Darzalex Faspro

Medical Editor: John P. Cunha, DO, FACOEP Last updated on RxList: 2/3/2022
Darzalex Faspro Side Effects Center

Medical Editor: John P. Cunha, DO, FACOEP

What Is Darzalex Faspro?

Darzalex Faspro (daratumumab and hyaluronidase-fihj) is a combination of a CD38-directed cytolytic antibody and an endoglycosidase used to treat 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 and dexamethasone in patients who have received at least one prior therapy; and 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.

What Are Side Effects of Darzalex Faspro?

Side effects of Darzalex Faspro monotherapy include:

  • upper respiratory tract infection
Side effects of Darzalex Faspro with D-VMP include:
  • upper respiratory tract infection,
  • constipation,
  • nausea,
  • fatigue,
  • fever,
  • numbness and pain in the hands or feet,
  • diarrhea,
  • cough,
  • insomnia,
  • vomiting, and
  • back pain
  • Side effects of Darzalex Faspro with D-Rd include:

    • fatigue,
    • diarrhea,
    • upper respiratory tract infection,
    • muscle spasms,
    • constipation,
    • fever,
    • pneumonia, and
    • shortness of breath

    Dosage for Darzalex Faspro

    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.

    Darzalex Faspro In Children

    Safety and effectiveness of Darzalex Faspro in pediatric patients have not been established.

    What Drugs, Substances, or Supplements Interact with Darzalex Faspro?

    Darzalex Faspro may interact with other medicines.

    Tell your doctor all medications and supplements you use.

    Darzalex Faspro During Pregnancy and Breastfeeding

    Tell your doctor if you are pregnant or plan to become pregnant before using Darzalex Faspro; it may harm a fetus. The combination of Darzalex Faspro and lenalidomide is contraindicated in pregnant women, because lenalidomide may cause birth defects and death of the unborn child. Females of reproductive potential are advised to use effective contraception during treatment with Darzalex Faspro and for 3 months after the last dose. There is no data on the presence of Darzalex Faspro in breast milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in the breastfed child when Darzalex Faspro is administered with lenalidomide and dexamethasone, breastfeeding is not recommended during treatment with Darzalex Faspro.

    Additional Information

    Our Darzalex Faspro (daratumumab and hyaluronidase-fihj) Injection, for Subcutaneous Use Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

    This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

    This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

    SLIDESHOW

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    Darzalex Faspro Consumer Information

    Get emergency medical help if you have signs of an allergic reaction: itching, hives; runny or stuffy nose, fever, chills, headache, nausea, vomiting; throat irritation, cough, chest pain, fast heartbeats, wheezing, difficult breathing; swelling of your face, lips, tongue, or throat.

    Call your doctor at once if you have:

    • a light-headed feeling, like you might pass out;
    • easy bruising, unusual bleeding, purple or red spots under your skin;
    • right-sided upper stomach pain, vomiting, loss of appetite, yellowing of your skin or eyes, and not feeling well;
    • low white blood cell counts--fever, mouth sores, skin sores, sore throat, cough, trouble breathing; or
    • a lung infection--fever, chills, cough with mucus, chest pain, feeling short of breath.

    Your cancer treatments may be delayed or permanently discontinued if you have certain side effects.

    Common side effects may include:

    • itching, swelling, bruising, or redness where the medicine was injected;
    • nausea, vomiting, diarrhea, constipation;
    • fever, low blood cell counts;
    • trouble breathing, lung infection;
    • numbness, tingling, or burning pain in your hands or feet;
    • feeling tired;
    • cold symptoms such as stuffy nose, sneezing, sore throat;
    • muscle spasm, back pain; or
    • sleep problems (insomnia).

