Dosing & Uses
Dosage Forms & Strengths
injection, lyophilized powder for reconstitution
- 180mg/vial
Breast Cancer
Triple-negative breast cancer
- Indicated for unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) in adults who have received ≥2 prior systemic therapies, at least one of them for metastatic disease
- Each cycle is 21 days
- Days 1 and 8: 10 mg/kg IV
- Continue treatment until disease progression or unacceptable toxicity
- Do not administer doses >10 mg/kg
HR-positive, HER2-negative breast cancer
- Indicated for unresectable locally advanced or metastatic hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative (IHC 0, IHC 1+ or IHC 2+/ISH–) breast cancer in adults who have received endocrine-based therapy and at least 2 additional systemic therapies in the metastatic setting
- Each cycle is 21 days
- Days 1 and 8: 10 mg/kg IV
- Continue treatment until disease progression or unacceptable toxicity
- Do not administer doses >10 mg/kg
Urothelial Cancer
Indicated for locally advanced or metastatic urothelial cancer (mUC) in adults previously treated with platinum-containing chemotherapy and either programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor
Each cycle is 21 days
Continue treatment until disease progression or unacceptable toxicity
Do not administer doses >10 mg/kg
Dosage Modifications
Infusion-related reactions
- Infusion-related reactions develop: Slow infusion rate or interrupt dose
- Life-threatening infusion-related reactions: Permanently discontinue
Severe neutropenia
-
Categorized as
- Grade 4 neutropenia ≥7 days, OR
- Grade 3 febrile neutropenia (absolute neutrophil count [ANC] <1,000/mm3 and fever ≥38.5ºC), OR
- At time of scheduled treatment, Grade 3-4 neutropenia that delay dose by 2-3 weeks for recovery to Grade ≤1
-
Recommended dose modifications
- First occurrence: 25% dose reduction and administer granulocyte colony-stimulating factor (G-CSF)
- Second occurrence: 50% dose reduction and administer G-CSF
- Third occurrence: Discontinue treatment and administer G-CSF
- At time of scheduled treatment, Grade 3-4 neutropenia that delay dose >3 weeks for recovery to Grade ≤1: Discontinue treatment
Severe non-neutropenic or nonhematologic toxicity
-
Categorized as
- Grade 4 nonhematologic toxicity of any duration, OR
- Any Grade 3-4 nausea, uncontrolled vomiting or diarrhea due to treatment that is refractory to antiemetics and antidiarrheal agents, OR
- Other Grade 3-4 nonhematologic toxicity persisting >48 hr despite optimal medical management, OR
- At time of scheduled treatment, Grade 3-4 toxicity that delay dose by 2-3 weeks for recovery to Grade ≤1
-
Recommended dose modifications
- First occurrence: 25% dose reduction
- Second occurrence: 50% dose reduction
- Third occurrence: Discontinue treatment
- Grade 3-4 non-neutropenic hematologic or non-hematologic toxicity that does not recover to Grade ≤1 within 3 weeks: Discontinue treatment
Renal impairment
- No data on pharmacokinetic of sacituzumab in renal impairment patients
Hepatic impairment
- Mild (serum bilirubin ≤1.5x ULN and AST/ALT <3x ULN): No dosage adjustment necessary
- Moderate-to-severe (serum bilirubin >1.5x ULN, or AST and ALT >3x ULN, OR AST and ALT >5x ULN and associated with liver metastases): Safety not established; no recommendations on starting dose
Dosing Considerations
Do NOT substitute for or use with other drugs containing irinotecan or its active metabolite SN-38
Verify pregnancy status in females of reproductive potential before initiation
Glioblastoma (Orphan)
Orphan designation for treatment of malignant glioma in adults and pediatric patients
Sponsor
- Immunomedicis, Inc. 300 The American Rd. Morris Plains, New Jersey 07950
Safety and efficacy not established
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (0)
Serious - Use Alternative (0)
Monitor Closely (1)
- siponimod
siponimod and sacituzumab govitecan both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.
