Danyelza

Last updated on RxList: 7/21/2021
Danyelza Side Effects Center

Medical Editor: John P. Cunha, DO, FACOEP

What Is Danyelza?

Danyelza (naxitamab-gqgk) is a GD2-binding monoclonal antibody indicated, in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), to treat pediatric patients 1 year of age and older and adult patients with relapsed or refractory high-risk neuroblastoma in the bone or bone marrow who have demonstrated a partial response, minor response, or stable disease to prior therapy.

What Are Side Effects of Danyelza?

Side effects of Danyelza include:

  • infusion-related reactions occurring on the day of infusion or the day following an infusion (low blood pressure, bronchospasm, flushing, wheezing, stridor, hives, shortness of breath, fever, swelling of the face/lips/tongue, respiratory tract edema, chills, low blood oxygen, itching, and rash)
  • pain (abdominal pain, pain in extremity, bone pain, neck pain, back pain, and musculoskeletal pain),
  • fast heart rate,
  • vomiting,
  • cough,
  • nausea,
  • diarrhea,
  • decreased appetite,
  • high blood pressure (hypertension),
  • fatigue,
  • erythema multiforme,
  • numbness and tingling of extremities,
  • hives not occurring on the day of infusion or the day following an infusion,
  • fever not occurring on the day of infusion or the day following an infusion,
  • headache,
  • injection site reaction,
  • fluid retention (edema),
  • anxiety,
  • localized swelling,
  • irritability,
  • decreased lymphocytes,
  • decreased neutrophils,
  • decreased hemoglobin,
  • decreased platelet count,
  • decreased potassium,
  • increased alanine aminotransferase,
  • decreased glucose,
  • decreased calcium,
  • decreased albumin,
  • decreased sodium, and
  • decreased phosphate

Dosage for Danyelza

The recommended dosage of Danyelza is 3 mg/kg/day (up to 150 mg/day), administered as an intravenous infusion after dilution on Days 1, 3, and 5 of each treatment cycle. Treatment cycles are repeated every 4 weeks until complete response or partial response, followed by 5 additional cycles every 4 weeks. Subsequent cycles may be repeated every 8 weeks.

Danyelza In Children

The safety and effectiveness of Danyelza, in combination with GM-CSF for the treatment of relapsed or refractory high-risk neuroblastoma in the bone or bone marrow who have demonstrated a partial response, minor response or stable disease following prior therapy, have been established in pediatric patients 1 year of age and older.

Safety and effectiveness have not been established in pediatric patients younger than 1 year of age.

What Drugs, Substances, or Supplements Interact with Danyelza?

Danyelza may interact with other medicines.

Tell your doctor all medications and supplements you use.

Danyelza During Pregnancy and Breastfeeding

Tell your doctor if you are pregnant or plan to become pregnant before using Danyelza; it may harm a fetus. Females of reproductive potential are advised to use effective contraception during treatment and for 2 months after the final dose of Danyelza. It is unknown if Danyelza passes into breast milk. Because of the potential for serious adverse reactions in a breastfed child from Danyelza, breastfeeding is not recommended while using Danyelza and for 2 months after the final dose.

dditional Information

Our Danyelza (naxitamab-gqgk) Injection, for Intravenous 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.

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Danyelza Consumer Information

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Some side effects may occur during the injection. Tell your caregiver if you feel dizzy, light-headed, itchy, warm or tingly, short of breath, or if you have a cough, noisy breathing, or swelling in your face.

Call your doctor at once if you have:

  • severe pain anywhere in your body;
  • numbness, tingling, or burning pain in your hands or feet;
  • severe headache, confusion, thinking problems, weakness, vision loss;
  • a seizure;
  • painful or difficult urination;
  • cold symptoms--such as runny or stuffy nose, sneezing, sore throat, cough, low fever, and not feeling well;
  • eye problems--blurred vision, trouble focusing, dilated pupils, unequal pupil size, being more sensitive to light;
  • high blood pressure--headache, nausea, vomiting, dizziness, vision changes, nosebleeds, chest pain, fast or pounding heartbeats, pounding in your neck or ears; or
  • low blood cell counts--fever, chills, tiredness, mouth sores, skin sores, easy bruising, unusual bleeding, pale skin, cold hands and feet, feeling light-headed or short of breath.

