MYLOTARG
Clinical safety rating: caution
Comprehensive clinical and safety monograph for MYLOTARG (MYLOTARG).
Gemtuzumab ozogamicin is a CD33-directed antibody-drug conjugate (ADC). The antibody portion binds to CD33 antigen expressed on leukemic cells, leading to internalization of the ADC. The conjugated calicheamicin derivative is released intracellularly, binds to DNA, and causes double-strand breaks, inducing apoptosis.
| Metabolism | Metabolized by non-CYP450 pathways; the calicheamicin derivative is primarily metabolized via nonenzymatic reduction. |
| Excretion | Primarily via biliary/fecal elimination (90%); renal excretion accounts for <10% of the administered dose as unchanged drug. |
| Half-life | Terminal elimination half-life is approximately 2.4 days (range 1.5–4.1 days), supporting a 3-week dosing interval. |
| Protein binding | 99% bound primarily to albumin and, to a lesser extent, α1-acid glycoprotein. |
| Volume of Distribution | Vd approximately 0.4–0.6 L/kg, indicating distribution into total body water and limited tissue binding. |
| Bioavailability | Not applicable; administered exclusively as an intravenous infusion. |
| Onset of Action | Intravenous: Clinical effect (e.g., bone marrow blast reduction) typically observed within 2–4 weeks after the first dose. |
| Duration of Action | Duration of response (e.g., remission) varies; median progression-free survival approximately 4–6 months in clinical trials. Continuous monitoring required. |
3 mg/m^2 intravenously on days 1, 4, and 7 for induction; 3 mg/m^2 intravenously on day 1 of each subsequent cycle for consolidation (up to 2 cycles).
| Dosage form | VIAL |
| Renal impairment | No dose adjustment recommended; monitor renal function periodically. |
| Liver impairment | Child-Pugh Class B: reduce dose to 2 mg/m^2; Child-Pugh Class C: avoid use (no safety data). |
| Pediatric use | Not established; safety and efficacy not assessed in pediatric patients. |
| Geriatric use | No specific dose adjustment; monitor for myelosuppression and hepatotoxicity. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for MYLOTARG (MYLOTARG).
| Breastfeeding | No data on presence in human milk, effects on breastfed infant, or milk production. M/P ratio unknown. Because of potential for serious adverse reactions in nursing infant (e.g., myelosuppression), advise women not to breastfeed during treatment and for at least 1 month after last dose. |
| Teratogenic Risk | Pregnancy category D. First trimester: Based on mechanism (anti-CD33 antibody-drug conjugate targeting CD33-positive cells, with calicheamicin toxin), there is embryo-fetal risk; avoid use. Second and third trimesters: Associated with severe fetal neutropenia and thrombocytopenia; mylotarg crosses placenta; cases of fetal myelosuppression reported. Contraindicated in pregnancy unless benefit outweighs risk. |
■ FDA Black Box Warning
Hepatotoxicity, including severe or fatal hepatic veno-occlusive disease (VOD). Hepatic venous-occlusive disease (VOD) occurred in patients with and without prior hematopoietic stem cell transplant (HSCT). Patients who receive MYLOTARG have an increased risk of VOD, especially those with prior HSCT, those with moderate or severe hepatic impairment, and those who receive MYLOTARG within 3.5 months after HSCT.
| Serious Effects |
["Known hypersensitivity to gemtuzumab ozogamicin or any component of the product."]
| Precautions | ["Hepatotoxicity: Monitor liver function tests; discontinue or interrupt for severe liver injury.","Hepatic veno-occlusive disease (VOD): Increased risk with prior HSCT, hepatic impairment, or use within 3.5 months after HSCT.","Infusion-related reactions: Premedicate and monitor during infusion; interrupt or discontinue for severe reactions.","Hemorrhage: Monitor platelet counts; bleeding events may occur.","Prolonged QT interval: Monitor electrolytes and ECG in patients at risk.","Fetal harm: Can cause fetal harm; advise women of reproductive potential of risk."] |
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| Fetal Monitoring | Monitor complete blood counts (CBC) with differential and platelets at baseline and weekly during treatment. Monitor liver function tests (ALT, AST, bilirubin, alkaline phosphatase) and serum creatinine at minimum monthly. Assess for signs of infection, bleeding, or anemia. In pregnancy, monitor fetal growth via ultrasound and consider fetal blood sampling for cytopenias if clinically indicated. |
| Fertility Effects | No dedicated fertility studies. Based on animal studies, mylotarg may impair male and female fertility. In rats, testicular degeneration and ovarian atrophy observed at clinically relevant doses. Advise patients of potential impact on reproductive capacity; consider fertility preservation before treatment. |