trastuzumab (Rx)

Brand and Other Names:Herceptin, Ogivri, more...Herzuma, Ontruzant, trastuzumab-dkst, trastuzumab-pkrb, trastuzumab-dttb, Trazimera, trastuzumab-qyyp
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

injection, powder for reconstitution

  • 150mg/single-dose vial (Herceptin, Ontruzant)
  • 420mg/multidose vial (Herceptin, Ogivri, Herzuma, Trazimera)

Biosimilar to Herceptin

  • Ogivri (trastuzumab-dkst)
  • Herzuma (trastuzumab-pkrb)
  • Ontruzant (trastuzumab-dttb)
  • Trazimera (trastuzumab-qyyp)
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Breast Cancer

Adjuvant treatment

  • Indicated for adjuvant treatment of HER-2 overexpressing breast cancer
  • In combination with doxorubicin, cyclophosphamide, and either paclitaxel or docetaxel
    • Herceptin, Ogivri, Herzuma, Ontruzant, Trazimera
    • 4 mg/kg IV over 90 min, THEN 
    • 2 mg/kg IV over 30 min qWeek during chemotherapy for the first 12 weeks (paclitaxel or docetaxel)
    • One week following the last weekly dose, initiate 6 mg/kg IV q3Weeks; infuse over 30-90 min
    • Administer for a total of 52 weeks
  • In combination with docetaxel and carboplatin
    • Herceptin, Ogivri, Herzuma, Ontruzant, Trazimera
    • 4 mg/kg IV over 90 min, THEN 
    • 2 mg/kg IV over 30 min qWeek during chemotherapy for the first 18 weeks (docetaxel/carboplatin)
    • One week following the last weekly dose, initiate 6 mg/kg IV q3Weeks; infuse over 30-90 min
    • Administer for a total of 52 weeks
  • As a single agent following completion of multi-modality, anthracycline-based chemotherapy
    • Herceptin, Ogivri, Trazimera, Ontruzant
    • 8 mg/kg IV over 90 min, THEN 
    • 6 mg/kg as an IV over 30−90 min q3Weeks
    • Administer for a total of 52 weeks
    • Extending adjuvant treatment beyond one year not recommended

Metastatic breast cancer

  • Herceptin, Ogivri, Herzuma, Trazimera, Ontruzant
  • Indicated for HER2-overexpressing metastatic breast cancer as first-line treatment in combination with paclitaxel OR as a single agent for patients who have received 1 or more chemotherapy regimens for metastatic disease
  • 4 mg/kg IV over 90 min, THEN 
  • 2 mg/kg IV over 30 min qWeek, continue until disease progression

Gastric Cancer

Herceptin, Ogivri, Ontruzant, Trazimera

Indicated, in combination with cisplatin and capecitabine or 5-fluorouracil, for patients with HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma who have not received prior treatment for metastatic disease

8 mg/kg IV over 90 min, THEN 

6 mg/kg IV q3wk; infuse IV over 30-90 min, continue until disease progression

See also Administration

Dosage Modifications

Modifications required for serious adverse events, including hypersensitivity reaction (anaphylaxis), infusion reactions (fatalities), decreased left ventricular function, and pulmonary events (ARDS)

Infusion reactions

  • Decrease infusion rate for mild-moderate infusion reactions
  • Interrupt infusion if dyspnea or clinically significant hypotension
  • Strongly consider permanent discontinuation if severe and life-threatening infusion reactions

Cardiomyopathy

  • Assess LVEF prior to initiation and frequently during treatment
  • Withhold for at least 4 weeks
    • ≥16% absolute decrease in LVEF from pretreatment values
    • LVEF below institutional limits of normal and ≥10% absolute decrease in LVEF from pretreatment values
    • Resume drug if, within 4-8 weeks, the LVEF returns to normal and absolute decrease from baseline is ≤15%
    • Permanently discontinue for a persistent (>8 weeks) LVEF decline or for suspension of drug on >3 occasions for cardiomyopathy