    This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

    Read the entire detailed patient monograph for Darzalex Faspro (Daratumumab and Hyaluronidase-fihj Injection)

    Darzalex Faspro Professional Information

    SIDE EFFECTS

    The following clinically significant adverse reactions are described elsewhere in the labeling:

    • Hypersensitivity and Other Administration Reactions [see WARNINGS AND PRECAUTIONS].
    • Cardiac Toxicity in Patients with Light Chain (AL) Amyloidosis [see WARNINGS AND PRECAUTIONS].
    • Neutropenia [see WARNINGS AND PRECAUTIONS].
    • Thrombocytopenia [see WARNINGS AND PRECAUTIONS].

    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]. 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% 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.

    Table 6 summarizes the adverse reactions in patients who received DARZALEX FASPRO with bortezomib, melphalan and prednisone (D-VMP) in PLEIADES.

    Table 6: Adverse Reactions (≥10%) in Patients Who Received DARZALEX FASPRO with Bortezomib, Melphalan and Prednisone (D-VMP) in PLEIADES

    Adverse Reaction DARZALEX FASPRO
    with Bortezomib, Melphalan and Prednisone
    (N=67)
    All Grades
    (%)
    Grades ≥3
    (%)
    Infections
      Upper respiratory tract infectiona 39 0
      Bronchitis 16 0
      Pneumoniaa 15 7#
    Gastrointestinal disorders
      Constipation 37 0
      Nausea 36 0
      Diarrhea 33 3#
      Vomiting 21 0
      Abdominal painc 13 0
    General disorders and administration site conditions
      Fatigued 36 3
      Pyrexia 34 0
      Edema peripherale 13 1#
    Nervous system disorders
      Peripheral sensory neuropathy 34 1#
      Dizziness 10 0
    Respiratory, thoracic and mediastinal disorders
      Coughf 24 0
    Psychiatric disorders
      Insomnia 22 3#
    Musculoskeletal and connective tissue disorders
      Back pain 21 3#
      Musculoskeletal chest pain 12 0
    Metabolism and nutrition disorders
      Decreased appetite 15 1#
    Skin and subcutaneous tissue disorders
      Rash 13 0
      Pruritus 12 0
    Vascular disorders
      Hypertension 13 6#
      Hypotension 10 3#
    a Upper respiratory tract infection includes nasopharyngitis, respiratory syncytial virus infection, respiratory tract infection, rhinitis, tonsillitis, upper respiratory tract infection, and viral pharyngitis.
    b 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) included:

    • 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 7 summarizes the laboratory abnormalities in patients who received DARZALEX FASPRO with bortezomib, melphalan and prednisone (D-VMP) in PLEIADES.

    Table 7: Select Hematology Laboratory Abnormalities Worsening from Baseline in Patients Who Received DARZALEX FASPRO with Bortezomib, Melphalan and Prednisone (D-VMP) in PLEIADES

    Laboratory Abnormality DARZALEX FASPRO
    with Bortezomib, Melphalan and Prednisonea
    All Grades (%) Grades 3-4 (%)
    Decreased leukocytes 96 52
    Decreased lymphocytes 93 84
    Decreased platelets 93 42
    Decreased neutrophils 88 49
    Decreased hemoglobin 48 19
    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]. 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 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 8 summarizes the adverse reactions in patients who received DARZALEX FASPRO with lenalidomide and dexamethasone (D-Rd) in PLEIADES.

    Table 8: Adverse Reactions (≥10%) in Patients Who Received DARZALEX FASPRO with Lenalidomide and Dexamethasone (D-Rd) in PLEIADES

