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

Metastatic Breast Cancer

Indicated for metastatic triple-negative breast cancer (mTNBC) in patients who have received ≥2 prior therapies 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

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 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 and administer granulocyte-colony stimulating
    • factor (G-CSF)
    • 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 prior to 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

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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
            • If severe diarrhea occurs, withhold dose 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

            Based on its mechanism of action, teratogenicity and/or embryofetal lethality may occur when administered to a pregnant female

            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 is a UGT1A1 substrate

            • UGT1A1 inhibitors
              • Avoid coadministration
              • Coadministration with UGT1A1 inhibitors may increase the incidence of adverse reactions due to potential increase in systemic exposure to SN-38
            • UGT1A1 inducers
              • Avoid coadministration
              • Concomitant use of sacituzumab with 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)
            • Allow the required number of vials to warm 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, whenever solution and container permit; reconstituted solution should be free of visible particulates, clear, and yellow; discard reconstituted solution if it is cloudy or discolored
            • Use immediately to prepare a diluted solution

            Dilution

            • Calculate required volume of the reconstituted solution needed to obtain the appropriate dose
            • Withdraw this amount from the vial(s); discard of any unused solution
            • Slowly inject reconstituted solution into a 0.9% NaCl polypropylene (PP) infusion bag, to minimize foaming; do not shake the contents
            • Adjust volume in the 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

            Premedications

            • Before each dose, premedicate patients to prevent infusion-related reactions and CINV
            • Premedicate with antipyretics, H1 and H2 blockers, and corticosteroids for patients who had prior infusion reactions
            • 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

            • First infusion: Infuse over 3 hr; monitor for signs or symptoms of infusion-related reactions during the infusion and for at least 30 min after infusion
            • Subsequent infusions: Infuse over 1-2 hr if prior infusions were tolerated; monitor during the infusion and for at least 30 min after infusion

            Storage

            Unopened vial

            • 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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            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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            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
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