Dosing Considerations

Do not substitute ado-trastuzumab emtansine (Kadcyla) for or with trastuzumab; see Black Box Warnings

Patient selection is based on HER2 protein overexpression or HER2 gene amplification; assessment of HER2 protein overexpression and gene amplification should be performed using FDA-approved tests specific for breast or gastric cancers by laboratories with demonstrated proficiency; FDA-approved tests for detection of HER2 protein overexpression and HER2 gene amplification is available at: http://www.fda.gov/CompanionDiagnostics

Pancreatic Cancer (Orphan)

Herceptin only

Indicated for the treatment of patients with pancreatic cancer that overexpress p185HER2

Orphan indication sponsor

  • Genentech, Inc; 1 DNA Way; South San Francisco, CA 94080-4990

Safety and efficacy not established

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Interactions

Interaction Checker

and trastuzumab

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

            All Interactions Sort By:
             activity indicator 
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            Adverse Effects

            >10% (Metastatic Breast Cancer)

            Pain (47%)

            Asthenia (42%)

            Fever (36%)

            Nausea (33%)

            Chills (32%)

            Cough (26%)

            Headache (26%)

            Diarrhea (25%)

            Vomiting (23%)

            Abdominal pain (22%)

            Back pain (22%)

            Dyspnea (22%)

            Infection (20%)

            Rash (18%)

            Anorexia (14%)

            Insomnia (14%)

            Dizziness (13%)

            1-10% (Adjuvant Breast Cancer Treatment)

            Headache (10%)

            Nasopharyngitis (8%)

            Diarrhea (7%)

            Nausea (6%)

            Pyrexia (6%)

            Peripheral edema (5%)

            Back pain (5%)

            Chills (5%)

            Asthenia (4.5%)

            Myalgia (4%)

            Hypertension (4%)

            Dizziness (4%)

            Influenza (4%)

            Rash (4%)

            Vomiting (3.5%)

            Bone pain (3%)

            UTI (3%)

            Influenza-like illness (2%)

            Nail disorders (2%)

            Pruritus (2%)

            Paresthesia (2%)

            1-10% (Metastatic Breast Cancer)

            Flu-like syndrome (10%)

            Peripheral edema (10%)

            CHF (7%)

            Depression (6%)

            Tachycardia (5%)

            UTI (5%)

            Anemia (4%)

            Hypersensitivity (3%)

            Leukopenia (3%)

            <1% (Adjuvant Breast Cancer Treatment)

            Cardiac failure (0.5%)

            Cardiac disorder (0.3%)

            Hypersensitivity (0.6%)

            Autoimmune thyroiditis (0.3%)

            Ventricular dysfunction (0.2%)

            Sudden death (0.06%)

            Postmarketing Reports

            Infusion 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

            Do not substitute ado-trastuzumab emtansine (Kadcyla) for or with trastuzumab (Herceptin); dosing and treatment schedules for Kadcyla and Herceptin are quite different, so confusion between these products could lead to dosing errors and potential harm to patients

            Cardiomyopathy

            • Administration can result in subclinical and clinical cardiac failure manifesting as CHF and decreased left ventricular ejection fraction (LVEF)
            • Evaluate LVEF in all patients prior to and during treatment with trastuzumab
            • Incidence and severity of left ventricular cardiac dysfunction is highest in patients who receive the drug concurrently with anthracycline-containing chemotherapy regimens
            • Discontinue if receiving adjuvant therapy for breast cancer, and strongly consider discontinuation with metastatic breast cancer who develop a clinically significant decrease in left ventricular function

            Infusion reactions, pulmonary toxicity

            • Can result in serious pulmonary toxicity and sometimes fatal infusion reactions
            • In most cases, symptoms occurred during or within 24 hr of administration
            • Interrupt infusion in patients experiencing dyspnea or clinically significant hypotension
            • Monitor until signs and symptoms completely resolve
            • Discontinue for infusion reactions manifesting as anaphylaxis, angioedema, interstitial pneumonitis, or acute respiratory distress syndrome