    Adverse Reaction DARZALEX FASPRO
    with Lenalidomide and Dexamethasone
    (N=65)
    All Grades
    (%)
    Grades ≥3
    (%)
    General disorders and administration site conditions
      Fatiguea 52 5#
      Pyrexia 23 2#
      Edema peripheral 18 3#
    Gastrointestinal disorders
      Diarrhea 45 5#
      Constipation 26 2#
      Nausea 12 0
      Vomiting 11 0
    Infections
      Upper respiratory tract infectionb 43 3#
      Pneumoniac 23 17
      Bronchitisd 14 2#
      Urinary tract infection 11 0
    Musculoskeletal and connective tissue disorders
      Muscle spasms 31 2#
      Back pain 14 0
    Respiratory, thoracic and mediastinal disorders
      Dyspneae 22 3
      Coughf 14 0
    Nervous system disorders
      Peripheral sensory neuropathy 17 2#
    Psychiatric disorders
      Insomnia 17 5#
    Metabolism and nutrition disorders
      Hyperglycemia 12 9#
      Hypocalcemia 11 0
    a Fatigue includes asthenia, and fatigue.
    b Upper respiratory tract infection includes nasopharyngitis, pharyngitis, respiratory tract infection viral, rhinitis, sinusitis, upper respiratory tract infection, and upper respiratory tract infection bacterial.
    c Pneumonia includes lower respiratory tract infection, lung infection, and pneumonia.
    d Bronchitis includes bronchitis, and bronchitis viral.
    e Dyspnea includes dyspnea, and dyspnea exertional.
    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 lenalidomide and dexamethasone (D-Rd) included:

    • Musculoskeletal and connective tissue disorders: arthralgia, musculoskeletal chest pain
    • Nervous system disorders: dizziness, headache, paresthesia
    • Skin and subcutaneous tissue disorders: rash, pruritus
    • Gastrointestinal disorders: abdominal pain
    • Infections: influenza, sepsis, herpes zoster
    • Metabolism and nutrition disorders: decreased appetite
    • Cardiac disorders: atrial fibrillation
    • General disorders and administration site conditions: chills, infusion reaction, injection site reaction
    • Vascular disorders: hypotension, hypertension

    Table 9 summarizes the laboratory abnormalities in patients who received DARZALEX FASPRO with lenalidomide and dexamethasone (D-Rd) in PLEIADES.

    Table 9: Select Hematology Laboratory Abnormalities Worsening from Baseline in Patients Who Received DARZALEX FASPRO with Lenalidomide and Dexamethasone (D-Rd) in PLEIADES

    Laboratory Abnormality DARZALEX FASPRO
    with Lenalidomide and Dexamethasonea
    All Grades
    (%)
    Grades 3-4
    (%)
    Decreased leukocytes 94 34
    Decreased lymphocytes 82 58
    Decreased platelets 86 9
    Decreased neutrophils 89 52
    Decreased hemoglobin 45 8
    a Denominator is based on the safety population treated with D-Rd (N=65).

    Monotherapy

    The safety of DARZALEX FASPRO as monotherapy was evaluated in COLUMBA [see Clinical Trials]. Patients received DARZALEX FASPRO 1,800 mg/30,000 units administered subcutaneously or daratumumab 16 mg/kg administered intravenously; each administered 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. Among patients receiving DARZALEX FASPRO, 37% were exposed for 6 months or longer and 1% were exposed for greater than one year.

    Serious adverse reactions occurred in 26% of patients who received DARZALEX FASPRO. Fatal adverse reactions occurred in 5% of patients. Fatal adverse reactions occurring in more than 1 patient were general physical health deterioration, septic shock, and respiratory failure.

    Permanent discontinuation due to an adverse reaction occurred in 10% of patients who received DARZALEX FASPRO. Adverse reactions resulting in permanent discontinuation of DARZALEX FASPRO in more than 2 patients were thrombocytopenia and hypercalcemia.

    Dosage interruptions due to an adverse reaction occurred in 26% of patients who received DARZALEX FASPRO. Adverse reactions requiring dosage interruption in >5% of patients included thrombocytopenia.

    The most common adverse reaction (≥20%) was upper respiratory tract infection.

    Table 10 summarizes the adverse reactions in COLUMBA.

