`
`HIGHLIGHTS OF PRESCRIBING INFORMATION
`
`These highlights do not include all the information needed to use
`
`
`
`DARZALEX FASPRO safely and effectively. See full prescribing
`
`information for DARZALEX FASPRO.
`
`
`DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj)
`
`injection, for subcutaneous use
`
`
`Initial U.S. Approval: 2020
`
`--------------------------RECENT MAJOR CHANGES---------------------------­
`
`
`Indications and Usage (1.1)
`7/2021
`
`
`Indications and Usage (1.2)
`1/2021
`
`
`Dosage and Administration (2.2)
`7/2021
`
`
`
`
`
`Dosage and Administration (2.3)
`1/2021
`
`
`Warnings and Precautions (5.1)
`7/2021
`
`
`
`
`Warnings and Precautions (5.2)
`1/2021
`
`
`-----------------------------INDICATIONS AND USAGE--------------------------­
`
`
`
`DARZALEX FASPRO is a combination of daratumumab, a CD38-directed
`
`
`
`cytolytic antibody, and hyaluronidase, an endoglycosidase, indicated for the
`
`treatment of adult patients with:
`
`
`
`
`
`• multiple myeloma in combination with bortezomib, melphalan and
`
`
`
`prednisone in newly diagnosed patients who are ineligible for autologous
`
`stem cell transplant
`
`
`
`
`
`• 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
`
`
`
`
`
`
`
`• multiple myeloma in combination with bortezomib, thalidomide, and
`
`dexamethasone in newly diagnosed patients who are eligible for
`
`autologous stem cell transplant
`
`
`
`
`
`
`• multiple myeloma in combination with bortezomib and dexamethasone in
`
`
`patients who have received at least one prior therapy
`
`• multiple myeloma in combination with pomalidomide and dexamethasone
`
`in patients who have received at least one prior line of therapy including
`
`lenalidomide and a proteasome inhibitor
`
`
`
`
`
`
`
`
`
`• multiple myeloma 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.
`
`
`
`
`
`light chain (AL) amyloidosis in combination with bortezomib,
`
`
`cyclophosphamide and dexamethasone in newly diagnosed patients. 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 a confirmatory trial(s). (1.2)
`
`Limitations of Use:
`• DARZALEX FASPRO is not indicated and is not recommended for the
`
`
`
`
`
`treatment of patients with light chain (AL) amyloidosis who have NYHA
`
`
`Class IIIB or Class IV cardiac disease or Mayo Stage IIIB outside of
`
`
`
`
`
`controlled clinical trials (1.2)
`
`
`------------------------DOSAGE AND ADMINISTRATION----------------------­
`For subcutaneous use only.
`
`• Pre-medicate with a corticosteroid, acetaminophen and a histamine-1
`
`
`
`
`
`receptor antagonist. (2.5)
`
`
`
`• The recommended dosage of DARZALEX FASPRO is (1,800 mg
`
`
`
`
`
`
`
`daratumumab and 30,000 units hyaluronidase) administered
`
`
`
`subcutaneously into the abdomen over approximately 3 to 5 minutes
`
`
`
`
`
`
`
`
`according to recommended schedule. (2.2, 2.3)
`
`• Administer post-medications as recommended. (2.5)
`
`
`
`
`
`
`
`FULL PRESCRIBING INFORMATION: CONTENTS*
`
`
`
`1
`INDICATIONS AND USAGE
`
`
`1.1 Multiple Myeloma
`
`
`Light Chain Amyloidosis
`1.2
`
`
`2 DOSAGE AND ADMINISTRATION
`
`
`2.1
`Important Dosing Information
`
`
`
`2.2 Recommended Dosage for Multiple Myeloma
`
`
`2.3 Recommended Dosage for Light Chain
`
`Amyloidosis
`
`
`2.4 Administration
`
`
`2.5 Recommended Concomitant Medications
`
`
`2.6 Dosage Modifications for Adverse Reactions
`
`
`2.7 Preparation and Administration
`
`
`3 DOSAGE FORMS AND STRENGTHS
`
`
`•
`
`
`
`Reference ID: 4824044
`
`
`
`
`
`
`
`
`
`----------------------DOSAGE FORMS AND STRENGTHS--------------------­
`
`• Injection: 1,800 mg daratumumab and 30,000 units hyaluronidase per
`
`
`
`
`15 mL (120 mg and 2,000 units/mL) solution in a single-dose vial (3)
`
`
`
`
`
`
`
