DARZALEX- daratumumab injection, solution, concentrate DARZALEX IV- daratumumab injection, solution, concentrate

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

DARATUMUMAB (UNII: 4Z63YK6E0E) (DARATUMUMAB - UNII:4Z63YK6E0E)

Available from:

Janssen Biotech, Inc.

INN (International Name):

Daratumumab

Composition:

Daratumumab 100 mg in 5 mL

Administration route:

INTRAVENOUS

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

DARZALEX is indicated for the treatment of adult patients with multiple myeloma: - in combination with lenalidomide and dexamethasone in newly diagnosed patients who are ineligible for autologous stem cell transplant and in patients with relapsed or refractory multiple myeloma who have received at least one prior therapy. - in combination with bortezomib, melphalan and prednisone in newly diagnosed patients who are ineligible for autologous stem cell transplant. - in combination with bortezomib, thalidomide, and dexamethasone in newly diagnosed patients who are eligible for autologous stem cell transplant. - in combination with bortezomib and dexamethasone in patients who have received at least one prior therapy. - in combination with carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy. - in combination with pomalidomide and dexamethasone in patients who have received at least two prior therapies including lenalidomide and a proteasome inhibitor. - as monotherapy, in patients 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. DARZALEX is contraindicated in patients with a history of severe hypersensitivity (e.g. anaphylactic reactions) to daratumumab or any of the components of the formulation [see Warnings and Precautions (5.1)] . Risk Summary DARZALEX 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 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 and lenalidomide, pomalidomide, or thalidomide is contraindicated in pregnant women, because lenalidomide, pomalidomide, and thalidomide may cause birth defects and death of the unborn child. Lenalidomide, pomalidomide, and thalidomide are only available through a REMS program. Refer to the lenalidomide, pomalidomide, or thalidomide 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 may cause depletion of fetal CD38 positive immune cells and decreased bone density. Defer administering live vaccines to neonates and infants exposed to DARZALEX in utero until a hematology evaluation is completed. Data Animal Data 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 regulating humoral immune responses (mice), feto-maternal immune tolerance (mice), and early embryonic development (frogs). Risk Summary There is no data on the presence of daratumumab 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 is administered with lenalidomide, pomalidomide, or thalidomide, advise women not to breastfeed during treatment with DARZALEX. Refer to lenalidomide, pomalidomide, or thalidomide prescribing information for additional information. DARZALEX can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)] . Pregnancy Testing With the combination of DARZALEX with lenalidomide, pomalidomide, or thalidomide, refer to the lenalidomide, pomalidomide, or thalidomide 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 and for 3 months after the last dose. Additionally, refer to the lenalidomide, pomalidomide, or thalidomide labeling for additional recommendations for contraception. Safety and effectiveness of DARZALEX in pediatric patients have not been established. Of the 2,459 patients who received DARZALEX at the recommended dose, 38% were 65 to 74 years of age, and 15% were 75 years of age or older. No overall differences in effectiveness were observed between these patients and younger patients. The incidence of serious adverse reactions was higher in older than in younger patients [see Adverse Reactions (6.1)] . Among patients with relapsed and refractory multiple myeloma (n=1,213), the serious adverse reactions that occurred more frequently in patients 65 years and older were pneumonia and sepsis. Within the DKd group in CANDOR, fatal adverse reactions occurred in 14% of patients 65 years and older compared to 6% of patients less than 65 years. Among patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant (n=710), the serious adverse reaction that occurred more frequently in patients 75 years and older was pneumonia.

Product summary:

How Supplied DARZALEX ® (daratumumab) injection is a colorless to pale yellow, preservative-free solution for intravenous infusion. NDC 57894-502-05 and NDC 57894-505-05 each contain one 100 mg/5 mL single-dose vial NDC 57894-502-20 and NDC 57894-505-20 each contain one 400 mg/20 mL single-dose vial Storage and Stability Store in a refrigerator at 2°C to 8°C (36°F to 46°F). Do not freeze or shake. Protect from light. This product contains no preservative.

Authorization status:

Biologic Licensing Application

Summary of Product characteristics

DARZALEX- DARATUMUMAB INJECTION, SOLUTION, CONCENTRATE
DARZALEX IV- DARATUMUMAB INJECTION, SOLUTION, CONCENTRATE
JANSSEN BIOTECH, INC.
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
DARZALEX SAFELY AND
EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR DARZALEX.
DARZALEX
(DARATUMUMAB) INJECTION, FOR INTRAVENOUS USE
INITIAL U.S. APPROVAL: 2015
INDICATIONS AND USAGE
DARZALEX is a CD38-directed cytolytic antibody indicated for the
treatment of adult patients with multiple
myeloma:
in combination with lenalidomide and dexamethasone in newly diagnosed
patients who are ineligible for
autologous stem cell transplant and in patients with relapsed or
refractory multiple myeloma who have
received at least one prior therapy
in combination with bortezomib, melphalan and prednisone in newly
diagnosed patients who are
ineligible for autologous stem cell transplant
in combination with bortezomib, thalidomide, and dexamethasone in
newly diagnosed patients who are
eligible for autologous stem cell transplant
in combination with bortezomib and dexamethasone in patients who have
received at least one prior
therapy
in combination with carfilzomib and dexamethasone in patients with
relapsed or refractory multiple
myeloma who have received one to three prior lines of therapy
in combination with pomalidomide and dexamethasone in patients who
have received at least two prior
therapies including lenalidomide and a proteasome inhibitor
as monotherapy, in patients 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. ( 1)
DOSAGE AND ADMINISTRATION
Pre-medicate with corticosteroids, antipyretics and antihistamines. (
2.3)
Dilute and administer as an intravenous infusion. ( 2.5)
Recommended dose is 16 mg/kg actual body weight. See full prescribing
information for drugs used in
combination and schedule ( 2.2)
Administer post-infusion medicat