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

Common side effects may include:

  • nausea, vomiting, diarrhea, loss of appetite;
  • low blood cell counts, or other abnormal lab tests;
  • skin rash or hives;
  • swelling;
  • headache, fever, feeling tired;
  • fast heart rate;
  • feeling anxious or irritable;
  • cough; or
  • pain, bruising, swelling, or irritation where the medicine was injected.

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 Danyelza (Naxitamab-gqgk Injection)

Danyelza Professional Information

SIDE EFFECTS

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

  • Serious Infusion-Related Reactions [see WARNINGS AND PRECAUTIONS]
  • Neurotoxicity [see WARNINGS AND PRECAUTIONS]
  • Hypertension [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.

The safety of DANYELZA in combination with GM-CSF was evaluated in patients with refractory or relapsed high-risk neuroblastoma in bone or bone marrow who had demonstrated a partial response, minor response, or stable disease following initial or subsequent therapy, and in patients who were in second complete remission, from two open-label, single arm studies, Study 201 (n=25) and Study 12-230 (n=72). Patients received DANYELZA 9 mg/kg/cycle administered as three separate intravenous infusions of 3 mg/kg (Day 1, 3 and 5) in the first week of each cycle. Patients also received GM-CSF 250 μg/m²/day subcutaneously on Days -4 to 0 and GM-CSF 500 μg/m²/day subcutaneously on Days 1 to 5 [see Clinical Studies].

The most common adverse reactions in Studies 201 and 12-230 (≥25% in either study) were infusion-related reaction, pain, tachycardia, vomiting, cough, nausea, diarrhea, decreased appetite, hypertension, fatigue, erythema multiforme, peripheral neuropathy, urticaria, pyrexia, headache, injection site reaction, edema, anxiety, localized edema and irritability. The most common Grade 3 or 4 laboratory abnormalities (≥5% in either study) were decreased lymphocytes, decreased neutrophils, decreased hemoglobin, decreased platelet count, decreased potassium, increased alanine aminotransferase, decreased glucose, decreased calcium, decreased albumin, decreased sodium and decreased phosphate.

Study 201

In Study 201, among 25 patients who received DANYELZA in combination with GM-CSF, 12% were exposed for 6 months or longer and none were exposed for greater than one year.

Serious adverse reactions occurred in 32% of patients who received DANYELZA in combination with GM-GSF. Serious adverse reactions in more than one patient included anaphylactic reaction (12%) and pain (8%). Permanent discontinuation of DANYELZA due to an adverse reaction occurred in 12% of patients. Adverse reactions resulting in permanent discontinuation of DANYELZA included anaphylactic reaction (8%) and respiratory depression (4%).

Dosage interruptions of DANYELZA due to an adverse reaction occurred in 84% of patients. Adverse reactions requiring dosage interruption in > 10% of patients included hypotension and bronchospasm.

Table 4 summarizes adverse reactions in Study 201.

Table 4: Adverse Reactions (>10%) in Patients with Refractory or Relapsed High-Risk Neuroblastoma in Bone or Bone Marrow Who Received DANYELZA with GM-CSF in Study 201