`-----------------------------CONTRAINDICATIONS--------------------------------­
`Patients with a history of severe hypersensitivity to daratumumab,
`
`
`hyaluronidase or any of the components of the formulation. (4)
`
`
`
`
`
`-------------------------WARNINGS AND PRECAUTIONS---------------------­
`
`• Hypersensitivity and Other Administration Reactions: Permanently
`
`
`
`
`
`
`discontinue DARZALEX FASPRO for life-threatening reactions. (5.1)
`
`
`
`
`
`
`• Cardiac Toxicity in Patients with Light Chain (AL) Amyloidosis: Monitor
`
`
`
`
`patients with cardiac involvement more frequently for cardiac adverse
`
`
`
`reactions and administer supportive care as appropriate. (5.2)
`
`
`
`
`
`
`• Neutropenia: Monitor complete blood cell counts periodically during
`
`treatment. Monitor patients with neutropenia for signs of infection.
`
`
`Consider withholding DARZALEX FASPRO to allow recovery of
`
`
`neutrophils. (5.3)
`
`
`• Thrombocytopenia: Monitor complete blood cell counts periodically
`
`
`
`during treatment. Consider withholding DARZALEX FASPRO to allow
`
`
`
`recovery of platelets. (5.4)
`
`• Embryo-Fetal Toxicity: Can cause fetal harm. Advise pregnant women of
`
`
`
`
`
`
`the potential risk to a fetus and advise females of reproductive potential to
`
`
`
`
`
`use effective contraception (5.5, 8.1, 8.3).
`
`• 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 FASPRO. (5.6, 7.1)
`
`
`
`
`
`
`------------------------------ADVERSE REACTIONS------------------------------­
`
`• The most common adverse reaction (≥20%) in patients with multiple
`
`
`
`
`
`
`
`
`myeloma who received DARZALEX FASPRO monotherapy is upper
`
`
`
`
`
`
`
`respiratory tract infection. (6.1)
`
`
`
`• The most common adverse reactions (≥20%) in patients with multiple
`
`
`
`
`
`
`
`
`
`myeloma who received DARZALEX FASPRO-VMP are upper respiratory
`
`
`
`
`tract infection, constipation, nausea, fatigue, pyrexia, peripheral sensory
`
`
`
`neuropathy, diarrhea, cough, insomnia, vomiting, and back pain. (6.1)
`
`
`
`
`
`
`
`
`• The most common adverse reactions (≥20%) in patients with multiple
`
`
`
`
`
`
`
`myeloma who received DARZALEX FASPRO-Rd are fatigue, diarrhea,
`
`
`
`
`
`
`upper respiratory tract infection, muscle spasms, constipation, pyrexia,
`
`
`
`
`pneumonia, and dyspnea. (6.1)
`
`
`
`• The most common adverse reactions (≥20%) in patients with multiple
`
`
`
`
`
`
`myeloma who received DARZALEX FASPRO-Pd are fatigue, pneumonia,
`
`
`
`
`upper respiratory tract infection, and diarrhea (6.1)
`
`• The most common adverse reactions (≥20%) in patients with light chain
`
`
`
`
`
`
`
`
`(AL) amyloidosis are upper respiratory tract infection, diarrhea, peripheral
`
`
`
`
`edema, constipation, fatigue, peripheral sensory neuropathy, nausea,
`
`
`
`
`
`insomnia, dyspnea, and cough. (6.1)
`
`
`
`
`• The most common (≥40%) hematology laboratory abnormalities with
`
`
`
`
`
`DARZALEX FASPRO are decreased leukocytes, decreased lymphocytes,
`
`
`
`decreased neutrophils, decreased platelets, and decreased hemoglobin.
`
`
`(6.1)
`
`
`To report SUSPECTED ADVERSE REACTIONS, contact Janssen
`
`
`Biotech, Inc. at 1-800-526-7736 (1-800-JANSSEN) or FDA at 1-800-FDA­
`
`1088 or www.fda.gov/medwatch.
`
`
`See 17 for PATIENT COUNSELING INFORMATION and FDA-
`
`
`
`approved patient labeling.
`
`
`Revised: 7/2021
`
`
`
`
`4 CONTRAINDICATIONS
`
`
`5 WARNINGS AND PRECAUTIONS
`
`5.1 Hypersensitivity and Other Administration
`
`Reactions
`
`5.2 Cardiac Toxicity in Patients with Light Chain (AL)
`
`
`
`
`Amyloidosis
`
`
`5.3 Neutropenia
`
`
`Thrombocytopenia
`5.4
`
`
`5.5 Embryo-Fetal Toxicity
`
`
`5.6
`Interference with Serological Testing
`
`
`
`5.7
`Interference with Determination of Complete
`
`
`Response
`
`
`6 ADVERSE REACTIONS
`
`
`
` 1
`
`

