TRODELVY
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TRODELVY (TRODELVY).
TRODELVY (sacituzumab govitecan) is an antibody-drug conjugate composed of a humanized anti-Trop-2 monoclonal antibody conjugated to SN-38, a topoisomerase I inhibitor. SN-38 binds to topoisomerase I-DNA complexes, preventing religation of DNA single-strand breaks, leading to DNA damage and apoptosis. The antibody targets Trop-2, a cell surface glycoprotein overexpressed in multiple cancers.
| Metabolism | SN-38 is metabolized via glucuronidation by UGT1A1 to form SN-38 glucuronide (inactive). The antibody moiety is catabolized to small peptides and amino acids. |
| Excretion | Primarily hepatobiliary excretion: ~63% of dose recovered in feces (as unchanged drug and metabolites), ~22% in urine (mostly metabolites). Less than 10% of dose excreted unchanged in urine. |
| Half-life | Terminal elimination half-life of sacituzumab govitecan (the antibody-drug conjugate) is approximately 13.2 hours. The active metabolite, SN-38, has a half-life of about 18.4 hours. The half-life supports every-21-day dosing. |
| Protein binding | SN-38 is highly protein bound (~94-95%), primarily to human serum albumin. The antibody-drug conjugate itself is also extensively protein bound. |
| Volume of Distribution | Central volume of distribution for sacituzumab govitecan is approximately 2.6 L (0.034 L/kg for a 70 kg adult). The large distribution suggests extensive tissue binding. |
| Bioavailability | Intravenous administration only (100% bioavailability). Oral bioavailability is not applicable. |
| Onset of Action | Clinical response (tumor shrinkage) typically observed after 2-3 cycles (6-9 weeks) of intravenous administration. |
| Duration of Action | Duration of response varies; median duration of response reported as approximately 7-9 months in clinical trials for metastatic triple-negative breast cancer. Treatment continues until disease progression or unacceptable toxicity. |
2.4 mg/kg IV over 3 hours on Day 1 of each 21-day cycle, followed by 0.6 mg/kg IV over 1 hour on Days 8 and 15 of each 21-day cycle.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (eGFR 30-89 mL/min). Not studied in severe renal impairment (eGFR <30 mL/min) or end-stage renal disease; use caution. |
| Liver impairment | Child-Pugh A: No dose adjustment. Child-Pugh B: Reduce dose to 1.6 mg/kg IV on Day 1 of each 21-day cycle (with same Day 8 and 15 doses of 0.4 mg/kg). Child-Pugh C: Not recommended. |
| Pediatric use | Safety and efficacy not established in pediatric patients. No recommended dosing. |
| Geriatric use | No specific dose adjustment recommended for elderly patients. Monitor for adverse reactions more frequently due to potential age-related renal or hepatic function decline. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for TRODELVY (TRODELVY).
| Breastfeeding | No data available on presence of sacituzumab govitecan or its metabolite in human milk, effects on breastfed child, or milk production. Because of potential for serious adverse reactions in breastfed infants, advise women not to breastfeed during treatment and for 1 month after last dose. M/P ratio unknown. |
| Teratogenic Risk | Based on its mechanism of action (topoisomerase I inhibitor), Trodelvy can cause fetal harm when administered to pregnant women. No adequate and well-controlled studies exist. In animal reproduction studies, administration of sacituzumab govitecan to pregnant rats during organogenesis caused embryofetal mortality and malformations at maternal exposures below the clinical dose. Advise pregnant women of potential risk to fetus. Use effective contraception during treatment and for 6 months after last dose. |
■ FDA Black Box Warning
WARNING: NEUTROPENIA AND SEVERE DIARRHEA. Neutropenia: Severe or life-threatening neutropenia may occur. Obtain blood counts prior to initiation of therapy and monitor throughout treatment. Withhold, reduce dose, or discontinue TRODELVY for severe neutropenia. Diarrhea: Severe diarrhea may occur. Monitor patients and treat with antidiarrheal agents as appropriate. Withhold, reduce dose, or discontinue TRODELVY for severe diarrhea.
| Serious Effects |
Severe hypersensitivity to sacituzumab govitecan or any of its components.
| Precautions | ["Neutropenia: Grade 3-4 neutropenia occurred in 39-45% of patients; febrile neutropenia occurred in 6-10%.","Diarrhea: Severe diarrhea occurred in 9-15% of patients; monitor and manage with loperamide, fluid replacement, and dose modifications.","Hypersensitivity reactions: including anaphylaxis; premedicate with antihistamines, antipyretics, and corticosteroids.","Nausea and vomiting: antiemetic prophylaxis recommended.","Increased risk of adverse reactions in patients with reduced UGT1A1 activity (e.g., Gilbert's syndrome).","Embryo-fetal toxicity: can cause fetal harm; advise women of reproductive potential of effective contraception."] |
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| Fetal Monitoring | Monitor complete blood counts prior to each dose due to neutropenia risk. Monitor for diarrhea and manage aggressively. Monitor liver function tests. Pregnancy testing should be performed prior to initiation in females of reproductive potential. Neonates of exposed mothers should be monitored for myelosuppression and diarrhea. |
| Fertility Effects | Based on animal studies, Trodelvy may impair fertility in females and males. In female rats, ovarian effects including decreased corpora lutea and increased atretic follicles were observed. In male rats, testicular degeneration and decreased sperm counts occurred. The reversibility of these effects is unknown. |