trastuzumab

High Alert

HER2-overexpressing metastatic gastric or gastroesophageal adenocarcinoma in patients who have not received prior treatment for metastatic disease (in combination with cisplatin and capecitabine or 5-fluorouracil).
HER2-overexpressing node-positive or node-negative breast cancer (as part of one of the following regimens: doxorubicin, cyclophosphamide, and either paclitaxel or docetaxel; or docetaxel and carboplatin) (as adjuvant therapy).
HER2-overexpressing node-positive or node-negative breast cancer (to be used alone after multimodality anthracycline-based therapy) (as adjuvant therapy).
HER2-overexpressing metastatic breast cancer (as first-line therapy) (in combination with paclitaxel).
HER2-overexpressing metastatic breast cancer in patients who have already received ≥1 other chemotherapy regimens for metastatic disease (as monotherapy).

Action ⬆ ⬇

A monoclonal antibody that binds to HER2 sites in breast cancer tissue and inhibits proliferation of cells that overexpress HER2 protein.

Therapeutic effects:

Regression of breast, gastric, or gastroesophageal cancer and metastases.

Pharmacokinetics ⬆ ⬇

Absorption: IV administration results in complete bioavailability.

Distribution: Unknown.

Metabolism/Excretion: Unknown.

Half-Life: Unknown.

Time/Action Profile ⬆ ⬇

( plasma concentrations)

ROUTE		ONSET		PEAK		DURATION
IV		unknown		unknown		unknown

Contraind./Precautions ⬆ ⬇

Contraindicated in:

OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Pre-existing pulmonary conditions;
Hypersensitivity to trastuzumab, Chinese hamster ovary cell proteins, or other components of the product;
Hypersensitivity to benzyl alcohol (use sterile water for injection instead of bacteriostatic water, which accompanies the vial);
Rep: Women of reproductive potential;
Pedi: Safety not established in children;
Geri: Older adults may have ↑ risk of cardiotoxicity.

Exercise Extreme Caution in:

Pre-existing cardiac dysfunction.

Adv. Reactions/Side Effects ⬆ ⬇

CV: ARRHYTHMIAS, edema, HF, hypertension, tachycardia

Derm: rash, acne, herpes simplex

EENT: pharyngitis, rhinitis, sinusitis

GI: abdominal pain, anorexia, diarrhea, nausea, vomiting

Hemat: anemia, leukopenia

MS: pain, arthralgia, bone pain

Neuro: depression, dizziness, headache, insomnia, neuropathy, paresthesia, peripheral neuritis, weakness

Resp: ACUTE RESPIRATORY DISTRESS SYNDROME, cough, dyspnea, INTERSTITIAL PNEUMONITIS, PULMONARY EDEMA, PULMONARY FIBROSIS

Misc: chills, fever, infection, flu-like syndrome, INFUSION REACTIONS (INCLUDING ANAPHYLAXIS AND ANGIOEDEMA)

Interactions ⬆ ⬇

Drug-drug:

Anthracyclines, including daunorubicin, doxorubicin, or idarubicin, may ↑ risk of cardiotoxicity; if possible, avoid anthracycline-based therapy for up to 7 mo after stopping trastuzumab.
Paclitaxel may ↑ levels and risk of toxicity.

Route/Dosage ⬆ ⬇

Adjuvant Treatment of Breast Cancer

IV (Adults ): During and following paclitaxel, docetaxel, or docetaxel/carboplatin: 4 mg/kg initially; then 2 mg/kg once weekly during chemotherapy for the 1st 12 wk (paclitaxel or docetaxel) or 18 wk (docetaxel/carboplatin); 1 wk after the last weekly dose, give 6 mg/kg every 3 wk. Do not exceed treatment duration of 1 yr. As single agent within 3 wk following completion of multimodality, anthracycline-based chemotherapy regimens: 8 mg/kg initially; then 6 mg/kg every 3 wk. Do not exceed treatment duration of 1 yr.

Metastatic Breast Cancer

IV (Adults ): 4 mg/kg initially; then 2 mg/kg once weekly until disease progression.

Metastatic Gastric Cancer

IV (Adults ): 8 mg/kg initially; then 6 mg/kg every 3 wk until disease progression.

Availability ⬆ ⬇

Lyophilized powder for injection: 150 mg/vial; 420 mg/vial
In combination with:
hyaluronidase (Herceptin Hylecta). See Combination Drugs.