`

`
`
`
`
`
`
`6.1 Clinical Trials Experience
`
`
`6.2
`Immunogenicity
`
`
`6.3 Postmarketing Experience
`
`
`7 DRUG INTERACTIONS
`
`
`7.1 Effects of Daratumumab on Laboratory Tests
`
`
`8 USE IN SPECIFIC POPULATIONS
`
`
`8.1 Pregnancy
`
`
`8.2
`Lactation
`
`
`8.3
`Females and Males of Reproductive Potential
`
`
`
`8.4 Pediatric Use
`
`
`8.5 Geriatric Use
`
`
`11 DESCRIPTION
`
`
`12 CLINICAL PHARMACOLOGY
`
`
`12.1 Mechanism of Action
`
`
`12.2 Pharmacodynamics
`
`
`
`12.3 Pharmacokinetics
`
`
`13 NONCLINICAL TOXICOLOGY
`
`13.1 Carcinogenesis, Mutagenesis, Impairment of
`
`
`
`Fertility
`
`
`
`14 CLINICAL STUDIES
`
`
`14.1 Newly Diagnosed Multiple Myeloma
`
`
`14.2 Relapsed/Refractory Multiple Myeloma
`
`
`14.3 Light Chain Amyloidosis
`
`
`15 REFERENCES
`
`
`16 HOW SUPPLIED/STORAGE AND HANDLING
`
`
`
`17 PATIENT COUNSELING INFORMATION
`
`*Sections or subsections omitted from the full prescribing information are not
`
`
`
`
`
`listed.
`
`
`Reference ID: 4824044
`
`
`
` 2
`
`

`

`
`
`
`
` FULL PRESCRIBING INFORMATION
`
`
`
` 1
` INDICATIONS AND USAGE
` 1.1 Multiple Myeloma
`
`
`
`
`
` DARZALEX FASPRO is indicated for the treatment of adult patients with multiple myeloma:
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`•
`
`
`•
`
`
`•
`
`
`•
`
`
`•
`
`
`•
`
`
` in combination with bortezomib, melphalan and prednisone in newly diagnosed patients who are
` ineligible for autologous stem cell transplant.
`
`
`
`
`
`
` 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, 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 pomalidomide and dexamethasone in patients who have received at least one prior
`
`line of therapy 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.
`
`
`Light Chain Amyloidosis
`1.2
`
`
`
`
`DARZALEX FASPRO in combination with bortezomib, cyclophosphamide and dexamethasone is indicated for
`
`
`
`
`
`the treatment of adult patients with newly diagnosed light chain (AL) amyloidosis.
`
`
`
`
`
`
`
`
`This indication is approved under accelerated approval based on response rate [see Clinical Studies (14.1)].
`
`
`
`
`Continued approval for this indication may be contingent upon verification and description of clinical benefit in
`
`
`
`
`
`a confirmatory trial(s).
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Limitations of Use
`
`
`DARZALEX FASPRO is not indicated and is not recommended for the treatment of patients with light chain
`
`
`
`
`
`
`(AL) amyloidosis who have NYHA Class IIIB or Class IV cardiac disease or Mayo Stage IIIB outside of
`
`
`
`
`
`
`
`
`
`
`
`controlled clinical trials [see Warnings and Precautions (5.2)].
`
`
`2 DOSAGE AND ADMINISTRATION
`
`
`2.1
`Important Dosing Information
`
`
`
`DARZALEX FASPRO is for subcutaneous use only.
`
`
`
`•
`Administer medications before and after administration of DARZALEX FASPRO to minimize
`
`
`
`
`
`
`
`•
`administration-related reactions [see Dosage and Administration (2.5)].
`
`
`
`Type and screen patients prior to starting DARZALEX FASPRO.
`
`
`
`
`•
`2.2 Recommended Dosage for Multiple Myeloma
`
`
`
`
`The recommended dose of DARZALEX FASPRO is 1,800 mg/30,000 units (1,800 mg daratumumab and
`
`
`
`
`
`
`
`
`
`30,000 units hyaluronidase) administered subcutaneously over approximately 3-5 minutes. Tables 1, 2, 3, and 4
`
`
`
`
`
`
`
`
`
`
` 1
`
`Reference ID: 4824044
`
`

