sacituzumab govitecan (Rx)

Brand and Other Names:Trodelvy, sacituzumab govitecan-hziy
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

injection, lyophilized powder for reconstitution

  • 180mg/vial

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

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
    • Third occurrence: Discontinue treatment
    • At the time of scheduled treatment, Grade 3-4 neutropenia that delay dose by >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
    • Grade 4 toxicity, 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 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
    • In the event of any other Grade 3-4 toxicities that delay dose by >3 weeks for recovery to Grade ≤1: 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 the onset of late diarrhea, evaluate for infectious causes and, if negative, promptly initiate loperamide
                  • Withhold therapy for Grade 3-4 diarrhea at time of scheduled treatment administration and resume when resolved to ≤Grade 1; 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

                  UGT1A1 substrate

                  • UGT1A1 inhibitors
                    • Avoid coadministration
                    • UGT1A1 inhibitors may increase the incidence of adverse reactions due to potential increase in systemic exposure to SN-38
                  • UGT1A1 inducers
                    • Avoid coadministration
                    • UGT1A1 enzyme inducers may substantially reduce exposure to SN-38
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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 administration; reconstituted solution should be free of visible particulates, clear, and yellow; discard if cloudy or discolored

                  Use immediately to prepare a diluted solution

                  Dilution

                  • Withdraw required volume from vial(s); discard of any unused solution
                  • Slowly inject reconstituted solution into a 0.9% NaCl polyvinyl chloride, polypropylene or ethylene/propylene copolymer infusion bag, to minimize foaming; do not shake contents
                  • Adjust volume in infusion bag as needed to obtain a final concentration of 1.1-3.4 mg/mL (total volume should not exceed 500 mL)
                  • Body weight >170 kg: Divide total dose equally between two 500-mL infusion bags and infuse sequentially via slow infusion

                  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

                  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 4 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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                  The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

                  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.
                  6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
                  NC NOT COVERED – Drugs that are not covered by the plan.
                  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.