Trodelvy Special Precautions

Neutropenia: Severe, life-threatening, or fatal neutropenia can occur in patients treated with TRODELVY. Neutropenia occurred in 64% of patients treated with TRODELVY. Grade 3-4 neutropenia occurred in 49% of patients. Febrile neutropenia occurred in 6% of patients. The median time to first onset of neutropenia (including febrile neutropenia) was 16 days and has occurred earlier in some patient populations [see Increased Risk of Adverse Reactions in Patients with Reduced UGT1A1 Activity as follows]. Neutropenic colitis occurred in 1.4% of patients.
Withhold TRODELVY for absolute neutrophil count below 1500/mm³ on Day 1 of any cycle or neutrophil count below 1000/mm³ on Day 8 of any cycle. Withhold TRODELVY for neutropenic fever. Dose modifications may be required due to neutropenia. Administer G-CSF as clinically indicated or indicated in Table 5 [See Dose Modifications for Adverse Reactions under Dosage & Administration].
Diarrhea: TRODELVY can cause severe diarrhea. Diarrhea occurred in 64% of all patients treated with TRODELVY. Grade 3-4 diarrhea occurred in 11% of all patients treated with TRODELVY. One patient had intestinal perforation following diarrhea. Diarrhea that led to dehydration and subsequent acute kidney injury occurred in 0.7% of all patients.
Withhold TRODELVY for Grade 3-4 diarrhea at the time of scheduled treatment administration and resume when resolved to ≤Grade 1 [see Dose Modifications for Adverse Reactions under Dosage & Administration].
At the onset of diarrhea, evaluate for infectious causes and if negative, promptly initiate loperamide, 4 mg initially followed by 2 mg with every episode of diarrhea for a maximum of 16 mg daily. Discontinue loperamide 12 hours after diarrhea resolves. Additional supportive measures (e.g., fluid and electrolyte substitution) may also be employed as clinically indicated.
Patients who exhibit an excessive cholinergic response to treatment with TRODELVY (e.g., abdominal cramping, diarrhea, salivation, etc.) can receive appropriate premedication (e.g., atropine) for subsequent treatments.
Hypersensitivity and Infusion-Related Reactions: Serious hypersensitivity reactions including life-threatening anaphylactic reactions have occurred with TRODELVY treatment. Severe signs and symptoms included cardiac arrest, hypotension, wheezing, angioedema, swelling, pneumonitis, and skin reactions [see Contraindications].
Hypersensitivity reactions within 24 hours of dosing occurred in 35% of patients treated with TRODELVY. Grade 3-4 hypersensitivity occurred in 2% of patients treated with TRODELVY. The incidence of hypersensitivity reactions leading to permanent discontinuation of TRODELVY was 0.2%. The incidence of anaphylactic reactions was 0.2%.
Premedication for infusion reactions in patients receiving TRODELVY is recommended. Have medications and emergency equipment to treat infusion-related reactions, including anaphylaxis, available for immediate use when administering TRODELVY [see Recommended Dosage under Dosage & Administration].
Closely monitor patients for hypersensitivity and infusion-related reactions during each TRODELVY infusion and for at least 30 minutes after completion of each infusion [see Dose Modifications for Adverse Reactions under Dosage & Administration].
Permanently discontinue TRODELVY for Grade 4 infusion-related reactions [see Dose Modifications for Adverse Reactions under Dosage & Administration].
Nausea and Vomiting: TRODELVY is emetogenic. Nausea occurred in 64% of all patients treated with TRODELVY. Grade 3-4 nausea occurred in 3% of patients.
Vomiting occurred in 35% of all patients treated with TRODELVY. Grade 3-4 vomiting occurred in 2% of these patients.
Premedicate with a two or three drug combination regimen (e.g., dexamethasone with either a 5-HT3 receptor antagonist or an NK₁ receptor antagonist as well as other drugs as indicated) for prevention of chemotherapy-induced nausea and vomiting (CINV) [see Recommended Dosage under Dosage & Administration].