`

`
`
` provide the recommended dosing schedule when DARZALEX FASPRO is administered as monotherapy or as
`
`
`
`
` part of a combination therapy.
`
`
`
`
`
`
`
`
`
` Monotherapy and In Combination with Lenalidomide (DARZALEX FASPRO-Rd) or Pomalidomide
`
`
`
`
`
` (DARZALEX FASPRO-Pd) and Dexamethasone
` Use the dosing schedule provided in Table 1 when DARZALEX FASPRO is administered:
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` in combination with lenalidomide and dexamethasone (4-week cycle) OR
`
`
`
`
`
`
`
`•
`
` in combination with pomalidomide and dexamethasone (4-week cycle) OR
`
`•
`as monotherapy.
`
`
`•
`
`
`
` DARZALEX FASPRO dosing schedule in combination with lenalidomide or pomalidomide and dexamethasone
`
` Table 1:
` (4-week cycle) and for monotherapy
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` Weeks
`
`
`
` Weeks 1 to 8
`
`
`
` Weeks 9 to 24a
`
`
`
` Week 25 onwards until disease progressionb
`
`a
`
`
` First dose of the every-2-week dosing schedule is given at Week 9
`
`
`b
`
` First dose of the every-4-week dosing schedule is given at Week 25
`
`
`
`
`
`When DARZALEX FASPRO is administered as part of a combination therapy, see Clinical Studies (14.2) and
`
`
`
`
`
`
`
`
`the prescribing information for dosage recommendations for the other drugs.
`
`
`
`
`
`
`
`
`
` weekly (total of 8 doses)
`
`
`
`
`
` every two weeks (total of 8 doses)
`
`
`
`
` every four weeks
`
`
`
`
`
`
`
`
`
` Schedule
`
`In Combination with Bortezomib, Melphalan and Prednisone (DARZALEX FASPRO-VMP)
`
`
`
`
` Use the dosing schedule provided in Table 2 when DARZALEX FASPRO is administered in combination with
`
`
`
`
`
`
`
`
`
` bortezomib, melphalan and prednisone (6-week cycle).
`
`
`
`
`
`
`
` Table 2:
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` DARZALEX FASPRO dosing schedule in combination with bortezomib, melphalan and prednisone (6-week
`
` cycle)
`
`
`
`
`
` Weeks
`
`
`
` Weeks 1 to 6
`
`
` Weeks 7 to 54a
`
`
`
` Week 55 onwards until disease progressionb
`
`
`
`a
`
`
` First dose of the every-3-week dosing schedule is given at Week 7
`
`
`
`
`b
`
`
` First dose of the every-4-week dosing schedule is given at Week 55
`
`
`
`
`
`
`
`
`
`
`
`
`
` When DARZALEX FASPRO is administered as part of a combination therapy, see Clinical Studies (14.1) and
`
` the prescribing information for dosage recommendations for the other drugs.
`
`
`
`
`
`
` Schedule
`
`
`
`
` weekly (total of 6 doses)
` every three weeks (total of 16 doses)
`
`
`
`
`
` every four weeks
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` In Combination with Bortezomib, Thalidomide, and Dexamethasone (DARZALEX FASPRO-VTd)
`Use the dosing schedule in Table 3 when DARZALEX FASPRO is administered in combination with
`
`
`
`
`
`
`bortezomib, thalidomide, and dexamethasone (4-week cycle).
`
`
`
` DARZALEX FASPRO dosing schedule in combination with bortezomib, thalidomide and dexamethasone (4­
`
` Table 3:
`
`
`
`
`
`
`
` week cycle)
`
` Treatment phase
`
` Induction
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` Weeks
` Schedule
`
`
` Weeks 1 to 8
` weekly (total of 8 doses)
`
`
`
`
` Weeks 9 to 16a
`
`
`
` every two weeks (total of 4 doses)
`
` Stop for high dose chemotherapy and ASCT
`
` every two weeks (total of 4 doses)
`
`
`
`
` Consolidation
` Weeks 1 to 8b
`
`
`a
`
`
` First dose of the every-2-week dosing schedule is given at Week 9
`
`
`
`
`
`
`b
` First dose of the every-2-week dosing schedule is given at Week 1 upon re-initiation of treatment following ASCT
`
`
`
`
`Reference ID: 4824044
`
`
`
` 2
`
`
`
`
`
`

