sacituzumab govitecan (Rx)

Brand and Other Names:Trodelvy, sacituzumab govitecan-hziy

Dosing & Uses

AdultPediatric

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

Days 1 and 8: 10 mg/kg IV  

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

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Interactions

Interaction Checker

and sacituzumab govitecan

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

            All Interactions Sort By:
             activity indicator 

            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)

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                  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%)
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                  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)
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                  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.

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                  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

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                  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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                  Patient Handout

                  A Patient Handout is not currently available for this monograph.
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                  Formulary

                  FormularyPatient Discounts

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                  Tier Description
                  1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
                  2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
                  3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
                  4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
                  5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
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                  Code Definition
                  PA Prior Authorization
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                  Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.