation through lactation with 990,000 U/kg hyaluronidase subcutaneously, which
is 134 times higher than the human doses.
Lactation
Risk Summary
There is no data on the presence of daratumumab and hyaluronidase in human milk, the effects on the
breastfed child, or the effects on milk production. Maternal immunoglobulin G 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. Because of the potential for serious adverse reactions in the breastfed
child when DARZALEX FASPRO is administered with lenalidomide and dexamethasone, advise women not
to breastfeed during treatment with DARZALEX FASPRO. Refer to lenalidomide prescribing information for
additional information.
Data
Animal Data
No systemic exposure of hyaluronidase was detected in monkeys given 22,000 U/kg subcutaneously
(12 times higher than the human dose) and there were no effects on post-natal development through sexual
maturity in offspring of mice treated daily during lactation with 990,000 U/kg hyaluronidase subcutaneously,
which is 134 times higher than the human doses.
Females and Males of Reproductive Potential
DARZALEX FASPRO can cause fetal harm when administered to a pregnant woman [see Use in Specific
Populations].
Pregnancy Testing
With the combination of DARZALEX FASPRO with lenalidomide, refer to the lenalidomide labeling for
pregnancy testing requirements prior to initiating treatment in females of reproductive potential.
Contraception
Advise females of reproductive potential to use effective contraception during treatment with DARZALEX
FASPRO and for 3 months after the last dose. Additionally, refer to the lenalidomide labeling for additional
recommendations for contraception.
Pediatric Use
Safety and effectiveness of DARZALEX FASPRO in pediatric patients have not been established.
Geriatric Use
Of the 291 patients who received DARZALEX FASPRO as monotherapy for relapsed and refractory multiple
myeloma, 37% were 65 to <75 years of age, and 19% were 75 years of age or older. No overall differences
in effectiveness were observed based on age. Adverse reactions occurring at a higher frequency (≥5%
difference) in patients ≥65 years of age included upper respiratory tract infection, urinary tract infection,
dizziness, cough, dyspnea, diarrhea, nausea, fatigue, and peripheral edema. Serious adverse reactions
occurring at a higher frequency (≥2% difference) in patients ≥65 years of age included pneumonia.
Clinical studies of DARZALEX FASPRO as part of a combination therapy did not include sufficient numbers
of patients aged 65 and older to determine whether they respond differently from younger patients.
REFERENCES
1. Chapuy, CI, RT Nicholson, MD Aguad, et al., 2015, Resolving the daratumumab interference with blood
compatibility testing, Transfusion, 55:1545-1554 (accessible at http://onlinelibrary.wiley.com/doi/10.1111/
trf.13069/epdf).
PATIENT COUNSELING INFORMATION
Advise the patient to read the FDA-approved patient labeling (Patient Information).
Hypersensitivity and Other Administration Reactions
Advise patients to seek immediate medical attention for any of the following signs and symptoms of
systemic administration-related reactions: itchy, runny or blocked nose; chills, nausea, throat irritation,
cough, headache, shortness of breath or difficulty breathing [see Warnings and Precautions].
Neutropenia
Advise patients to contact their healthcare provider if they have a fever [see Warnings and Precautions].
DARZALEX FASPRO™ (daratumumab and hyaluronidase-fihj) injection
Thrombocytopenia
Advise patients to contact their healthcare provider if they have bruising or bleeding [see Warnings and
Precautions].
Embryo-Fetal Toxicity
Advise pregnant women of the potential hazard to a fetus. Advise females of reproductive potential to inform
their healthcare provider of a known or suspected pregnancy [see Warnings and Precautions, Use in Specific
Populations].
Advise females of reproductive potential to avoid becoming pregnant during treatment with DARZALEX
FASPRO and for at least 3 months after the last dose [see Use in Specific Populations].
Advise patients that lenalidomide has the potential to cause fetal harm and has specific requirements
regarding contraception, pregnancy testing, blood and sperm donation, and transmission in sperm.
Lenalidomide is only available through a REMS program [see Use in Specific Populations].
Interference with Laboratory Tests
Advise patients to inform their healthcare provider, including personnel at blood transfusion centers, that
they are taking DARZALEX FASPRO, in the event of a planned transfusion [see Warnings and Precautions].
Advise patients that DARZALEX FASPRO can affect the results of some tests used to determine complete
response in some patients and additional tests may be needed to evaluate response [see Warnings and
Precautions].
Hepatitis B Virus (HBV) Reactivation
Advise patients to inform healthcare providers if they have ever had or might have a hepatitis B infection
and that DARZALEX FASPRO could cause hepatitis B virus to become active again [see Adverse Reactions].
Product of Switzerland
Manufactured by:
Janssen Biotech, Inc.
Horsham, PA 19044
U.S. License Number 1864
© 2020 Janssen Pharmaceutical Companies
cp-144557v1