`

`
`
`
`
`
`
`
` When DARZALEX FASPRO is administered as part of a combination therapy, see the prescribing information
`
` for dosage recommendations for the other drugs.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` In Combination with Bortezomib and Dexamethasone (DARZALEX FASPRO-Vd)
`
` Use the dosing schedule in Table 4 when DARZALEX FASPRO is administered in combination with
`
`
`
`
`
` bortezomib and dexamethasone (3-week cycle).
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` DARZALEX FASPRO dosing schedule in combination with bortezomib and dexamethasone (3-week cycle)
`
` Schedule
`
`
`
`
`
`
`
`
`
`
` Table 4:
` Weeks
`
`
`
` Weeks 1 to 9
`
`
`
` Weeks 10 to 24a
`
`
`
`
` Week 25 onwards until disease progressionb
`
`
`a
`
`
` First dose of the every-3-week dosing schedule is given at Week 10
`
`
`
`b
`
`
` First dose of the every-4-week dosing schedule is given at Week 25
`
`
` When DARZALEX FASPRO is administered as part of a combination therapy, see the prescribing information
`
`
`
`
`
`
` for dosage recommendations for the other drugs.
` 2.3 Recommended Dosage for Light Chain Amyloidosis
`
`
`
`
`
`
`
`
`
` weekly (total of 9 doses)
` every three weeks (total of 5 doses)
`
`
`
` every four weeks
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` In Combination with Bortezomib, Cyclophosphamide and Dexamethasone (DARZALEX FASPRO-
`VCd)
`
`
`
`
`
`
`
`
`
`
`
`
`
`Use the dosing schedule provided in Table 5 when DARZALEX FASPRO is administered in combination with
`
`
`bortezomib, cyclophosphamide and dexamethasone (4-week cycle).
`
`
`
`
`
` Table 5:
`
`
`
`
`
` DARZALEX FASPRO dosing schedule in combination with bortezomib, cyclophosphamide and dexamethasone
`
`
` (4-week cycle)
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` Schedule
`
` weekly (total of 8 doses)
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`
`
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`
`
` every two weeks (total of 8 doses)
`
` every four weeks
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`
` Weeks
`
`
`
` Weeks 1 to 8
`
`
` Weeks 9 to 24a
` Week 25 onwards until disease progression or a maximum of
`
` 2 yearsb
`
`a
`
`
`
`
`
`
` First dose of the every-2-week dosing schedule is given at Week 9
`
`
`b
`
`
` First dose of the every-4-week dosing schedule is given at Week 25
`
`
`
`
` When DARZALEX FASPRO is administered as part of a combination therapy, see Clinical Studies (14.2) and
`
`
`
`
`
`
` the prescribing information for dosage recommendations for the other drugs.
`
` 2.4 Administration
`
`
`
`
`
` If a dose of DARZALEX FASPRO is missed, administer the dose as soon as possible and adjust the dosing
`
`
` schedule to maintain the dosing interval.
`
`
`
`
` 2.5 Recommended Concomitant Medications
`
`
`
` Pre-medication
`
` Administer the following pre-medications 1-3 hours before each dose of DARZALEX FASPRO:
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`
`•
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`•
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`•
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` Acetaminophen 650 to 1,000 mg orally
`
`
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`
`
`
`
` Diphenhydramine 25 to 50 mg (or equivalent) orally or intravenously
` Corticosteroid (long- or intermediate-acting)
`
`
`
`
`
`
`
`
`Reference ID: 4824044
`
`
`
` 3
`
`

`

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` Monotherapy
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`
`
` Administer methylprednisolone 100 mg (or equivalent) orally or intravenously. Consider reducing the
`
`
`
`
`
` dose of methylprednisolone to 60 mg (or equivalent) following the second dose of DARZALEX
`
`
`
`
`
` FASPRO.
`
`
` In Combination
`
` Administer dexamethasone 20 mg (or equivalent) orally or intravenously prior to every DARZALEX
`
` FASPRO administration.
`
`
`
`
`
`
`
` When dexamethasone is the background regimen-specific corticosteroid, the dexamethasone dose that is
`
` part of the background regimen will serve as pre-medication on DARZALEX FASPRO administration
`
`
`
`
`
`
`
`
` days [see Clinical Studies (14)].
`
`
`
`
`
`
`
` Do not administer background regimen-specific corticosteroids (e.g. prednisone) on DARZALEX
`
`
` FASPRO administration days when patients have received dexamethasone (or equivalent) as a pre­
`
`
`
`
`
`
` medication.
`
` Post-medication
`
`Administer the following post-medications:
`
`
`
`Monotherapy
`
`Administer methylprednisolone 20 mg (or an equivalent dose of an intermediate- or long-acting
`
`
`
`
`
`
`
`
`
`corticosteroid) orally for 2 days starting the day after the administration of DARZALEX FASPRO.
`
`
`
`
`
`
`
`In Combination
`
`
`Consider administering oral methylprednisolone at a dose of less than or equal to 20 mg (or an
`
`
`
`
`
`
`
`
`
`equivalent dose of an intermediate- or long-acting corticosteroid) beginning the day after administration
`
`
`
`
`
`
`
`of DARZALEX FASPRO.
`
`
`
`If a background regimen-specific corticosteroid (e.g. dexamethasone, prednisone) is administered the
`
`
`
`
`day after the administration of DARZALEX FASPRO, additional corticosteroids may not be needed
`
`
`
`
`
`
`
`[see Clinical Studies (14)].
`
`
`If the patient does not experience a major systemic administration-related reaction after the first 3 doses of
`
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`
`
`
`
`
`
`DARZALEX FASPRO, consider discontinuing the administration of corticosteroids (excluding any background
`
`
`
`
`
`
`regimen-specific corticosteroid).
`
`
`For patients with a history of chronic obstructive pulmonary disease, consider prescribing short and long-acting
`
`
`
`
`
`bronchodilators and inhaled corticosteroids. Following the first 4 doses of DARZALEX FASPRO, consider
`
`
`
`
`
`
`
`
`discontinuing these additional post-medications, if the patient does not experience a major systemic
`
`
`
`
`
`
`
`
`administration-related reaction.
`
`Prophylaxis for Herpes Zoster Reactivation
`
`
`
`
`
`Initiate antiviral prophylaxis to prevent herpes zoster reactivation within 1 week after starting DARZALEX
`
`
`
`
`
`
`FASPRO and continue for 3 months following the end of treatment [see Adverse Reactions (6.1)].
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`
`
`Reference ID: 4824044
`
`
`
` 4
`
`

