Version July 2025
Dosage guidance:
Clinical considerations: Zolbetuximab is associated with a high emetic potential; provide antiemetic prophylaxis with an NK-1 receptor antagonist, a 5HT3 receptor antagonist, and other antiemetics to prevent nausea and vomiting. If a patient is experiencing nausea and/or vomiting prior to administration of first infusion of zolbetuximab, ensure the symptoms are resolved to ≤ grade 1 prior to administration. Select patients for zolbetuximab treatment based on CLDN18.2 positivity in tumors (defined as ≥75% of tumor cells demonstrating moderate to strong membranous CLDN18 immunohistochemical staining).
Gastric or gastroesophageal junction adenocarcinoma, locally advanced unresectable or metastatic, HER2 negative, CLDN18.2 positive:
Initial dose: IV: 800 mg/m2 on cycle 1, day 1 (in combination with either oxaliplatin, fluorouracil, and leucovorin [mFOLFOX regimen] or oxaliplatin and capecitabine [CAPOX regimen]) (Ref).
Subsequent doses: IV: 600 mg/m2 once every 3 weeks or 400 mg/m2 once every 2 weeks; in combination with either a total of 4 cycles (each cycle is 42 days) of mFOLFOX or a total of 8 cycles of CAPOX, followed by zolbetuximab and either fluorouracil/leucovorin or capecitabine until disease progression or unacceptable toxicity (Ref).
CrCl ≥30 mL/minute: There are no dosage adjustments provided in the manufacturer’s labeling; however, there were no clinically relevant differences in zolbetuximab pharmacokinetics in patients with mild to moderate kidney impairment.
CrCl <30 mL/minute: There are no dosage adjustments provided in the manufacturer’s labeling (effect on pharmacokinetics is unknown).
Mild impairment (total bilirubin ≤ ULN and AST >ULN or total bilirubin >1 to 1.5 times ULN and any AST): There are no dosage adjustments provided in the manufacturer’s labeling; however, there were no clinically relevant differences in zolbetuximab pharmacokinetics in patients with mild hepatic impairment.
Moderate or severe impairment: There are no dosage adjustments provided in the manufacturer’s labeling (effect on pharmacokinetics is unknown).
American Society of Clinical Oncology guidelines for appropriate systemic therapy dosing in adults with cancer with a BMI ≥30 kg/m2: The dosing in the FDA-approved prescribing information should be followed in all patients, regardless of obesity status. If a patient with a BMI ≥30 kg/m2 experiences high-grade toxicity from systemic anticancer therapy, the same dosage modification recommendations should be followed for all patients, regardless of obesity status (Ref).
Note: No dosage reduction for zolbetuximab is recommended. Other concomitant anticancer therapies may also require treatment interruption, dosage reduction, and/or discontinuation.
|
Adverse reaction |
Severity |
Zolbetuximab dosage modification |
|---|---|---|
|
Hypersensitivity or infusion-related reaction |
Grade 2 |
Interrupt zolbetuximab infusion until resolves to ≤ grade 1, then resume at a reduced rate for the remainder of infusion. Premedicate with antihistamines prior to the next infusion. |
|
Grade 3 or 4, or anaphylaxis |
Immediately stop infusion and permanently discontinue zolbetuximab. Manage symptoms according to standard medical care, and monitor until symptoms resolve. | |
|
GI toxicity: Nausea and vomiting (infusion-related) |
Any |
Manage during and after infusion with antiemetics and/or fluid replacement. Based on the severity, interrupt the infusion, or permanently discontinue zolbetuximab. |
|
Grade 3 |
Interrupt zolbetuximab infusion until resolves to ≤ grade 1, then resume at a reduced rate for the remainder of infusion. |
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions are for combination fluoropyrimidine- and platinum-containing chemotherapy in adults.
>10%:
Cardiovascular: Peripheral edema (18%)
Endocrine & metabolic: Decreased serum albumin (66% to 78%), decreased serum glucose (24% to 45%), decreased serum magnesium (≥15%), decreased serum potassium (28%), decreased serum sodium (29%), increased serum glucose (≥15%), increased serum phosphate (≥15%), weight loss (20%)
Gastrointestinal: Abdominal pain (≥15%), constipation (≥15%), decreased appetite (41% to 47%), diarrhea (≥15%), nausea (69% to 82%; grades 3/4: 9% to 16%), vomiting (66% to 67%; grades 3/4: 12% to 16%)
Hematologic & oncologic: Decreased hemoglobin (≥15%), decreased platelet count (≥15%), leukopenia (66%; grades 3/4: 6%), lymphocytopenia (≥15%), neutropenia (20%; grades 3/4: 7%)
Hepatic: Increased serum alanine aminotransferase (≥15%), increased serum alkaline phosphatase (≥15%), increased serum aspartate aminotransferase (≥15%)
Hypersensitivity: Hypersensitivity reaction (18%; including anaphylaxis, infusion-related reaction [3%], severe hypersensitivity reaction [2%])
Nervous system: Fatigue (≥15%), peripheral sensory neuropathy (≥15%)
Renal: Increased serum creatinine (≥15%)
Miscellaneous: Fever (≥15%)
1% to 10%:
Cardiovascular: Pulmonary embolism (2%)
Gastrointestinal: Intestinal obstruction (3%), upper gastrointestinal bleeding (serious: 3%)
Hematologic & oncologic: Febrile neutropenia (serious: 3%)
Infection: Sepsis (2%)
Respiratory: Pneumonia (serious: 2% to 3%), respiratory failure (2%)
Frequency not defined: Cardiovascular: Hypertension
There are no contraindications listed in the manufacturer's labeling.
