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 liver dysfunction prior to treatment were 8.7 times more likely to develop VOD compared to those without moderate/severe liver dysfunction at baseline, and patients treated with gemtuzumab ozogamicin for relapse after hematopoietic stem cell transplantation (HSCT) were 2.6 times more likely to develop VOD compared to those without prior HSCT. ALT, AST, total bilirubin, and alkaline phosphatase should be assessed prior to each dose of gemtuzumab ozogamicin. After treatment with this drug, patients should be monitored frequently for signs/symptoms of VOD; 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/symptoms of hepatotoxicity is recommended. Treatment should be discontinued in patients who develop VOD. The pharmacokinetics of gemtuzumab ozogamicin in patients with moderate (total bilirubin greater than 1.5 to 3 times the upper limit of normal [1.5 to 3 x ULN]) or severe (total bilirubin greater than 3 x ULN) liver dysfunction are unknown; mild liver dysfunction had no clinically significant effect on the pharmacokinetics of this drug.

Gemtuzumab ozogamicin is a myelosuppressive agent and can cause fatal or life-threatening hemorrhage due to prolonged thrombocytopenia. Blood counts should be assessed prior to each dose of this drug and monitored frequently after treatment until resolution of cytopenias. Patients should be monitored for signs/symptoms of bleeding during treatment with gemtuzumab ozogamicin. Severe bleeding, hemorrhage, or persistent thrombocytopenia should be managed using dose delay or permanent discontinuation of this drug, and supportive care should be provided per standard practice.

QT interval prolongation has been observed in patients treated with other 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, ECGs and electrolytes should be obtained prior to the start of treatment and as needed during administration.

The pharmacokinetics of gemtuzumab ozogamicin in patients with severe renal dysfunction (CrCl 15 to 29 mL/min) are unknown. Mild or moderate renal dysfunction (CrCl 30 to 89 mL/min [calculated by Cockcroft-Gault equation]) had no clinically significant effect on the pharmacokinetics of this drug.