`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 FASPROTM (daratumumab and hyaluronidase-fihj)
`
`
`injection, for subcutaneous use
`
`Initial U.S. Approval: 2020
`
`
`
`--------------------------RECENT MAJOR CHANGES----------------------------
`
`Indications and Usage (1)
`01/2021
`
`
`Dosage and Administration (2)
`01/2021
`
`
`-----------------------------INDICATIONS AND USAGE---------------------------
`
`DARZALEX FASPRO is a combination of daratumumab, a CD38-directed
`
`
`cytolytic antibody, and hyaluronidase, an endoglycosidase, 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
`
` 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-----------------------
`For subcutaneous use only.
`
`
` Pre-medicate with a corticosteroid, acetaminophen and a histamine-1
`
`
`receptor antagonist. (2.3)
`
` 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)
`
`
` Administer post-medications as recommended. (2.3)
`
`----------------------DOSAGE FORMS AND STRENGTHS---------------------
`
` Injection: 1,800 mg daratumumab and 30,000 units hyaluronidase per
`
`
`15 mL (120 mg and 2,000 units/mL) solution in a single-dose vial (3)
`
`
`
`
`
`
`
`-----------------------------CONTRAINDICATIONS---------------------------------
`Patients with a history of severe hypersensitivity to daratumumab 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)
`
`
`
` 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. (5.2)
`
`
`
` Thrombocytopenia: Monitor complete blood cell counts periodically
`
`
`during treatment. Consider withholding DARZALEX FASPRO to allow
`
`
`recovery of platelets. (5.3)
`
`
`
` 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 (5.4, 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. (5.5, 7.1)
`
`------------------------------ADVERSE REACTIONS-------------------------------
`
`
` The most common adverse reaction (≥20%) with DARZALEX FASPRO
`
`
`monotherapy is: upper respiratory tracts infection. (6.1)
`
`
`
`
`
` The most common adverse reactions (≥20%) with D-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%) with D-Rd are fatigue,
`
`
`
`diarrhea, upper respiratory tract infection, muscle spasms, constipation,
`
`
`
`
`pyrexia, pneumonia and dyspnea. (6.1)
`
`
`
`
` The most common hematology laboratory abnormalities (≥40%) 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: 01/2021
`
`
`
` 
` 
`Effects of Daratumumab on Laboratory Tests
`7.1
`
` 
` 
`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
` 
` 
`15 REFERENCES
` 
` 
`16 HOW SUPPLIED/STORAGE AND HANDLING
` 
` 
`17 PATIENT COUNSELING INFORMATION
`
`
`*Sections or subsections omitted from the full prescribing information are not
`
`
`listed.
`
`1
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`FULL PRESCRIBING INFORMATION: CONTENTS*
`
` 
` 
`1
`INDICATIONS AND USAGE
` 
` 
`2 DOSAGE AND ADMINISTRATION
`
` 
` 
`Important Dosing Information
`2.1
` 
` 
`2.2
`Recommended Dosage
` 
` 
`2.3
`Recommended Concomitant Medications
` 
` 
`2.4
`Dosage Modifications for Adverse Reactions
` 
` 
`2.5
`Preparation and Administration
` 
` 
`3 DOSAGE FORMS AND STRENGTHS
`
` 
` 
`4 CONTRAINDICATIONS
` 
` 
`5 WARNINGS AND PRECAUTIONS
`
`
` 
`Hypersensitivity and Other Administration
`5.1
`
` 
`Reactions
` 
` 
`5.2
`Neutropenia
` 
` 
`Thrombocytopenia
`5.3
` 
` 
`5.4
`Embryo-Fetal Toxicity
` 
` 
`5.5
`Interference with Serological Testing
` 
`5.6
`Interference with Determination of Complete
` 
`Response
` 
` 
`6 ADVERSE REACTIONS
` 
` 
`Clinical Trials Experience
`6.1
` 
` 
`6.2
`Immunogenicity
` 
` 
`6.3
`Postmarketing Experience
` 
` 
`7 DRUG INTERACTIONS
`
`Reference ID: 4729465
`
`

