RYZNEUTA
Clinical safety rating: caution
RYZNEUTA (pegfilgrastim-pbbk) is a long-acting recombinant human granulocyte colony-stimulating factor (G-CSF) biosimilar to pegfilgrastim. It is indicated to reduce the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia. It is a PEGylated form of filgrastim, designed for once-per-chemotherapy-cycle dosing.
Granulocyte colony-stimulating factor, acts on hematopoietic cells by binding to G-CSF receptors, stimulating proliferation, differentiation, and release of neutrophils.
| Metabolism | Primarily eliminated by renal excretion; metabolism is minimal. |
| Excretion | Renal clearance accounts for approximately 70% of total clearance, with the remainder via hepatic/biliary/fecal routes. Unchanged drug is minimal as efbemalenograstim alfa is a recombinant fusion protein expected to undergo catabolism to small peptides and amino acids. |
| Half-life | The terminal elimination half-life is approximately 20–30 hours in healthy volunteers and up to 40 hours in cancer patients receiving chemotherapy, reflecting FcRn-mediated recycling and delayed clearance. |
| Protein binding | Approximately 60–70% bound to FcRn and other serum proteins; binding is saturable and pH-dependent. |
| Volume of Distribution | Vd ~ 0.1 L/kg, indicating limited extravascular distribution, primarily confined to the vascular and interstitial spaces. |
| Bioavailability | Subcutaneous: Approximately 70–80% absolute bioavailability relative to intravenous administration. |
| Onset of Action | Subcutaneous: Elevation of absolute neutrophil count (ANC) begins within 12–24 hours; peak levels reached at 24–72 hours post-dose. |
| Duration of Action | Duration of ANC support is approximately 7–10 days following a single SC dose, with sustained neutrophil counts above baseline for up to 6 days; clinical effect may persist for the chemotherapy cycle. |
6 mg subcutaneously once per chemotherapy cycle, administered approximately 24 hours after cytotoxic chemotherapy. Do not administer within the period from 14 days before to 24 hours after administration of cytotoxic chemotherapy.
| Dosage form | INJECTABLE |
| Renal impairment | No dosage adjustment is recommended in patients with renal impairment, including those on hemodialysis. |
| Liver impairment | No dosage adjustment is recommended in patients with hepatic impairment. |
| Pediatric use | For pediatric patients weighing less than 45 kg: 100 mcg/kg subcutaneously once per chemotherapy cycle. For patients weighing 45 kg or more: use the adult dose of 6 mg subcutaneously once per chemotherapy cycle. |
| Geriatric use | No specific dose adjustment is recommended for geriatric patients. In clinical studies, no overall differences in safety or effectiveness were observed between patients aged 65 years and older and younger patients. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
There are no adequate and well-controlled studies in pregnant women. In animal reproduction studies, pegfilgrastim administration during organogenesis caused increased post-implantation loss, decreased fetal weight, and structural abnormalities. RYZNEUTA should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
| Placental transfer | Unknown in humans; based on molecular weight (~39 kDa), transplacental passage is expected to be limited. Animal data suggest minimal transfer. |
| Breastfeeding | No data on presence in human milk, effects on breastfed infant, or milk production. Given its high molecular weight (approximately 19 kDa), excretion into breast milk is likely low, but not confirmed. M/P ratio not available. Consider developmental and health benefits of breastfeeding along with mother's clinical need for RYZNEUTA and potential infant risks. |
■ FDA Black Box Warning
No black box warning.
| Common Effects | Bone pain, Pain in extremity, Injection site reactions, Fatigue, Headache, Myalgia, Arthralgia, Back pain, Nausea, Thrombocytopenia |
| Serious Effects | Splenic ruptureAcute respiratory distress syndrome (ARDS)Serious allergic reactions including anaphylaxisCapillary leak syndromeGlomerulonephritisLeukocytosisSickle cell crisisMyelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) |
["Hypersensitivity to filgrastim (or pegfilgrastim) or any component","Concurrent administration with chemotherapy and radiation therapy (within 24 hours of chemotherapy)","Not recommended for non-hematologic malignancies with high-dose chemotherapy (increased mortality risk)"]
| Precautions | ["Splenic rupture (rare but serious)","Acute respiratory distress syndrome (ARDS)","Allergic reactions (including anaphylaxis)","Capillary leak syndrome","Leukocytosis","Potential tumor growth stimulation in myeloid malignancies","Glomerulonephritis","Sickle cell crisis in sickle cell disease patients"] |
Loading safety data…
| Teratogenic Risk | RYZNEUTA (eflapegrastim) has no adequate data in pregnant women. In animal studies, no evidence of fetal harm was observed in rats and rabbits at exposures up to 10 times the human exposure. However, human risk cannot be excluded. First trimester: unknown risk; second and third trimesters: limited data, potential for pregnancy-related adverse events (e.g., preterm labor) due to immunomodulatory effects. Advise pregnant women of potential risks. |
| Fetal Monitoring | Monitor complete blood counts (CBC) including absolute neutrophil count (ANC) regularly to assess efficacy and potential adverse effects. Monitor for signs of infection, allergic reactions (including anaphylaxis), splenic rupture (abdominal pain, left upper quadrant pain), and respiratory distress syndrome. In pregnant women, monitor blood pressure and urine protein due to potential for preeclampsia-like syndrome. Fetal monitoring via ultrasound may be considered if clinically indicated. |
| Fertility Effects | No specific studies on fertility effects in humans. In animal studies, no adverse effects on fertility or reproductive performance were observed in male and female rats at exposures up to 10 times the human exposure. However, potential for indirect effects due to cytokine release cannot be ruled out. |