`

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`•
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`•
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`•
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`•
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`•
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`•
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`•
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`•
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`
` 2.6 Dosage Modifications for Adverse Reactions
`
`
`
`
`
` No dose reductions of DARZALEX FASPRO are recommended. Consider withholding DARZALEX FASPRO
`
`
` to allow recovery of blood cell counts in the event of myelosuppression [see Warnings and Precautions (5.3,
`
`
`
`
`
` 5.4)].
`
`
`
`
` Preparation and Administration
` 2.7
` DARZALEX FASPRO should be administered by a healthcare provider.
`
`
`
`
`
`
` To prevent medication errors, check the vial labels to ensure that the drug being prepared and administered is
`
`
`
`
` DARZALEX FASPRO for subcutaneous use. Do not administer DARZALEX FASPRO intravenously.
`
`
`
`
`
`
`
`
`
` DARZALEX FASPRO is ready to use.
`
`
`
`
`
` Preparation
`
`
`
`
`
`
`
` Remove the DARZALEX FASPRO vial from refrigerated storage [2°C to 8°C (36°F to 46°F)] and
`
`•
`
` equilibrate to ambient temperature [15°C to 30°C (59°F to 86°F)]. Store the unpunctured vial at ambient
`
`
`
`
`
` temperature and ambient light for a maximum of 24 hours. Keep out of direct sunlight. Do not shake.
`
`
`
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`
`
`
`
`
`
`
`
` Withdraw 15 mL from the vial into a syringe.
`
`
`
`
`
`
`
`
`
` DARZALEX FASPRO
` is compatible with polypropylene or polyethylene syringe material;
`
` polypropylene, polyethylene, or polyvinyl chloride (PVC) subcutaneous infusion sets; and stainless steel
`
`
`
`
`
`
`
` transfer and injection needles. Use the product immediately.
`
`
`
`
`
`
`
`
` After the solution of DARZALEX FASPRO is withdrawn into the syringe, replace the transfer needle
`
`
`
` with a syringe closing cap. Label the syringe appropriately to include the route of administration per
`
`
`
`
`
`
`
` institutional standards. Label the syringe with the peel-off label.
`
`
`
`
` To avoid needle clogging, attach the hypodermic injection needle or subcutaneous infusion set to the
`
` syringe immediately prior to injection.
`
`
`
`
`
`
`
`
`
` Parenteral drug products should be inspected visually for particulate matter and discoloration prior to
`
`
`
` administration, whenever solution and container permit. Do not use if opaque particles, discoloration or
`
`
`
`
`
` other foreign particles are present.
`
`
`
` Storage
`
`
`
`
`
`If the syringe containing DARZALEX FASPRO is not used immediately, store the DARZALEX
`•
`
`
`
`
`
`
`
`
`
`
`FASPRO solution for up to 4 hours at ambient temperature and ambient light. Discard after 4 hours, if
`
`not used.
`
`Administration
`into the subcutaneous tissue of the abdomen
`Inject 15 mL of DARZALEX FASPRO
`
`
`
`
`
`
`
`
`
`
`•
`approximately 3 inches [7.5 cm] to the right or left of the navel over approximately 3-5 minutes.
`
`
`
`
`
`
`
`
`No data are available on performing the injection at other sites of the body.
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`
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`
`
`
`Rotate injection sites for successive injections.
`
`
`
`
`Never inject DARZALEX FASPRO into areas where the skin is red, bruised, tender, hard or areas
`
`
`
`
`where there are scars.
`
`Pause or slow down delivery rate if the patient experiences pain. In the event pain is not alleviated by
`
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`
`
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`
`
`pausing or slowing down delivery rate, a second injection site may be chosen on the opposite side of the
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`
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`abdomen to deliver the remainder of the dose.
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`
`
`
`Reference ID: 4824044
`
`
`
` 5
`
`