Minor (0)
Adverse Effects
>10%
All grades
- Decreased hemoglobin (93%)
- Decreased leukocytes (91%)
- Decreased neutrophils (82%)
- Increased activated partial thromboplastin time (60%)
- Neutropenia (64%)
- Nausea (69%)
- Diarrhea (63%)
- Fatigue (57%)
- Increased alkaline phosphatase (57%)
- Anemia (52%)
- Decreased magnesium (51%)
- Decreased calcium (49%)
- Vomiting (49%)
- Increased glucose (48%)
- Increased AST (45%)
- Decreased albumin (39%)
- Alopecia (38%)
- Increased ALT (35%)
- Constipation (34%)
- Rash (31%)
- Decreased platelets (30%)
- Decreased appetite (30%)
- Decreased potassium (30%)
- Decreased phosphate (29%)
- Abdominal pain (26%)
- Respiratory tract infection (26%)
- Decreased sodium (25%)
- Increased magnesium (24%)
- Hyperglycemia (24%)
- Neuropathy (24%)
- Headache (23%)
- Back pain (23%)
- Dizziness (22%)
- Cough (22%)
- Dyspnea (21%)
- Hypomagnesemia (21%)
- Urinary tract infection (21%)
- Decreased glucose (19%)
- Hypokalemia (19%)
- Edema (19%)
- Pruritus (17%)
- Arthralgia (17%)
- Hypophosphatemia (16%)
- Dry skin (15%)
- Pyrexia (14%)
- Mucositis (14%)
- Thrombocytopenia (14%)
- Insomnia (13%)
- Dehydration (13%)
- Dysgeusia (11%)
- Pain in extremity (11%)
Grade 3-4
- Neutropenia (43%)
- Decreased neutrophils (32%)
- Decreased leukocytes (26%)
- Anemia (12%)
- Increased activated partial thromboplastin time (12%)
1-10%
Grade 3-4
- Diarrhea (9%)
- Hypophosphatemia (9%)
- Fatigue (8%)
- Nausea (6%)
- Vomiting (6%)
- Decreased hemoglobin (6%)
- Decreased phosphate (5%)
- Dehydration (5%)
- Decreased sodium (4.7%)
- Hyperglycemia (4%)
- Increased magnesium (4%)
- Thrombocytopenia (3%)
- Rash (3%)
- Urinary tract infection (3%)
- Respiratory tract infection (3%)
- Dyspnea (3%)
- Decreased platelets (3%)
- Decreased magnesium (3%)
- Decreased calcium (3%)
- Increased glucose (3%)
- Increased AST (3%)
- Decreased potassium (3%)
- Hypokalemia (2%)
- Increased alkaline phosphatase (2%)
- Increased ALT (2%)
- Decreased glucose (2%)
- Decreased albumin (1%)
- Headache (1%)
- Constipation (1%)
- Abdominal pain (1%)
- Mucositis (1%)
- Decreased appetite (1%)
- Hypomagnesemia (1%)
Warnings
Black Box Warnings
Neutropenia
- Severe neutropenia may occur; withhold for ANC <1,500/mm3 or neutropenic fever
- Monitor blood cell counts periodically during treatment
- Consider G-CSF for secondary prophylaxis
- Initiate anti-infective treatment in patient with febrile neutropenia without delay
Diarrhea
- Severe diarrhea may occur
- Monitor patients with diarrhea and give fluid and electrolytes as needed
- Administer atropine, if not contraindicated, for early diarrhea of any severity
- At onset of diarrhea, evaluate for infectious causes; if negative, promptly initiate loperamide
- If severe diarrhea occurs, withhold therapy until resolved to Grade ≤1 and reduce subsequent doses
Contraindications
Hypersensitivity to sacituzumab
Cautions
Therapy is emetogenic; premedicate for prevention of chemotherapy-induced nausea and vomiting (CINV)
Individuals who are homozygous for the uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1)*28 allele are at increased risk for neutropenia and may be at increased risk for other adverse reactions following initiation of treatment; closely monitor for severe neutropenia; appropriate dose in these patients is unknown and should be based on individual patient tolerance to treatment
Closely monitor patients with known reduced UGT1A1 activity for adverse reactions; withhold or permanently discontinue drug based on severity of observed adverse reactions in patients with evidence of acute early-onset or unusually severe adverse reactions, which may indicate UGT1A1 reduced function
Teratogenicity and/or embryofetal lethality may occur when administered to pregnant females
Hypersensitivity
- Severe and life-threatening hypersensitivity reactions occur
- Anaphylactic reactions have been observed in clinical trials
- Premedicate and monitor for signs and symptoms of infusion-related reactions during and for 30 min after each infusion
Neutropenia
- May cause severe or life-threatening neutropenia
- Withhold for ANC <1,500/mm3 on Day 1 or ANC <1,000/mm3 on Day 8 of any cycle, or neutropenic fever
- Febrile neutropenia also occurred, including patients with mTNBC after <2 prior therapies
Diarrhea
- Severe diarrhea may occur
- At the onset of diarrhea, evaluate for infectious causes, and, if negative, promptly initiate loperamide 4 mg initially followed by 2 mg per episode of diarrhea (not to exceed 16 mg/day)
- Discontinue loperamide 12 hr after diarrhea resolves; consider additional supportive measures (eg, fluid and electrolyte substitution) as clinically indicated
- Patients who exhibit an excessive cholinergic response to treatment (eg, abdominal cramping, diarrhea, salivation) can receive appropriate premedication (eg, atropine) for subsequent treatments
Drug interaction overview
- Sacituzumab govitecan is a UGT1A1 substrate
-
UGT1A1 inhibitors
- Avoid coadministration
- UGT1A1 inhibitors may increase adverse reactions due to potential increase in systemic exposure to SN-38 (active metabolite)
-
UGT1A1 inducers
- Avoid coadministration