Adverse ReactionDANYELZA with GM-CSF1
(n=25)
All Grades (%)Grade 3 or 4 (%)
Body system
General disorders and administration site conditions
Pain210072
Infusion-related reaction310068
Edema280
Fatigue4280
Pyrexia5280
Respiratory, thoracic and mediastinal disorders
Cough600
Rhinorrhea240
Vascular disorders
Hypertension444
Gastrointestinal disorders
Vomiting604
Diarrhea568
Nausea560
Skin and subcutaneous tissue disorders
Urticaria7324
Cardiac disorders
Tachycardia6844
Nervous system disorders
Peripheral neuropathy8320
Headache288
Depressed level of consciousness2416
Eye disorders
Neurological disorders of the eye9240
Immune system disorders
Anaphylactic reaction1212
Metabolism and nutrition disorders
Decreased appetite160
Infections and infestations
Influenza120
Rhinovirus infection120
Upper respiratory tract infection120
Investigations
Weight decreased120
Psychiatric disorders
Anxiety120
1 Adverse reactions were graded using CTCAE version 4.0.
2Pain includes pain, abdominal pain, pain in extremity, bone pain, neck pain, back pain, and musculoskeletal pain.
3Infusion-related reaction includes hypotension, bronchospasm, flushing, wheezing, stridor, urticaria, dyspnea, pyrexia, infusion-related reaction, face edema, edema mouth, tongue edema, lip edema, respiratory tract edema, chills, hypoxia, pruritis and rash occurring on the day of infusion or the day following an infusion.
4Fatigue includes fatigue, asthenia.
5Pyrexia not occurring on the day of infusion or the day following an infusion
6Tachycardia includes sinus tachycardia and tachycardia
7Urticaria, not occurring on the day of infusion or the day following an infusion
8Peripheral neuropathy includes peripheral sensory neuropathy, paresthesia, neuralgia.
9Neurological disorders of the eye includes unequal pupils, blurred vision, and mydriasis.

Clinically relevant adverse reactions occurring in ≤10% of patients who received DANYELZA with GM-CSF included peripheral edema (8%).

Table 5 summarizes the laboratory abnormalities in Study 201.

Table 5: Selected Laboratory Abnormalities (>20%) Worsening from Baseline in Patients with Refractory or Relapsed High-Risk Neuroblastoma in Bone or Bone Marrow Who Received DANYELZA with GM-CSF in Study 201

Laboratory AbnormalityDANYELZA with GM-CSF1
n=25
All Grades (%)Grade 3 or 4 (%)
Chemistry
Decreased potassium638
Decreased albumin500
Increased alanine aminotransferase428
Decreased sodium290
Hematology
Decreased lymphocytes7430
Decreased platelet count6517
Decreased neutrophils6139
Decreased hemoglobin484
1The table presents laboratory parameters with available grading according to CTCAE version 4.0. Baseline evaluation was the last non-missing value prior to first DANYELZA dosing. Each test incidence is based on the number of patients who had both a baseline value and at least one on-study laboratory measurement (range: 23 to 24 patients).

Study 12-230

In Study 12-230, among 72 patients who received DANYELZA in combination with GM-CSF, 32% were exposed for 6 months or longer and 8% were exposed for greater than one year.

Serious adverse reactions occurred in 40% of patients who received DANYELZA in combination with GM-GSF. Serious adverse reactions in > 5% of patients included hypertension (14%), hypotension (11%), and pyrexia (8%). Permanent discontinuation of DANYELZA due to an adverse reaction occurred in 8% of patients. Four (6%) patients permanently discontinued DANYELZA due to hypertension and one (1.4%) patient discontinued due to RPLS.

Table 6 summarizes adverse reactions in Study 12-230.

Table 6: Adverse Reactions (>10%) in Patients with Refractory or Relapsed High-Risk Neuroblastoma in Bone or Bone Marrow Who Received DANYELZA with GM-CSF in Study 12-230