`

`
`
`
`Reference ID: 4729465
`Reference ID: 4729465
`
`2
`
`

`

`
`FULL PRESCRIBING INFORMATION
`
`1
` INDICATIONS AND USAGE
`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.
`
` 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.
`2 DOSAGE AND ADMINISTRATION
`Important Dosing Information
`2.1
`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 (2.3)].
`
`Type and screen patients prior to starting DARZALEX FASPRO.
`
`2.2 Recommended Dosage
`
`
`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 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 and Dexamethasone (D-Rd)
`Use the dosing schedule provided in Table 1 when DARZALEX FASPRO is administered:
`
`
`
`
`
`
`
`in combination with lenalidomide and dexamethasone (4-week cycle) OR
`as monotherapy.
`
`Reference ID: 4729465
`
`3
`
`

`

`
`
`Table 1:
`
`
` DARZALEX FASPRO dosing schedule in combination with lenalidomide and dexamethasone
` (4-week cycle) and for monotherapy
`
`
`
`
`
`
`
`
`
` Schedule
` Weeks
`
`weekly (total of 8 doses)
`Weeks 1 to 8
`every two weeks (total of 8 doses)
`Weeks 9 to 24a
`every four weeks
`
` 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.
`
`In Combination with Bortezomib, Melphalan and Prednisone (D-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
`
`weekly (total of 6 doses)
`Weeks 1 to 6
`Weeks 7 to 54a
`
` every three weeks (total of 16 doses)
`Week 55 onwards until disease progressionb
`every four weeks
`
`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
`
`
`
`In Combination with Bortezomib, Thalidomide, and Dexamethasone (D-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
`
`
`
` Table 3:
`
`dexamethasone (4-week cycle)
`
`
`
`Schedule
`Treatment phase
`Weeks
`weekly (total of 8 doses)
`Weeks 1 to 8
`Induction
`every two weeks (total of 4 doses)
`Weeks 9 to 16a
`
`Stop for high dose chemotherapy and ASCT
`Consolidation
`
` Weeks 1 to 8b
` every two weeks (total of 4 doses)
`
`
`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
`
` 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 (D-Vd)
`Use the dosing schedule in Table 4 when DARZALEX FASPRO is administered in combination
`with bortezomib and dexamethasone (3-week cycle).
`
`4
`
`Reference ID: 4729465
`
`

`

`
` Table 4:
`
`
`
` DARZALEX FASPRO dosing schedule in combination with bortezomib and dexamethasone (3-
`
`week cycle)
`
`
`
`
`
`
`Schedule
`weekly (total of 9 doses)
`every three weeks (total of 5 doses)
`every four weeks
`
`
`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.
`Missed DARZALEX FASPRO Doses
`
` 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.
`2.3 Recommended Concomitant Medications
`
`Pre-medication
`Administer the following pre-medications 1-3 hours before each dose of DARZALEX FASPRO:
`
`
`
`
`
`
`
`
`
`
`
`Acetaminophen 650 to 1,000 mg orally
`
`Diphenhydramine 25 to 50 mg (or equivalent) orally or intravenously
`
`Corticosteroid (long- or intermediate-acting)
`
`
`
`Monotherapy
`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.
`the
`When dexamethasone
`is
`regimen-specific corticosteroid,
`the background
`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.
`
`Reference ID: 4729465
`
`5
`
`

`

`
`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 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)].
`2.4 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 (5.2, 5.3)].
`2.5 Preparation and Administration
`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.
`
`6
`
`Reference ID: 4729465
`
`

`

`
`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.
`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
`Inject 15 mL of DARZALEX FASPRO into the subcutaneous tissue of the abdomen
`
`
`
`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.
`
`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 pausing or slowing down delivery rate, a second injection site may be
`chosen on the opposite side of the abdomen to deliver the remainder of the dose.
`
`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.
`
`
`
`
`
`
`
`
`
`
`
`
`Reference ID: 4729465
`
`7
`
`