Assessment ⬆ ⬇

Assess for infusion-related symptoms (chills, fever, nausea, vomiting, pain [in some cases at tumor sites], headache, dizziness, dyspnea, hypotension, rash, asthenia) following initial infusion. Severe reactions (bronchospasm, anaphylaxis, angioedema, hypoxia, severe hypotension) may occur during or immediately following the initial infusion. May be treated with epinephrine, corticosteroids, diphenhydramine, bronchodilators, and oxygen. If dyspnea or severe hypotension occurs, interrupt infusion. If severe reaction occurs, permanently discontinue trastuzumab.
Assess for signs and symptoms of HF (dyspnea, ↑ cough, paroxysmal nocturnal dyspnea, peripheral edema, S₃ gallop, ↓ left ventricular ejection fraction [LVEF]) prior to and frequently during therapy. Perform baseline assessment of cardiac history, physical exam, and LVEF with ECG or multiple gated acquisition (MUGA) scan. Monitor LVEF every 3 mo, at completion of therapy, and then every 6 mo for ≥2 yr. If ≥16% absolute ↓ in LVEF from pretreatment values or an LVEF value below institutional limits of normal and ≥10% absolute ↓ in LVEF from pretreatment values occurs, hold trastuzumab. Repeat LVEF measures every 4 wk if dose is held for significant left ventricular dysfunction.
Monitor patient for signs of pulmonary hypersensitivity reactions (dyspnea, pulmonary infiltrates, pleural effusion, noncardiogenic pulmonary edema, hypoxia, acute respiratory distress syndrome). Patients with symptomatic pulmonary disease or extensive lung tumor involvement are at ↑ risk. If severe symptoms occur, discontinue trastuzumab.

Lab Test Considerations:

Verify negative pregnancy test before starting therapy.HER2 protein overexpression is used to determine whether treatment with trastuzumab is indicated. HER2 protein overexpression is detected by HercepTest (IHC assay) and PathVysion (FISH assay).
- May cause anemia and leukopenia.

Implementation ⬆ ⬇

High Alert: Do not confuse trastuzumab with ado-trastuzumab.
High Alert: Fatalities have occurred with chemotherapeutic agents. Before administering, clarify all ambiguous orders; double-check single, daily, and course-of-therapy dose limits; have second practitioner independently double-check original order, dose calculations, and infusion pump settings.
May be administered in the outpatient setting.
If a dose is missed by ≤1 wk, administer usual maintenance dose as soon as possible. Do not wait until next planned cycle. Administer subsequent maintenance doses 7 days or 21 days later according to the weekly or three-weekly schedules, respectively. If a dose is missed by >1 wk, administer a reloading dose as soon as possible. Administer subsequent maintenance doses 7 days or 21 days later according to weekly or three-weekly schedules, respectively.

IV Administration:

Intermittent Infusion:
Y-Site Compatibility:
- acyclovir
- aminophylline
- ampicillin
- ampicillin/sulbactam
- bleomycin
- bumetanide
- buprenorphine
- busulfan
- butorphanol
- calcium gluconate
- carboplatin
- carmustine
- cefazolin
- ceftazidime
- ceftriaxone
- cefuroxime
- ciprofloxacin
- cisplatin
- cyclophosphamide
- cytarabine
- dactinomycin
- daunorubicin
- dexamethasone
- digoxin
- diphenhydramine
- dobutamine
- docetaxel
- dopamine
- doxorubicin hydrochloride
- doxorubicin liposomal
- doxycycline
- droperidol
- enalaprilat
- etoposide phosphate
- famotidine
- fentanyl
- filgrastim
- fluconazole
- fluorouracil
- ganciclovir
- gemcitabine
- gentamicin
- granisetron
- haloperidol
- heparin
- hydrocortisone
- hydromorphone
- ifosfamide
- imipenem/cilastatin
- leucovorin
- lorazepam
- magnesium sulfate
- mannitol
- meperidine
- mesna
- methotrexate
- methylprednisolone
- metoclopramide
- metronidazole
- minocycline
- mitomycin
- mitoxantrone
- paclitaxel
- pentamidine
- potassium chloride
- prochlorperazine
- promethazine
- remifentanil
- sargramostim
- sodium bicarbonate
- theophylline
- thiotepa
- tobramycin
- trimethoprim/sulfamethoxazole
- vancomycin
- vinblastine
- vincristine
- vinorelbine
- zidovudine
Y-Site Incompatibility:
- aldesleukin
- amikacin
- amphotericin B deoxycholate
- aztreonam
- cefotaxime
- cefotetan
- cefoxitin
- chlorpromazine
- clindamycin
- cyclosporine
- fludarabine
- furosemide
- idarubicin
- irinotecan
- levofloxacin
- morphine
- nalbuphine
- ondansetron
- piperacillin/tazobactam
- topotecan