Adverse ReactionDANYELZA with GM-CSF1,2
(n=72)
All Grades (%)Grade 3 or 4 (%)
Body system
General disorders and administration site conditions
Infusion-related reaction39432
Pain4942.8
Fatigue5440
Injection site reaction280
Localized edema250
Pyrexia6110
Vascular disorders
Hypertension287
Gastrointestinal disorders
Vomiting632.8
Nausea571.4
Diarrhea504.2
Constipation150
Skin and subcutaneous tissue disorders
Erythema multiforme330
Hyperhidrosis170
Erythema110
Respiratory, thoracic and mediastinal disorders
Cough570
Oropharyngeal pain150
Rhinorrhea150
Nervous system disorders
Peripheral neuropathy7250
Headache180
Lethargy140
Metabolism and nutrition disorders
Decreased appetite534.2
Cardiac disorders
Sinus tachycardia441.4
Psychiatric disorders
Anxiety260
Irritability250
Investigations
Breath sounds abnormal150
Injury and procedural complications
Contusion150
Infections and infestations
Rhinovirus infection140
Enterovirus infection130
Eye Disorders
Neurological disorders of the eye 8190
1In Study 12-230, all adverse reactions occurring in Cycle 1 and 2, and adverse reactions of ≥ Grade 3 severity occurring in subsequent cycles were reported. In the dose finding phase, Grade 2 unexpected adverse reactions were also reported for Cycles 3 and later.
2Adverse reactions were graded using CTCAE version 4.0.
3Infusion-related reaction includes hypotension, bronchospasm, flushing, wheezing, stridor, urticaria, dyspnea, pyrexia, face edema, periorbital edema, lip swelling, swollen tongue, chills, hypoxia, pruritis, rash maculopapular and rash erythematous occurring on the day of infusion or the day following an infusion.
4Pain includes pain, abdominal pain, pain in extremity, bone pain, neck pain, back pain, non-cardiac chest pain, flank pain, and musculoskeletal pain.
5Fatigue includes fatigue, asthenia.
6Pyrexia not occurring on the day of infusion or the day following an infusion.
7Peripheral neuropathy includes peripheral sensory neuropathy, peripheral motor neuropathy, paresthesia, neuralgia.
8Neurological disorders of the eye includes unequal pupils, blurred vision, accommodation disorder, visual impairment and photophobia.

Clinically relevant adverse reactions in ≤10% of patients who received DANYELZA with GM-CSF included apnea (4.2%), hypopnea (2.8%), generalized edema (2.8%), peripheral edema (8.3%), and device related infection (4.2%).

Table 7 summarizes the laboratory abnormalities in Study 12-230.

Table 7: Selected Laboratory Abnormalities (>20%) Worsening from Baseline in Patients with Refractory or Relapsed High-Risk Neuroblastoma in Bone or Bone Marrow Who Received DANYELZA with GM-CSF in Study 12-230

Laboratory AbnormalityDANYELZA with GM-CSF1
n=72
All Grades (%)Grade 3 or 4 (%)
Chemistry
Increased glucose740
Decreased albumin687
Decreased calcium648
Increased alanine aminotransferase559
Decreased magnesium540
Increased aspartate aminotransferase494
Decreased phosphate475
Decreased potassium4732
Decreased sodium386
Decreased glucose298
Hematology
Decreased lymphocytes7956
Decreased hemoglobin7642
Decreased neutrophils7246
Decreased platelets7140
1The table presents laboratory parameters with available grading according to CTCAE version 4.0. Baseline evaluation was the last non-missing value prior to first DANYELZA dosing. Each test incidence is based on the number of patients who had both a baseline value and at least one on-study laboratory measurement (range 19 to 72 patients).

Immunogenicity

As with all therapeutic proteins, there is a potential for immunogenicity. The detection of anti-drug antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of anti-drug 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 anti-drug antibodies in the studies described below with the incidence of anti-drug antibodies in other studies or to other naxitamab products may be misleading.

In Study 201, 2 of 24 (8%) patients tested positive for anti-drug antibodies (ADA) after treatment with DANYELZA.

In Study 12-230, 27 of 117 patients (23%) tested positive for ADA after treatment with DANYELZA by an assay that was not fully validated; therefore, the incidence of ADA may not be reliable.

Postmarketing Experience/Spontaneous Reports

The following adverse reactions have been identified from expanded access reports with use of DANYELZA. 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.

Neurological: Transverse myelitis

Read the entire FDA prescribing information for Danyelza (Naxitamab-gqgk Injection)

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

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