`

`
` 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.
`
`Systemic Reactions
`
`
`
`
`In a pooled safety population of 490 patients who received DARZALEX FASPRO as
`
`monotherapy or in combination, 11% of patients experienced a systemic administration-related
`reaction (Grade 2: 3.9%, Grade 3: 1.4%). Systemic administration-related reactions occurred in
`10% of patients with the first injection, 0.2% with the second injection, and cumulatively 0.8%
`with subsequent injections. The median time to onset was 3.7 hours (range: 9 minutes to
`3.5 days). Of the 84 systemic administration-related reactions that occurred in 52 patients,
`
`73 (87%) occurred on the day of DARZALEX FASPRO administration. Delayed systemic
`administration-related reactions have occurred in less than 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 (2.3)]. 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 (2.3)].
`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 7 minutes (range: 0 minutes to 4.7 days)
`
`
`
`after starting administration of DARZALEX FASPRO. Monitor for local reactions and consider
`symptomatic management.
`
`Reference ID: 4729465
`
`8
`
`

`

`
`
`
`5.2 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.
`5.3
`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.
`5.4 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 density. Advise pregnant women of the potential risk to a fetus. Advise
`
`females with reproductive potential to 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 is contraindicated in pregnant
`
`
`women, because lenalidomide may cause birth defects and death of the unborn child. Refer to the
`
`lenalidomide prescribing information on use during pregnancy.
`5.5
`Interference with Serological Testing
`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 patient has received DARZALEX FASPRO. Type and screen patients prior to
`
`starting DARZALEX FASPRO [see Dosage and Administration (2.1)].
`5.6
`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
`
`
`
`
`9
`
`Reference ID: 4729465
`
`

`

`
`monitoring of endogenous M-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:
`
`
`
`
`
`
` Hypersensitivity and Other Administration Reactions [see Warning and Precautions
`(5.1)].
`
`Neutropenia [see Warning and Precautions (5.2)].
`
`
`Thrombocytopenia [see Warning and Precautions (5.3)].
`
`6.1 Clinical Trials Experience
`
` Because clinical trials are conducted under widely varying conditions, adverse reaction rates
`
`
`
`
`
` observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials
` of another drug and may not reflect the rates observed in practice.
`
`
` Newly Diagnosed Multiple Myeloma
`In Combination with Bortezomib, Melphalan and Prednisone
`The safety of DARZALEX FASPRO with bortezomib, melphalan and prednisone (D-VMP) was
`evaluated in a single-arm cohort of PLEIADES [see Clinical Studies (14.1)]. Patients received
`
`
`DARZALEX FASPRO 1,800 mg/30,000 units administered subcutaneously once weekly from
`weeks 1 to 6, once every 3 weeks from weeks 7 to 54 and once every 4 weeks starting with
`
`
`
`week 55 until disease progression or unacceptable toxicity (N=67) in combination with
`
`
`bortezomib, melphalan and prednisone. Among these patients, 93% were exposed for 6 months
`
`or longer and 19% were exposed for greater than one year.
`Serious adverse reactions occurred in 39% of patients who received DARZALEX FASPRO.
`
`
`
`
`Serious adverse reactions in >5% of patients included pneumonia and pyrexia. Fatal adverse
`
`reactions occurred in 3.0% of patients.
`Permanent discontinuation of DARZALEX FASPRO due to an adverse reaction occurred in
`
`4.5% of patients. The adverse reaction resulting in permanent discontinuation of DARZALEX
`FASPRO in more than 1 patient was neutropenic sepsis.
`Dosage interruptions (defined as dose delays or skipped doses) due to an adverse reaction
`occurred in 51% of patients who received DARZALEX FASPRO. Adverse reactions requiring
`dosage interruptions in >5% of patients included thrombocytopenia, neutropenia, anemia, and
`pneumonia.
` The most common adverse reactions (≥20%) were upper respiratory tract infection, constipation,
`
`
`nausea, fatigue, pyrexia, peripheral sensory neuropathy, diarrhea, cough, insomnia, vomiting,
`and back pain.
`
`Reference ID: 4729465
`
`
`
` 10
`
`