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of medication to patient. Advise patient to read Patient Information before starting therapy.
Advise patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care provider before taking other medications.
Advise patients to contact a health care provider immediately if signs and symptoms of HF (new onset or worsening shortness of breath, cough, swelling of the ankles/legs, swelling of face, palpitations, weight gain >5 pounds in 24 hr, dizziness, loss of consciousness) or hypersensitivity reactions (dizziness, nausea, chills, fever, vomiting, diarrhea, urticaria, angioedema, breathing problems, chest pain) occur.
Caution patient to avoid crowds and persons with known infections.
Advise patient not to receive any vaccinations without advice of health care provider.
Rep: May cause fetal harm. Advise women of reproductive potential to notify health care provider immediately if pregnancy is planned or suspected and to avoid breastfeeding. Caution patient to use effective contraception during therapy and for 7 mo following last dose. Monitor infants exposed to trastuzumab for oligohydramnios, pulmonary hypoplasia, skeletal abnormalities, and neonatal death. Encourage women who may be exposed during pregnancy to report exposure to the Genentech Adverse Event Line at 1-888-835-2555.

Evaluation/Desired Outcomes ⬆ ⬇

Regression of breast, gastric, or gastroesophageal cancer and metastases.

US Brand Names ⬆ ⬇

Herceptin, Hercessi, Herzuma, Kanjinti, Ogivri, Ontruzant, Trazimera

Code ⬆

NDC Code

12714- Boehringer Ingelheim Pharma GmbH and Co. KG
- 12714-235-
  - 12714-235-87- 87 mg in 1 TANK (12714-235-87)

50242- Genentech, Inc.
- 50242-132- Herceptin
  - 50242-132-01- 1 VIAL, SINGLE-DOSE in 1 CARTON (50242-132-01) / 15 mL in 1 VIAL, SINGLE-DOSE

63459- Cephalon, Inc.
- 63459-303- HERZUMA
  - 63459-303-43- 1 VIAL, SINGLE-DOSE in 1 CARTON (63459-303-43) / 20 mL in 1 VIAL, SINGLE-DOSE

63459- Cephalon, Inc.
- 63459-305- HERZUMA
  - 63459-305-47- 1 KIT in 1 CARTON (63459-305-47) * 50 mL in 1 VIAL, MULTI-DOSE (63459-307-41) * 20 mL in 1 VIAL (63459-221-20)

63552- Patheon Manufacturing Services LLC
- 63552-037-
  - 63552-037-00- 143 VIAL in 1 TRAY (63552-037-00) / 15 mL in 1 VIAL

67457- Mylan Institutional LLC
- 67457-847- OGIVRI
  - 67457-847-44- 1 KIT in 1 CARTON (67457-847-44) * 20 mL in 1 VIAL, MULTI-DOSE (67457-845-50) * 20 mL in 1 VIAL (67457-846-20)

67457- Mylan Institutional LLC
- 67457-991- OGIVRI
  - 67457-991-15- 1 VIAL in 1 CARTON (67457-991-15) / 15 mL in 1 VIAL

67643- Lonza Biologics, Inc.
- 67643-0022-
  - 67643-0022-1- 300 L in 1 DEWAR (67643-0022-1)

69438- Lonza Biologics Tuas Pte. Ltd.
- 69438-0008-
  69438-0008-1- 300 L in 1 DEWAR (69438-0008-1)

78206- Organon LLC
- 78206-147- Ontruzant
  78206-147-01- 1 VIAL, SINGLE-DOSE in 1 CARTON (78206-147-01) / 1 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION in 1 VIAL, SINGLE-DOSE (78206-147-99)

78848- Fareva
- 78848-006-
  - 78848-006-01- 6.36 mL in 1 VIAL (78848-006-01)

78848- Fareva
- 78848-007-
  78848-007-01- 17.6 mL in 1 VIAL (78848-007-01)

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