Concerns related to adverse effects:
• Hypersensitivity: Hypersensitivity reactions, including serious anaphylaxis reactions, and serious and fatal infusion-related reactions (IRRs) have been reported with zolbetuximab. Any grade hypersensitivity reactions, including anaphylactic reactions, occurring with zolbetuximab (in combination with oxaliplatin, fluorouracil, and leucovorin [mFOLFOX6] or oxaliplatin and capecitabine [CAPOX]) was reported in nearly one-fifth of patients. Severe (grade 3 or 4) hypersensitivity reactions, including anaphylactic reactions, occurred in a small percentage of patients. A small percentage of patients experienced IRRs (all grades) with zolbetuximab (in combination with mFOLFOX6 or CAPOX), including severe (grade 3) reactions. Hypersensitivity reactions and IRRs resulted in dosage modifications (treatment interruptions, reduced infusion rates, and/or permanent discontinuation) in some cases. Signs/symptoms of hypersensitivity that are highly suggestive of anaphylaxis include urticaria, repetitive cough, wheeze, and/or throat tightness/change in voice. Signs/symptoms of IRRs including nausea, vomiting, abdominal pain, salivary hypersecretion, pyrexia, chest discomfort, chills, back pain, cough, and/or hypertension.
• Nausea and vomiting: Zolbetuximab is emetogenic. Nausea and vomiting occurred more often during the first treatment cycle. When used in combination with mFOLFOX6 or CAPOX, nausea and vomiting (all grades) occurred in a majority of patients and grade 3 nausea and vomiting events were reported. Nausea and/or vomiting led to treatment interruption in over one-fourth of patients and permanent zolbetuximab discontinuation in a small percentage of patients. Antiemetic prophylaxis is recommended.
Dosage form specific issues:
• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Ref). Thrombocytopenia, ascites, pulmonary deterioration, and kidney and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Ref). See manufacturer's labeling.
Other warnings/precautions:
• Appropriate use: Select patients for zolbetuximab treatment if tumors are CLDN18.2-positive (defined as ≥75% of tumor cells demonstrating moderate to strong membranous CLDN18 immunohistochemical staining) and HER2-negative. Information on tests approved for detection of CLDN18.2 is available at https://www.fda.gov/CompanionDiagnostics.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous:
Vyloy: Zolbetuximab-clzb 100 mg (1 ea) [contains polysorbate 80]
Solution Reconstituted, Intravenous [preservative free]:
Vyloy: Zolbetuximab-clzb 300 mg (1 ea) [contains polysorbate 80]
No
Solution (reconstituted) (Vyloy Intravenous)
100 mg (per each): $1,920.00
300 mg (per each): $5,760.00
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Zolbetuximab is available through specialty pharmacies/distributors and various specialty institutions or accounts. Examples from the manufacturer may be found at https://www.vyloysupportsolutions.com.
IV: For IV infusion only; do not administer as IV push or bolus. Inline filters (pore size 0.2 micron) are recommended during infusion. Do not infuse other medications in same line with zolbetuximab.
|
Zolbetuximab dose |
Initial infusion rate (first 30 to 60 minutes)a |
Subsequent infusion rate | |
|---|---|---|---|
|
a In the absence of adverse reactions, after 30 to 60 minutes, may increase the infusion rate to the subsequent infusion rate as tolerated. | |||
|
First dose |
800 mg/m2 |
100 mg/m2/houra |
200 to 265 mg/m2/hour |
|
Subsequent doses |
600 mg/m2 every 3 weeks |
75 mg/m2/houra |
150 to 265 mg/m2/hour |
|
400 mg/m2 every 2 weeks |
50 mg/m2/houra |
100 to 200 mg/m2/hour | |
Zolbetuximab is associated with a high emetic potential; provide antiemetic prophylaxis with an NK-1 receptor antagonist, a 5HT3 receptor antagonist, and other antiemetics to prevent nausea and vomiting.
