Gemtuzumab Disease Interactions

Hepatotoxicity, including severe or fatal hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), has been reported in association with the use of gemtuzumab ozogamicin as a single agent, and as part of a combination chemotherapy regimen. Patients who had moderate/severe hepatic impairment prior to treatment were 8.7 times more likely to develop VOD compared to patients without moderate/severe hepatic impairment at baseline. Caution is advised in patients with hepatic impairment, with close monitoring of ALT, AST, total bilirubin, and alkaline phosphatase prior to each dose. After treatment, signs and symptoms of VOD should be monitored frequently; these may include elevations in ALT, AST, total bilirubin, hepatomegaly (which may be painful), rapid weight gain, and ascites. Monitoring only total bilirubin may not identify all patients at risk of VOD. For patients who develop abnormal liver tests, more frequent monitoring of liver tests and clinical signs and symptoms of hepatotoxicity is recommended. Treatment should be discontinued in patients that develop VOD.

Gemtuzumab ozogamicin is a myelosuppressive agent. Assess blood counts prior to each dose and monitor blood counts frequently after treatment until resolution of cytopenias. Monitor patients for signs and symptoms of bleeding during treatment with gemtuzumab ozogamicin . Manage severe bleeding, hemorrhage or persistent thrombocytopenia using dose delay or permanent discontinuation of treatment, and provide supportive care per standard practice.

QT interval prolongation has been observed in patients treated with drugs containing calicheamicin. When administering gemtuzumab ozogamicin to patients who have a history of or predisposition for QTc prolongation, who are taking medicinal products that are known to prolong QT interval, and in patients with electrolyte disturbances, obtain electrocardiograms (ECGs) and electrolytes prior to the start of treatment and as needed during administration.

The pharmacokinetics of gemtuzumab ozogamicin in patients with severe renal impairment (CrCL 15-29 mL/min) is unknown. Caution is advised if used on these patients.