- UGT1A1 enzyme inducers may substantially reduce exposure to SN-38 (active metabolite)
Pregnancy & Lactation
Pregnancy
Based on its mechanism of action, teratogenicity and/or embryofetal lethality may occur when administered to a pregnant female
No data available in pregnant women to inform the drug-associated risk
Sacituzumab contains a genotoxic component, SN-38, and is toxic to rapidly dividing cells
Advise pregnant females and those of reproductive potential of the potential risk to a fetus
Verify pregnancy status of females of reproductive potential prior to initiation
Contraception
- Females of reproductive potential: Use effective contraception during treatment and for 6 months after final dose
- Males of female partners of reproductive potential: Use effective contraception during treatment and for 3 months final dose
Infertility
- Based on findings in animals, fertility may be impaired in females of reproductive potential
Lactation
No information available on the presence of sacituzumab govitecan-hziy or SN-38 in human milk, effects on breastfed children, or effects on milk production
Advise females not to breastfeed during treatment and for 1 month after final dose
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Sacituzumab govitecan is an antibody-drug conjugate that contains SN-38, the active metabolite of irinotecan
Binds to topoisomerase I-DNA complex and prevents ligation of the cleaved DNA strand; this results in double-strand DNA breaks and, ultimately, cell death and termination of cellular replication
Absorption
Peak plasma concentration
- Sacituzumab: 243,000 ng/mL
- Free SN-38: 127 ng/mL
AUC
- Sacituzumab: 5,210,000 ng⋅hr/mL
- Free SN-38: 3,900 ng⋅hr/mL
Distribution
- Vd: 0.045 L/kg
Metabolism
No metabolism studies conducted
SN-38 (the small molecule moiety of sacituzumab govitecan-hziy) is metabolized via UGT1A1
Glucuronide metabolite of SN-38 (SN-38G) was detectable in the serum of patients
Elimination
Clearance: 0.002 L⋅hr/kg
Mean half-life
- Sacituzumab: 16 hr
- Free SN-38: 18 hr
Pharmacogenomics
Genetic variants of the UGT1A1 gene (eg, UGT1A1*28 allele) lead to reduced UGT1A1 enzyme activity
Individuals who are homozygous for the UGT1A1*28 allele are at increased risk for neutropenia
~20% of the Black or African American population, 10% of the white population, and 2% of the East Asian population are homozygous for the UGT1A1*28 allele
Decreased function alleles other than UGT1A1*28 may be present in certain populations
Administration
IV Incompatibilities
Stability of the reconstituted product has not been determined with other infusion-based solutions
Do not mix or infuse with other medicinal products
IV Compatibilities
0.9% NaCl
IV Preparation
Reconstitution
- Cytotoxic drug; follow applicable special handling and disposal procedures
- Calculate required dose (mg)
- Remove vials from refrigerate and calibrate them to room temperature
- Slowly inject 20 mL of 0.9% NaCl into each vial; resulting concentration will be 10 mg/mL
- Gently swirl vials and allow to dissolve for up to 15 minutes; do not shake
- Visually inspect vial(s) for particulate matter and discoloration before administering; reconstituted solution should be free of visible particulates, clear, and yellow; discard if cloudy or discolored
- Use immediately to prepare a diluted solution
Dilution
- Calculate required amount of the reconstituted solution needed
- Determine final volume of infusion bag; final concentration range: 1.1-3.4 mg/mL
- Use a polyvinyl chloride, polypropylene/polyethylene, polyolefin, or ethylene vinyl acetate infusion bag.
- Withdraw and discard volume of 0.9% NaCl from final infusion bag that is necessary to achieve indicated final concentration after adding calculated amount of reconstituted solution
- Withdraw required volume from vial(s); discard of any unused solution
- To minimize foaming, slowly inject calculated amount of reconstituted solution into infusion bag; do not shake contents
Premedication
- Patients who had prior infusion reactions: Premedicate with antipyretics, H1- and H2- blockers, and corticosteroids
- Premedicate with a 2- or 3-drug combination regimen (eg, dexamethasone with either a 5-HT3 receptor antagonist or a NK1-receptor antagonist, as well as other drugs as indicated)
IV Administration
IV infusion only; do not administer as IV push or bolus
Protect infusion bag from light
Upon completion, flush IV line with 20 mL 0.9% NaCl
May use an infusion pump
Infusion times
- Monitor for signs or symptoms of infusion-related reactions during infusion and for at least 30 min after infusion
- First infusion: Infuse over 3 hr
- Subsequent infusions: Infuse over 1-2 hr if prior infusions were tolerated
Storage
Unopened vials
- Refrigerate at 2-8°C (36-46°F)Do not freeze
- Protect from light until time of reconstitution
Diluted solution
- Must use immediately
- If not used immediately, refrigerate at 2-8ºC (36-46ºF) for up to 4 hr
- After refrigeration, administer diluted solution within 6 hr (including infusion time)
- Do not freeze or shake
- Protect from light
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Formulary
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