DANYELZA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DANYELZA (DANYELZA).
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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for DANYELZA (DANYELZA).
| Breastfeeding | No data on presence in human milk, effects on breastfed infant, or effects on milk production. Because of the potential for serious adverse reactions, advise women not to breastfeed during treatment and for at least 2 months after the last dose. |
| 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. |
■ 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 |
None known.
| 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. |
Loading safety data…
| 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. |