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. |
| Molecular Weight | 1809.1 Da |
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 | Avoid. There are no adequate human data; based on mechanism of action, it may cause fetal harm. Animal studies are lacking. |
| 2nd trimester | Avoid. Same risks as first trimester; fetal toxicity anticipated. |
| 3rd trimester | Avoid. Potential for myelosuppression and severe adverse effects in the neonate. |
Clinical note
Comprehensive clinical and safety monograph for TRODELVY (TRODELVY).
| Placental transfer | Expected to cross the placenta due to low molecular weight and high lipid solubility; no human data available. |
| Breastfeeding | No human data. Due to potential for serious adverse reactions in nursing infants, advise women not to breastfeed during treatment and for at least 1 month after the last dose. |
| Lactation Rating |
■ 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 excipients
| 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. |
| Food/Dietary |
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| L5 (Contraindicated) |
| 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. |
| 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. |
| Avoid grapefruit, grapefruit juice, and Seville oranges (bitter oranges) because they may increase the risk of side effects. No other food restrictions are recommended. |
| Clinical Pearls | Premedicate with antipyretics, antihistamines, and antiemetics prior to infusion to reduce infusion-related reactions. Monitor for neutropenia; consider G-CSF in high-risk patients. TRODELVY (sacituzumab govitecan) is an antibody-drug conjugate targeting Trop-2, and it can cause severe diarrhea (both early-onset and late-onset). Manage diarrhea promptly with loperamide or other antidiarrheals, and consider dose interruption or reduction for severe cases. Uridine triacetate is the specific antidote for overdose, but not indicated for routine management. Do not use in patients with moderate or severe hepatic impairment. |
| Patient Advice | Tell your doctor right away if you have diarrhea, especially if it is watery or bloody, or if you have stomach pain or fever. · You may have low white blood cell counts; wash hands often, avoid crowds or people sick with infection, and report fever or chills immediately. · Nausea, vomiting, and loss of appetite are common; your doctor will give you medicines to help prevent these. · Do not breast-feed during treatment and for 1 month after your last dose. · Use effective contraception during treatment and for at least 6 months after the last dose if you are a woman of childbearing age. · Avoid grapefruit, grapefruit juice, and Seville oranges (bitter oranges) during treatment. · Tell your doctor about all medicines you take, including prescription, over-the-counter, vitamins, and herbal products. |