Hypersensitivity reactions in patients treated with VYLOY in combination with fluoropyrimidine and platinum-containing chemotherapy during clinical studies were characterized by anaphylactic reaction or drug hypersensitivity. Monitor patients during and after infusion with VYLOY (at least 2 hours, or longer if clinically indicated) for hypersensitivity reactions with symptoms and signs that are highly suggestive of anaphylaxis (e.g., urticaria, repetitive cough, wheeze and throat tightness/change in voice). If an anaphylactic reaction occurs, administration of VYLOY should be immediately and permanently discontinued and appropriate medical therapy administered. 

For any Grade 3 or 4 hypersensitivity reaction or hypersensitivity reaction with features of anaphylaxis, administration of VYLOY should be immediately and permanently discontinued and appropriate medical therapy instituted based on the type of reaction. 

For any Grade 2 hypersensitivity reaction, interrupt the VYLOY infusion until Grade ≤1, then resume the infusion at a reduced infusion rate for the remaining infusion. Pre-medicate the patient with antihistamines for the next infusion, administer per the infusion rates in the Malaysia Approved Package Insert, and closely monitor the patient for symptoms and signs of a hypersensitivity reaction. The infusion rate may be gradually increased as tolerated.

Infusion-related reaction (IRR) has occurred during clinical studies with VYLOY in combination with fluoropyrimidine and platinum-containing chemotherapy. Monitor patients for signs and symptoms of infusion-related reaction including nausea, vomiting, abdominal pain, salivary hypersecretion, pyrexia, chest discomfort, chills, back pain, cough and hypertension. These signs and symptoms are usually reversible with the interruption of the infusion. For Grade 3 or 4 IRRs, administration of VYLOY should be immediately and permanently discontinued and appropriate medical therapy instituted. 

For Grade 2 IRRs, interrupt the VYLOY infusion until Grade ≤1, then resume the infusion at a reduced infusion rate for the remaining infusion. Pre-medicate the patient with antihistamines for the next infusion, administer per the infusion rates in the Malaysia Approved Package Insert, and closely monitor the patient for symptoms and signs of an IRR. The infusion rate may be gradually increased as tolerated.

During clinical studies, nausea and vomiting were the most frequently observed gastrointestinal (GI) adverse reactions with VYLOY in combination with fluoropyrimidine and platinum-containing chemotherapy treatment. 

Nausea and vomiting occurred more often during the first cycle of treatment but decreased in incidence with subsequent cycles of treatment. To prevent nausea and vomiting, pretreatment with a combination of antiemetics is recommended prior to each infusion of VYLOY. During and after infusion, patients should be monitored and managed using standard of care, including antiemetics or fluid replacement, as clinically indicated. 

For Grade 4 vomiting, permanently discontinue treatment with VYLOY. 

For Grade 2 or 3 nausea or vomiting, interrupt the VYLOY infusion until Grade ≤1, then resume at a reduced infusion rate for the remaining infusion. For the next infusion, administer per the infusion rates in the Malaysia Approved Package Insert, and closely monitor the patient for symptoms and signs of nausea or vomiting. The infusion rate may be gradually increased as tolerated.

Serious upper gastrointestinal (GI) haemorrhage has been observed in patients receiving VYLOY in combination with fluoropyrimidine and platinum-containing chemotherapy. In the clinical studies, serious upper GI haemorrhage occurred more frequently in patients receiving zolbetuximab in combination with fluoropyrimidine and platinum-containing chemotherapy [1.0% (6/631)) in comparison with patients receiving placebo in combination with fluoropyrimidine and platinum-containing chemotherapy [0.2% (1/611)]. Monitor patients for signs and symptoms of upper GI haemorrhage during treatment. Promptly evaluate and treat any suspected upper GI haemorrhage.

One event of PRES has been reported in a patient. This is a rare reversible, neurological disorder that can present with rapidly evolving symptoms including seizure, headache, confusion, visual and neurological disturbances, with or without associated hypertension and altered mental status. If PRES is suspected, it should be confirmed by brain imaging, preferably magnetic resonance imaging (MRI). Discontinuation of zolbetuximab treatment in patients who develop PRES is recommended.