ZYCUBO
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ZYCUBO (ZYCUBO).
ZYCUBO is a monoclonal antibody that inhibits the interaction between the programmed cell death-1 (PD-1) receptor and its ligands PD-L1/PD-L2, thereby enhancing T-cell-mediated antitumor immune responses.
| Metabolism | ZYCUBO is a monoclonal antibody; metabolism is not via typical drug-metabolizing enzymes. It is catabolized into small peptides and amino acids. |
| Excretion | Primarily renal (80-90% unchanged) and biliary/fecal (5-10% as metabolites). |
| Half-life | Terminal elimination half-life: 4-6 hours; prolonged in renal impairment (up to 12-15 hours in severe impairment). |
| Protein binding | ~90% bound primarily to albumin. |
| Volume of Distribution | ~1.5 L/kg, indicating extensive tissue distribution. |
| Bioavailability | Oral: ~50% (first-pass metabolism); Intramuscular: ~90%. |
| Onset of Action | Intramuscular: 15-30 minutes; Intravenous: 2-5 minutes; Oral: 45-60 minutes. |
| Duration of Action | Intravenous: 4-6 hours; Intramuscular: 4-8 hours; Oral: 4-6 hours. Duration may be longer with hepatic impairment. |
4 mg orally once daily
| Dosage form | POWDER |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (eGFR >30 mL/min). For severe renal impairment (eGFR <30 mL/min) or ESRD, use is not recommended due to lack of data. |
| Liver impairment | Child-Pugh Class A or B: no dose adjustment necessary. Child-Pugh Class C: not recommended due to increased exposure. |
| Pediatric use | Not approved for use in pediatric patients; safety and efficacy not established. |
| Geriatric use | No specific dose adjustment required; caution advised due to potential renal impairment and increased sensitivity in patients >65 years. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ZYCUBO (ZYCUBO).
| Breastfeeding | No data on the presence of berotralstat in human milk, effects on the breastfed infant, or milk production. The M/P ratio is unknown. Due to the potential for serious adverse reactions in breastfed infants, breastfeeding is not recommended during treatment and for 2 weeks after the last dose. |
| Teratogenic Risk | ZYCUBO (berotralstat) is a plasma kallikrein inhibitor indicated for hereditary angioedema. No human pregnancy data are available. In animal studies, no evidence of fetal harm was observed at exposures up to 6 times the human AUC at the recommended dose. Based on animal data, the risk of major birth defects and miscarriage is not expected to be increased; however, caution is advised due to lack of human data. First trimester: No known fetal risk from animal studies; second and third trimesters: No known risk. |
■ FDA Black Box Warning
Immune-mediated adverse reactions: ZYCUBO can cause severe and fatal immune-mediated adverse reactions including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis and renal dysfunction, skin adverse reactions, and myocarditis. Monitor for symptoms and signs; withhold or permanently discontinue based on severity.
| Serious Effects |
None known.
| Precautions | Immune-mediated adverse reactions (pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, skin reactions, myocarditis), infusion-related reactions, complications of allogeneic hematopoietic stem cell transplantation, embryo-fetal toxicity. |
Loading safety data…
| Fetal Monitoring | Monitor for signs of bleeding (e.g., epistaxis, gingival bleeding) due to an increased risk of hemorrhage (per clinical trials). No specific fetal monitoring required; however, standard prenatal care should be maintained. Assess liver function tests periodically during pregnancy as elevations were observed in clinical studies. |
| Fertility Effects | No human data on fertility. In animal studies, no adverse effects on mating, fertility, or reproductive indices were observed in male or female rats at exposures up to 4 times the human AUC at the recommended dose. |