Monitor during zolbetuximab infusion and for 2 hours after completion of infusion (or longer if clinically indicated) for signs/symptoms of hypersensitivity reactions or anaphylaxis (eg, urticaria, repetitive cough, wheeze, and throat tightness/change in voice). Monitor for signs and symptoms of infusion-related reactions (IRRs) (eg, nausea, vomiting, abdominal pain, salivary hypersecretion, pyrexia, chest discomfort, chills, back pain, cough, and/or hypertension). Hypersensitivity or IRRs may require infusion interruption or discontinuation and symptom management.
Administration sequence: If administering on the same day as fluoropyrimidine and platinum-containing chemotherapy, administer zolbetuximab first.
Zolbetuximab infusion solution is compatible with IV tubing composed of polyethylene (PE), polyvinyl chloride (PVC; with DEHP, or trioctyl trimellitate [TOTM], or di(2-ethylhexyl) terephthalate plasticizers), polybutadiene (PB), or elastomer modified polypropylene (PP) with in-line filter membranes composed of polyethersulfone (PES) or polysulfone. No incompatibilities have been observed with closed system transfer devices composed of PP, PE, stainless steel, silicone (rubber/oil/resin), polyisoprene, PVC with TOTM plasticizer, acrylonitrile-butadiene-styrene (ABS) copolymer, methyl methacrylate-ABS copolymer, thermoplastic elastomer, polytetrafluoroethylene, polycarbonate, PES, acrylic copolymer, polybutylene terephthalate, PB, or EVA copolymer. Incompatibilities have not been observed with central ports composed of silicone rubber, titanium alloy or PVC with TOTM plasticizer.
Gastric or gastroesophageal junction adenocarcinoma, locally advanced unresectable or metastatic, HER2 negative, CLDN18.2 positive: First-line treatment (in combination with fluoropyrimidine-and platinum-containing chemotherapy) of locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)–negative gastric or gastroesophageal junction adenocarcinoma, in adults whose tumors are claudin (CLDN) 18.2-positive, as determined by an approved test.
Vyloy may be confused with Yervoy.
Zolbetuximab may be confused with brentuximab vedotin, cetuximab, dinutuximab, isatuximab, loncastuximab tesirine, margetuximab, mirvetuximab soravtansine, rituximab, siltuximab, ublituximab.
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (chemotherapeutic agent, parenteral and oral) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care, Community/Ambulatory Care, and Long-Term Care Settings).
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Efgartigimod Alfa: May decrease therapeutic effects of Fc Receptor-Binding Agents. Risk C: Monitor
Nipocalimab: May decrease therapeutic effects of Fc Receptor-Binding Agents. Risk C: Monitor
Rozanolixizumab: May decrease therapeutic effects of Fc Receptor-Binding Agents. Risk C: Monitor
Zolbetuximab is used in combination with fluoropyrimidine- or platinum-containing chemotherapy; refer to individual monographs for pregnancy testing and contraception recommendations.
Adverse events were not observed in animal reproduction studies conducted in mice with doses ~1.9 times the recommended human dose (based on AUC).
Zolbetuximab is a chimeric mouse/human monoclonal antibody (IgG1) that may cross the placenta. Fetal exposure is dependent upon the IgG subclass, maternal serum concentrations, placental integrity, newborn birth weight, and GA, generally increasing as pregnancy progresses. The lowest exposure would be expected during the period of organogenesis and the highest during the third trimester (Ref).
It is not known if zolbetuximab is present in breast milk.
Zolbetuximab is a chimeric mouse/human monoclonal antibody (IgG1). Human IgG is present in breast milk; concentrations are dependent upon IgG subclass and postpartum age (Ref).
Due to the potential for adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during therapy and for 8 months after the last dose of zolbetuximab.
Assess Claudin 18.2 positivity (prior to treatment). Monitor during zolbetuximab infusion and for 2 hours after completion of infusion (or longer if clinically indicated, for signs/symptoms of hypersensitivity reactions or anaphylaxis (eg, urticaria, repetitive cough, wheeze, and throat tightness/change in voice). Monitor for signs and symptoms of IRRs (eg, nausea, vomiting, abdominal pain, salivary hypersecretion, pyrexia, chest discomfort, chills, back pain, cough, and/or hypertension). Monitor for nausea and vomiting.
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Zolbetuximab is a chimeric monoclonal antibody that targets claudin 18 isoform 2 (CLDN18.2); CLDN18.2 is a protein expressed in normal gastric mucosal cells, and is retained in most gastric and gastroesophageal junction adenocarcinomas (Ref). Zolbetuximab binds to CLDN18.2 leading to antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity (Ref). In CLDN18.2-expressing animal tumor models, the combination of zolbetuximab and chemotherapy had increased antitumor activity, compared to either zolbetuximab or chemotherapy alone.
Distribution: Vdss: 14 L.
Metabolism: Zolbetuximab is expected to be catabolized into small peptides and amino acids.
Half-life elimination: 41 days.
Excretion: Clearance: 0.013 L/hour.