`

`
` Table 5 summarizes the adverse reactions in patients who received DARZALEX FASPRO with
`bortezomib, melphalan and prednisone (D-VMP) in PLEIADES.
`
`
`
`Table 5:
`
`
` Adverse Reactions (≥10%) in Patients Who Received DARZALEX FASPRO with Bortezomib,
` Melphalan and Prednisone (D-VMP) in PLEIADES
`
`
`
`
`
`
`
`
`
`
`
`
` DARZALEX FASPRO
`
`
` with Bortezomib, Melphalan and Prednisone
`
` (N=67)
`
`All Grades
`
`(%)
`
`
`Grades ≥3
`
`(%)
`
`
` Adverse Reaction
`
`Infections
`Upper respiratory tract infectiona
`Bronchitis
`Pneumoniab
`Gastrointestinal disorders
`Constipation
`
` Nausea
`
`Diarrhea
`Vomiting
` Abdominal painc
`
`
`
`General disorders and administration site conditions
`Fatigued
`
` Pyrexia
`Edema peripherale
`
`
` Nervous system disorders
` Peripheral sensory neuropathy
`
`
` Dizziness
`
`Respiratory, thoracic and mediastinal disorders
`Coughf
`
`Psychiatric disorders
`Insomnia
` Musculoskeletal and connective tissue disorders
`Back pain
`Musculoskeletal chest pain
`
`
`Metabolism and nutrition disorders
` Decreased appetite
`
` Skin and subcutaneous tissue disorders
`
`Rash
` Pruritus
`
`
`Vascular disorders
`13
`
` Hypertension
`
` 6#
`10
`
` 3#
`Hypotension
` a Upper respiratory tract infection includes nasopharyngitis, respiratory syncytial virus infection, respiratory tract infection, rhinitis, tonsillitis,
`
`
`
`upper respiratory tract infection, and viral pharyngitis.
` Pneumonia includes lower respiratory tract infection, lung infection, pneumocystis jirovecii pneumonia, pneumonia, and pneumonia
`
`
`
`
`bacterial.
`
`
` c Abdominal pain includes abdominal pain, and abdominal pain upper.
`
`d
`
` Fatigue includes asthenia, and fatigue.
`
`e
`
` Edema peripheral includes edema, edema peripheral, and peripheral swelling.
`
`
`f
` Cough includes cough, and productive cough.
`
`
` # Only grade 3 adverse reactions occurred.
`
`
` Clinically relevant adverse reactions in <10% of patients who received DARZALEX FASPRO
`
`with bortezomib, melphalan and prednisone (D-VMP) include:
`
`39
`16
`15
`
`37
`36
`33
`21
`13
`
`36
`34
`13
`
`34
`10
`
`24
`
`22
`
`21
`12
`
`15
`
`13
`12
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` 0
`
`0
`
` 7#
`
`0
`0
`
`3#
`
` 0
`
` 0
`
`
` 3
`
` 0
`
` 1#
`
`
` 1#
`
` 0
`
`
`
` 0
`
`
`3#
`
`
`3#
`
` 0
`
`
`
` 1#
`
`
`0
`
` 0
`
`
`
`
`
`
`
`
`
`b
`
`
`
`
`
`Reference ID: 4729465
`
`
`
` 11
`
`

