trastuzumab/hyaluronidase (Rx)

Brand and Other Names:Herceptin Hylecta, trastuzumab-hyaluronidase-oysk
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Dosing & Uses

AdultPediatricGeriatric

Dosage Forms & Strengths

trastuzumab/hyaluronidase

injectable solution, single-dose vial

  • (120mg/2,000 units)/mL
  • Ready-to-use SC solution contains trastuzumab and hyaluronidase human

Adjuvant Breast Cancer

Indicated for adjuvant treatment of HER2-overexpressing breast cancer for the following:

In combination with doxorubicin, cyclophosphamide, and either paclitaxel or docetaxel OR

In combination with docetaxel and carboplatin OR

As a single agent following multimodality anthracycline-based therapy

600 mg trastuzumab/10,000 units hyaluronidase SC q3Weeks

Continue treatment for 52 weeks or until disease recurrence, whichever occurs first; extending treatment in adjuvant breast cancer >1 year is not recommended

Metastatic Breast Cancer

Indicated for HER2-overexpressing metastatic breast cancer in combination with paclitaxel for first-line treatment or as a single agent in patients who have received ≥1 chemotherapy regimens for metastatic disease

600 mg trastuzumab/10,000 units hyaluronidase SC q3Weeks

Continue until disease progression

Dosage Modifications

Cardiomyopathy

  • Withhold dose for ≥4 weeks
    • ≥16% absolute decrease in left ventricular ejection fraction (LVEF) from baseline
    • LVEF below institutional limits of normal and ≥10% absolute decrease in LVEF from baseline
    • Resume if, within 4−8 weeks, LVEF returns to normal limits and absolute decrease from baseline is ≤15%
  • Permanently discontinue
    • Persistent (>8 weeks) LVEF decline
    • Withheld dose on >3 occurrences for cardiomyopathy

Dosing Considerations

No loading dose is required

No dose adjustments for body weight or for different concomitant chemotherapy regimens are required

Do not substitute trastuzumab/hyaluronidase for or with ado-trastuzumab emtansine

Cardiac monitoring

  • Conduct thorough cardiac assessment (eg, history, physical examination, and determination of LVEF by echocardiogram, multigated acquisition scan)
  • Baseline LVEF measurement immediately prior to initiation
  • LVEF measurements q3Months during and upon completion of treatment
  • Repeat LVEF measurement at 4-week intervals if dose is withheld
  • LVEF measurements q6Months for ≥2 yr following completion of trastuzumab/hyaluronidase as a component of adjuvant therapy

Patient selection

  • Select patients based on an FDA-approved companion diagnostic for trastuzumab
  • Assess HER2 protein overexpression and HER2 gene amplification using FDA-approved tests specific for breast cancer by laboratories with demonstrated proficiency
  • Information on FDA-approved tests for detecting HER2 protein overexpression and HER2 gene amplification is available at: http://www.fda.gov/CompanionDiagnostics

Safety and efficacy not established

In patients receiving IV trastuzumab, risk of cardiac dysfunction was increased in geriatric patients as compared with younger patients, in both those receiving treatment for adjuvant therapy or metastatic disease

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Interactions

Interaction Checker

and trastuzumab/hyaluronidase

No Results

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    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

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            Adverse Effects

            >10% (All Grades)

            Alopecia (63%)

            Nausea (49%)

            Fatigue (46%)

            Neutropenia (44%)

            Diarrhea (34%)

            Rash (26%)

            Upper respiratory tract infection (24%)

            Vomiting (23%)

            Stomatitis (21%)

            Myalgia (21%)

            Peripheral neuropathy (20%)

            Decreased appetite (20%)

            Arthralgia (18%)

            Headache (17%)

            Nail disorder (14%)

            Abdominal pain (14%)

            Flushing (14%)

            Edema (14%)

            Pyrexia (13%)

            Anemia (12%)

            Cough (12%)

            Dyspepsia (11%)

            Leukopenia (11%)

            Back pain (11%)

            Incision site complication (11%)

            >10% (Grade ≥3)

            Neutropenia (30%)

            1-10% (All Grades)

            Mucosal inflammation (10%)

            Injection site reactions (10%)

            Pain in extremity (10%)

            Dizziness (10%)

            Dysgeusia (10%)

            Pruritus (9%)

            Skin discoloration (9%)

            Pain (8%)

            Hypertension (8%)

            Erythema (7%)

            Dyspnea (7%)

            Hypersensitivity (7%)

            Febrile neutropenia (6%)

            Bone pain (6%)

            Epistaxis (6%)

            Abnormal liver function tests (6%)

            Pain (5%)

            Nasal inflammation/discomfort (5%)

            Arrhythmia (5%)

            Urinary tract infection (4%)

            1-10% (Grade ≥3)

            Febrile neutropenia (6%)

            Leukopenia (5%)

            Diarrhea (2.7%)

            Hypertension (2.4%)

            Alopecia (1.3%)

            Nausea (1.3%)

            Vomiting (1%)

            Upper respiratory tract infection (1%)

            Back pain (1%)

            Hypersensitivity (1%)

            Abnormal liver function tests (1%)

            <1% (Grade ≥3)

            Erythema

            Rash

            Stomatitis

            Fatigue

            Mucosal inflammation

            Anemia

            Bone pain

            Pain

            Headache

            Dizziness

            Cough

            Flushing

            Decreased appetite

            Postmarketing Reports

            Administration-related reaction

            Oligohydramnios or oligohydramnios sequence, including pulmonary hypoplasia, skeletal abnormalities, and neonatal death