    Table 10: Adverse Reactions (≥10%) in Patients Who Received DARZALEX FASPRO or Intravenous Daratumumab in COLUMBA

    Adverse Reaction DARZALEX FASPRO
    (N=260)
    Intravenous Daratumumab
    (N=258)
    All Grades
    (%)
    Grade ≥3
    (%)
    All Grades
    (%)
    Grade ≥3
    (%)
    Infections
      Upper respiratory tract infectiona 24 1# 22 1#
      Pneumoniab 8 5 10 6@
    Gastrointestinal disorders
      Diarrhea 15 1# 11 0.4#
      Nausea 8 0.4# 11 0.4#
    General disorders and administration site conditions
      Fatiguec 15 1# 16 2#
      Infusion reactionsd 13 2# 34 5#
      Pyrexia 13 0 13 1#
      Chills 6 0.4# 12 1#
    Musculoskeletal and connective tissue disorders
      Back pain 10 2# 12 3#
    Respiratory, thoracic and mediastinal disorders
      Coughe 9 1# 14 0
      Dyspneaf 6 1# 11 1#
    a Upper respiratory tract infection includes acute sinusitis, nasopharyngitis, pharyngitis, respiratory syncytial virus infection, respiratory tract infection, rhinitis, rhinovirus infection, sinusitis, and upper respiratory tract infection.
    b Pneumonia includes lower respiratory tract infection, lung infection, pneumocystis jirovecii pneumonia, and pneumonia.
    c Fatigue includes asthenia, and fatigue.
    d Infusion reactions includes terms determined by investigators to be related to infusion.
    e Cough includes cough, and productive cough.
    f Dyspnea includes dyspnea, and dyspnea exertional.
    # Only grade 3 adverse reactions occurred.
    @ Grade 5 adverse reactions occurred.

    Clinically relevant adverse reactions in <10% of patients who received DARZALEX FASPRO included:

    • General disorders and administration site conditions: injection site reaction, peripheral edema
    • Musculoskeletal and connective tissue disorders: arthralgia, musculoskeletal chest pain, muscle spasms
    • Gastrointestinal disorders: constipation, vomiting, abdominal pain
    • Metabolism and nutrition disorders: decreased appetite, hyperglycemia, hypocalcemia, dehydration
    • Psychiatric disorders: insomnia
    • Vascular disorders: hypertension, hypotension
    • Nervous system disorders: dizziness, peripheral sensory neuropathy, paresthesia
    • Infections: bronchitis, influenza, urinary tract infection, herpes zoster, sepsis, hepatitis B virus reactivation
    • Skin and subcutaneous tissue disorders: pruritus, rash
    • Cardiac disorders: atrial fibrillation
    • Respiratory, thoracic and mediastinal disorders: pulmonary edema

    Table 11 summarizes the laboratory abnormalities in COLUMBA.

    Table 11: Select Hematology Laboratory Abnormalities Worsening from Baseline in Patients Receiving DARZALEX FASPRO or Intravenous Daratumumab in COLUMBA

    Laboratory Abnormality DARZALEX FASPROa Intravenous Daratumumaba
    All Grades
    (% )
    Grades 3-4
    (%)
    All Grades
    (%)
    Grades 3-4
    (%)
    Decreased leukocytes 65 19 57 14
    Decreased lymphocytes 59 36 56 36
    Decreased neutrophils 55 19 43 11
    Decreased platelets 43 16 45 14
    Decreased hemoglobin 42 14 39 16
    a Denominator is based on the safety population treated with DARZALEX FASPRO (N=260) and Intravenous Daratumumab (N=258).

    Light Chain Amyloidosis

    In Combination with Bortezomib, Cyclophosphamide and Dexamethasone

    The safety of DARZALEX FASPRO with bortezomib, cyclophosphamide and dexamethasone (D-VCd) was evaluated in ANDROMEDA [see Clinical Studies]. 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 or a maximum of 2 years. Among patients who received D-VCd, 74% were exposed for 6 months or longer and 32% were exposed for greater than one year.

    Serious adverse reactions occurred in 43% of patients who received DARZALEX FASPRO in combination with VCd. Serious adverse reactions that occurred in at least 5% of patients in the D-VCd arm were pneumonia (9%), cardiac failure (8%), and sepsis (5%). Fatal adverse reactions occurred in 11% of patients. Fatal adverse reactions that occurred in more than one patient included cardiac arrest (4%), sudden death (3%), cardiac failure (3%), and sepsis (1%).

