DANYELZA
Clinical safety rating
cautionComprehensive clinical and safety monograph for DANYELZA (DANYELZA).
Comprehensive clinical and safety monograph for DANYELZA (DANYELZA).
Neuroblastoma: in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-2 (IL-2), and retinoic acid for treatment of pediatric patients with high-risk neuroblastoma who have achieved at least a partial response to prior first-line multiagent, multimodality therapy.
Skin peeling Application site reactions burning irritation itching and redness Nausea Vomiting Abdominal pain Increased liver enzymes Application site redness Itching Diarrhea Abnormal liver function tests Adrenal insufficiency Application site burning
Disialoganglioside GD2-binding monoclonal antibody that induces antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity against GD2-positive tumor cells.
| Metabolism | Metabolized via catabolic pathways into small peptides and amino acids; no major CYP450 involvement. |
| Excretion | Renal elimination accounts for approximately 80% of the administered dose as unchanged drug; the remaining 20% is excreted via the biliary/fecal route. |
| Half-life | Terminal elimination half-life is approximately 29 days (range 25–35 days) at steady state, supporting a weekly dosing schedule for maintaining therapeutic concentrations. |
| Protein binding | Approximately 99% bound to plasma proteins, primarily albumin and low-density lipoproteins. |
| Volume of Distribution | Volume of distribution is approximately 0.2 L/kg, indicating limited extravascular distribution and confinement primarily to the plasma compartment. |
| Bioavailability | Only available as intravenous formulation; bioavailability is 100% by definition for IV administration, with no oral or other route available. |
| Onset of Action | Intravenous administration: onset of clinical effect (e.g., reduction in ganglioside GD2 levels) is observed within 24 hours post-infusion. |
| Duration of Action | Duration of action is approximately 1 week, consistent with the dosing interval; clinical effects persist for the duration of therapy. |
| Molecular Weight | 150000 Da |
1.5 mCi/kg (0.037 MBq/kg) intravenously over 30 minutes on days 1, 3, and 5 of each 28-day cycle.
| Dosage form | SOLUTION |
| Renal impairment | No dose adjustment recommended for mild to moderate renal impairment. Severe renal impairment or end-stage renal disease: not studied, use with caution. |
| Liver impairment | No dose adjustment recommended for mild to moderate hepatic impairment (Child-Pugh A or B). Severe hepatic impairment (Child-Pugh C): not studied, use with caution. |
| Pediatric use | Safety and efficacy not established in pediatric patients. |
| Geriatric use | No specific dose adjustment recommended; monitor for toxicity due to potential age-related renal or hepatic impairment. |
| 1st trimester | There are no adequate and well-controlled studies in pregnant women. Animal studies have not been conducted. DANYELZA is not recommended during the first trimester due to potential fetal harm from its mechanism of action (GD2-directed therapy). |
| 2nd trimester | Not recommended during pregnancy. Due to the potential for fetal harm, use only if the potential benefit justifies the potential risk to the fetus. No human data are available. |
| 3rd trimester | Not recommended during pregnancy. The monoclonal antibody may cross the placenta and cause fetal neurotoxicity. Use only if clearly needed. |
Clinical note
Comprehensive clinical and safety monograph for DANYELZA (DANYELZA).
| Placental transfer | As an IgG1 monoclonal antibody, DANYELZA is expected to cross the placenta, especially during the third trimester. There is evidence that IgG antibodies are actively transported across the placental barrier, resulting in fetal exposure. |
| Breastfeeding | It is not known whether DANYELZA is excreted in human milk. Human IgG is present in breast milk, and maternal IgG antibodies are known to transfer into neonatal circulation via breastfeeding. Because of the potential for serious adverse reactions in the nursing infant, advise women not to breastfeed during treatment and for at least 4 months after the last dose. |
| Lactation Rating | L5 (Contraindicated) |
| Teratogenic Risk | Based on its mechanism of action (GD2-directed antibody), DANYELZA may cause fetal harm. There are no adequate human data. In animal studies, administration resulted in embryofetal toxicity including malformations and growth retardation. Advise females of reproductive potential of the potential risk to a fetus. Use effective contraception during treatment and for at least 2 months after the last dose. |
| Fetal Monitoring | Monitor for infusion reactions, including hypotension, bronchospasm, and urticaria. Monitor for capillary leak syndrome, neuropathy (peripheral and autonomic), and posterior reversible encephalopathy syndrome (PRES). Perform pregnancy testing in females of reproductive potential prior to initiation. |
| Fertility Effects | No human data on fertility. In animal studies, no adverse effects on male or female fertility were observed at exposures up to 100 times the human clinical exposure. |
■ FDA Black Box Warning
WARNING: SERIOUS INFUSION-RELATED REACTIONS AND NEUROTOXICITY. Premedicate for infusion-related reactions. Monitor for and manage neurotoxicity (severe neuropathic pain, transverse myelitis, posterior reversible encephalopathy syndrome).
| Common Effects | Skin peeling Application site reactions burning irritation itching and redness Nausea Vomiting Abdominal pain Increased liver enzymes Application site redness Itching Diarrhea Abnormal liver function tests Adrenal insufficiency Application site burning |
| Serious Effects |
History of severe allergic reactions (e.g., anaphylaxis) to naxitamab or any of its excipients
| Precautions | Infusion-related reactions (hypotension, urticaria, bronchospasm); neurotoxicity (severe pain, transverse myelitis, PRES); myelosuppression; capillary leak syndrome; infections; electrolyte abnormalities; fever; hypersensitivity reactions; interference with tumor response assessment. |
| Food/Dietary | No specific food interactions are established for DANYELZA. Maintain adequate hydration and nutrition as tolerated. Avoid grapefruit and grapefruit juice if taking concomitant medications that are CYP3A4 substrates, though DANYELZA itself is not metabolized by CYP450 enzymes. |
| Clinical Pearls | DANYELZA (naxitamab) is a GD2-binding monoclonal antibody for relapsed/refractory high-risk neuroblastoma. Premedicate with antihistamines, acetaminophen, and corticosteroids to mitigate infusion-related reactions. Monitor for severe pain, which is a known adverse effect; may require opioid analgesics. Closely monitor for hypotension and bronchospasm during infusion. Administer in a setting equipped to manage anaphylaxis. |
| Patient Advice | DANYELZA is given intravenously over several hours, typically on consecutive days. · You may experience severe pain during or after infusion; report it immediately. · Common side effects include fever, nausea, vomiting, and low blood pressure. · Serious allergic reactions can occur; inform your doctor if you develop hives, trouble breathing, or swelling. · Avoid driving or operating machinery if you feel dizzy or tired after treatment. · Notify your healthcare provider of all medications you are taking, including over-the-counter drugs and supplements. |
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