            Glomerulopathy

            Immune thrombocytopenia

            Tumor lysis syndrome

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            Warnings

            Black Box Warnings

            Cardiomyopathy

            • Administration can result in subclinical and clinical cardiac failure
            • Highest incidence and severity occurred in patients receiving trastuzumab/hyaluronidase with anthracycline-containing chemotherapy regimens
            • Evaluate left ventricular function prior to and during treatment
            • Discontinue treatment in patients receiving adjuvant therapy and withhold dose in patients with metastatic disease for clinically significant decrease in left ventricular function

            Pulmonary toxicity

            • Serious and fatal pulmonary toxicity reported
            • Symptoms usually occur during or within 24 hr of administration
            • Discontinue treatment for anaphylaxis, angioedema, interstitial pneumonitis, or acute respiratory distress syndrome)
            • Monitor until symptoms completely resolve

            Embryo-fetal toxicity

            • Exposure to trastuzumab/hyaluronidase during pregnancy can result in oligohydramnios and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death
            • Inform patients of these risks and to use effective contraception

            Contraindications

            None

            Cautions

            Left ventricular cardiac dysfunction, arrhythmias, hypertension, disabling cardiac failure, cardiomyopathy, and cardiac death may occur as well as asymptomatic decline in LVEF (see Black Box Warnings)

            Fetal harm may occur when administered to a pregnant woman (see Black Box Warnings and Pregnancy)

            Pulmonary toxicity (eg, dyspnea, interstitial pneumonitis, pulmonary infiltrates, pleural effusions, noncardiogenic pulmonary edema, pulmonary insufficiency and hypoxia, acute respiratory distress syndrome, pulmonary fibrosis) reported; patients with symptomatic intrinsic lung disease or with extensive tumor involvement of the lungs, resulting in dyspnea at rest, appear to have more severe toxicity (see Black Box Warnings)

            Chemotherapy-induced neutropenia may be exacerbated

            Severe administration-related reactions (ARRs), including hypersensitivity and anaphylaxis, reported; patients experiencing dyspnea at rest due to complications of advanced malignancy and comorbidities may be at increased risk of a severe or fatal ARR

            Drug interaction overview

            • Since trastuzumab/hyaluronidase has a long washout period, patients who receive anthracycline after stopping trastuzumab/hyaluronidase may be at increased risk of cardiac dysfunction
            • If possible, avoid anthracycline-based therapy for at least 7 months after discontinuing trastuzumab/hyaluronidase
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            Pregnancy & Lactation

            Pregnancy

            Fetal harm when administered to a pregnant woman

            Verify pregnancy status of females of reproductive potential before initiation

            Female: Use effective contraception during treatment and for 7 months following the last dose

            Pregnancy pharmacovigilance program

            • If administered during pregnancy, or if a patient becomes pregnant while during treatment or within 7 months following the last dose, immediately report exposure to Genentech at 1-888-835-2555
            • In postmarketing reports, use of trastuzumab during pregnancy resulted in cases of oligohydramnios and of oligohydramnios sequence, manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death
            • Advise patient of the potential risks to a fetus

            Clinical considerations

            • Monitor women who received treatment during pregnancy or within 7 months prior to conception for oligohydramnios
            • If oligohydramnios occurs, perform fetal testing that is appropriate for gestational age and consistent with community standards of care

            Lactation

            There is no information regarding the presence of trastuzumab or hyaluronidase in human milk, the effects on the breastfed infant, or the effects on milk production

            Published data suggest human IgG is present in human milk but does not enter the neonatal and infant circulation in substantial amounts

            Present in the milk of lactating cynomolgus monkeys but not associated with neonatal toxicity

            Consider developmental and health benefits of breastfeeding along with the mother’s clinical need for treatment and any potential adverse effects on the breastfed child or from the underlying maternal condition; also take into account the trastuzumab wash-out period of 7 months

            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

            Trastuzumab

            • Monoclonal antibody; inhibits growth of tumor cells that overexpress HER2

            Hyaluronidase

            • Human hyaluronidase increases permeability of SC tissue by temporarily depolymerizing hyaluronan
            • Effects are reversible and permeability of SC tissue is restored within 24-48 hr

            Absorption

            Peak plasma concentration: 79.3 mcg/mL (Cycle 1); 149 mcg/mL (Cycle 7)

            Minimum plasma concentration: 28.2 mcg/mL (Cycle 1); 75 mcg/mL (Cycle 7)

            AUC: 1065 mcg/mL·day (Cycle 1); 2337 mcg/mL·day (Cycle 7)

            Absolute bioavailability: 0.77

            Peak plasma time: 3 days

            Steady-state reached after Cycle 7

            Distribution

            Vd: 2.9 L

            Elimination

            Linear elimination clearance: 0.11 L/day

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            Administration

            SC Administration

            SC administration only

            To prevent medication errors, check vial labels to ensure that the prepared drug to be administered is trastuzumab/hyaluronidase and not ado-trastuzumab emtansine or IV trastuzumab

            Compatible with polypropylene and polycarbonate syringe material and stainless steel transfer and injection needles

            Alternate injection site between the left and right thigh

            Administer new injections ≥2.5 cm from previous site on healthy skin; never inject into areas where the skin is red, bruised, tender, or hard, or areas where there are moles or scars

            During treatment course, inject other SC medicinal products at different sites

            Administer over ~2-5 min

            Missed dose

            • If 1 dose is missed, administer missed dose as soon as possible; interval between subsequent doses should not be <3 weeks

            Storage

            Protect from light; do not shake or freeze

            If syringe is not immediately used, refrigerate (2-8°C [36-46°F]) for up to 24 hr and subsequently at room temperature (20-25°C [68-77°F]) for up to 4 hr

            Vials

            • Refrigerate at 2-8°C (36-46°F) in original carton
            • Once removed from refrigerator, administer within 4 hr and keep <30°C (86°F)
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            Images

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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.
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            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
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            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
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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.