    Permanent discontinuation of DARZALEX FASPRO due to an adverse reaction occurred in 5% of patients. Adverse reactions resulting in permanent discontinuation of DARZALEX FASPRO in more than one patient were pneumonia, sepsis, and cardiac failure.

    Dosage interruptions (defined as dose delays or skipped doses) due to an adverse reaction occurred in 36% of patients who received DARZALEX FASPRO. Adverse reactions which required a dosage interruption in ≥3% of patients included upper respiratory tract infection (9%), pneumonia (6%), cardiac failure (4%), fatigue (3%), herpes zoster (3%), dyspnea (3%), and neutropenia (3%).

    The most common adverse reactions (≥20%) were upper respiratory tract infection, diarrhea, peripheral edema, constipation, fatigue, peripheral sensory neuropathy, nausea, insomnia, dyspnea, and cough.

    Table 12 below summarizes the adverse reactions in patients who received DARZALEX FASPRO with VCd in ANDROMEDA.

    Table 12: Adverse Reactions (≥10%) in Patients with AL Amyloidosis Who Received DARZALEX FASPRO with Bortezomib, Cyclophosphamide and Dexamethasone (D-VCd) with a Difference Between Arms of >5% Compared to VCd in ANDROMEDA

    Adverse Reaction D-VCd
    (N=193)
    VCd
    (N=188)
    All Grades
    (%)
    Grades 3-4
    (%)
    All Grades
    (%)
    Grades 3-4
    (%)
    Infections
      Upper respiratory tract infectiona 40 1# 21 1#
      Pneumoniab 15 10 9 5
    Gastrointestinal disorders
      Diarrhea 36 6# 30 4
      Constipation 34 2# 29 0
    Nervous system disorders
      Peripheral sensory neuropathy 31 3# 20 2#
    Respiratory, thoracic and mediastinal disorders
      Dyspneac 26 4 20 4#
      Coughd 20 1# 11 0
    Musculoskeletal and connective tissue disorders
      Back pain 12 2# 6 0
      Arthralgia 10 0 5 0
      Muscle spasms 10 1# 5 0
    Cardiac disorders
      Arrhythmiae 11 4 5 2
    General disorders and administration site conditions
      Injection site reactionsf 11 0 0 0
    # Only grade 3 adverse reactions occurred.
    a Upper respiratory tract infection includes laryngitis, nasopharyngitis, pharyngitis, respiratory syncytial virus infection, respiratory tract infection, respiratory tract infection viral, rhinitis, rhinovirus infection, sinusitis, tonsillitis, tracheitis, upper respiratory tract infection, upper respiratory tract infection bacterial, and viral upper respiratory tract infection.
    b Pneumonia includes lower respiratory tract infection, pneumonia, pneumonia aspiration, and pneumonia pneumococcal.
    c Dyspnea includes dyspnea, and dyspnea exertional.
    d Cough includes cough, and productive cough.
    e Arrhythmia includes atrial flutter, atrial fibrillation, supraventricular tachycardia, bradycardia, arrhythmia, bradyarrhythmia, cardiac flutter, extrasystoles, supraventricular extrasystoles, ventricular arrhythmia, ventricular extrasystoles, atrial tachycardia, ventricular tachycardia
    f Injection site reactions includes terms determined by investigators to be related to daratumumab injection.

    Clinically relevant adverse reactions not included in Table 12 and occurred in patients who received DARZALEX FASPRO with bortezomib, cyclophosphamide and dexamethasone (D-VCd) included:

    • Skin and subcutaneous tissue disorders: rash, pruritus
    • Nervous system disorders: paresthesia
    • General disorders and administration site conditions: infusion reaction, chills
    • Cardiac disorders: cardiac failurea, cardiac arrest
    • Metabolism and nutrition disorders: hyperglycemia, hypocalcemia, dehydration
    • Infections: bronchitis, herpes zoster, sepsis, urinary tract infection, influenza
    • Vascular disorders: hypertension
    • Musculoskeletal and connective tissue disorders: musculoskeletal chest pain
    • Gastrointestinal disorders: pancreatitis
    • Respiratory, thoracic and mediastinal disorders: pulmonary edema

    a Cardiac failure includes cardiac dysfunction, cardiac failure, cardiac failure congestive, cardiovascular insufficiency, diastolic dysfunction, pulmonary edema, and left ventricular dysfunction occurred in 11% of patients.