`

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`•
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` During treatment with DARZALEX FASPRO, do not administer other medications for subcutaneous
` use at the same site as DARZALEX FASPRO.
`
`
`
`
` 3
`
`
`
` DOSAGE FORMS AND STRENGTHS
` Injection: 1,800 mg daratumumab and 30,000 units hyaluronidase per 15 mL (120 mg and 2,000 units/mL)
`
`
`
`
`
`
` colorless to yellow and clear to opalescent solution in a single-dose vial.
`
`
`
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`
`
` 4 CONTRAINDICATIONS
`
`
`
`
`
`
`
`
` DARZALEX FASPRO is contraindicated in patients with a history of severe hypersensitivity to daratumumab,
`
`
`
` hyaluronidase or any of the components of the formulation [see Warnings and Precautions (5.1) and Adverse
`
`
`
`
` Reactions (6.3)].
`
`
`
`
` 5 WARNINGS AND PRECAUTIONS
`
`
`
` 5.1 Hypersensitivity and Other Administration Reactions
`
`
`
`
`
`
` Both systemic administration-related reactions, including severe or life-threatening reactions, and local
`
`
`
`injection-site reactions can occur with DARZALEX FASPRO. Fatal reactions have been reported with
`
`
`
`
`
`
`daratumumab-containing products, including DARAZLEX FASPRO [see Adverse Reactions (6.3)].
`
`
`
`
`Systemic Reactions
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`In a pooled safety population of 832 patients with multiple myeloma (N=639) or light chain (AL) amyloidosis
`(N=193) who received DARZALEX FASPRO as monotherapy or as part of a combination therapy, 9% of
`
`
`
`
`
`
`
`patients experienced a systemic administration-related reaction (Grade 2: 3.5%, Grade 3: 0.8%). Systemic
`
`
`
`
`
`
`
`
`administration-related reactions occurred in 8% of patients with the first injection, 0.4% with the second
`
`
`
`
`
`
`
`
`injection, and cumulatively 1% with subsequent injections. The median time to onset was 3.2 hours (range:
`
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`
`
`9 minutes to 3.5 days). Of the 129 systemic administration-related reactions that occurred in 74 patients,
`110 (85%) occurred on the day of DARZALEX FASPRO administration. Delayed systemic administration-
`
`
`
`
`
`
`
`
`
`related reactions have occurred in 1% of the patients.
`
`
`
`
`
`
`
`
`Severe reactions included hypoxia, dyspnea, hypertension and tachycardia. Other signs and symptoms of
`
`
`
`
`
`
`systemic administration-related reactions may include respiratory symptoms, such as bronchospasm, nasal
`
`
`
`
`
`
`congestion, cough, throat irritation, allergic rhinitis, and wheezing, as well as anaphylactic reaction, pyrexia,
`
`
`
`
`
`
`
`chest pain, pruritus, chills, vomiting, nausea, and hypotension.
`
`
`
`
`
`Pre-medicate patients with histamine-1 receptor antagonist, acetaminophen and corticosteroids [see Dosage and
`
`
`
`
`
`Administration (2.5)]. Monitor patients for systemic administration-related reactions, especially following the
`
`
`
`
`
`
`
`first and second injections. For anaphylactic reaction or life-threatening (Grade 4) administration-related
`
`
`
`
`
`reactions,
`immediately and permanently discontinue DARZALEX FASPRO. Consider administering
`
`
`
`
`
`
`
`corticosteroids and other medications after the administration of DARZALEX FASPRO depending on dosing
`
`
`
`
`
`regimen and medical history to minimize the risk of delayed (defined as occurring the day after administration)
`
`
`
`
`
`
`systemic administration-related reactions [see Dosage and Administration (2.5)].
`
`
`
`
`
`
`
`Local Reactions
`
`
`In this pooled safety population, injection-site reactions occurred in 8% of patients, including Grade 2 reactions
`
`
`
`
`in 0.6%. The most frequent (>1%) injection-site reaction was injection site erythema. These local reactions
`
`
`
`
`
`
`
`
`occurred a median of 5.5 minutes (range: 0 minutes to 6.5 days) after starting administration of DARZALEX
`
`
`
`
`
`
`
`
`
`
`
`
`
`FASPRO. Monitor for local reactions and consider symptomatic management.
`
`
`
`
`Reference ID: 4824044
`
`
`
` 6
`
`

