SACITUZUMAB GOVITECAN Drug Interactions: What You Need to Know

INTERACTIONS UGT1A1 inhibitors or inducers: Avoid concomitant use. ( 7 )

7.1 Effect of Other Drugs on TRODELVY UGT1A1 Inhibitors Concomitant administration of TRODELVY with inhibitors of UGT1A1 may increase the incidence of adverse reactions due to potential increase in systemic exposure to SN-38 <span class="opacity-50 text-xs">[see Warning and Precaution (5.5) and Clinical Pharmacology (12.3 , 12.5) ]</span> . Avoid administering UGT1A1 inhibitors with TRODELVY. UGT1A1 Inducers Exposure to SN-38 may be reduced in patients concomitantly receiving UGT1A1 enzyme inducers <span class="opacity-50 text-xs">[see Warning and Precaution (5.5) and Clinical Pharmacology (12.3 , 12.5) ]</span> . Avoid administering UGT1A1 inducers with TRODELVY.

TRODELVY is contraindicated in patients who have experienced a severe hypersensitivity reaction to TRODELVY [see Warnings and Precautions (5.3) ] . Severe hypersensitivity reaction to TRODELVY. ( 4 , 5.3 )

AND PRECAUTIONS Hypersensitivity and Infusion-Related Reactions: Hypersensitivity reactions including severe anaphylactic reactions have been observed. Monitor patients for infusion-related reactions. Permanently discontinue TRODELVY if severe or life-threatening reactions occur. ( 5.3 ) Nausea/Vomiting: Use antiemetic preventive treatment and withhold TRODELVY for patients with Grade 3 nausea or Grade 3–4 vomiting at the time of scheduled treatment. ( 5.4 ) Patients with Reduced UGT1A1 Activity: Individuals who are homozygous for the uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1)*28 allele are at increased risk for neutropenia, febrile neutropenia, and anemia following initiation of TRODELVY treatment. ( 5.5 ) Embryo-Fetal Toxicity: TRODELVY can cause fetal harm. Advise patients of potential risk to a fetus and to use effective contraception. ( 5.6 , 8.1 , 8.3 )

5.1 Neutropenia TRODELVY can cause severe, life-threatening, or fatal neutropenia as early as the first cycle of treatment. 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 (range: 1 to 435 days). Neutropenia occurred earlier in patients with reduced UGT1A1 activity [see Warnings and Precautions (5.5) ] . Neutropenic colitis occurred in 1.4% of patients. Primary prophylaxis with G-CSF is recommended starting in the first cycle of treatment in all patients at increased risk of febrile neutropenia, including older patients, patients with previous neutropenia, poor performance status, organ dysfunction, or multiple comorbidities. Monitor absolute neutrophil count (ANC) during treatment. Withhold TRODELVY for ANC below 1500/mm 3 on Day 1 of any cycle or below 1000/mm 3 on Day 8 of any cycle. Withhold TRODELVY for neutropenic fever. Dose modifications may be required due to neutropenia. Treat neutropenia with G-CSF and administer prophylaxis in subsequent cycles as clinically indicated or indicated in Table 2 [see Dosage and Administration (2.3) ] .

5.2 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 Dosage and Administration (2.3) ]. 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.

5.3 Hypersensitivity and Infusion-Related Reactions TRODELVY can cause serious hypersensitivity reactions including life-threatening anaphylactic reactions. Severe signs and symptoms included cardiac arrest, hypotension, wheezing, angioedema, swelling, pneumonitis, and skin reactions <span class="opacity-50 text-xs">[see Contraindications (4) ]</span> . 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 Dosage and Administration (2.2) ]. 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 Dosage and Administration (2.3) ] . Permanently discontinue TRODELVY for Grade 4 infusion-related reactions [see Dosage and Administration (2.3) ] .

5.4 Nausea and Vomiting TRODELVY is emetogenic and can cause severe nausea and vomiting. 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 NK 1 receptor antagonist as well as other drugs as indicated) for prevention of chemotherapy-induced nausea and vomiting (CINV) [ see Dosage and Administration (2.2) ]. 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 Dosage and Administration (2.3) ]. 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.

5.5 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% <span class="opacity-50 text-xs">[see Clinical Pharmacology (12.5) ]</span> . 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 <span class="opacity-50 text-xs">[see Dosage and Administration (2.3) ]</span>.

5.6 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 <span class="opacity-50 text-xs">[see Clinical Pharmacology (12.1) and Nonclinical Toxicology (13.1) ]</span>. 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 <span class="opacity-50 text-xs">[see Use in Specific Populations (8.1 , 8.3) ]</span> .