    Table 13 summarizes the laboratory abnormalities in patients who received DARZALEX FASPRO with VCd in ANDROMEDA.

    Table 13: Select Hematology Laboratory Abnormalities Worsening from Baseline in Patients Who Received DARZALEX FASPRO with Bortezomib, Cyclophosphamide and Dexamethasone (D-VCd) in ANDROMEDA

    Laboratory Abnormality D-VCd VCd
    All Grades
    (%)
    Grades 3-4
    (%)
    All Grades
    (%)
    Grades 3-4
    (%)
    Decreased lymphocytes 81 54 71 46
    Decreased hemoglobin 66 6 70 6
    Decreased leukocytes 60 7 46 4
    Decreased platelets 46 3 40 4
    Decreased neutrophils 30 6 18 4
    Denominator is based on the number of patients with a baseline and post-baseline laboratory value for each laboratory test, N=188 for D-VCd and N=186 for VCd.

    Cardiac Adverse Reactions in Light Chain (AL) Amyloidosis

    Among patients who received DARZALEX FASPRO in combination with VCd, 72% of patients had baseline cardiac involvement with Mayo Cardiac Stage I (3%), Stage II (46%) and Stage III (51%). Serious cardiac disorders occurred in 16% of patients (8% of patients with Mayo Cardiac Stage I and II and 28% of patients with Stage III). Serious cardiac disorders in >2% of patients included cardiac failure (8%), cardiac arrest (4%) and arrhythmia (4%). Fatal cardiac disorders occurred in 10% of patients (5% of patients with Mayo Cardiac Stage I and II and 19% of patients with Stage III) who received DARZALEX FASPRO in combination with VCd. Fatal cardiac disorders that occurred in more than one patient in the D-VCd arm included cardiac arrest (4%), sudden death (3%), and cardiac failure (3%).

    Immunogenicity

    As with all therapeutic proteins, there is the potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies in the studies described below with the incidence of antibodies in other studies or to other daratumumab products or other hyaluronidase products may be misleading.

    In patients with multiple myeloma and light chain (AL) amyloidosis who received DARZALEX FASPRO as monotherapy or as part of a combination therapy, less than 1% of 633 patients developed treatment-emergent anti-daratumumab antibodies.

    In patients with multiple myeloma and light chain (AL) amyloidosis who received DARZALEX FASPRO as monotherapy or as part of a combination therapy, 7% of 628 patients developed treatment-emergent anti-rHuPH20 antibodies. The anti-rHuPH20 antibodies did not appear to affect daratumumab exposure. None of the patients who tested positive for anti-rHuPH20 antibodies tested positive for neutralizing antibodies.

    Postmarketing Experience

    The following adverse reactions have been identified with post-approval use of daratumumab. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

    • Immune System: Anaphylactic reaction
    • Gastrointestinal: Pancreatitis
    • Infections: Cytomegalovirus, Listeriosis

    DRUG INTERACTIONS

    Effects Of Daratumumab On Laboratory Tests

    Interference With Indirect Antiglobulin Tests (Indirect 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 binding [see REFERENCES] or genotyping. Since the Kell blood group system is also sensitive to DTT treatment, supply K-negative units after ruling out or identifying alloantibodies using DTT-treated RBCs.

    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.

    Read the entire FDA prescribing information for Darzalex Faspro (Daratumumab and Hyaluronidase-fihj Injection)

    © Darzalex Faspro Patient Information is supplied by Cerner Multum, Inc. and Darzalex Faspro Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

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