            Embryo-fetal toxicity

            • Exposure during pregnancy can result in oligohydramnios, in some cases complicated by pulmonary hypoplasia, skeletal abnormalities, and neonatal death

            Contraindications

            Hypersensitivity to drug/class/component or hamster protein

            Cautions

            Use extreme caution in cardiac disease, cardiotoxic agent history, ejection fraction decrease, pulmonary disease, elderly (see Black Box Warnings)

            Risk of ventricular dysfunction and CHF - strongly consider discontinuation if clinically significant decrease in left ventricular function (concurrent anthracyclines and cyclophosphamide increase incidence and severity)

            Verify pregnancy status of females of reproductive potential prior to the initiation of therapy (see Pregnancy)

            CHF: At a median follow-up duration of 8 yr, the incidence of severe CHF (NYHA III and IV) was 0.8%, and the rate of mild symptomatic and asymptomatic left ventricular dysfunction was 4.6%

            Patients who receive anthracycline after stopping trastuzumab therapy may be at increased risk of cardiac dysfunction

            Exposure to trastuzumab during pregnancy or within 7 months prior to conception can result in fetal harm; females of reproductive potential should use effective contraception during treatment and for 7 months following last dose of trastuzumab

            In clinical trials, per-patient incidences of Grade 3 to 4 neutropenia and of febrile neutropenia were higher in patients receiving trastuzumab in combination with myelosuppressive chemotherapy as compared to those who received chemotherapy alone

            Tumor lysis syndrome (TLS) reported; patients with significant tumor burden (e.g. bulky metastases) may be at a higher risk; patients could present with hyperuricemia, hyperphosphatemia, and acute renal failure which may represent possible TLS; providers should consider additional monitoring and/or treatment as clinically indicated

            Preinfusion treatment

            • Symptoms such as chills and/or fever observed in ~40% of patients
            • Usually mild-to-moderate severity
            • Pretreat with acetaminophen, diphenhydramine, and meperidine (with or without reduction in infusion rate)
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            Pregnancy & Lactation

            Pregnancy

            May cause fetal harm when administered to a pregnant woman

            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

            Herceptin pregnancy registry

            • If administered during pregnancy, or if a patient becomes pregnant while receiving trastuzumab or within 7 months following last dose, health care providers and patients should immediately report exposure to Genentech at 1-888-835-2555

            Contraception

            • Verify pregnancy status of females of reproductive potential prior to initiating
            • Advise pregnant women and females of reproductive potential that exposure during pregnancy or within 7 months prior to conception can result in fetal harm
            • Advise females of reproductive potential to use effective contraception during treatment and for 7 months following last dose

            Lactation

            No information regarding the presence of trastuzumab in human milk, the effects on breastfed infants, or the effects on milk production

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

            Trastuzumab was present in the milk of lactating cynomolgus monkeys but not associated with neonatal toxicity

            Assess the developmental and health benefits of breastfeeding along with the mother’s clinical need for treatment and any potential adverse effects on the breastfed child from the drug or from the underlying maternal condition (unwrap)

            Consider 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.

            more...
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            Pharmacology

            Mechanism of Action

            Monoclonal antibody, inhibits growth of tumor cells that overexpress HER2

            Absorption

            Breast cancer

            • Peak plasma concentration: 178 mcg/mL (8 mg/kg); 88.3 mcg/mL (4 mg/kg)
            • Peak plasma concentration at steady state: 179 mcg/mL (8 mg/kg); 109 mcg/mL (4 mg/kg)
            • AUC: 1373 mcg·day/mL (8 mg/kg); 1066 mcg·day/mL (4 mg/kg)
            • AUC at steady state: 1794 mcg·day/mL (8 mg/kg); 1765 mcg·day/mL (4 mg/kg)
            • Steady state: 12 weeks

            Metastatic gastric cancer

            • Peak plasma concentration: 132 mcg/mL (8 mg/kg)
            • Peak plasma concentration at steady state: 131 mcg/mL (8 mg/kg)
            • AUC: 1109 mcg·day/mL (8 mg/kg)
            • AUC at steady state: 1338 mcg·day/mL (8 mg/kg)
            • Steady state: 9 weeks