`

`
`
`
`
`
`
`
`
`
`
` General disorders and administration site conditions: infusion reaction, injection site
`
` reaction, chills
` Infections: herpes zoster, urinary tract infection, influenza, sepsis
`
`
`
` Musculoskeletal and connective tissue disorders: arthralgia, muscle spasms
`
`
`
` Nervous system disorders: headache, paresthesia
`
`
` Metabolism and nutrition disorders: hypocalcemia, hyperglycemia
`
`
`
` Respiratory, thoracic and mediastinal disorders: dyspnea, pulmonary edema
`
`
`
` Cardiac disorders: atrial fibrillation
`
`
` Table 6 summarizes the laboratory abnormalities in patients who received DARZALEX
`
`
` FASPRO with bortezomib, melphalan and prednisone (D-VMP) in PLEIADES.
` Select Hematology Laboratory Abnormalities Worsening from Baseline in Patients Who
`
`
`Table 6:
`
` Received DARZALEX FASPRO with Bortezomib, Melphalan and Prednisone (D-VMP) in
`
` PLEIADES
`
`
`
`
`
` DARZALEX FASPRO
`
`
` with Bortezomib, Melphalan and Prednisonea
`
`
`All Grades
`Grades 3-4
`
`
`(%)
`(%)
` Laboratory Abnormality
`
`96
`52
`Decreased leukocytes
`
`93
` 84
` Decreased lymphocytes
`
`42
`93
`Decreased platelets
`88
`49
`Decreased neutrophils
`
`48
` 19
` Decreased hemoglobin
`
`
` a Denominator is based on the safety population treated with D-VMP (N=67).
`
`
`Relapsed/Refractory Multiple Myeloma
`In Combination with Lenalidomide and Dexamethasone
` The safety of DARZALEX FASPRO with lenalidomide and dexamethasone (D-Rd) was
`
`
`
`
` evaluated in a single-arm cohort of PLEIADES [see Clinical Studies (14.2)]. Patients received
`DARZALEX FASPRO 1,800 mg/30,000 units administered subcutaneously once weekly from
` weeks 1 to 8, once every 2 weeks from weeks 9 to 24 and once every 4 weeks starting with
`
`
`
` week 25 until disease progression or unacceptable toxicity (N=65) in combination with
`
`
`lenalidomide and dexamethasone. Among these patients, 92% were exposed for 6 months or
`longer and 20% were exposed for greater than one year.
`
`
`
`
` Serious adverse reactions occurred in 48% of patients who received DARZALEX FASPRO.
`Serious adverse reactions in >5% of patients included pneumonia, influenza and diarrhea. Fatal
`adverse reactions occurred in 3.1% of patients.
`
` Permanent discontinuation of DARZALEX FASPRO due to an adverse reaction occurred in 11%
`
` of patients who received DARZALEX FASPRO. Adverse reactions resulting in permanent
`
`discontinuation of DARZALEX FASPRO in more than 1 patient were pneumonia and anemia.
`
`
`
` Dosage interruptions due to an adverse reaction occurred in 63% of patients who received
`DARZALEX FASPRO. Adverse reactions requiring dosage interruptions in >5% of patients
`
`Reference ID: 4729465
`
`
`
` 12
`
`

`

`
`included neutropenia, pneumonia, upper respiratory tract infection, influenza, dyspnea, and
`blood creatinine increased.
`The most common adverse reactions (≥20%) were fatigue, diarrhea, upper respiratory tract
`infection, muscle spasms, constipation, pyrexia, pneumonia, and dyspnea.
`Table 7 summarizes the adverse reactions in patients who received DARZALEX FASPRO with
`
`lenalidomide and dexamethasone (D-Rd) in PLEIADES.
`
` Adverse Reactions (≥10%) in Patients Who Received DARZALEX FASPRO with Lenalidomide
`Table 7:
` and Dexamethasone (D-Rd) in PLEIADES
`
`
`
` DARZALEX FASPRO
`
`
`with Lenalidomide and Dexamethasone
`
`(N=65)
`
`All Grades
`(%)
`
`
`Grades ≥3
`(%)
`
` Adverse Reaction
`
`
`
`General disorders and administration site conditions
`Fatiguea
`
` Pyrexia
`Edema peripheral
`Gastrointestinal disorders
`
`Diarrhea
`Constipation
`
` Nausea
`Vomiting
`
`Infections
`Upper respiratory tract infectionb
`Pneumoniac
`Bronchitisd
`Urinary tract infection
`
`Musculoskeletal and connective tissue disorders
`
`Muscle spasms
`Back pain
`
`Respiratory, thoracic and mediastinal disorders
`Dyspneae
`Coughf
`
`
`Nervous system disorders
` Peripheral sensory neuropathy
`
` Psychiatric disorders
`
`Insomnia
` Metabolism and nutrition disorders
`
`Hyperglycemia
`
` Hypocalcemia
`
`a
` Fatigue incl