`

`
`
`
`
`
`
`
`
`
`
` 5.2 Cardiac Toxicity in Patients with Light Chain (AL) Amyloidosis
` Serious or fatal cardiac adverse reactions occurred in patients with light chain (AL) amyloidosis who received
`
`
`
`
`
`
`
`DARZALEX FASPRO in combination with bortezomib, cyclophosphamide and dexamethasone [see Adverse
`
`
`
`
`
`
`Reactions (6.1)]. Serious cardiac disorders occurred in 16% and fatal cardiac disorders occurred in 10% of
`
`
`
`
`
`
`
`
`
`
`
`
`patients. Patients with NYHA Class IIIA or Mayo Stage IIIA disease may be at greater risk. Patients with
`
`
`
`
`
`
`
`
`
`
`NYHA Class IIIB or IV disease were not studied.
`
`
`
`
`
`
`Monitor patients with cardiac involvement of light chain (AL) amyloidosis more frequently for cardiac adverse
`
`
`
`
`
`
`
`
`reactions and administer supportive care as appropriate.
`
`
`
`
`
`5.3 Neutropenia
`
`
`Daratumumab may increase neutropenia induced by background therapy [see Adverse Reactions (6.1)].
`
`
`
`
`
`
`
`
`Monitor complete blood cell counts periodically during treatment according to manufacturer’s prescribing
`
`
`
`information for background therapies. Monitor patients with neutropenia for signs of infection. Consider
`
`
`
`
`
`
`
`withholding DARZALEX FASPRO until recovery of neutrophils. In lower body weight patients receiving
`
`
`
`
`
`
`
`
`DARZALEX FASPRO, higher rates of Grade 3-4 neutropenia were observed.
`
`
`
`
`
`5.4
`Thrombocytopenia
`
`
`Daratumumab may increase thrombocytopenia induced by background therapy [see Adverse Reactions (6.1)].
`
`
`
`
`
`
`Monitor complete blood cell counts periodically during treatment according to manufacturer’s prescribing
`
`
`
`
`information for background therapies. Consider withholding DARZALEX FASPRO until recovery of platelets.
`
`
`
`
`
`
`
`
`
`
`5.5 Embryo-Fetal Toxicity
`
`
`
`Based on the mechanism of action, DARZALEX FASPRO can cause fetal harm when administered to a
`
`
`
`
`
`
`
`
`pregnant woman. DARZALEX FASPRO may cause depletion of fetal immune cells and decreased bone
`
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`
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`
`
`
`density. Advise pregnant women of the potential risk to a fetus. Advise females with reproductive potential to
`
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`
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`
`
`
`use effective contraception during treatment with DARZALEX FASPRO and for 3 months after the last dose
`
`
`
`
`
`
`
`
`
`[see Use in Specific Populations (8.1, 8.3)].
`
`The combination of DARZALEX FASPRO with lenalidomide, thalidomide or pomalidomide is contraindicated
`
`
`
`
`
`
`
`
`in pregnant women, because lenalidomide, thalidomide or pomalidomide may cause birth defects and death of
`
`
`
`
`
`
`the unborn child. Refer to the lenalidomide, thalidomide or pomalidomide prescribing information on use
`
`
`
`
`
`during pregnancy.
`
`Interference with Serological Testing
`5.6
`
`
`
`
`Daratumumab binds to CD38 on red blood cells (RBCs) and results in a positive Indirect Antiglobulin Test
`
`
`
`
`
`
`
`
`
`(Indirect Coombs test). Daratumumab-mediated positive indirect antiglobulin test may persist for up to
`
`
`
`
`6 months after the last daratumumab administration. Daratumumab bound to RBCs masks detection of
`
`
`
`
`
`
`
`
`antibodies to minor antigens in the patient’s serum [see References (15)]. The determination of a patient’s ABO
`
`
`
`
`
`
`and Rh blood type are not impacted [see Drug Interactions (7.1)].
`
`
`
`
`
`Notify blood transfusion centers of this interference with serological testing and inform blood banks that a
`
`
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`
`
`
`patient has received DARZALEX FASPRO. Type and screen patients prior to starting DARZALEX FASPRO
`
`
`
`
`
`[see Dosage and Administration (2.1)].
`
`
`
`5.7
`Interference with Determination of Complete Response
`
`
`
`
`Daratumumab is a human IgG kappa monoclonal antibody that can be detected on both the serum protein
`
`
`
`
`
`
`
`
`electrophoresis (SPE) and immunofixation (IFE) assays used for the clinical monitoring of endogenous M-
`
`
`
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`
`
` 7
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`
`
`Reference ID: 4824044
`
`

`

`
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` protein [see Drug Interactions (7.1)]. This interference can impact the determination of complete response and
`
` of disease progression in some DARZALEX FASPRO-treated patients with IgG kappa myeloma protein.
`
`
`
`
`
`
`
` 6
` ADVERSE REACTIONS
` The following clinically significant adverse reactions are described elsewhere in the labeling:
`
`
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`
`
` Hyperse