            Pharmacogenomics

            Mediates antibody-dependent cellular cytotoxicity against cells that overproduce HER2, and lacks effect on cells not overexpressing HER2

            HER2 testing should be performed

            Patients with breast cancers with intensive staining (3+) should definitely receive anti-HER2 therapy; the clinical relevance of 2+ staining is uncertain

            Genetic testing laboratories

            • The following companies currently offer IHC and/or FISH testing for HER2 overexpression
            • Dako (http://www.dakousa.com/)
            • Ventana Medical Systems (http://www.ventanamed.com/)
            • Vysis/Abbott Molecular (http://www.abbottmolecular.com/)
            • Invitrogen (http://www.invitrogen.com/)
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            Administration

            IV Incompatibilities

            Dextrose solutions

            Not to be mixed with other drugs

            IV Preparation

            420 mg multiple-dose vial

            • Reconstitute powder with 20 mL of supplied diluent (bacteriostatic water for injection [BWFI]; contains 1.1% benzyl alcohol as a preservative)
            • If patient has known hypersensitivity to benzyl alcohol, drug may be reconstituted with sterile water for injection (SWI), but use SWI-reconstituted drug immediately
            • Reconstituted vial yields 21 mg/mL
            • Slowly inject 20 mL of diluent into vial; stream of diluent should be directed into the lyophilized cake
            • Do not shake; swirl vial gently to aid reconstitution
            • Slight foaming of the product may be present upon reconstitution; allow vial to stand undisturbed for ~5 minutes
            • Solution should be free of visible particulates; appear clear to slightly opalescent and colorless to pale yellow
            • See also Storage

            150 mg single-dose vial

            • Reconstitute with 7.4 mL of Sterile Water for Injection (SWFI) (not supplied) to yield a solution containing 21 mg/mL trastuzumab
            • Do not shake; swirl vial gently to aid reconstitution
            • Slight foaming of the product may be present upon reconstitution; allow vial to stand undisturbed for ~5 minutes
            • Solution should be free of visible particulates; appear clear to slightly opalescent and colorless to pale yellow

            Further dilution

            • Withdraw calculated dose from reconstituted vial and add to a polyvinylchloride- or polyethylene-bag containing 250 mL 0.9% NaCl
            • Gently invert the bag to mix the solution

            IV Administration

            Not for IV push or bolus administration

            Administer initial IV infusion over 90 min

            Subsequent weekly IV infusions may be administered over 30 min if prior infusions are well tolerated

            Missed dose ≤1 week

            • Usual maintenance dose (weekly schedule: 2 mg/kg; three-weekly schedule: 6 mg/kg) should be administered as soon as possible
            • Do not wait until next planned cycle
            • Subsequent maintenance doses should be administered 7 days or 21 days later according to qWeek or q3Weeks schedule, respectively

            Missed dose >1 week

            • Reload dose (weekly schedule: 4 mg/kg; three-weekly schedule: 8 mg/kg) over ~90 min, as soon as possible
            • Subsequent maintenance doses (weekly schedule: 2 mg/kg; three-weekly schedule 6 mg/kg) should be administered 7 days or 21 days later according to qWeek or q3Weeks schedule, respectively

            Storage

            Do not freeze

            Unopened vials: Stable at 2-8°C (36-46°F) prior to reconstitution

            Unopened vials (Trazimera only): If needed, may store at room temperature up to 30°C (86°F) for a single period of up to 3 months in original carton to protect from light; once removed from refrigerator, do not return to the refrigerator and discard after 3 months or by vial expiration date, whichever occurs first; write revised expiration date in the space provided on the carton labeling

            Reconstituted vials with BWFI: Once reconstituted with BWFI, may be stored in refrigerator (2-8°C) for 28 days

            Reconstituted vials with SWI: Vials reconstituted with unpreserved SWI (not supplied) should be used immediately and not stored

            Diluted solution: May be refrigerated (2-8°C) for up to 24 hr

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            Images

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            Formulary

            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

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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.
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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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