Dosing & Uses
Dosage Forms & Strengths
injection, powder for reconstitution
- Indicated for adjuvant treatment of HER-2 overexpressing breast cancer
- Administer during and following paclitaxel, docetaxel, or docetaxel/carboplatin
- 4 mg/kg IV over 90 minutes, THEN
- 2 mg/kg IV over 30 minutes qWeek during chemotherapy for the first 12 weeks (paclitaxel or docetaxel) or 18 weeks (docetaxel/carboplatin)
- One week following the last weekly dose administer at 6 mg/kg as an IV infusion over 30−90 min every three weeks
- As single agent within three wk following completion of multi-modality, anthracycline based chemotherapy regimens: Initial dose at 8 mg/kg as an IV infusion over 90 min; subsequent doses at 6 mg/kg as an IV infusion over 30−90 min every three wks
- Extending adjuvant treatment beyond one year not recommended
Indicated for treatment of HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma
Administered in combination with cisplatin and capecitabine or 5-fluorouracil who have not received prior treatment for metastatic disease
Subsequent cycles: 6 mg/kg IV q3wk; infuse IV over 30-90 min
Continue q3week cycles until disease progression
Modifications required for serious adverse events, including hypersensitivity reaction (anaphylaxis), infusion reactions (fatalities), decreased left ventricular function, and pulmonary events (ARDS)
- 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
- Assess LVEF prior to initiation and frequently during treatment
- Withhold for at least 4 weeks and repeat LVEF assessment q4Weeks for either of the following: 1) 16% absolute decrease in LVEF from pre-treatment values, 2) LVEF below institutional limits of normal and 10% absolute decrease in LVEF from pre-treatment values
- Drug may be resumed 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
Do not substitute ado-trastuzumab emtansine (Kadcyla) for or with trastuzumab (Herceptin); see Black Box Warnings
If patient has missed a dose by one week or less, 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 the weekly or three-weekly schedules, respectively
If patient has missed a dose by more than one week, a re-loading dose should be administered over approximately 90 min (weekly schedule: 4 mg/kg; three-weekly schedule: 8 mg/kg), 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 the weekly or three-weekly schedules, respectively
Pancreatic Cancer (Orphan)
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
Serious - Use Alternative
Significant - Monitor Closely
Abdominal pain (22%)
Back pain (22%)
Flu-like syndrome (10%)
Peripheral edema (10%)
Oligohydramnios or oligohydramnios sequence, including pulmonary hypoplasia, skeletal abnormalities, and neonatal death
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
- 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
- Exposure during pregnancy can result in oligohydramnios, in some cases complicated by pulmonary hypoplasia, skeletal abnormalities, and neonatal death
Hypersensitivity to drug/class/component or hamster protein
Use extreme cautioin in cardiac disease, cardiotoxic agent history, ejection fraction decrease, pulmonary disease, elderly
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; advise pregnant women and females of reproductive potential that therapy during pregnancy or within 7 months prior to conception can result in fetal harm; advise females of reproductive potential to avoid becoming pregnant while in therapy; if contraceptive methods are being considered, use effective contraception during treatment and for at least 7 months after receiving last dose of trastuzumab; if patient becomes pregnant while in therapy or within 7 months following last dose of therapy, apprise patient of potential hazard to fetus
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
Possibility of severe hypersensitivity reactions (including anaphylaxis), infusion reactions, and pulmonary events - strongly consider discontinuation/suspension in patients showing signs of the above
- 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)
Pregnancy & Lactation
Pregnancy Category: D; postmarketing reports suggest that use during pregnancy increases the risk of oligohydramnios during the second and third trimesters
Lactation: not known if excreted in breast milk, discontinue nursing during treatment and for 6 months after last dose
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.
Mechanism of Action
Monoclonal antibody, inhibits growth of tumor cells that overexpress HER2
Half-life: 6 days
Peak plasma: 377 mcg/mL
Vd: 44 mL/kg
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/)
Not to be mixed with other drugs
Prepare each vial by reconstituting 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
Using a sterile syringe, slowly inject the 20 mL of diluent into the vial containing the lyophilized cake; the stream of diluent should be directed into the lyophilized cake
Do not shake; swirl the vial gently to aid reconstitution
Slight foaming of the product may be present upon reconstitution; allow the vial to stand undisturbed for ~5 minutes
The solution should be free of visible particulates, clear to slightly opalescent and colorless to pale yellow
- Withdraw calculated dose from reconstituted vial and add to infusion bag containing 250 mL 0.9% NaCl
- Gently invert the bag to mix the solution
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 by ≤1 week: Usual maintenance dose (weekly schedule: 2 mg/kg; 3-weekly schedule: 6 mg/kg) should be administered as soon as possible; do not wait until the next planned cycle; give subsequent scheduled doses 7 or 21 days later accordingly
- Missed dose by >1 week: Reloading dose should be administered over ~90 minutes (weekly schedule: 4 mg/kg; three-weekly schedule: 8 mg/kg), as soon as possible; do not wait until the next planned cycle; give subsequent scheduled doses 7 or 21 days later accordingly
Do not freeze
Unopened vials: Stable at 2-8°C (36-46°F) prior to reconstitution
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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