Withhold TRODELVY doses for Grade 3 nausea or Grade 3-4 vomiting at the time of scheduled treatment administration and resume with additional supportive measures when resolved to ≤Grade 1 [see Dose Modifications for Adverse Reactions under Dosage & Administration].
Additional antiemetics and other supportive measures may also be employed as clinically indicated. All patients should be given take-home medications with clear instructions for prevention and treatment of nausea and vomiting.
Increased Risk of Adverse Reactions in Patients with Reduced UGT1A1 Activity: Patients homozygous for the uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1)*28 allele are at increased risk for neutropenia, febrile neutropenia, and anemia; and may be at increased risk for other adverse reactions when treated with TRODELVY.
The incidence of neutropenia and anemia was analyzed in 948 patients who received TRODELVY and had UGT1A1 genotype results. In patients homozygous for the UGT1A1 *28 allele (n=112), the incidence of Grade 3-4 neutropenia was 58%. In patients heterozygous for the UGT1A1*28 allele (n=420), the incidence of Grade 3-4 neutropenia was 49%. In patients homozygous for the wild-type allele (n=416), the incidence of Grade 3-4 neutropenia was 43% [see Pharmacology: Pharmacogenomics under Actions]. In patients homozygous for the UGT1A1 *28 allele, the incidence of Grade 3-4 anemia was 21%. In patients heterozygous for the UGT1A1*28 allele, the incidence of Grade 3-4 anemia was 10%. In patients homozygous for the wild-type allele, the incidence of Grade 3-4 anemia was 9%.
The median time to first neutropenia including febrile neutropenia was 9 days in patients homozygous for the UGT1A1*28 allele, 15 days in patients heterozygous for the UGT1A1*28 allele, and 20 days in patients homozygous for the wild-type allele. The median time to first anemia was 21 days in patients homozygous for the UGT1A1*28 allele, 25 days in patients heterozygous for the UGT1A1*28 allele, and 28 days in patients homozygous for the wild-type allele.
Closely monitor patients with known reduced UGT1A1 activity for adverse reactions. Withhold or permanently discontinue TRODELVY based on clinical assessment of the onset, duration and severity of the observed adverse reactions in patients with evidence of acute early-onset or unusually severe adverse reactions, which may indicate reduced UGT1A1 enzyme activity [see Dose Modifications for Adverse Reactions under Dosage & Administration].
Embryo-Fetal Toxicity: Based on its mechanism of action, TRODELVY can cause teratogenicity and/or embryo-fetal lethality when administered to a pregnant woman. TRODELVY contains a genotoxic component, SN-38, and targets rapidly dividing cells [see Pharmacology: Mechanism of Action; Toxicology: Nonclinical Toxicology: Carcinogenesis, Mutagenesis, Impairment of Fertility under Actions]. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with TRODELVY and for 6 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with TRODELVY and for 3 months after the last dose [see Pregnancy; Females and Males of Reproductive Potential under Use in Pregnancy & Lactation].
Hepatic Impairment: No adjustment to the starting dosage is required when administering TRODELVY to patients with mild hepatic impairment [see Pharmacology: Pharmacokinetics under Actions]).
The safety of TRODELVY in patients with moderate (total bilirubin >1.5 to 3.0 × ULN) or severe (total bilirubin >3.0 × upper limit of normal [ULN]) hepatic impairment has not been established. TRODELVY has not been tested in patients with AST or ALT >3 ULN without liver metastases, or AST or ALT >5 ULN with liver metastases. No recommendations can be made for the starting dosage in these patients.
Use in Children: Safety and effectiveness of TRODELVY have not been established in pediatric patients.
Use in the Elderly: Of the 366 patients with TNBC who were treated with TRODELVY, 19% of patients were 65 years and 3% were 75 years and older. No overall differences in safety and effectiveness were observed between patients ≥65 years of age and younger patients.
Of the 322 patients with HR+/HER2- breast cancer who were treated with TRODELVY, 26% of patients were 65 years and older and 6% were 75 years and older. No overall differences in effectiveness were observed between patients ≥65 years of age and younger patients. There was a higher discontinuation rate due to adverse reactions in patients aged 65 years or older (14%) compared with younger patients (3%).